Liver stiffness in hepatocellular carcinoma and chronic hepatitis patients: Hepatitis B virus infection and transaminases should be considered.

BACKGROUND: Liver condition is a crucial prognostic factor for patients with hepatocellular carcinoma (HCC), but a convenient and comprehensive method to assess liver condition is lacking. Liver stiffness (LS) measured by two-dimensional shear wave elastography may help in assessing liver fibrosis and liver condition. Chronic hepatitis B (CHB) is an important risk factor for HCC progression, but LS was found to be less reliable in assessing liver fibrosis following hepatitis viral eradication. We hypothesize that the status of hepatitis virus infection would affect the accuracy of LS in assessing the liver condition. AIM: To test the feasibility and impact factors of using LS to assess liver condition in patients with HCC and CHB. METHODS: A total of 284 patients were retrospectively recruited and classified into two groups on the basis of serum CHB virus hepatitis B virus (HBV)-DNA levels [HBV-DNA ≥ 100.00 IU/mL as Pos group (n = 200) and < 100.00 IU/mL as Neg group (n = 84)]. Correlation analyses and receiver operating characteristic analyses were conducted to evaluate the relationship between LS and liver condition. RESULTS: A significant correlation was found between LS and most of the parameters considered to have the ability to evaluate liver condition (P < 0.05). When alanine aminotransferase (ALT) concentrations were normal (≤ 40 U/L), LS was correlated with liver condition indices (P < 0.05), but the optimal cutoff of LS to identify a Child-Pugh score of 5 was higher in the Neg group (9.30 kPa) than the Pos group (7.40 kPa). When ALT levels were elevated (> 40 U/L), the correlations between LS and liver condition indices were not significant (P > 0.05). CONCLUSION: LS was significantly correlated with most liver condition indices in patients with CHB and HCC. However, these correlations varied according to differences in HBV-DNA and transaminase concentrations.

Ultrasomics in liver cancer: Developing a radiomics model for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma using contrast-enhanced ultrasound.

BACKGROUND: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) represent the predominant histological types of primary liver cancer, comprising over 99% of cases. Given their differing biological behaviors, prognoses, and treatment strategies, accurately differentiating between HCC and ICC is crucial for effective clinical management. Radiomics, an emerging image processing technology, can automatically extract various quantitative image features that may elude the human eye. Reports on the application of ultrasound (US)-based radiomics methods in distinguishing HCC from ICC are limited. AIM: To develop and validate an ultrasomics model to accurately differentiate between HCC and ICC. METHODS: In our retrospective study, we included a total of 280 patients who were diagnosed with ICC (n = 140) and HCC (n = 140) between 1999 and 2019. These patients were divided into training (n = 224) and testing (n = 56) groups for analysis. US images and relevant clinical characteristics were collected. We utilized the XGBoost method to extract and select radiomics features and further employed a random forest algorithm to establish ultrasomics models. We compared the diagnostic performances of these ultrasomics models with that of radiologists. RESULTS: Four distinct ultrasomics models were constructed, with the number of selected features varying between models: 13 features for the US model; 15 for the contrast-enhanced ultrasound (CEUS) model; 13 for the combined US + CEUS model; and 21 for the US + CEUS + clinical data model. The US + CEUS + clinical data model yielded the highest area under the receiver operating characteristic curve (AUC) among all models, achieving an AUC of 0.973 in the validation cohort and 0.971 in the test cohort. This performance exceeded even the most experienced radiologist (AUC = 0.964). The AUC for the US + CEUS model (training cohort AUC = 0.964, test cohort AUC = 0.955) was significantly higher than that of the US model alone (training cohort AUC = 0.822, test cohort AUC = 0.816). This finding underscored the significant benefit of incorporating CEUS information in accurately distinguishing ICC from HCC. CONCLUSION: We developed a radiomics diagnostic model based on CEUS images capable of quickly distinguishing HCC from ICC, which outperformed experienced radiologists.

Nomogram based on liver stiffness and spleen area with ultrasound for posthepatectomy liver failure: A multicenter study.

