Unexpected asymmetric distribution of cholesterol and phospholipids in equilibrium model membranes.

Lipid compositional asymmetry across the leaflets of the plasma membrane is a ubiquitous feature in eukaryotic cells. How this asymmetry is maintained is thought to be primarily controlled by active transport of lipids between leaflets. This strategy is facilitated by the fact that long tail phospholipids and sphingolipids diffuse through the lipid bilayer slowly - taking many hours or days. However, a lipid like cholesterol - which is the most abundant lipid in the plasma membrane of animal cells - has been harder to pin-point in terms of its favored side. In the present work we show that when a saturated lipid is added to a mix of the unsaturated lipid palmitoyl-oleoyl-phosphatidylcholine (POPC) and cholesterol, both cholesterol and the long tail phospholipids organize asymmetrically across the membrane's leaflets naturally. In these extruded unilamellar vesicles, most cholesterol as well as the saturated lipid - dipalmitoylphosphatidylcholine (DPPC) or sphingomyelin (SM) - segregated to the inner leaflet while POPC preferentially localized in the outer leaflet. This asymmetric arrangement generated a slight phospholipid number imbalance favoring the outer leaflet and thus opposite to where cholesterol and the saturated lipids preferentially partitioned. These results were obtained using Magic Angle Spinning (MAS) NMR in combination with Small Angle Neutron Scattering (SANS) using isotope labeling to differentiate lipid species. We suggest that sidedness in membranes can be driven by thermodynamic processes. In addition, our MAS NMR results show that the lower bound for cholesterol's flip-flop half-time at 45°C is 10ms, which is at least two orders of magnitude slower than current MD simulations predict. This result stands in stark contrast to previous work that suggested that cholesterol's flip-flop half-time at 37°C has an upper bound of 10ms.

GSDMD-Dependent Neutrophil Extracellular Traps Mediate Portal Vein Thrombosis and Associated Fibrosis in Cirrhosis.

Portal vein thrombosis (PVT) is a challenging and controversial complication of cirrhosis. Experimental models that reproduce cirrhotic PVT and effective pharmacological therapies are limited. We aimed to investigate the nature course and mechanisms of PVT in cirrhosis. A novel PVT model was developed via two-step total portal vein ligation in healthy and thioacetamide (TAA)-cirrhotic rats. Circulating and liver-infiltrating neutrophils were isolated from individuals with cirrhosis to examine neutrophil extracellular traps (NETs) and explore their unique characteristics and implications in PVT-associated fibrosis in cirrhosis. We further validated macrophage-myofibroblast transition (MMT) via multiplex immunofluorescence and single-cell sequencing. In the experimental model, cirrhosis promoted PVT development and portal vein intimal thickening. Interestingly, cirrhosis promoted spontaneous resolution of PVT due to instability of thrombus structure, along with pulmonary and intrahepatic clots. NETs-MMT mediate cirrhotic PVT and PVT-associated fibrosis, including fibrotic thrombus remodeling and increased hepatic collagen deposition. Mechanistically, caspase-4-dependent activation of neutrophils and GSDMD mediated the formation of NETs. The extracellular DNA of NETs promoted TGF-ß1/Smad3-driven MMT. Inhibiting GSDMD with disulfiram suppressed cirrhotic PVT and prevented associated fibrosis. The cirrhotic PVT model reflected the following three main characteristics of cirrhotic PVT: spontaneous resolution, immunothrombosis, and intimal fibrosis. Targeting NETs with GSDMD inhibitors may serve as a new therapeutic concept to treat cirrhotic PVT.

Quantitative US fat fraction for noninvasive assessment of hepatic steatosis in suspected metabolic-associated fatty liver disease.

