Feasibility and Measurement Value of Pancreatic 2-D Shear Wave Elastography in Healthy Adults: Evaluation, Influencing Factors, Reference Range, Measurement Stability and Reproducibility.

OBJECTIVE: The present study was aimed at assessing the success rate and measurement value, determining the influencing factors and reference range and examining the intra-operator stability and inter-operator reproducibility of pancreatic 2-D shear wave elastography (SWE) measurement in healthy adults. METHODS: In 2022, 387 healthy adults were prospectively recruited. Logistic regression and linear regression analyses were used to explore the factors influencing the success rate and the measurement value of pancreatic 2-D SWE measurement, respectively. A two-sided 95% reference range was estimated accordingly. The intraclass correlation coefficient was calculated to evaluate the intra-operator stability and inter-operator reproducibility of the pancreatic 2-D SWE measurement. RESULTS: The pancreatic body (89.6%) bore the highest while the tail (72.8%) bore the lowest success rate of pancreatic 2-D SWE measurement. Sex and body mass index (BMI) were the independent factors influencing measurement success rate in all three parts of the pancreas. Mean measurement values (Emean) were not the same in the three parts of the pancreas of the same participant. BMI and image depth were the independent factors influencing Emean in the pancreatic body, while region of interest depth and BMI were the only independent factors influencing Emean in the pancreatic head and tail, respectively. The intra-operator stability of pancreatic 2-D SWE measurement was found to be excellent, whereas its inter-operator reproducibility was poor to good. CONCLUSION: Pancreatic 2-D SWE is a reliable technique for evaluating pancreatic stiffness in healthy adults, but its success rate and measurement value are influenced by multiple factors.

An Interpretable Radiomics Model Based on Two-Dimensional Shear Wave Elastography for Predicting Symptomatic Post-Hepatectomy Liver Failure in Patients with Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to develop and validate an interpretable radiomics model based on two-dimensional shear wave elastography (2D-SWE) for symptomatic post-hepatectomy liver failure (PHLF) prediction in patients undergoing liver resection for hepatocellular carcinoma (HCC). METHODS: A total of 345 consecutive patients were enrolled. A five-fold cross-validation was performed during training, and the models were evaluated in the independent test cohort. A multi-patch radiomics model was established based on the 2D-SWE images for predicting symptomatic PHLF. Clinical features were incorporated into the models to train the clinical-radiomics model. The radiomics model and the clinical-radiomics model were compared with the clinical model comprising clinical variables and other clinical predictive indices, including the model for end-stage liver disease (MELD) score and albumin-bilirubin (ALBI) score. Shapley Additive exPlanations (SHAP) was used for post hoc interpretability of the radiomics model. RESULTS: The clinical-radiomics model achieved an AUC of 0.867 (95% CI 0.787-0.947) in the five-fold cross-validation, and this score was higher than that of the clinical model (AUC: 0.809; 95% CI: 0.715-0.902) and the radiomics model (AUC: 0.746; 95% CI: 0.681-0.811). The clinical-radiomics model showed an AUC of 0.822 in the test cohort, higher than that of the clinical model (AUC: 0.684, p = 0.007), radiomics model (AUC: 0.784, p = 0.415), MELD score (AUC: 0.529, p < 0.001), and ALBI score (AUC: 0.644, p = 0.016). The SHAP analysis showed that the first-order radiomics features, including first-order maximum 64 × 64, first-order 90th percentile 64 × 64, and first-order 10th percentile 32 × 32, were the most important features for PHLF prediction. CONCLUSION: An interpretable clinical-radiomics model based on 2D-SWE and clinical variables can help in predicting symptomatic PHLF in HCC.

Stiffness on shear wave elastography as a potential microenvironment biomarker for predicting tumor recurrence in HBV-related hepatocellular carcinoma.