BACKGROUND: Liver stiffness (LS) measurement with two-dimensional shear wave elastography (2D-SWE) correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve. The size of the spleen increases due to tissue proliferation, fibrosis, and portal vein congestion, which can indirectly reflect the situation of liver fibrosis/cirrhosis. It was reported that the size of the spleen was related to posthepatectomy liver failure (PHLF). So far, there has been no study combining 2D-SWE measurements of LS with spleen size to predict PHLF. This prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area (SPA) for the prediction of PHLF in hepatocellular carcinoma (HCC) patients and to develop a risk prediction model. AIM: To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction model. METHODS: This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March 2022. Within 1 wk before partial hepatectomy, ultrasound examination was performed to measure LS and SPA, and blood was drawn to evaluate the patient's liver function and other conditions. Least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a nomogram. Nomogram performance was validated further. The diagnostic performance of the nomogram was evaluated with receiver operating characteristic curve compared with the conventional models, including the model for end-stage liver disease (MELD) score and the albumin-bilirubin (ALBI) score. RESULTS: A total of 562 HCC patients undergoing hepatectomy (500 in the training cohort and 62 in the validation cohort) were enrolled in this study. The independent predictors of PHLF were LS, SPA, range of resection, blood loss, international normalized ratio, and total bilirubin. Better diagnostic performance of the nomogram was obtained in the training [area under receiver operating characteristic curve (AUC): 0.833; 95% confidence interval (95%CI): 0.792-0.873; sensitivity: 83.1%; specificity: 73.5%] and validation (AUC: 0.802; 95%CI: 0.684-0.920; sensitivity: 95.5%; specificity: 52.5%) cohorts compared with the MELD score and the ALBI score. CONCLUSION: This PHLF nomogram, mainly based on LS by 2D-SWE and SPA, was useful in predicting PHLF in HCC patients and presented better than MELD score and ALBI score.

Ultrasound findings and clinical characteristics in differentiating renal urothelial carcinoma from endophytic clear cell renal cell carcinoma.

OBJECTIVE: This study aimed to evaluate the clinical characteristics and features of conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) in differentiating between renal urothelial carcinomas (RUC) and endophytic clear cell renal cell carcinomas (EccRCC). METHODS: A total of 72 RUCs and 120 EccRCCs confirmed by pathology were assessed retrospectively. Both CUS and CEUS were performed within 4 weeks before the surgery. Logistic regression analyses were used to select statistically significant variables of clinical, CUS, and CEUS features for the differentiation of RUC and EccRCC. Sensitivity (SEN), specificity (SPE), and the area under the receiver-operating characteristic curve (AUC) were assessed for diagnostic performance. Inter- and intra-observer agreements of CUS and CEUS features were evaluated using the intra-class correlation coefficient(ICC). RESULTS: Multiple logistic regression analysis demonstrated that clinical (age >50 years old and hematuria), CUS (size <4.0 cm, hypo-echogenicity, irregular shape, hydronephrosis) and CEUS (absence of non-enhancement area, iso- /hypo-enhancement in cortical phase and absence of rim-like enhancement) features were independent factors for RUC diagnosis. When combining clinical characters with CUS and CEUS features into an integrated diagnostic criterion, the AUC reached 0.917 (95% CI 0.873-0.961), with a sensitivity of 95.8% and specificity of 87.5%. ICC ranged from 0.756 to 0.907 for inter-observer agreement and 0.791 to 0.934 for intra-observer agreement for CUS and CEUSfeatures. CONCLUSIONS: The combination of clinical features of age and hematuria with imaging features of CUS and CEUS can be useful for the differentiation between RUC and EccRCC.

Radiating blood flow signal: A new ultrasound feature of thyroid carcinoma.

