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Exosomes are widely distributed extracellular vesicles (EVs), which are currently a major research hotspot for researchers based on their wide range of sources, stable membrane structure, low immunogenicity, and containing a variety of biomolecules. A large number of literatures have shown that exosomes and exosome cargoes (especially microRNAs) play an important role in the activation of inflammation, development of tumor, differentiation of cells, regulation of immunity and so on. Studies have found that exosomes can stimulate the immune response of the body and participate in the occurrence and development of various diseases, including autoimmune diseases. Furthermore, the potential of exosomes as therapeutic tools in various diseases has also attracted much attention. Autoimmune thyroid disease (AITD) is one of the most common autoimmune diseases, mainly composed of Graves' disease (GD) and Hashimoto's thyroiditis (HT), which affects the health of many people and has a genetic predisposition, but its pathogenesis is still being explored. Starting from the relevant biological characteristics of exosomes, this review summarizes the current research status of exosomes and the association between exosomes and some diseases, with a focus on the situation of AITD and the potential role of exosomes (including substances in their vesicles) in AITD in combination with the current published literature, aiming to provide new directions for the pathogenesis, diagnosis or therapy of AITD. Supplemental data for this article is available online at [ABSTRACT FROM AUTHOR]

Objectives: In this study, we used the recently developed ultrasound elastography techniques sound touch elastography (STE) and sound touch quantification (STQ) to quantify portal hypertension (PHT) severity in a rat model of carbon tetrachloride (CCl4)‐induced cirrhotic PHT. Methods: In total, 60 rats were used. Various degrees of PHT were established. Liver and spleen stiffness were measured by STE (L‐STE and S‐STE, respectively) and STQ (L‐STQ and S‐STQ, respectively). We measured portal pressure (PP) after ultrasonographic examination. The performance of the STE and STQ parameters in the identification of PHT was evaluated using receiver operating characteristic (ROC) analyses. Results: Liver and spleen stiffness measurements obtained with STE and STQ correlated positively with the PP (r = 0.566–0.882, all P <.001). The areas under ROC curves for L‐STE, S‐STE, L‐STQ, and S‐STQ values were 0.931 (95% confidence interval [CI], 0.847–1.000), 0.982 (95% CI, 0.956–1.000), 0.796 (95% CI, 0.680–0.912), and 0.925 (95% CI, 0.858–0.993), respectively, for PP ≥5 mmHg; 0.937 (95% CI, 0.865–1.000), 0.938 (95% CI, 0.864–1.000), 0.967 (95% CI, 0.923–1.000), and 0.960 (95% CI, 0.897–1.000), respectively, for PP ≥10 mmHg; and 0.954 (95% CI, 0.897–1.000), 0.790 (95% CI, 0.652–0.928), 0.808 (95% CI, 0.680–0.935), and 0.740 (95% CI, 0.595–0.885), respectively, for PP ≥12 mmHg. Conclusions: STE and STQ are reliable noninvasive tools for the assessment of PHT severity, especially for PP ≥10 mmHg, in a rat model of CCl4‐induced cirrhotic PHT. [ABSTRACT FROM AUTHOR]

Contrast-enhanced ultrasound (CEUS) has been proposed for detecting clinically significant portal hypertension (CSPH) and severe portal hypertension (SPH) in patients with chronic liver diseases (CLD). Studies were selected that investigated the diagnostic performance of CEUS in patients with CLD up to 10 October 2022. The summary area under the receiver operating characteristic curve (AUROC), the summary diagnostic odds ratios, and the summary sensitivities and specificities were used to assess the performance of CEUS for detecting CSPH and SPH. A total of 7 studies were included in this meta-analysis. The summary sensitivity and specificity of this method for CSPH were 92% (95% confidence interval (CI), 76%–97%) and 78% (95% CI, 67%–86%), respectively, and the summary AUROC was 0.89 (95% CI, 0.86–0.92). Those for SPH were 81% (95% CI, 60%-93%), 82% (95% CI, 76%-86%), and 0.82 (95% CI, 0.79–0.85), respectively. A subgroup analysis of 3 subharmonic aided pressure estimation (SHAPE) studies revealed similar diagnostic performance (sensitivity: 95%; specificity: 74%; AUROC: 0.93) for detecting CSPH. CEUS shows good performance in diagnosing CSPH as well as SPH. SHAPE technique may play a more important role in evaluating CSPH in the future. The meta-analysis was not registered. [ABSTRACT FROM AUTHOR]