OBJECTIVES: To evaluate the agreement between quantitative ultrasound system fat fraction (USFF) and proton magnetic resonance spectroscopy (1H-MRS) and the diagnostic value of USFF in assessing metabolic-associated fatty liver disease (MAFLD). METHODS: The participants with or suspected of MAFLD were prospectively recruited and underwent 1H-MRS, USFF, and controlled attenuation parameter (CAP) measurements. The correlation between USFF and 1H-MRS was assessed using Pearson correlation coefficients. The USFF diagnostic performance for different grades of steatosis was evaluated using receiver operating characteristic curve analysis (ROC) and was compared with CAP, visual hepatic steatosis grade (VHSG). RESULTS: A total of 113 participants (mean age 44.79 years ± 13.56 (SD); 71 males) were enrolled, of whom 98 (86.73%) had hepatic steatosis (1H-MRS ≥ 5.56%). USFF showed a good correlation (Pearson r = 0.76) with 1H-MRS and showed a linear relationship, which was superior to the correlation between CAP and 1H-MRS (Pearson r = 0.61). The USFF provided high diagnostic performance for different grades of hepatic steatosis, with ROC from 0.84 to 0.98, and the diagnostic performance was better than that of the CAP and the VHSG. The cut-off values of the USFF were different for various grades of steatosis, and the cut-off values for S1, S2, and S3 were 12.01%, 19.98%, and 22.22%, respectively. CONCLUSIONS: There was a good correlation between USFF and 1H-MRS. Meanwhile, USFF had good diagnostic performance for hepatic steatosis and was superior to CAP and VHSG. USFF represents a superior method for noninvasive quantitative assessment of MAFLD. CRITICAL RELEVANCE STATEMENT: Quantitative ultrasound system fat fraction (USFF) accurately assesses liver fat content and has a good correlation with magnetic resonance spectroscopy (1H-MRS) for the assessment of metabolic-associated fatty liver disease (MAFLD), as well as for providing an accurate quantitative assessment of hepatic steatosis. KEY POINTS: Current diagnostic and monitoring modalities for metabolic-associated fatty liver disease have limitations. USFF correlated well with 1H-MRS and was superior to the CAP. USFF has good diagnostic performance for steatosis, superior to CAP and VHSG.

Photosynthetic Bacteria-Hitchhiking 2D iMXene-mRNA Vaccine to Enable Photo-Immunogene Cancer Therapy.

Therapeutic mRNA vaccines have become powerful therapeutic tools for severe diseases, including infectious diseases and malignant neoplasms. mRNA vaccines encoding tumor-associated antigens provide unprecedented hope for many immunotherapies that have hit the bottleneck. However, the application of mRNA vaccines is limited because of biological instability, innate immunogenicity, and ineffective delivery in vivo. This study aims to construct a novel mRNA vaccine delivery nanosystem to successfully co-deliver a tumor-associated antigen (TAA) encoded by the Wilms' tumor 1 (WT1) mRNA. In this system, named PSB@Nb1.33C/mRNA, photosynthetic bacteria (PSB) efficiently delivers the iMXene-WT1 mRNA to the core tumor region using photo-driven and hypoxia-driven properties. The excellent photothermal therapeutic (PTT) properties of PSB and 2D iMxene (Nb1.33C) trigger tumor immunogenic cell death, which boosts the release of the WT1 mRNA. The released WT1 mRNA is translated, presenting the TAA and amplifying immune effect in vivo. The designed therapeutic strategy demonstrates an excellent ability to inhibit distant tumors and counteract postsurgical lung metastasis. Thus, this study provides an innovative and effective paradigm for tumor immunotherapy, i.e., photo-immunogene cancer therapy, and establishes an efficient delivery platform for mRNA vaccines, thereby opening a new path for the wide application of mRNA vaccines.

Validation of Baveno VII criteria for clinically significant portal hypertension by two-dimensional shear wave elastography.