OBJECTIVE: To summary radiating blood flow signals and evaluate their diagnostic value in differentiating benign and malignant thyroid nodules. MATERIALS AND METHODS: We retrospectively recruited consecutive patients undergoing US at 4 hospitals from 2018 to 2022. In a training dataset, the correlations of US features with malignant thyroid nodules were assessed by multivariate logistic analysis. Multivariate logistic regression models involving the ACR TI-RADS score, radiating blood flow signals and their combination were built and validated internally and externally. The AUC with 95% asymptotic normal confidence interval as well as sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) with 95% exact binomial confidence intervals were calculated. RESULTS: Among 2475 patients (1818 women, age: 42.47 ± 11.57; 657 men, age: 42.16 ± 11.69), there were 3187 nodules (2342 malignant nodules and 845 benign nodules). Radiating blood flow signals were an independent risk factor for diagnosing thyroid carcinoma. In the training set, the AUC of the model using the combination of radiating blood flow signals and the ACR TI-RADS score (0.95 95 % CI: [0.94, 0.97]; P < 0.001) was significantly higher than that of the ACR TI-RADS model (0.91 [0.89, 0.93]). In the two internal validation sets and the external validation set, the AUCs of the combination model were 0.97 [0.96, 0.98], 0.92 [0.88, 0.96], and 0.91 [0.86, 0.95], respectively, and were all significantly higher than that of the ACR TI-RADS score (0.92 [0.90, 0.95], 0.86 [0.81, 0.91], 0.84 [0.79, 0.89]; P < 0.001). CONCLUSION: Radiating blood flow is a new US feature of thyroid carcinomas that can significantly improve the diagnostic performance vs. the ACR TI-RADS score.

Diagnosis and Treatment of Radioactive Iodine-Induced Sialadenitis: A 10-Year Endoscopic Experience.

OBJECTIVES: The aim of this study was to explore the endoscopic characteristics of radioactive iodine-induced sialadenitis (RAIS), and to evaluate the treatment outcomes of endoscopic intervention for RAIS. STUDY DESIGN: Retrospective case series. METHODS: Eighty-two consecutive patients (11 males and 71 females) diagnosed as RAIS from Nov. 2012 to Sep. 2023 were retrospectively included. All patients underwent endoscopic exploration and intervention of the affected glands. The endoscopic features were collected, and treatment outcomes were followed-up and evaluated through post to pre-operative comparisons of gland status. RESULTS: Overall, endoscopic procedures were undertaken for 162 parotid glands (PGs) and 62 submandibular glands (SMGs). Endoscopy showed severe lumen stricture (49.3%) and ductal atresia (23.5%) in PGs, as well as severe stenosis of the anterior duct and ectasia of the proximal duct (59.7%) in SMGs. During a median six months' follow-up, the treatment outcomes of PGs were evaluated as "improvement" in 23.4%，"lesion maintenance" in 45.1% and "lesion aggravation" in 31.5% of the glands. As for SMGs, the treatment outcomes were scored as "improvement"in 29.0%，"lesion maintenance"in 54.8%, and"lesion aggravation"in 16.1% of the glands. No significant differences of treatment outcomes were found relative to RAI treatment sessions and cumulative dosage. CONCLUSION: RAIS is characteristic of severe lumen stricture and ductal atresia in PGs, and stenosis of the distal duct and ectasia of the proximal duct in SMGs. Endoscopy can alleviate clinical symptoms of RAIS and help to preserve the gland function. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

US-based Sequential Algorithm Integrating an AI Model for Advanced Liver Fibrosis Screening.