Two-dimensional shear wave elastography (2D-SWE) has recently been proposed to detect clinically significant portal hypertension (CSPH), we aimed to perform a meta-analysis based on the published data to assess the diagnostic accuracy of 2D-SWE for detecting CSPH. Literature databases were searched up until 1 August 2021. The summary area under receiver operating characteristics curve (AUROC), the summary diagnostic odds ratio (DOR), and the summary sensitivity and specificity were used to examine the accuracy of 2D-SWE for evaluating CSPH. Heterogeneity was explored using meta-regression. Finally 9 studies with 956 patients were included in this study for evaluation and meta-analysis. 2D-SWE showed good diagnostic performance for detecting CSPH with a summary sensitivity of 83% (95% confidence interval [CI]: 76%-88%) and summary specificity of 78% (95% CI: 65%-87%); the summary AUROC was 0.88 (95% CI: 0.84–0.90). Summary positive likelihood ratio (LR), negative LR, and DOR of 2D-SWE for detecting CSPH were 3.7 (95% CI: 2.4–5.9), 0.22 (95% CI: 0.16–0.30), and 17 (95% CI: 10–29), respectively. 2D-SWE showed good performance in diagnosing CSPH and can be considered as an important and noninvasive adjunctive approach in the management of patients with CSPH. [ABSTRACT FROM AUTHOR]

Background: Aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) are the two most widely studied noninvasive markers of liver fibrosis. We aimed to assess the diagnostic accuracy of APRI and FIB-4 for liver fibrosis in patients with autoimmune hepatitis (AIH) using liver biopsy as the reference standard. Methods: PubMed, EMBASE, Cochrane Library and Web of Science databases were searched for studies (published as of May 1st, 2021) that assessed the diagnostic performance of APRI and FIB-4 for liver fibrosis in AIH. The summary area under receiver operating characteristics curve (AUROC), sensitivity, specificity, diagnostic odds ratios were used to assess the diagnostic accuracy of APRI and FIB-4 for detecting liver fibrosis. Results: Fourteen studies (including 1015 patients) were selected with 13 studies each evaluating the use of APRI and FIB-4 for detecting different stages of fibrosis in AIH. For prediction of significant fibrosis, advanced fibrosis, and cirrhosis, the summary AUROC value was 0.66 [95% confidence interval (CI): 0.61–0.70], 0.71 (95% CI: 0.67–0.75), and 0.75 (95% CI: 0.71–0.79) for APRI, and the summary AUROC value was 0.75 (95% CI: 0.71–0.79), 0.73 (95% CI: 0.69–0.77) and 0.79 (95% CI: 0.75–0.82) for FIB-4, respectively. The summary sensitivity and specificity for diagnosis of significant fibrosis, advanced fibrosis, and cirrhosis were 90% and 36%, 78% and 55%, and 77% and 61% for APRI, and 70% and 70%, 65% and 70%, and 78% and 65% for FIB-4, respectively. Conclusions: APRI and FIB-4 showed suboptimal diagnostic performance for identifying liver fibrosis in AIH with mediocre sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Aim: This study assessed the diagnostic performance of liver stiffness measurement (LSM) in detecting liver fibrosis in paediatric patients with non‐alcoholic fatty liver disease (NAFLD) through meta‐analysis. Methods: Online database searches of PubMed, EMBASE, the Cochrane Library and the Web of Science were conducted for studies that evaluated the performance of LSM for diagnosing liver fibrosis in paediatric patients with NAFLD until 1 January 2021. The Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2) tool was used to assess the quality of the included studies. Three measures were used to assess the performance of LSM for detecting liver fibrosis in paediatric patients with NAFLD, including the summary sensitivities and specificities, the summary area under the receiver operating characteristic curves and the summary diagnostic odds ratios. Results: Our final data included seven studies with a total of 436 paediatric patients with NAFLD for meta‐analysis. The overall prevalence of mild fibrosis, significant fibrosis, advanced fibrosis and cirrhosis was 66.3, 31.5, 14.9 and 1.2%, respectively. The summary sensitivity, specificity and area under the receiver operating characteristic values of LSM were 80, 92 and 0.94 for the prediction of mild fibrosis; 91, 97 and 0.98 for the prediction of significant fibrosis; and 89, 93 and 0.96 for the prediction of advanced fibrosis, respectively. Conclusion: Liver stiffness measurement exhibited good diagnostic performance in predicting liver fibrosis and can be used as a non‐invasive tool in the management of paediatric patients with non‐alcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

