Red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain through stimulating the expressions of TNF-α and IL-1ß.

Our previous study has identified that glutamate in the red nucleus (RN) facilitates the development of neuropathic pain through metabotropic glutamate receptors (mGluR). Here, we further explored the actions and possible molecular mechanisms of red nucleus mGluR Ⅰ (mGluR1 and mGluR5) in the development of neuropathic pain induced by spared nerve injury (SNI). Our data indicated that both mGluR1 and mGluR5 were constitutively expressed in the RN of normal rats. Two weeks after SNI, the expressions of mGluR1 and mGluR5 were significantly boosted in the RN contralateral to the nerve injury. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN contralateral to the nerve injury at 2 weeks post-SNI significantly ameliorated SNI-induced neuropathic pain. However, unilateral administration of mGluRⅠ agonist DHPG to the RN of normal rats provoked a significant mechanical allodynia, this effect could be blocked by LY367385 or MTEP. Further studies indicated that the expressions of TNF-α and IL-1ß in the RN were also elevated at 2 weeks post-SNI. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN at 2 weeks post-SNI significantly inhibited the elevations of TNF-α and IL-1ß. However, administration of mGluR Ⅰ agonist DHPG to the RN of normal rats significantly enhanced the expressions of TNF-α and IL-1ß, these effects were blocked by LY367385 or MTEP. These results suggest that activation of red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain by stimulating the expressions of TNF-α and IL-1ß. mGluR Ⅰ maybe potential targets for drug development and clinical treatment of neuropathic pain.

Deciphering the role of apoptosis signature on the immune dynamics and therapeutic prognosis in breast cancer: Implication for immunotherapy.

Background: In breast cancer oncogenesis, the precise role of cell apoptosis holds untapped potential for prognostic and therapeutic insights. Thus, it is important to develop a model predicated for breast cancer patients' prognosis and immunotherapy response based on apoptosis-related signature. Methods: Our approach involved leveraging a training dataset from The Cancer Genome Atlas (TCGA) to construct an apoptosis-related gene prognostic model. The model's validity was then tested across several cohorts, including METABRIC, Sun Yat-sen Memorial Hospital Sun Yat-sen University (SYSMH), and IMvigor210, to ensure its applicability and robustness across different patient demographics and treatment scenarios. Furthermore, we utilized Quantitative Polymerase Chain Reaction (qPCR) analysis to explore the expression patterns of these model genes in breast cancer cell lines compared to immortalized mammary epithelial cell lines, aiming to confirm their differential expression and underline their significance in the context of breast cancer. Results: Through the development and validation of our prognostic model based on seven apoptosis-related genes, we have demonstrated its substantial predictive power for the survival outcomes of breast cancer patients. The model effectively stratified patients into high and low-risk categories, with high-risk patients showing significantly poorer overall survival in the training cohort and across all validation cohorts. Importantly, qPCR analysis confirmed that the genes constituting our model indeed exhibit differential expression in breast cancer cell lines when contrasted with immortalized mammary epithelial cell lines. Conclusion: Our study establishes a groundbreaking prognostic model using apoptosis-related genes to enhance the precision of breast cancer prognosis and treatment, particularly in predicting immunotherapy response.

A domain knowledge-based interpretable deep learning system for improving clinical breast ultrasound diagnosis.

BACKGROUND: Though deep learning has consistently demonstrated advantages in the automatic interpretation of breast ultrasound images, its black-box nature hinders potential interactions with radiologists, posing obstacles for clinical deployment. METHODS: We proposed a domain knowledge-based interpretable deep learning system for improving breast cancer risk prediction via paired multimodal ultrasound images. The deep learning system was developed on 4320 multimodal breast ultrasound images of 1440 biopsy-confirmed lesions from 1348 prospectively enrolled patients across two hospitals between August 2019 and December 2022. The lesions were allocated to 70% training cohort, 10% validation cohort, and 20% test cohort based on case recruitment date. RESULTS: Here, we show that the interpretable deep learning system can predict breast cancer risk as accurately as experienced radiologists, with an area under the receiver operating characteristic curve of 0.902 (95% confidence interval = 0.882 - 0.921), sensitivity of 75.2%, and specificity of 91.8% on the test cohort. With the aid of the deep learning system, particularly its inherent explainable features, junior radiologists tend to achieve better clinical outcomes, while senior radiologists experience increased confidence levels. Multimodal ultrasound images augmented with domain knowledge-based reasoning cues enable an effective human-machine collaboration at a high level of prediction performance. CONCLUSIONS: Such a clinically applicable deep learning system may be incorporated into future breast cancer screening and support assisted or second-read workflows.