Background Noninvasive tests can be used to screen patients with chronic liver disease for advanced liver fibrosis; however, the use of single tests may not be adequate. Purpose To construct sequential clinical algorithms that include a US deep learning (DL) model and compare their ability to predict advanced liver fibrosis with that of other noninvasive tests. Materials and Methods This retrospective study included adult patients with a history of chronic liver disease or unexplained abnormal liver function test results who underwent B-mode US of the liver between January 2014 and September 2022 at three health care facilities. A US-based DL network (FIB-Net) was trained on US images to predict whether the shear-wave elastography (SWE) value was 8.7 kPa or higher, indicative of advanced fibrosis. In the internal and external test sets, a two-step algorithm (Two-step#1) using the Fibrosis-4 Index (FIB-4) followed by FIB-Net and a three-step algorithm (Three-step#1) using FIB-4 followed by FIB-Net and SWE were used to simulate screening scenarios where liver stiffness measurements were not or were available, respectively. Measures of diagnostic accuracy were calculated using liver biopsy as the reference standard and compared between FIB-4, SWE, FIB-Net, and European Association for the Study of the Liver guidelines (ie, FIB-4 followed by SWE), along with sequential algorithms. Results The training, validation, and test data sets included 3067 (median age, 42 years [IQR, 33-53 years]; 2083 male), 1599 (median age, 41 years [IQR, 33-51 years]; 1124 male), and 1228 (median age, 44 years [IQR, 33-55 years]; 741 male) patients, respectively. FIB-Net obtained a noninferior specificity with a margin of 5% (P < .001) compared with SWE (80% vs 82%). The Two-step#1 algorithm showed higher specificity and positive predictive value (PPV) than FIB-4 (specificity, 79% vs 57%; PPV, 44% vs 32%) while reducing unnecessary referrals by 42%. The Three-step#1 algorithm had higher specificity and PPV compared with European Association for the Study of the Liver guidelines (specificity, 94% vs 88%; PPV, 73% vs 64%) while reducing unnecessary referrals by 35%. Conclusion A sequential algorithm combining FIB-4 and a US DL model showed higher diagnostic accuracy and improved referral management for all-cause advanced liver fibrosis compared with FIB-4 or the DL model alone. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ghosh in this issue.

Divergent Total Syntheses of Lycorine Alkaloids via a Sequential C-H Functionalization Strategy.

A Pd-catalyzed one-pot sequential C-H functionalization strategy was utilized to prepare four lycorine alkaloids and one pseudo-lycorine alkaloid from the common intermediate 4. By switching the followed oxidative conditions of air, DMSO/H2O/I2, and DMSO/O2, based on the Pd(PPh3)4/K2CO3/toluene catalytic system, three key intermediates 12a, 12b, and 12c with different substitution patterns could be obtained in a well-controlled manner. As a result, four natural products γ-lycorane, hippadine, anhydrolycorinone, and anhydrolycorine as well as a pseudo-lycorine alkaloid Δ(4a,10b)-6-oxodihydrolycorine were successfully synthesized within 10 steps through this divergent route.

Preliminary findings on diagnostic performance of computed tomography perfusion images for intracranial arterial stenosis: a retrospective study.

OBJECTIVES: Computed tomographic perfusion (CTP) can play an auxiliary role in the selection of patients with acute ischemic stroke for endovascular treatment. However, data on CTP in non-stroke patients with intracranial arterial stenosis are scarce. We aimed to investigate images in patients with asymptomatic intracranial arterial stenosis to determine the detection accuracy and interpretation time of large/medium-artery stenosis or occlusion when combining computed tomographic angiography (CTA) and CTP images. METHODS: We retrospectively reviewed 39 patients with asymptomatic intracranial arterial stenosis from our hospital database from January 2021 to August 2023 who underwent head CTP, head CTA, and digital subtraction angiography (DSA). Head CTA images were generated from the CTP data, and the diagnostic performance for each artery was assessed. Two readers independently interpreted the CTA images before and after CTP, and the results were analyzed. RESULTS: After adding CTP maps, the accuracy (area under the curve) of diagnosing internal carotid artery (R1: 0.847 vs. 0.907, R2: 0.776 vs. 0.887), middle cerebral artery (R1: 0.934 vs. 0.933, R2: 0.927 vs. 0.981), anterior cerebral artery (R1: 0.625 vs. 0.750, R2: 0.609 vs. 0.750), vertebral artery (R1: 0.743 vs. 0.764, R2: 0.748 vs. 0.846), and posterior cerebral artery (R1: 0.390 vs. 0.575, R2: 0.390 vs. 0.585) occlusions increased for both readers (p < 0.05). Mean interpretation time (R1: 72.4 ± 6.1 s vs. 67.7 ± 6.4 s, R2: 77.7 ± 3.8 s vs. 72.6 ± 4.7 s) decreased when using a combination of both images both readers (p < 0.001). CONCLUSIONS: The addition of CTP images improved the accuracy of interpreting CTA images and reduced the interpretation time in asymptomatic intracranial arterial stenosis. These findings support the use of CTP imaging in patients with asymptomatic intracranial arterial stenosis.