Two-dimensional shear wave elastography (2D-SWE), magnetic resonance elastography (MRE), aspartate transaminase-to-platelet ratio index (APRI), fibrosis index based on 4 factors (FIB-4), and King's score have been proposed for diagnosing fibrosis. Literature databases were searched until October 1st, 2020. The summary area under the receiver operating characteristic curve (AUROC), the summary diagnostic odds ratios, and the summary sensitivities and specificities were used to assess the performance of these noninvasive methods for staging fibrosis. Our final data contained 72 studies. The prevalence of significant fibrosis, advanced fibrosis, and cirrhosis was 58.3%, 36.2%, and 20.5%, respectively, in chronic hepatitis B (CHB). For 2D-SWE and MRE, the summary AUROCs were 0.89 and 0.97, 0.95 and 0.97, and 0.94 and 0.97 for significant fibrosis, advanced fibrosis, and cirrhosis, respectively. The summary AUROCs using APRI and FIB-4 for detecting significant fibrosis, advanced fibrosis, and cirrhosis were 0.76 and 0.75, 0.74 and 0.77, and 0.77 and 0.82, respectively. The summary AUROCs of King's score for detecting significant fibrosis and cirrhosis were 0.77 and 0.83, respectively. MRE and 2D-SWE may show the best diagnostic accuracy for predicting fibrosis in CHB. Among the three serum markers, King's score may be more useful for diagnosing fibrosis. [ABSTRACT FROM AUTHOR]

Background & Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model., Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvedilol-treating cohort., Results: In the meta-analysis with six studies (n = 819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new "CSPH risk" model. In the HVPG cohort (n = 151), the new model accurately predicted CSPH with cutoff values of 0 and -0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n = 1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <-0.68 (low-risk), -0.68 to 0 (medium-risk), and >0 (high-risk). In the carvedilol-treated cohort, patients with high-risk CSPH treated with carvedilol (n = 81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n = 613 before propensity score matching [PSM], n = 162 after PSM)., Conclusions: Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: Long noncoding RNAs (lncRNAs) have been shown to be involved in the regulation of numerous biological processes in embryonic development. We aimed to explore lncRNA expression profiles in ventricular septal defects (VSDs) and reveal their potential roles in heart development., Methods: Microarray analyses were performed to screen differentially expressed lncRNAs (DE-lncRNAs) and mRNAs (DE-mRNAs) in the amniotic fluid between the VSD group and the control group. Bioinformatics analyses were further used to identify the functional enrichment and signaling pathways of important mRNAs. Then, a coding-noncoding gene coexpression (CNC) network and competitive endogenous RNAs (ceRNA) network were drawn. Finally, qRT ‒ PCR was performed to verify several hub lncRNAs and mRNAs in the network., Results: A total of 710 DE-lncRNAs and 397 DE-mRNAs were identified in the VSD group. GO and KEGG analyses revealed that the DE-mRNAs were enriched in cardiac development-related biological processes and pathways, including cell proliferation, cell apoptosis, and the Sonic Hedgehog signaling pathway. Four VSD related mRNAs was used to construct the CNC network, which included 149 pairs of coexpressing lncRNAs and mRNAs. In addition, a ceRNA network, including 15 lncRNAs, 194 miRNAs, and four mRNAs, was constructed to reveal the potential regulatory relationship between lncRNAs and protein-coding genes. Finally, seven RNAs in the ceRNA network were validated, including IDS, NR2F2, GPC3, LINC00598, GATA3-AS1, PWRN1, and LINC01551., Conclusion: Our study identified some lncRNAs and mRNAs may be potential biomarkers and therapeutic targets for foetuses with VSD, and described the lncRNA-associated ceRNA network in the progression of VSD., Competing Interests: The authors declare that they have no competing interests., (© 2023 Wang et al.)