Breast cancer is one of the most common cancers, and finding it early can greatly improve patients' chances of survival and recovery. We create a tool based on artificial intelligence (AI)­whereby computer software learns to perform tasks that normally require human thinking­called MUP-Net. MUP-Net can analyze medical images to predict a patient's risk of having breast cancer. To make this AI tool usable in clinical practice, we enabled doctors to see the reasoning behind the AI's predictions by visualizing the key image features it analyzed. We showed that our AI tool not only makes doctors more confident in their diagnosis but also helps them make better decisions, especially for less experienced doctors. With further testing, our AI tool may help clinicians to diagnose breast cancer more accurately and quickly, potentially improving patient outcomes.

Regulation of CTLs/Tregs via Highly Stable and Ultrasound-Responsive Cerasomal Nano-Modulators for Enhanced Colorectal Cancer Immunotherapy.

Immunotherapy is showing good potential for colorectal cancer therapy, however, low responsive rates and severe immune-related drug side effects still hamper its therapeutic effectiveness. Herein, a highly stable cerasomal nano-modulator (DMC@P-Cs) with ultrasound (US)-controlled drug delivery capability for selective sonodynamic-immunotherapy is fabricated. DMC@P-Cs' lipid bilayer is self-assembled from cerasome-forming lipid (CFL), pyrophaeophorbid conjugated lipid (PL), and phospholipids containing unsaturated chemical bonds (DOPC), resulting in US-responsive lipid shell. Demethylcantharidin (DMC) as an immunotherapy adjuvant is loaded in the hydrophilic core of DMC@P-Cs. With US irradiation, reactive oxygen species (ROS) can be effectively generated from DMC@P-Cs, which can not only kill tumor cells for inducing immunogenic cell death (ICD), but also oxidize unsaturated phospholipids-DOPC to change the permeability of the lipid bilayers and facilitate controlled release of DMC, thus resulting in down-regulation of regulatory T cells (Tregs) and amplification of anti-tumor immune responses. After intravenous injection, DMC@P-Cs can efficiently accumulate at the tumor site, and local US treatment resulted in 94.73% tumor inhibition rate. In addition, there is no detectable systemic toxicity. Therefore, this study provides a highly stable and US-controllable smart delivery system to achieve synergistical sonodynamic-immunotherapy for enhanced colorectal cancer therapy.

Synergistic role of activated CD4+ memory T cells and CXCL13 in augmenting cancer immunotherapy efficacy.

The development of immune checkpoint inhibitors (ICIs) has significantly advanced cancer treatment. However, their efficacy is not consistent across all patients, underscoring the need for personalized approaches. In this study, we examined the relationship between activated CD4+ memory T cell expression and ICI responsiveness. A notable correlation was observed between increased activated CD4+ memory T cell expression and better patient survival in various cohorts. Additionally, the chemokine CXCL13 was identified as a potential prognostic biomarker, with higher expression levels associated with improved outcomes. Further analysis highlighted CXCL13's role in influencing the Tumor Microenvironment, emphasizing its relevance in tumor immunity. Using these findings, we developed a deep learning model by the Multi-Layer Aggregation Graph Neural Network method. This model exhibited promise in predicting ICI treatment efficacy, suggesting its potential application in clinical practice.

Nanomaterials augmented bioeffects of ultrasound in cancer immunotherapy.

Immunotherapy as a milestone in cancer treatment has made great strides in the past decade, but it is still limited by low immune response rates and immune-related adverse events. Utilizing bioeffects of ultrasound to enhance tumor immunotherapy has attracted more and more attention, including sonothermal, sonomechanical, sonodynamic and sonopiezoelectric immunotherapy. Moreover, the emergence of nanomaterials has further improved the efficacy of ultrasound mediated immunotherapy. However, most of the summaries in this field are about a single aspect of the biological effects of ultrasound, which is not comprehensive and complete currently. This review proposes the recent progress of nanomaterials augmented bioeffects of ultrasound in cancer immunotherapy. The concept of immunotherapy and the application of bioeffects of ultrasound in cancer immunotherapy are initially introduced. Then, according to different bioeffects of ultrasound, the representative paradigms of nanomaterial augmented sono-immunotherapy are described, and their mechanisms are discussed. Finally, the challenges and application prospects of nanomaterial augmented ultrasound mediated cancer immunotherapy are discussed in depth, hoping to pave the way for cancer immunotherapy and promote the clinical translation of ultrasound mediated cancer immunotherapy through the reasonable combination of nanomaterials augmented ultrasonic bioeffects.