Bowel Stiffness Assessed by Shear-Wave Ultrasound Elastography Predicts Disease Behavior Progression in Patients With Crohn's Disease.

INTRODUCTION: There is a lack of reliable predictors of disease behavior progression in patients with Crohn's disease (CD). Real-time shear-wave elastography (SWE) is a novel method for evaluating tissue stiffness. However, its value for assessing CD has not yet been investigated. We aimed to explore the value of SWE and other ultrasound parameters at diagnosis in predicting CD behavior progression. METHODS: We retrospectively collected data from patients with CD with the nonstenotic nonpenetrating disease (B1 phenotype based on the Montreal classification). All patients underwent intestinal ultrasound at baseline and were followed up. The end point was defined as disease behavior progression to stricturing (B2) or penetrating (B3) disease. Cox regression analysis was performed for the association between baseline characteristics and subsequent end points. In addition, a multivariate nomogram was established to predict the risk of disease behavior progression quantitatively. RESULTS: A total of 130 patients with CD with B1 phenotype were enrolled. Twenty-seven patients (20.8%) developed B2 or B3 disease, with a median follow-up of 33 months. Multivariate analysis identified that SWE was the only independent predictor of disease behavior progression (hazard ratio 1.08, 95% confidence interval 1.03-1.12, P = 0.001). A reverse of the HR appeared at the cutoff 12.75 kPa. The nomogram incorporating SWE and other clinical characteristics showed a good prediction performance (area under the curve = 0.792). DISCUSSION: Intestinal stiffness assessed using SWE is an independent predictor of disease behavior progression in patients with CD. Patients with CD with SWE >12.75 kPa at diagnosis are prone to progress toward stricturing or penetrating diseases.

Imaging-based diagnosis and classification of radioactive iodine-induced sialadenitis.

OBJECTIVES: To establish an inflammation grading system for radioactive iodine-induced sialadenitis (RAIS) based on spiral computed tomography (CT), ultrasonography and sialography. METHODS: In all, 120 RAIS patients (18 males and 102 females) were retrospectively included. Spiral CT, ultrasonography and sialography appearances were analysed and categorized as follows: grade I, approximately normal or mild sialadenitis; grade II, moderate sialadenitis; and grade III, severe sialadenitis. Adenitis severity was analysed relative to sex, age, RAI treatment sessions and cumulative doses. RESULTS: Spiral CT showed heterogeneous (78.9%) and atrophic changes (36.8%) in the parotid glands (PGs) and duct ectasia (24.8%) in the submandibular glands (SMGs). Ultrasonography showed heterogeneous echogenicity (54.3%) and diminished gland size (30.2%) in PGs and duct ectasia in SMGs (34.7%). Sialography showed duct obliteration in 25.3% PGs and 3.2% SMGs. Statistical analysis showed good consistency among the three imaging grading results. The incidence and severity of PG lesions were significantly higher than that of SMGs (p < 0.001). As for PGs, adenitis severity was associated with both treatment sessions and cumulative doses; but in SMGs, disease severity was only related to treatment sessions. CONCLUSIONS: A grading system for severity of RAIS was established based on spiral CT, ultrasonography and sialography appearances.

Hosimosines A-E, structurally diverse cytisine derivatives from the seeds of Ormosia hosiei Hemsl. et Wils.