BACKGROUND: The Baveno VII consensus proposed criteria for the non-invasively diagnosis of clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease (cACLD). The performance of Baveno VII criteria for assessing CSPH by two-dimensional shear wave elastography (2D-SWE) had not been well validated. We aimed to validate the performance of Baveno VII criteria for rule-in and rule-out CSPH by 2D-SWE. METHOD: This is an international multicenter study including cACLD patients from China and Croatia with paired liver stiffness measurement (LSM), spleen stiffness measurement (SSM) by 2D-SWE, and hepatic venous pressure gradient (HVPG) were included. CSPH was defined as HVPG ≥ 10 mmHg. RESULT: A total of 146 patients with cACLD were enrolled, and finally 118 patients were included in the analysis. Among them, CSPH was documented in 79 (66.9%) patients. Applying the Baveno VII criteria for rule-out CSPH by 2D-SWE, [LSM ≤ 15 kPa and platelet count ≥ 150 × 109/L] OR SSM < 21 kPa, could exclude CSPH with sensitivity > 90% (93.5 or 98.7%) but negative predictive value < 90% (74.1 or 85.7%). Using the Baveno VII criteria for rule-in CSPH by 2D-SWE, LSM ≥ 25 kPa OR SSM ≥ 50 kPa, could diagnose CSPH with 100% specificity and 100% positive predictive values. CONCLUSION: Baveno VII criteria by 2D-SWE showed a good diagnostic performance for ruling in but not for ruling out CSPH, which might become an emerging non-invasive elastography tool to select the patients who needed non-selective beta blocker therapy.

Interoperator reproducibility of quantitative ultrasound analysis of hepatic steatosis in participants with suspected MASLD: A prospective study.

OBJECTIVES: To evaluate the reproducibility of tissue attenuation imaging (TAI) and tissue scatter distribution imaging (TSI) measurements in adults with suspected metabolic dysfunction-associated steatotic liver disease (MASLD) between radiologists with varying experience. MATERIALS AND METHODS: Participants with suspected MASLD were prospectively recruited. TAI and TSI were performed for each participant by two radiologists with different levels of experience. Interoperability reliability was assessed on the basis of Bland-Altman analysis and intraclass correlation coefficients (ICCs). The study determined and compared the diagnostic performance of TAI and TSI with clinical prediction models using proton magnetic resonance spectroscopy (1H-MRS) as a reference. RESULTS: A total of 180 participants (women, n = 56; men, n = 124, mean age, 46.98 ± 14.92 years; mean BMI, 25.81 ± 4.47) were enrolled from August 2022 to September 2022. Bland-Altman plots showed only slight deviation in the TAI and TSI results of the two radiologists; there was good interoperator reproducibility for TAI (ICC = 0.92) and TSI (ICC = 0.86). Senior and junior radiologists performed examinations labeled as TAI-1 and TSI-1, and TAI-2 and TSI-2, respectively. The areas under the curves (AUCs) of TAI-1, TAI-2, TSI-1, and TAI-2 for the detection of ≥5 % hepatic steatosis were 0.90, 0.96, 0.91 and 0.96, respectively. According to ROC analysis, the diagnostic performance of both radiologists for TAI and TSI was statistically similar and superior to that of the clinical prediction model. CONCLUSIONS: TAI and TSI have good reproducibility between radiologists with different levels of experience. Meanwhile, both TAI and TSI demonstrated good diagnostic performance for hepatic steatosis (≥5%), surpassing that of clinical prediction models.

Genomic full-length sequence of the HLA-C*07:154 allele was identified by full-length group-specific sequencing.

Genomic full-length sequence of HLA-C*07:154 was identified by group-specific sequencing in a Chinese individual.

A prospective comparison of three ultrasound-based techniques in quantitative diagnosis of hepatic steatosis in NAFLD.