BACKGROUND: To explore the pathologic basis and prognostic value of tumor and liver stiffness measured pre-operatively by two-dimensional shear wave elastography (2D-SWE) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who undergo hepatic resection. METHODS: A total of 191 HBV-infected patients with solitary resectable HCC were prospectively enrolled. The stiffness of intratumoral tissue, peritumoral tissue, adjacent liver tissue, and distant liver tissue was evaluated by 2D-SWE. The correlations between stiffness and pathological characteristics were analyzed in 114 patients. The predictive value of stiffness for recurrence-free survival (RFS) was evaluated, and Cutoff Finder was used for determining optimal cut-off stiffness values. Cox proportional hazards analysis was used to identify independent predictors of RFS. RESULTS: Pathologically, intratumoral stiffness was associated with stroma proportion and microvascular invasion (MVI) while peritumoral stiffness was associated with tumor size, capsule, and MVI. Adjacent liver stiffness was correlated with capsule and liver fibrosis stage while distant liver stiffness was correlated with liver fibrosis stage. Peritumoral stiffness, adjacent liver stiffness, and distant liver stiffness were all correlated to RFS (all p < 0.05). Higher peritumoral stiffness (> 49.4 kPa) (HR = 1.822, p = 0.023) and higher adjacent liver stiffness (> 24.1 kPa) (HR = 1.792, p = 0.048) were significant independent predictors of worse RFS, along with tumor size and MVI. The nomogram based on these variables showed a C-index of 0.77 for RFS prediction. CONCLUSIONS: Stiffness measured by 2D-SWE could be a tumor microenvironment and tumor invasiveness biomarker. Peritumoral stiffness and adjacent liver stiffness showed important values in predicting tumor recurrence after curative resection in HBV-related HCC. CLINICAL RELEVANCE STATEMENT: Tumor and liver stiffness measured by two-dimensional shear wave elastography serve as imaging biomarkers for predicting hepatocellular carcinoma recurrence, reflecting biological behavior and tumor microenvironment. KEY POINTS: • Stiffness measured by two-dimensional shear wave elastography is a useful biomarker of tumor microenvironment and invasiveness. • Higher stiffness indicated more aggressive behavior of hepatocellular carcinoma. • The study showed the prognostic value of peritumoral stiffness and adjacent liver stiffness for recurrence-free survival. • The nomogram integrating peritumoral stiffness, adjacent liver stiffness, tumor size, and microvascular invasion showed a C-index of 0.77.

High-resolution monophenolase/diphenolase/radical scavenging profiling for rapid screening of natural whitening candidates from Rosa rugosa cv. 'Plena'.

Antioxidants and tyrosinase inhibitory components were successfully screened and separated from Rosa rugosa cv. 'Plena' by high-performance liquid chromatography microfractionation bioactive screening combined with several separation and purification methods. Ethyl acetate extract of Rosa rugosa cv. 'Plena' showed high antioxidant activity and tyrosinase inhibitory activity. High-speed countercurrent chromatography, silica gel column chromatography, and semi-preparative high-performance liquid chromatography were used for the preparative separation of four bioactive components from ethyl acetate extract. Two tyrosinase-inhibiting active substances, flavogallonic acid, and N1 -N5 -N10 -tri-4-p-coumaroylspermidine, were isolated from Rosa rugosa cv. 'Plena', and they showed great monophenolase inhibition activity (half-maximal inhibitory concentration: 664.60 and 23.77 µg/ml, respectively) and excellent diphenolase inhibition activity (half-maximal inhibitory concentration: 23 614.61 and 16.80 µg/ml, respectively). Meanwhile, gallic acid, flavogallonic acid, and ellagic acid were shown to have excellent 1,1-diphenyl-2-picryl-hydrazyl antioxidant activity (half maximal inhibitory concentration: 6.66, 20.17, and 13.45 µg/ml), and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) antioxidant activity (half maximal inhibitory concentration: 3.53, 3.83, and 2.78 µg/ml). Molecular docking revealed that flavogallonic acid and N1 -N5 -N10 -tri-4-p-coumaroylspermidine had a strong binding affinity (-9.3 and -10 kcal/mol, respectively) to tyrosinase through hydrogen bonding and hydrophobic interactions.

Predicting Post-hepatectomy Liver Failure Preoperatively for Child-Pugh A5 Hepatocellular Carcinoma Patients by Liver Stiffness.

BACKGROUND: Post-hepatectomy liver failure (PHLF) represents the major source of mortality after liver resection (LR) in hepatocellular carcinoma (HCC) patients. Child-Pugh (CP) score 5 is always considered to indicate a normal liver function but represents a heterogeneous population with a considerable number suffering from PHLF. The present study aimed to access the ability of liver stiffness (LS) measured by two-dimensional shear wave elastography (2D-SWE) to predict PHLF in HCC patients with a CP score of 5. METHODS: From August 2018 to May 2021, 146 HCC patients with a CP score of 5 who underwent LR were reviewed. The patients were randomly divided into training (n = 97) and validation (n = 49) groups. Logistic analyses were conducted for the risk factors and a linear model was built to predict the development of PHLF. The discrimination and calibration were assessed in the training and validation cohorts by the areas under the receiver operating characteristic curve (AUC). RESULTS: Analyses revealed that the minimum of LS (Emin) higher than 8.05 (p = 0.006, OR = 4.59) and future liver remnant / estimated total liver volume (FLR/eTLV) (p < 0.001, OR < 0.01) were independent predictors of PHLF in HCC patients with CP score 5, and the AUC calculated by the model based on them for differentiation of PHLF in the training and validation group was 0.78 and 0.76, respectively. CONCLUSION: LS was associated with the development of PHLF. A model combining Emin and FLR/eTLV showed proper ability in predicting PHLF in HCC patients with a CP score of 5.