Application of comprehensive unit-based safety program model to improve chemotherapy-induced nausea and vomiting in patients with ovarian cancer: a retrospective study.

BACKGROUND: To explore the effect of intervention programs constructed under the guidance of the comprehensive unit-based safety program (CUSP) model on chemotherapy-induced nausea and vomiting (CINV) in patients with ovarian cancer. METHOD: According to the time of admission, 90 ovarian cancer chemotherapy patients in the first affiliated Hospital of Anhui Medical University from June 2019 to September 2020 were divided into an intervention group and a control group with 45 cases each. Both groups of patients received routine intervention, and the intervention group implemented the CUSP program on this basis. The intervention lasted 8 months. Before and after the intervention, the patients in the ward were used the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool, the Functional Living Index-Emesis (FLIE), and the Hospital Anxiety and Depression Scale (HADS) for the effect evaluation. RESULTS: After the intervention, the degree of nausea and vomiting frequency in the intervention group were significantly lower than that in the control group, especially the degree of nausea in the delayed phase (P < 0.05). The score of the functional living index-emesis in the intervention group was significantly higher than that in the control group (P < 0.05), and the anxiety and depression in the intervention group were significantly relieved compared to the control group (P < 0.05). CONCLUSION: The intervention program guided by the CUSP model can significantly alleviate patients' nausea and vomiting, improve the quality of life, and relieve anxiety and depression. The CUSP model is suitable for clinical practice and has guiding significance for clinical work.

Association between Blood Donation and Malignant and Benign Tumour Risk: A Population-Based Study of 3.4 Million Participants in China.

This study aims to identify the relationship between blood donation and malignant and benign tumour hospitalization risk. The cohort study was constructed in Shaanxi, China, to include blood donors and match nonblood donors one-to-one by gender, age, and county of residence. The study compared the hospitalization records of two groups from 2012 to 2018. A log-binomial regression model was used to estimate the relative risk (RR) of tumour risk between donors and nonblood donors among different age groups. A total of 1,625,599 donors were recruited (including 968,823 males) and compared with the matched nonblood donor group. Significantly lower risk of malignancy in males was found among donors (adjusted RR: 0.82, 95% CI: 0.75-0.92). Lower risks for specific types of tumours among donors were observed, including liver (0.42, [0.28-0.67]), lung (0.74, [0.59-0.87]), lymphoma (0.75, [0.62-0.85]), and oesophagus (0.55, [0.41-0.72]). However, the risk of brain cancer was higher among male donors (RR 1.19 [1.06-1.29]). Among female donors, lower risk of liver (0.57, [0.42-0.79]) and oesophagus malignancy (0.73, [0.62-0.88]) was observed. For benign tumours, male donors have a lower risk of benign skin tumour (0.79, [0.62-0.94]) and hemangioma and lymphangioma (0.75, [0.51-0.89]), while female donors have a lower risk in hemangioma and lymphangioma (0.65, [0.44-0.83]). We also found that the risk decreased with age among donors in the prevalence of tumours compared to that in nonblood donors (p < 0.05). Blood donation appears to be significantly associated with various tumour risks among both males and females. Overall, the risk of tumours decreased more substantially with age in blood donors compared with nonblood donors. Further research is warranted to investigate the impact of 'health donor effects' on these findings.

Clinical Evidence of Chemotherapy or Endocrine Therapy Maintenance in Patients with Metastatic Breast Cancer: Meta-Analysis of Randomized Clinical Trials and Propensity Score Matching of Multicenter Cohort Study.