PURPOSE: To investigate the correlation between different ultrasound attenuation-based techniques and to compare their diagnostic performances using proton magnetic resonance spectroscopy (1H-MRS) as a reference standard. METHODS: Participants who had clinical suspicion of nonalcoholic fatty liver disease (NAFLD) were prospectively recruited. Each subject had ultrasound with attenuation imaging (ATI) or quantitative ultrasound including tissue attenuation imaging (TAI) and tissue scatter-distribution imaging (TSI), and controlled-attenuation parameter (CAP) and 1H-MRS if available. The technical success rates, intra-observer repeatabilities of attenuation and backscattering coefficient were evaluated. ATI, TAI and CAP were three attenuation-based techniques. Spearman coefficient was used to test correlations among them and 1H-MRS. In addition, the diagnostic performances of these parameters for detecting ≥ 5% or 10% hepatic steatosis were evaluated. RESULTS: 130 participants had ultrasound scanning. Among them, 67 had CAP and 48 had 1H-MRS. The technical success rates were all 100%. The intra-observer repeatabilities of them were also excellent (ICCs > 0.90) and AC-ATI correlated well with AC-TAI (r = 0.752). AC-ATI, AC-TAI showed moderate correlation with CAP, (rATI = 0.623, 95% CI 0.446-0.752, P < 0.001; rTAI = 0.573, 95% CI 0.377-0.720, P < 0.001). For correlation with 1H-MRS, ATI and TAI performed better than CAP(rATI = 0.587; rTAI = 0.712; r CAP = 0.485). The AUCs of ATI, TAI, TSI and CAP for detecting ≥ 5% hepatic steatosis were 0.883, 0.862, 0.870 and 0.868, respectively. The AUC improved to 0.907 when TAI and TSI were combined (P < 0.05). When detecting ≥ 10% hepatic steatosis, the AUCs were 0.855, 0.702, 0.822 and 0.838, respectively. CONCLUSION: Different ultrasound attenuation-based techniques were well correlated and exhibited good diagnostic performances in quantitative diagnosis of hepatic steatosis, however, the threshold values were different. Combinations of multiple parameters may improve the diagnostic performance in detecting hepatic steatosis. TRIAL REGISTRATION: The study has been registered online ( https://www.chictr.org.cn ; unique identifier: ChiCTR2300069459).

Implications of ultrasound-based deep learning model for preoperatively differentiating combined hepatocellular-cholangiocarcinoma from hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

OBJECTIVES: The current study developed an ultrasound-based deep learning model to make preoperative differentiation among hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma (cHCC-ICC). METHODS: The B-mode ultrasound images of 465 patients with primary liver cancer were enrolled in model construction, comprising 264 HCCs, 105 ICCs, and 96 cHCC-ICCs, of which 50 cases were randomly selected to form an independent test cohort, and the rest of study population was assigned to a training and validation cohorts at the ratio of 4:1. Four deep learning models (Resnet18, MobileNet, DenseNet121, and Inception V3) were constructed, and the fivefold cross-validation was adopted to train and validate the performance of these models. The following indexes were calculated to determine the differential diagnosis performance of the models, including sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), F-1 score, and area under the receiver operating characteristic curve (AUC) based on images in the independent test cohort. RESULTS: Based on the fivefold cross-validation, the Resnet18 outperformed other models in terms of accuracy and robustness, with the overall training and validation accuracy as 99.73% (± 0.07%) and 99.35% (± 0.53%), respectively. Furthers validation based on the independent test cohort suggested that Resnet 18 yielded the best diagnostic performance in identifying HCC, ICC, and cHCC-ICC, with the sensitivity, specificity, accuracy, PPV, NPV, F1-score, and AUC of 84.59%, 92.65%, 86.00%, 85.82%, 92.99%, 92.37%, 85.07%, and 0.9237 (95% CI 0.8633, 0.9840). CONCLUSION: Ultrasound-based deep learning algorithm appeared a promising diagnostic method for identifying cHCC-ICC, HCC, and ICC, which might play a role in clinical decision making and evaluation of prognosis.

Contrast-enhanced ultrasound features of hepatic sarcomatoid carcinoma different from hepatocellular carcinoma.

BACKGROUND: Hepatic sarcomatoid carcinoma (HSC) is a rare malignancy of the liver. The ultrasound and clinical features of HSC have not been determined. OBJECTIVE: To investigate and compare the ultrasound and clinical features of HSC and hepatocellular carcinoma (HCC), and to reveal the valuable features of HSC. METHODS: The ultrasound features and clinical data of pathologically proven HSC (n = 37) were compared with HCC (n = 92) in a matching ratio of 1:4 using the propensity score (age, gender and tumor size). RESULTS: The HSC patients were more likely to accompany with clinical symptoms and vascular invasion than HCC patients (40.5% vs 17.4%, 24.3% vs 6.5%, P < 0.05). The size of HSCs was significantly larger than that of HCCs (P < 0.05). The proportion of patients with elevated alpha-fetoprotein was significantly lower in HSC (35.1% vs 54.3%, P < 0.05). On gray-scale ultrasound images, the HSCs were more likely to demonstrate as indistinct margin and irregular shape lesions compared to HCCs (78.4% vs 48.8%; 70.3% vs 23.9%, P < 0.05). Under color Doppler flow imaging (CDFI), the blood flow signals were more frequently detected in HSC lesions (75.7% vs 56.5%, P < 0.05). Resistance index (RI) was higher in HSCs than in HCCs [0.78 (0.70,0.82) vs 0.70 (0.62,0.76), P < 0.05]. On contrast-enhanced ultrasound (CEUS), HSCs mainly showed entirety heterogeneous hyper-enhancement (48.6%), entirety homogeneous enhancement (18.9%), peripheral and internal septal enhancement (18.9%). The incidence of non-enhanced areas inside HSC lesions was higher than that inside HCC lesions (56.8% vs 31.5%, P < 0.05). During the portal venous and late phases, most of the lesions revealed hypo-enhancement in both groups, whereas earlier washout was observed in HSCs [43.0 s (30.5,58.0) vs 60.0 s (46.3,100.0), P < 0.05]. CONCLUSIONS: CEUS features are useful in preoperative and non-invasive differentiation of hepatic sarcomatoid carcinoma and hepatocellular carcinoma.