Ormosia hosiei Hemsl. et Wils (Fabaceae family) is an arbor species endemic to China. The seeds of O. hosiei have been used as traditional Chinese medicine to treat hernia, abdominal pain, blood stasis and amenorrhea. Cytisine-like and angustifoline type alkaloids were main components identified from this plant. In our research on the bioactive alkaloids from the promising Chinese medicinal plants, four new angustifoline type alkaloids (1-4) and a new cytisine-like alkaloid (5), named hosimosine A-E, together with 13 known analogues (6-18) were isolated from the seeds of O. hosiei. Their structures were elucidated by the extensive spectroscopic methods, especially the interpretation of NMR spectra and specific rotations, along with the methods of NMR and ECD calculation. Compounds 1-4 were identified as two pairs of epimers, whose relative configurations were deduced from density functional theory (DFT) calculations of NMR chemical shifts and DP4+ analysis, and absolute configurations were determined by comparison of their experimental and theoretical ECD spectra. Compound 5 displayed two sets of NMR data caused by the existence of tautomeric forms. Compounds 14, 17 and 18 were determined to be enantiomers of literature compounds. Some of the isolates exhibited moderate cytotoxic effects against HepG2, A2780 and MCF-7 cells.

[Research progress on chemical structures and pharmacological effects of natural cytisine and its derivatives].

Cytisine derivatives are a group of alkaloids containing the structural core of cytisine, which are mainly distributed in Fabaceae plants with a wide range of pharmacological activities, such as resisting inflammation, tumors, and viruses, and affecting the central nervous system. At present, a total of 193 natural cytisine and its derivatives have been reported, all of which are derived from L-lysine. In this study, natural cytisine derivatives were classified into eight types, namely cytisine type, sparteine type, albine type, angustifoline type, camoensidine type, cytisine-like type, tsukushinamine type, and lupanacosmine type. This study reviewed the research progress on the structures, plant sources, biosynthesis, and pharmacological activities of alkaloids of various types.

Dermoscopic features of children scabies.

Scabies is a common skin disorder, caused by the ectoparasite Sarcoptes scabiei. The scabies mites burrow is highly diagnostic but illegible by the naked eye, because it is tiny and may completely be obscured by scratch and crust. The classic technique is opening the end of an intact mite burrow with a sharp instrument and inspecting its contents in the light microscope under loupe vision. Dermatoscope is a new method to diagnose scabies, with the advantages of non-invasive and more sensitive. This study verified the characteristic manifestations of scabies under dermoscopy. Under the closer examination of the curvilinear scaly burrow, the scabies mite itself may be seen as a dark equilateral triangular structure, which is often referred to as a "jet with contrail." Besides, this study found that the positive detection rate of microscopic characteristic manifestations under the dermoscopy ordered by the external genitals, the finger seams and the trunk, which were statistically different (P-value < 0.05). Of note, this is the first study to explore the regional distribution of the characteristic dermoscopic manifestations of scabies. We are the first to propose to focus on examining the external genitalia and finger seams with dermoscopy.

Long-term outcomes of combined radiofrequency ablation and multipronged ethanol ablation for the treatment of unfavorable hepatocellular carcinoma

PURPOSE: To evaluate the local efficacy, safety, and long-term outcomes of combined radiofrequency ablation (RFA) and multipronged ethanol ablation (EA) in the treatment of unfavorable hepatocellular carcinoma (HCC) and to determine the prognostic factors for survival. METHODS: Between August 2009 and December 2017, 98 patients with 110 unfavorable HCC nodules who underwent combined RFA and multipronged EA were retrospectively enrolled in the study. Unfavorable HCC was defined as a medium (3.1-5.0 cm) or large (5.1-7.0 cm) HCC nodule, a tumor located at a high-risk site, or a perivascular tumor. The treatment response, overall survival (OS), and recurrence-free survival (RFS) were analyzed. The Kaplan-Meier method and Cox proportional hazards regression model were used to evaluate the prognostic factors. RESULTS: Complete ablation was obtained in 80.9% (89/110) of the tumors after initial treatment. Major complications were observed in 3 (3.1%) patients. The cumulative incidence of local tumor progression (LTP) was 23.5% at five years, and no variable was found to be an independent predictive factor for LTP. The five-year OS and RFS rates were 41.9% and 34.0%, respectively. Multivariate analysis showed that the serum alpha-fetoprotein level, tumor size, presence of residual tumor after ablation, and extrahepatic metastases were significant prognostic factors for OS (P = 0.023, P = 0.030, P = 0.001, and P = 0.010, respectively). Tumor type and the number of tumors were predictive factors for RFS (P = 0.029 and P = 0.001, respectively). A perivascular tumor was not an independent predictive factor for OS or RFS. CONCLUSION: Combined RFA and multipronged EA is a safe and effective treatment for unfavorable HCC, especially for perivascular tumors.