PURPOSE: This study aims to comprehensively evaluate the clinical efficacy of chemotherapy or endocrine therapy maintenance in metastatic breast cancer (MBC) patients. MATERIALS AND METHODS: The meta-analysis of randomized clinical trials (RCTs) and propensity score matching of multicenter cohort study evaluated MBC patients who underwent first-line chemotherapy or endocrine therapy maintenance. This study is registered with PROSPERO: CRD42017071858 and ClinicalTrials.gov: NCT04258163. RESULTS: A total of 2,867 patients from 15 RCTs and 760 patients from multicenter cohort were included. The results from meta-analysis showed that chemotherapy maintenance improved progression-free survival (PFS) (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.54 to 0.73; p < 0.001; moderate-quality evidence) and overall survival (OS) (HR, 0.87; 95% CI 0.78 to 0.97; p=0.016; high-quality evidence) than observation. In the cohort study, for hormone receptor-positive MBC patients, chemotherapy maintenance improved PFS (HR, 0.67; 95% CI, 0.52 to 0.85; p < 0.001) and OS (HR, 0.55; 95% CI 0.42 to 0.73; p < 0.001) compared with observation, and endocrine therapy maintenance also improved PFS (HR, 0.65; 95% CI, 0.53 to 0.80; p < 0.001) and OS (HR, 0.55; 95% CI, 0.44 to 0.69; p < 0.001). There were no differences between chemotherapy and endocrine therapy maintenance in PFS and OS (all p > 0.05). Regardless of the continuum or switch maintenance therapy, showed prolonged survival in MBC patients who were response to first-line treatment. CONCLUSION: This study provided evidences for survival benefits of chemotherapy and endocrine therapy maintenance in MBC patients, and there was no difference efficacy between chemotherapy and endocrine therapy maintenance for hormone receptor-positive patients.

Babao Dan is a robust anti-tumor agent via inhibiting wnt/ß-catenin activation and cancer cell stemness.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) is being increasingly used worldwide due to its diverse efficacy and relatively low side effects. Babao Dan (BBD) is a well-known TCM formula that is currently used for the effective treatment of various cancers, however its underlying molecular mechanism remains unknown. AIM OF THE STUDY: Tumor growth and tumor recurrence are characterized by two distinct populations of cells, namely the well-differentiated cancer cells composing the majority of tumor bulk, and cancer stem cells (CSCs) involved in tumor relapse, which are both strongly associated with excessive activation of Wnt/ß-catenin signaling. Our study aims to elucidate the underlying molecular mechanisms associated with the anti-tumor proliferative effects of Babao Dan (BBD). MATERIALS AND METHODS: We used a hepatoblastoma cell line HepG2 with stem cell-like traits that harbors a constitutively active mutant of ß-catenin in order to study the anti-tumor ability of BBD via targeting Wnt/ß-catenin signaling. RESULTS: BBD robustly attenuated both the intrinsic and extrinsic activation of Wnt/ß-catenin pathway in HepG2 hepatoblastoma cells, as well as Wnt target genes. Moreover, BBD significantly inhibited both the proliferation of well-differentiated cancer cells, as well as the stem-like property of CSCs as evidenced by EpCAM, a Wnt target gene and a novel marker of cancer cell stemness. In addition, mice administered with BBD using HepG2 cell line derived xenograft model had marked reductions in tumor size and weight, as well as significantly decreased expressions of Wnt target genes and cancer cell stemness. CONCLUSION: Our findings elucidated the underlying molecular mechanisms associated with the robust anti-tumor effects of BBD via potent inhibition of Wnt/ß-catenin signaling, and implicate its use in the clinical treatment of cancers.

Prospective assessment of breast cancer risk from multimodal multiview ultrasound images via clinically applicable deep learning.

The clinical application of breast ultrasound for the assessment of cancer risk and of deep learning for the classification of breast-ultrasound images has been hindered by inter-grader variability and high false positive rates and by deep-learning models that do not follow Breast Imaging Reporting and Data System (BI-RADS) standards, lack explainability features and have not been tested prospectively. Here, we show that an explainable deep-learning system trained on 10,815 multimodal breast-ultrasound images of 721 biopsy-confirmed lesions from 634 patients across two hospitals and prospectively tested on 912 additional images of 152 lesions from 141 patients predicts BI-RADS scores for breast cancer as accurately as experienced radiologists, with areas under the receiver operating curve of 0.922 (95% confidence interval (CI) = 0.868-0.959) for bimodal images and 0.955 (95% CI = 0.909-0.982) for multimodal images. Multimodal multiview breast-ultrasound images augmented with heatmaps for malignancy risk predicted via deep learning may facilitate the adoption of ultrasound imaging in screening mammography workflows.