Background: Biliary atresia (BA) is a severe inflammatory obliterative cholangiopathy of infancy that requires early diagnosis and prompt surgical intervention. In this study, we aimed to obtain comprehensive evidence on the diagnostic performance of liver stiffness measurement by ultrasound elastography in the detection of BA through a meta-analysis., Methods: The PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched for studies that investigated the diagnostic performance of ultrasound elastography in the detection of BA up to January 10, 2022. In this study, in order to summarize the diagnostic performance of ultrasound elastography, the summary receiver operating characteristic (SROC) modeling was constructed. Heterogeneity was estimated with the I 2 statistic. Multiple subgroup analyses were also performed., Results: Fourteen studies from eleven articles, including 774 BA patients, 850 non-BA patients, and 173 controls were included in the present meta-analysis. The summary sensitivity and specificity of ultrasound elastography for liver stiffness were 85% [95% confidence interval (CI): 79-89%] and 82% (95% CI: 73-88%) with the I 2 value of 82.90 and 84.33%, respectively. The area under the SROC curve (AUROC) using ultrasound elastography for diagnosing BA was 0.90 (95% CI: 0.87-0.92). In addition, a subgroup analysis of 9 two-dimensional shear wave elastography studies was also performed. Subgroup analysis revealed that the summary sensitivity and specificity were 85% (95% CI: 77-91%) and 79% (95% CI: 71-86%), respectively, and the summary AUROC was 0.89 (95% CI: 0.86-0.92)., Conclusions: Ultrasound elastography exhibits good diagnostic accuracy for BA and can be served as a non-invasive tool to facilitate the differential diagnosis of BA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dong, Weng, Lyu, Yang and Wang.)

In contrast to the declining incidence in older populations, the incidence of very early onset colorectal cancer (VEO-CRC) patients (aged ≤40 years) has been increasing in different regions of the world. In this study, we aimed to establish nomogram models for the prognostic prediction of patients with VEO-CRC for both overall survival (OS) and cancer-specific survival (CSS). Patients diagnosed with VEO-CRC between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were collected and randomly assigned to the training cohort and validation cohort at a ratio of 7:3 for model construction and internal validation. Using univariate and multivariate Cox regression analysis to screen important variables, which were then used to construct a nomogram. The nomogram was evaluated using calibration curves and the receiver operating characteristic (ROC) curves. A total of 3061 patients were included and randomly divided into the training cohort (n = 2145) and validation cohort (n = 916). Five independent prognostic factors, including race, grade, tumor size, AJCC stage, and AJCC T stage were all significantly identified in OS multivariate Cox regression analysis. Meanwhile in CSS, multivariate Cox regression analysis demonstrated that race, grade, tumor size, AJCC stage, AJCC T stage, AJCC N stage, and SEER stage were independent prognostic factors.  The calibration plots of the established nomograms indicated high correlations between the predicted and observed results. C-index and ROC analysis implied that our nomogram model has a strong predictive ability. Moreover, nomograms also showed higher C-index values compared to tumor-node-metastasis (TNM) and SEER stages. We established and validated a simple-to-use nomogram to evaluate the 1-, 3-, and 5-year OS and CSS prognosis of patients with VEO-CRC. This tool can assist clinicians to optimize individualized treatment plans.

Background: Measurement of hepatic venous pressure gradients is the gold standard for assessing portal hypertension (PH) but is invasive with potential complications. We aimed to assess the performance in liver and spleen stiffness measurement (LSM and SSM, respectively) by two-dimensional shear wave elastography (2D-SWE) and composite scores including liver stiffness-spleen diameter to platelet ratio score (LSPS), platelet (PLT) count/spleen diameter ratio (PSR), aspartate aminotransferase (AST)/alanine aminotransferase ratio (AAR), and AST-to-PLT ratio index (APRI) for diagnosing PH in nonalcoholic fatty liver disease (NAFLD) rat models., Methods: Animal models with PH in NAFLD were established in 65 rats, which then underwent 2D-SWE measurements. Morphological and biological parameters were collected for calculation of four composite scores. Correlations of noninvasive methods with portal venous pressure were evaluated by Spearman correlation analysis. The area under the receiver operating characteristic curve (AUC) was used to assess the performance of noninvasive methods in predicting PH., Results: LSM and SSM were significantly associated with portal venous pressure ( r = 0.636 and 0.602, respectively; all P < 0.001). The AUCs of LSM and SSM in the diagnosis of PH were 0.906 (95% confidence interval [CI]:0.841-0.97) and 0.87 (95% CI:0.776-0.964), respectively, and were significantly higher than those in composite scores. The AUCs for LSPS, PSR, AAR, and APRI were 0.793, 0.52, 0.668, and 0.533, respectively, for diagnosing PH. The AUCs of the combined models of LSM and SSM, LSM and PLT, SSM and PLT, and LSM, SSM and PLT were 0.923, 0.913, 0.872, and 0.923, respectively. The four combined models showed no statistical differences compared to LSM and SSM in evaluating PH (all P > 0.05)., Conclusions: LSM and SSM by 2D-SWE can be used as promising noninvasive parameters for diagnosing PH in NAFLD and have higher accuracy than composite scores. The combined models, compared to LSM and SSM, did not significantly improve the performance in diagnosing PH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dong, Chen, Lyu, Chen and Qin.)