A Strategy for Pinpointing Natural Bioactive Components Using Two-Dimensional Bioassay Profilings Combined with Comprehensive Two-Dimensional Countercurrent Chromatography × High-Performance Liquid Chromatography.

Inspired by the interpretation of two-dimensional (2D) nuclear magnetic resonance spectra, an efficient strategy was proposed for pinpointing bioactive components from complex natural products. An off-line comprehensive countercurrent chromatography (CCC) × high-performance liquid chromatography (HPLC) was employed to achieve a 2D chemical chromatogram, and 2D bioassay profilings were obtained from bioassays of the eluent of the first dimension (1D) CCC and the eluent of the second dimension (2D) HPLC. Then 2D chemical chromatograms and 2D bioassay profilings were matched for pinpointing bioactive natural components from complex matrices. Thus, bioactive components in a complex matrix could be efficiently analyzed, separated, and bioactivity-determined. This experimental scheme was successfully demonstrated with a traditional medicinal herb Polygonum cuspidatum Sieb. et Zucc. The feasibility of this 2D strategy was verified with tyrosinase inhibition assay, α-glucosidase inhibition assay, DPPH radical scavenging assay, and ABTS•+ decolorization assay. Eight natural inhibitors were successfully pinpointed and identified from P. cuspidatum. Both pieceid-2″-O-gallate (10) and vanicoside B (20) were screened and identified as natural tyrosinase inhibitors for the first time. Meanwhile, vanicoside B (20) was also found as the strongest α-glucosidase inhibitor among all the isolated components. Most of the compounds exhibited much higher radical scavenging activities. Compared with traditional methodology based on one-dimensional chromatographic separation, the present 2D strategy would be more precise, efficient, and convenient to screen and separate bioactive compounds from complex matrices.

A nomogram based on multi-modal ultrasound for prediction of microvascular invasion and recurrence of hepatocellular carcinoma.

OBJECTIVE: To establish and validate a nomogram based on multi-modal ultrasound for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC), and to assess the ability thereof to stratify recurrence-free survival (RFS). METHODS: A total of 287 HCC patients undergoing surgical resection were prospectively enrolled, including 210 patients in the training cohort and 77 patients in the test cohort. All patients underwent conventional ultrasound, contrast-enhanced ultrasonography, and shear wave elastography examinations within one week before surgery. Taking histopathological examination result as the reference standard, independent factors associated with MVI in HCC were determined by logistic regression and a nomogram was established and further evaluated. The Kaplan-Meier method was used to analyze the prognostic value of histologic MVI status and nomogram-predicted MVI status. RESULTS: Multivariate analysis showed that tumor diameter, echogenicity, tumor shape, arterial phase peritumoral enhancement and enhancement level in portal venous phase were independent predictors of MVI (all p < 0.05). The nomogram based on these variables showed good discrimination and calibration with the areas under the receiver operating characteristic curve (AUC) of 0.821 (0.762-0.870) and 0.789 (0.681-0.874) in the training and test cohorts. There was a significant difference in RFS between the nomogram-predicted MVI positive and the nomogram-predicted MVI negative groups in training and test cohorts (p < 0.001 and p = 0.004 respectively). CONCLUSIONS: The multimodal ultrasound features were effective imaging markers for preoperative prediction of MVI of HCC and the nomogram might be an effective tool to stratify the risk of recurrence and guide the individualized treatment of HCC.

The value of liver stiffness measured by two-dimensional shear wave elastography for predicting symptomatic posthepatectomy liver failure in patients with hepatocellular carcinoma.