Chemerin located in bone marrow promotes osteogenic differentiation and bone formation via Akt/Gsk3ß/ß-catenin axis in mice.

Chemerin, a secreted protein mainly produced by adipocytes and hepatocytes, plays a variety of roles in endocrine or paracrine signaling. As reported in human epidemiology, chemerin was correlated with osteoporosis. And the previous in vitro study found that chemerin knockdown promoted osteogenesis and inhibited adipogenesis. However, the function of chemerin in bone metabolism and the underlying mechanism remains unclear. In this study, we uncovered the in vivo function of chemerin in bone homeostasis. We discovered that in obese mice, chemerin was increased in serum, while decreased in the bone marrow; and the chemerin expression in bone tissue was positively correlated with osteogenic genes. To further investigate the function of chemerin in bone metabolism, we generated chemerin deficiency and overexpression mice. We found bone mass and osteogenesis were decreased in chemerin deficiency mice, while were increased in chemerin overexpression mice. Furthermore, we observed that the chemerin expression increased during osteogenic differentiation of MSCs. Besides, we verified that chemerin promoted osteogenic differentiation in C3H10T1/2 cells and BMSCs through Akt/Gsk3ß/ß-catenin axis. Treatment with Akt inhibitor (MK2206) abolished the promoting effect of chemerin on osteogenic differentiation and active ß-catenin. Together, our results suggest chemerin in bone marrow, not in serum, promotes osteogenic differentiation and bone formation via Akt/Gsk3ß/ß-catenin axis. Chemerin may serve as a therapeutic strategy for osteoporosis.

Neoadjuvant camrelizumab, nab-paclitaxel, and carboplatin in patients with stage IB-IIIA non-small cell lung cancer (NANE-LC): a study protocol of prospective, single-arm, multicenter, phase II study.

BACKGROUND: Previous studies have shown that neoadjuvant immune checkpoint inhibitors (ICIs) combined with chemotherapy in patients with stage IB-IIIA non-small cell lung cancer (NSCLC) significantly improved the major pathological response (MPR) and the pathological complete response (pCR) rates. However, high-level evidence-based medical data confirming this effect are still lacking. In addition, there is an urgent need to develop an appropriate strategy to predict the benefit for patients receiving ICIs. In this study, we describe an ongoing study on the effect of neoadjuvant therapy with camrelizumab, nab-paclitaxel, and carboplatin on stage IB-IIIA NSCLC patients. The aim of this study is to establish a multiomics artificial intelligence system for predicting neoadjuvant therapy efficacy and assisting decision-making. METHODS: This prospective, single-arm, multicenter, phase II trial will enroll a total of 40 patients who will undergo surgery after three cycles of neoadjuvant therapy with camrelizumab, nab-paclitaxel, and carboplatin. The MPR rate is the primary endpoint, while the rates of pCR, complete resection, objective response, disease-free survival (DFS), adverse events (AEs), and quality of life (QOL) are secondary endpoints. Exploratory endpoints will serve to establish a multiomics artificial intelligence system for neoadjuvant therapy effect prediction and decision-making assistance based on radiomics, metabolism, genetic, and clinic-pathological characteristics and to explore the mechanisms of drug resistance. DISCUSSION: The efficacy of ICIs is influenced by many factors, including patient's driver genes and smoking status. Thus, further subgroup analysis is needed. This study will indicate if our new multiomics artificial intelligence system constitutes a valid strategy for neoadjuvant therapy effect prediction and decision-making assistance in the context of neoadjuvant camrelizumab, nab-paclitaxel, and carboplatin treatment for patients with stage IB-IIIA NSCLC. TRIAL REGISTRATION: This trial has been registered at ClinicalTrials.gov (identification number: NCT04541251).

Effect of the location and size of thyroid nodules on the diagnostic performance of ultrasound elastography: A retrospective analysis.