Toroidal-spiral particles as a CAR-T cell delivery device for solid tumor immunotherapy.

Chimeric antigen receptor (CAR) T cell therapy has resulted in positive effects on patients with hematologic malignancy but shows limited efficacy in solid tumor treatments due to insufficient trafficking and tumor infiltration, intensive CAR-T-related toxicities, and antigen escape. In this work, we developed and investigated a biodegradable and biocompatible polymeric toroidal-spiral particle (TSP) as a in vivo cell incubator and delivery device that can be implanted near tumor through a minimally invasive procedure or injected near or into solid tumors by using a biopsy needle. The main matrix structure of the millimeter-sized TSP is made from crosslinking of gelatin methacrylamine (GelMA) and poly (ethylene glycol) diacrylate (PEGDA) with a tunable degradation rate from a few days to months, providing appropriate mechanical properties and sustained release of co-encapsulated drugs and/or stimulation compounds. The toroidal-spiral layer of the particles, presenting an internal void volume for high-capacity cell loading and flexibility of co-encapsulating small and large molecular compounds with individually manipulated release schedules, is filled with collagen and suspended T cells. The TSPs promote cell proliferation, activation, and migration in the tumor micro-environment in a prolonged and sustained manner. In this study, the efficacy of mesothelin (MSLN) CAR-T cells released from the TSPs was tested in preclinical mouse tumor models. Compared to systemic and intratumoral injection, peritumoral delivery of MSLN CAR-T cells using the TSPs resulted in a superior antitumor effect. The TSPs made of FDA approved materials as an in vivo reactor may provide an option for efficiently local delivery of CAR-T cells to solid tumors for higher efficacy and lower toxicity, with a minimally invasive administration procedure.

Pulmonary Cryoablation Outcomes in Octogenarians and Nonagenarians with Primary Lung Cancer.

PURPOSE: To characterize the effectiveness, safety, and length of stay (LOS) associated with pulmonary cryoablation for management of primary lung malignancies in patients aged ≥80 years. MATERIALS AND METHODS: A retrospective single-center database was compiled of all consecutive patients aged ≥80 years who underwent percutaneous computed tomography-guided cryoablation using modified triple-freeze protocol (1-3 ablation probes) for Stage IA-IIB primary lung malignancies between March 2017 and March 2020 (n = 19; 53% women; mean age, 85 years ± 3.5; range, 80-94 years). Follow-up imaging was assessed for local recurrence. Adverse events and LOS were recorded from chart review. Kaplan-Meier analysis was performed to assess both overall and local recurrence-free survival. RESULTS: Mean patient follow-up period was 21.6 months ± 10.8, and mean imaging follow-up period was 19.2 months ± 9.6. Overall survival at 3 years was 94% (95% CI, 81%-100%). Local recurrence-free survival was 100% throughout the imaging follow-up period. Intraprocedural pneumothorax occurred in 37% (7 of 19) of patients; pneumothorax risk was significantly associated with increased tumor distance from pleura (odds ratio, 1.2; P = .018). Sixty-three percent (12 of 19) of patients were discharged on the day of the procedure, with a mean LOS of 7.7 hours ± 1.6, whereas 37% of patients required overnight observation (2 of 19) or admission (5 of 19), with a mean LOS of 48.1 hours ± 19.4. Overall LOS for all patients was 22.6 hours ± 22.9. CONCLUSIONS: Percutaneous cryoablation of primary pulmonary malignancies can be performed in select octogenarians and nonagenarians with high 3-year overall and recurrence-free survival. Despite nonnegligible risk of pneumothorax, most patients are discharged on the day of the procedure.