Matrix metalloproteinase-9 overexpression in the hippocampus reduces alcohol-induced conditioned-place preference by regulating synaptic plasticity in mice.

Extracellular matrix proteins appear to be necessary for the synaptic plasticity that underlies addiction memory. In the brain, matrix metalloproteinases (MMPs), especially matrix metalloproteinase-9 (MMP-9), have been recently implicated in processes involving alcohol reward and memory. Here, we showed for the first time, the positive effects of MMP-9 on alcohol-induced conditioned place preference (CPP) behavior and hippocampal neuron plasticity in C57BL/6 mice. Using recombinant adeno-associated viruses to overexpress MMP-9 in the hippocampus, we investigated the NMDAR, PSD-95, and cellular cytoskeleton proteins F-actin/G-actin in the modulation of alcohol reward behavior in mice exposed to CPP. We found that hippocampal infusions of MMP-9 decreased alcohol-induced place preference suggesting a reduction in alcohol reward. Western blot analysis demonstrated that protein expression of NMDA receptors (GluN1, GluN2A and GluN2B) in the hippocampus of alcohol-exposed mice were higher than that of the saline group. Further, the expression of these proteins was decreased in MMP-9 overexpressing mice. MMP-9 also regulated the ratio of F-actin/G-actin (dendritic spines cytoskeleton proteins), which might be the key mediator for behavioral changes in mice. Consequently, our results highlight new evidence that MMP-9 may play an important role in the molecular mechanism underlying alcohol reward and preference.

Efficacy of radiofrequency ablation following transarterial chemoembolisation combined with sorafenib for intermediate stage recurrent hepatocellular carcinoma: a retrospective, multicentre, cohort study.

Background: The evidence of radiofrequency ablation (RFA) following transarterial chemoembolisation (TACE) combined with sorafenib for intermediate-stage recurrent hepatocellular carcinoma (RHCC) is limited. Patient responses to this treatment vary because of the heterogeneous nature of RHCC, making it important to identify patients who are most likely to benefit from this combination therapy. The aim of this study was to evaluate the efficacy of RFA following TACE and sorafenib for the intermediate-stage RHCC. Methods: This retrospective, multicentre, cohort study included 363 patients with intermediate-stage RHCC underwent TACE combined with sorafenib (TACE-sorafenib group) or RFA following TACE and sorafenib (TACE-sorafenib + RFA group) between January 01, 2009 to December 31, 2015 from four institutions in China. Overall survival (OS), progression-free survival (PFS) and efficacy of patients were compared between the two groups by propensity score-matching (PSM). Findings: The 1-, 3-, and 5-year OS rates were 97.7%, 83.7%, 54.7% in TACE-sorafenib + RFA group, and 93.3%, 57.0%, 32.7% in TACE-sorafenib group. The 1-, 2-, and 3-year PFS rates were 85.3%, 58.0%, 26.9% in TACE-sorafenib + RFA group, and 55.3%, 30.7%, 15.3% in TACE-sorafenib group. Compared with the TACE-sorafenib group, the TACE-sorafenib + RFA group had significantly longer OS (HR, 0.54; 95%CI, 0.40-0.73; P < 0.001) and PFS (HR, 0.52; 95% CI, 0.41-0.66; P < 0.001). Subgroup analysis was conducted to precisely screen out the beneficial population from RFA treatment. Interpretation: Our findings suggest that addition of RFA following TACE and sorafenib combination was superior to TACE combined with sorafenib for intermediate-stage RHCC, resulting in longer OS and PFS. Patients who had good response to TACE and achieved downstaging successfully could not benefit from the RFA therapy. Funding: This research was funded by National Natural Science Foundation of China (No. 81627803), Chen Xiao-Ping Science and Technology Development Fund (CXPJJH1200009-06).