OBJECTIVES: Ultrasound-guided fine-needle aspiration biopsies are recommended for the detection of suspicious thyroid nodules. However, the best approach regarding suspicious ultrasound features for thyroid nodules is still unclear. This study aimed to evaluate the effect of location and size of thyroid nodules on the diagnostic performance of strain ultrasound elastography. In addition, this study evaluated whether ultrasound elastography predicts malignancy in thyroid nodules. METHODS: Data regarding the size, depth, and distance from the carotid artery of nodules, the elasticity contrast index, and the nature of nodules were analyzed. RESULTS: There was no significant difference in the depth (p=0.092) and the distance from the carotid artery (p=0.061) between benign and suspicious nodules. Suspicious nodules were smaller than benign nodules (p<0.0001, q=23.84) and had a higher elasticity contrast index (p<0.0001, q=21.05). The depth of nodules and the size of the nodule were not associated with the correct value of the elasticity contrast index (p>0.05 for both). The diagnostic performance of ultrasound elastography was not affected by the distance of the nodules from the carotid artery if they were located ≥15 mm from the carotid artery (p=0.5960). However, if the suspicious nodules were located <15 mm from the carotid artery, the diagnostic accuracy was hampered (p=0.006). CONCLUSIONS: The strain ultrasound elastography should be carefully evaluated when small thyroid nodules are located near the carotid artery.

Association of survival and genomic mutation signature with immunotherapy in patients with hepatocellular carcinoma.

BACKGROUND: Current guidelines lack recommendations for the use of immunotherapy and immune-related biomarkers for hepatocellular carcinoma (HCC). We aim to provide reliable evidence of the association of survival with HCC immunotherapy and to demonstrate that genomic mutation signature could be an effective biomarker to predict immunotherapy efficacy of HCC patients. METHODS: We conducted a meta-analysis of 17 randomized trials with 2055 patients and an individual patient-level analysis of 31 patients. Trial data were identified in PubMed, EMBASE and Cochrane Central library, and individual patient data were obtained from the cBioPortal database. Overall survival (OS) and progression-free survival (PFS) were assessed with the hazard ratio (HR) and 95% CI. This study is registered with PROSPERO, number CRD42018083991. RESULTS: The meta-analysis showed that compared to conventional therapy, immunotherapy resulted in prolonged OS (HR =0.65, P<0.0001, high quality) and PFS (HR =0.81, P<0.0001, high quality); the benefits were observed for cellular immunotherapy, tumor vaccine, and cytokine immunotherapy. Findings were robust to subgroup and trial sequential analyses. In the individual patient-level analysis of patients treated with immune checkpoint inhibitor, mutations in TERT, CTNNB1, BRD4, or MLL, and co-mutations in TP53 and TERT or BRD4 were associated with significantly worse survival. These oncogenes were used to develop a novel integrated mutation risk score, which exhibited better utility in predicting survival than the tumor mutation burden (TMB). Patients with low- versus high- mutation risk score had longer OS (HR =0.18, P=0.02) and PFS (HR =0.33, P=0.018). A nomogram comprising the mutation risk score and essential clinical factors further improved the predictive accuracy (AUC =0.840 for both 1- and 2-year OS). CONCLUSIONS: Immunotherapy showed longer OS and PFS than conventional therapy among HCC patients, especially patients with a low mutation risk score. The nomogram based on genomic and clinical characteristics is effective in predicting survival of HCC patients undergoing immune checkpoint inhibitor.

Prognosis value of liver stiffness measurements by 2D-SWE in primary HBV-positive hepatocellular carcinoma following radiofrequency ablation.

BACKGROUND: Liver fibrosis is closely associated with the occurrence of hepatocellular carcinoma (HCC), which can be evaluated by liver stiffness measurements (LSM). The clinical significance of LSMin patient with hepatitis B virus (HBV) related HCC underwent radiofrequency ablation (RFA) was evaluated. METHODS: Total of 273 patients underwent RFA for primary HBV-positive HCC were included. LSM values were measured by using by 2D-shear wave elastography (2D-SWE) prior to RFA. The relationship between pretreatment LSM value and survival outcome was evaluated. The cutoff value for LSM to predict survival outcome was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: At the endpoint of this study, 88 (32.2%) and 73 (26.7%) patients out of all 273 patients studied had died and recurrent, respectively. All patients were divided into two groups based on the cutoff value (13.4 kPa) of LSM. Patients with a LSM ≥13.4 kPa had lower mean overall survival (62.5 vs. 48.5 months, P=0.01) and lower recurrent free survival (60.4 vs. 47.3 months, P=0.02) than patients with a LSM <13.4 kPa in univariate analysis and LSM also been evaluated as independent predictive factor for survival outcome for HCC following RFA. Otherwise, LSM also was related to liver cirrhosis and TNM stage (both P<0.05). CONCLUSIONS: LSM measured by 2D-SWE can sever as an independent prognostic indictor for patients undergoing RFA for HBV-positive HCC.