PURPOSE: To assess and compare the value of liver stiffness measurement (LSM) by two-dimensional shear wave elastography (2D-SWE) with the diagnosis of clinically significant portal hypertension (CSPH) and pathological examination in predicting symptomatic posthepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC). METHOD: A total of 130 patients who underwent liver resection for HCC between August 2018 and July 2021 were enrolled. Preoperative assessments for LSM and other clinicopathological tests were performed in all patients. The performance of LSM, CSPH and fibrosis stage in predicting symptomatic PHLF was assessed and compared. Univariate and multivariate analyses were conducted on the risk factors for symptomatic PHLF. RESULTS: Symptomatic PHLF occurred in 40 patients (30.8%). The best LSM cutoff value for predicting symptomatic PHLF was 9.5 kPa. The areas under the receiver operating characteristic curve (AUCs) of LSM ≥ 9.5 kPa, fibrosis stage and CSPH for predicting symptomatic PHLF were 0.732 (95% CI: 0.638-0.826, p < 0.001), 0.655 (95% CI: 0.553-0.758, p = 0.005) and 0.594 (95% CI: 0.484-0.705, p = 0.086), respectively. The AUC of LSM ≥ 9.5 kPa was significantly higher than that of CSPH (p = 0.010), and was comparable to that of fibrosis stage (p = 0.073). Multivariate analysis identified LSM ≥ 9.5 kPa (p = 0.001), major hepatectomy (p = 0.007) and CSPH diagnosis (p = 0.040) as independent predictors of symptomatic PHLF. CONCLUSIONS: LSM by 2D-SWE was promising for predicting symptomatic PHLF in HCC patients. The predictive performance was higher than that of CSPH and comparable to that of pathological fibrosis stage.

Malignancy risk stratification and FNA recommendations for thyroid nodules: A comparison of ACR TI-RADS, AACE/ACE/AME and ATA guidelines.

OBJECTIVE: To compare diagnostic performance and malignancy risk stratification among guidelines set forth by the American Thyroid Association (ATA) in 2015, the American Association of Clinical Endocrinologists (AACE), the American College of Endocrinology (ACE) and the Association Medici Endocrinologi (AME) in 2016, and the American College of Radiology (ACR) in 2017. METHODS: The retrospective study was approved by the hospital ethics committee, and the informed consent requirement was waived. From October 2015 to March 2016, a total of 230 patients with 230 consecutive thyroid nodules were enrolled in this study. Each nodule was classified by one junior and one senior radiologist separately according to ACR TI-RADS, AACE/ACE/AME and ATA guidelines. The malignancy diagnostic performance and the number of FNA recommendations were pairwise compared among three guidelines using chi-square tests. RESULTS: Of the 230 thyroid nodules, 137 were malignant, and 93 were benign. However, 19.6% of the nodules (45 of 230) did not match any pattern using the ATA guidelines but with a high risk of malignancy (68.9%). The ACR TI-RADS derived the highest diagnostic performance, from both junior radiologist (AUC 0.815) and senior radiologist (AUC 0.864). The ACR guidelines also showed the greatest level of sensitivity (junior: 86.1%, senior: 94.9%), compared with AACE/ACE/AME and ATA guidelines. The number of thyroid nodules recommended to fine-needle aspiration (FNA) was the lowest (37.8%, 40.4%) by ACR TI-RADS, and meanwhile, the malignant detection rate within these nodules was highest (64.4%, 68.8%). CONCLUSIONS: The ACR guidelines present a higher level of diagnostic indicators and may offer a meaningful reduction in FNA recommendations with a higher malignancy detection rate.

Clinical Efficacy of Alprostadil Combined with α-lipoic Acid in the Treatment of Elderly Patients with Diabetic Nephropathy.

OBJECTIVE: To evaluate the effect and toxicity of alprostadil combined with thioctic acid injection in the treatment of patients with diabetic nephropathy (DN). METHODS: Sixty two patients with DN were included in this study and randomly divided into control group (n=32) and experiment group (n=30). Patients in the control group were given alprostadil 20ug+NS 100ml ivgtt, qd and patients in the experiment group were given alprostadil 20ug+NS 100ml ivgtt combined with thioctic acid injection of 0.45g+100ml ivgtt, qd for 14 days. After treatment, the renal function and serum level of CRP, IL-6 and TNF-α were compared between the two groups. RESULTS: After two weeks of treatment, the serum level of CysC and UAER significant decreased for both control and experiment group with statistical difference of p<0.05. After treatment, the serum level of CysC were 1.40 ±0.46 mg/L and 1.02±0.33 for control and experiment group respectively (p<0.05). The post-treatment UAER in experiment group was significantly lower than those of control group with statistical difference (81.02±0.33 vs112.45±20.32, p<0.05) ug/min. The serum level of CRP, IL-6 and TNF-α were significantly decreased after treatment for both control and experiment group (p<0.05). And the post-treatment serum CRP, IL-6 and TNF-α in experiment group were significantly lower than those of control group with statistical difference (p<0.05). No significant side effects were found for the two groupsin the course of treatment. CONCLUSION: Alprostadil combined with α-lipoic acid may improve renal function in patients with diabetic nephropathy by decreasing the levels of serum inflammatory factors.