Identification of the origin of tumor in vein: comparison between CEUS LI-RADS v2017 and v2016 for patients at high risk.

OBJECTIVES: To compare the diagnostic performance of the Contrast-Enhanced Ultrasound (CEUS) Liver Imaging Report and Data System (LI-RADS) v2016 and v2017 in identifying the origin of tumor in vein (TIV). METHODS: From April 2014 to December 2018, focal liver lesions (FLLs) accompanied by TIV formation in patients at high risk for hepatocellular carcinoma (HCC) were enrolled. Histologic evaluation or composite imaging reference standard were served as the reference standard. Each case was categorized according to the CEUS LI-RADS v2016 and v2017, respectively. Diagnostic performance of CEUS LI-RADS v2016 and v2017 in identifying the originated tumor of TIV was validated via sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value. RESULTS: A total of 273 FLLs with TIV were analyzed finally, including 266 HCCs and 7 non-HCCs. In v2016, when adopting all TIV as LR-5V, the accuracy and PPV in identifying the originated tumor were both 97.4%. In v2017, when assigning TIV according to contiguous FLLs CEUS LI-RADS category, the accuracy and PPV were 61.9% and 99.4% in subclass of LR-5 as the diagnostic criteria of HCC, and 64.1% and 99.4% in subclass of LR-4/5 as the criteria of HCC diagnosis. There were significant differences in diagnostic accuracy between CEUS LI-RADS v2016 and v2017 in identifying the originated tumor of TIV (p < 0.001). CONCLUSIONS: CEUS LI-RADS v2016 could be better than v2017 in identifying the originated tumor of TIV.

Circulating tumour cell counts and ultrasomics signature-based nomogram for preoperative prediction of early recurrence of hepatocellular carcinoma after radical treatment.

METHODS: Between December 2017 and December 2018, 153 HCC patients (134 males and 19 females; mean age, 56.0 ± 10.2 years; range, 28-78 years) treated with radical therapy were enrolled in our retrospective study and were divided into a training cohort (n = 107) and a validation cohort (n = 46). All patients underwent preoperative CTC tests and CEUS examinations before treatment. The ultrasomics signature was extracted and built from CEUS images. Univariate and multivariate logistic regression analyses were used to identify the significant variables related to ER, which were then combined to build a predictive nomogram. The performance of the nomogram was evaluated by its discrimination, calibration and clinical utility. The predictive model was further evaluated in the internal validation cohort. RESULTS: HBV DNA, serum AFP level, CTC status, tumour size and ultrasomics score were identified as independent predictors associated with ER (all p < 0.05). Multivariable logistic regression analysis showed that the CTC status (OR = 7.02 [95% CI, 2.07 to 28.38], p = 0.003) and ultrasomics score (OR = 148.65 [95% CI, 25.49 to 1741.72], p < 0.001) were independent risk factors for ER. The nomogram based on ultrasomics score, CTC status, serum AFP level and tumour size exhibited C-indexes of 0.933 (95% CI, 0.878 to 0.988) and 0.910 (95% CI, 0.765 to 1.055) in the training and validation cohorts, respectively, fitting well in calibration curves. Decision curve analysis further confirmed the clinical usefulness of the nomogram. CONCLUSION: The nomogram incorporating CTC, ultrasomics features and independent clinical risk factors achieved satisfactory preoperative prediction of ER in HCC patients after radical treatment. ADVANCES IN KNOWLEDGE: 1. CTC status and ultrasomics score were identified as independent predictors associated with ER of HCC after radical treatment. 2. The nomogram constructed by ultrasomics score generated by 17 ultrasomics features, combined with CTCs and independent clinical risk factors such as AFP and tumour size. 3. The nomogram exhibited satisfactory discriminative power, and could be clinically useful in the preoperative prediction of ER after radical treatment in HCC patients.