Effect of the location and size of thyroid nodules on the diagnostic performance of ultrasound elastography: A retrospective analysis

OBJECTIVES: Ultrasound-guided fine-needle aspiration biopsies are recommended for the detection of suspicious thyroid nodules. However, the best approach regarding suspicious ultrasound features for thyroid nodules is still unclear. This study aimed to evaluate the effect of location and size of thyroid nodules on the diagnostic performance of strain ultrasound elastography. In addition, this study evaluated whether ultrasound elastography predicts malignancy in thyroid nodules. METHODS: Data regarding the size, depth, and distance from the carotid artery of nodules, the elasticity contrast index, and the nature of nodules were analyzed. RESULTS: There was no significant difference in the depth (p=0.092) and the distance from the carotid artery (p=0.061) between benign and suspicious nodules. Suspicious nodules were smaller than benign nodules (p<0.0001, q=23.84) and had a higher elasticity contrast index (p<0.0001, q=21.05). The depth of nodules and the size of the nodule were not associated with the correct value of the elasticity contrast index (p>0.05 for both). The diagnostic performance of ultrasound elastography was not affected by the distance of the nodules from the carotid artery if they were located ≥15 mm from the carotid artery (p=0.5960). However, if the suspicious nodules were located <15 mm from the carotid artery, the diagnostic accuracy was hampered (p=0.006). CONCLUSIONS: The strain ultrasound elastography should be carefully evaluated when small thyroid nodules are located near the carotid artery.

cAMP-MicroRNA-203-IFNγ network regulates subcutaneous white fat browning and glucose tolerance.

OBJECTIVE: Brown and beige adipocytes in humans and rodents are specialized to burn lipids for heat generation as a natural defense against cold and obesity, which is advantageous to metabolic homeostasis. MicroRNAs as another regulatory layer to regulate metabolic homeostasis attracted a lot of attentions. Our previous work revealed microRNA (miR)-203 as a brown adipocyte-enriched microRNA involved in brown adipocytes development. However, the potential role of miR-203 in adipose tissue metabolic homeostasis has not been determined in vivo. In this study, we investigate the potential role of miR-203 in subcutaneous white adipose tissue (sub-WAT) browning and metabolic homeostasis. METHODS: We investigated the relationship between miR-203 and energy homeostasis in adipose tissue from cold exposed, high fat diet (HFD) fed, ob/ob and db/db mice. The functions of miR-203 on sub-WAT browning were validated through miR-203 knockdown or overexpression. The miR-203 targeted signal pathway was screened by RNAseq analysis. Luciferase report assay, western blot, and qPCR were performed to establish the miR-203 related upstream and downstream signal pathway in vivo and in vitro. The functions of miR-203 on obesity and metabolic homeostasis were validated through GTT/ITT and western blot on high fat diet-induced obesity in C57 mice. ELISA was used to determine the concentration of IFN-γ. Flow cytometry analysis was performed to determine the infiltration of macrophages in adipose tissue. RESULTS: MiR-203 expression positively correlates with energy expenditure, and overexpression of miR-203 could enhance sub-WAT browning in normal diet (ND) condition. Mechanistically, the expression of miR-203 is activated by cAMP-dependent C/EBPß up-regulation. Subsequently, miR-203 inhibits IFN-γ signal pathway activation by directly targeting Lyn, which is an activator of Jak1-Stat1. Moreover, the forced expression of miR-203 could improve insulin sensitivity and resist high fat diet-induced obesity by inhibiting IFN-γ. CONCLUSIONS: MicroRNA-203 (miR-203) promotes white adipose tissue browning in cold exposed mice and improves glucose tolerance in HFD fed mice by repressing IFN-γ. Since miR-203 is activated by cAMP-dependent C/EBPß up-regulation and directly represses IFN-γ signal pathway, we declare that miR-203 acts as a messenger between cAMP signal pathway and IFN-γ signal pathway.