Quantitative Diagnosis of Nonalcoholic Fatty Liver Disease with Ultrasound Attenuation Imaging in a Biopsy-Proven Cohort.

RATIONALE AND OBJECTIVES: To evaluate the performance of attenuation imaging (ATI) based on ultrasound for detection of hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: This prospective study was approved by our institutional review board (B2021-092R). Written informed consent was obtained from all patients. This study included 60 patients who had clinical suspicion of NAFLD and were referred for liver biopsy after ATI and controlled attenuation parameter (CAP) examinations between September 2020 and December 2021. The histologic hepatic steatosis was graded. The area under curve (AUC) analysis was performed. RESULTS: The success rate of the ATI examination was 100%. The intraobserver reproducibility of ATI was 0.981. The AUCs of ATI for detecting ≥S1, ≥S2, and S3 were 0.968 (cut-off value of 0.671 dB/cm/MHz), 0.911 (cut-off value of 0.726 dB/cm/MHz), and 0.766 (cut-off value of 0.757 dB/cm/MHz), respectively. The AUCs of CAP for detecting ≥S1, ≥S2, and S3 were 0.916 (cut-off value of 258.5 dB/m), 0.872 (cut-off value of 300.0 dB/m), and 0.807 (cut-off value of 315.0 dB/m), respectively. The diagnostic values showed no significant difference between ATI and CAP in detecting ≥S1, ≥S2, and S3 (P = .281, P = .254, and P = .330, respectively). The ATI had significant correlations with high-density lipoprotein cholesterol (P < .001), and with triglycerides (P = .015). CONCLUSION: ATI showed good feasibility and diagnostic performance in the detection of varying degrees of hepatic steatosis in NAFLD patients.

Comparison of contrast-enhanced ultrasound, IOTA simple rules and O-RADS for assessing the malignant risk of sonographically appearing solid ovarian masses.

PURPOSE: To explore the diagnostic accuracy of ovarian solid tumors by 2D ultrasound and contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: We retrospectively evaluated the CEUS characteristics of prospectively enrolled 16 benign and 19 malignant ovarian solid tumors. We performed International Ovarian Tumor Analysis (IOTA) simple rules and Ovarian-Adnexal Reporting and Data System (O-RADS) for all lesions, and evaluated their characteristics on CEUS. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of IOTA simple rules, O-RADS and CEUS in the diagnosis of ovarian solid malignancies were calculated. RESULTS: The combination of time to wash-in earlier than or equal to the myometrium, time to PI earlier than or equal to the myometrium and the intensity at peak were higher than or equal to myometrium with sensibility of 0.947, specificity of 0.938, and PPV of 0.947, NPV of 0.938 which were higher than IOTA simple rules and O-RADS. According to the definition of ovarian solid tumor, the diagnostic accuracy of O-RADS 3 and CEUS were both 100%, CEUS improved the accuracy of O-RADS 4 from 47.4% to 87.5%, the accuracy of solid smooth CS 4 in O-RADS 5 and CEUS were both 100%, CEUS improved the accuracy of solid irregular in O-RADS 5 from 70% to 87.5%. CONCLUSION: For ovarian solid tumors that are difficult to distinguish between benign and malignant, the introduction of CEUS on the basis of 2D classification criteria can significantly improve the diagnostic accuracy.

Clinical application of preoperative shear wave dispersion for prediction of post liver failure in patients with hepatocellular carcinoma after hepatectomy.

OBJECTIVE: The aim in this study was to determine the efficacy of shear wave dispersion (SWD) technique for the prediction of post hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma after hepatectomy and develop an SWD based risk prediction model. METHODS & MATERIALS: We prospectively enrolled 205 consecutive patients who were scheduled to undergo hepatectomy for hepatocellular carcinoma (HCC), pre-operative SWD examination, laboratory data and some other clinicopathological tests were collected. The risk factors of PHLF were identified according to univariate and multivariate analysis, a predictive model was established based on logistic regression analyses. RESULTS: SWD examination was successfully performed in 205 patients. PHLF occurred in 51 patients (24.9%), including 37/11/3 patients with Grade A/B/C, respectively. There was a high correlation between SWD value of liver and liver fibrosis stage (r = 0.873, p < 0.05). Patients with PHLF has a higher median SWD value of liver than patients without PHLF [17.4 vs 14.7 (m/s)/kHz, p < 0.05]. The SWD value of liver, total bilirubin (TB), international normalized ratio of prothrombin time (INR) and splenomegaly were significantly related to PHLF based on the multivariate analysis. A new prediction model (PM) for PHLF was established (PM = -12.918 + 0.183× SWD + 6.668× INR +0.100×TB+1.240×splenomegaly). The optimal cutoff value of SWD for predicting PHLF was 16.7 (m/s)/kHz. The area under the curve (AUC) of the PM for PHLF was 0.833, which was higher than that of SWD, INR, Forns, FIB4, APRI (p < 0.005, respectively). CONCLUSION: SWD is a promising and reliable method for PHLF prediction in patients with HCC who were undergoing hepatectomy. Compared with SWD, Forns, APRI and FIB-4, PM demonstrate better efficacy for preoperative PHLF prediction.

A novel HLA-C*07 allele, HLA-C*07:1024, was identified in a Chinese individual.

One nucleotide replacement at nucleotide 397 of HLA-C*07:02:01:01 results in a new allele, HLA-C*07:1024.

A Comparative Study of Ultrasound Attenuation Imaging, Controlled Attenuation Parameters, and Magnetic Resonance Spectroscopy for the Detection of Hepatic Steatosis.

OBJECTIVES: To investigate the methodology and clinical application of ultrasound attenuation imaging (ATI) and comparative analyze the diagnostic performance of ATI and controlled attenuation parameters (CAP) for detecting and grading hepatic steatosis. METHODS: A total of 159 patients with NAFLD were prospectively enrolled. CAP and ATI examinations were performed within a week before proton magnetic resonance spectroscopy (1 H-MRS). Ten liver attenuation coefficient (AC) measurements by ATI were obtained in each patient. The interclass correlation coefficients (ICCs) of the intraobserver consistencies and the ICCs between the median of the first two through the first nine measurements and all 10 measurements were calculated. The correlations between 1 H-MRS, CAP, biological data, and ATI were evaluated. The significant factors associated with ATI and the diagnostic performance of ATI and CAP for detecting hepatic steatosis was evaluated. RESULTS: The median value of AC for detecting hepatic steatosis was 0.831 dB/cm/MHz. For the intraobserver consistency of ATI, the ICC was 0.931. Compared with 10 measurements, a minimum of four ATI measurements was required. The correlation of AC with hepatic fat fraction (HFF) was significantly higher than that of CAP (0.603 vs 0.326, P = .0015). The HFF and triglyceride (TG) were the significant factors for the ATI. The area under the receiver operating characteristics (ROC) curves of ATI and CAP were 0.939 and 0.788 for detecting ≥10% hepatic steatosis; 0.751 and 0.572 for detecting >33% hepatic steatosis. The cutoff values of ATI and CAP were 0.697 dB/cm/MHz and 310 dB/m for detecting ≥10% hepatic steatosis; 0.793 dB/cm/MHz and 328 dB/m for detecting >33% hepatic steatosis. The sensitivity of ATI and CAP were 85.92% and 52.11% for detecting ≥10% hepatic steatosis; 87.50% and 82.14% for detecting >33% hepatic steatosis. The specificity of ATI and CAP were 94.12% and 100% for detecting ≥10% hepatic steatosis; 54.37% and 43.69% for detecting >33% hepatic steatosis. CONCLUSIONS: ATI technology showed excellent intraobserver consistency and the optimal minimum number of ATI measurements was 4. ATI is a promising noninvasive, quantitative and convenient tool for assessing hepatic steatosis.