Clinical efficacy and molecular mechanism of Chinese medicine in the treatment of autoimmune thyroiditis.

ETHNOPHARMACOLOGICAL RELEVANCE: Autoimmune Thyroiditis (AIT) is a common refractory autoimmune disease of the endocrine system that may eventually lead to complete loss of thyroid function, with subsequent severe effects on the metabolism. Because of the deficiency in current clinical management of AIT, the need for alternative therapies is highlighted. With its multi-component and multi-target characteristics, Chinese medicine has good potential as an alternative therapy for AIT. AIM OF THE STUDY: The aim of this study was to systematically summarize the clinical efficacy and safety evaluation of TCM and its active ingredients in the treatment and regulation of AIT. Additionally, we provide an in-depth discussion of the relevant mechanisms and molecular targets to understand the protective effects of traditional Chinese medicine on AIT and explore new ideas for clinical treatment. MATERIALS AND METHODS: The literature related to "Hashimoto", "autoimmune thyroiditis", "traditional Chinese medicine," and "Chinese herbal medicine" was systematically summarized and reviewed from Web of Science Core Collection, PubMed, CNKI, and other databases. Domestic and international literature were analyzed, compared, and reviewed. RESULTS: An increasing number of studies have demonstrated that herbal medicines can intervene in immunomodulation, with pharmacological effects such as antibody lowering, anti-inflammatory, anti-apoptotic thyroid follicular cells, regulation of intestinal flora, and regulation of estrogen and progesterone levels. The signaling pathways and molecular targets of the immunomodulatory effects of Chinese herbal medicine for AIT may include Fas/FasL, Caspase, BCL-2, and TLRs/MyD88/NF-κB et al. CONCLUSIONS: The use of Chinese herbs in the treatment and management of AIT is clinically experienced, satisfactory, and safe. Future studies may evaluate the influence of herbal medicines on the occurrence and development of AIT by modulating the interaction between immune factors and conventional signaling pathways.

Integrative radiomics and transcriptomics analyses reveal subtype characterization of non-small cell lung cancer.

OBJECTIVES: To assess whether integrative radiomics and transcriptomics analyses could provide novel insights for radiomic features' molecular annotation and effective risk stratification in non-small cell lung cancer (NSCLC). METHODS: A total of 627 NSCLC patients from three datasets were included. Radiomics features were extracted from segmented 3-dimensional tumour volumes and were z-score normalized for further analysis. In transcriptomics level, 186 pathways and 28 types of immune cells were assessed by using the Gene Set Variation Analysis (GSVA) algorithm. NSCLC patients were categorized into subgroups based on their radiomic features and pathways enrichment scores using consensus clustering. Subgroup-specific radiomics features were used to validate clustering performance and prognostic value. Kaplan-Meier survival analysis with the log-rank test and univariable and multivariable Cox analyses were conducted to explore survival differences among the subgroups. RESULTS: Three radiotranscriptomics subtypes (RTSs) were identified based on the radiomics and pathways enrichment profiles. The three RTSs were characterized as having specific molecular hallmarks: RTS1 (proliferation subtype), RTS2 (metabolism subtype), and RTS3 (immune activation subtype). RTS3 showed increased infiltration of most immune cells. The RTS stratification strategy was validated in a validation cohort and showed significant prognostic value. Survival analysis demonstrated that the RTS strategy could stratify NSCLC patients according to prognosis (p = 0.009), and the RTS strategy remained an independent prognostic indicator after adjusting for other clinical parameters. CONCLUSIONS: This radiotranscriptomics study provides a stratification strategy for NSCLC that could provide information for radiomics feature molecular annotation and prognostic prediction. KEY POINTS: • Radiotranscriptomics subtypes (RTSs) could be used to stratify molecularly heterogeneous patients. • RTSs showed relationships between molecular phenotypes and radiomics features. • The RTS algorithm could be used to identify patients with poor prognosis.

Molecular hallmarks of breast multiparametric magnetic resonance imaging during neoadjuvant chemotherapy.

PURPOSE: To identify molecular basis of four parameters obtained from dynamic contrast-enhanced magnetic resonance imaging, including functional tumor volume (FTV), longest diameter (LD), sphericity, and contralateral background parenchymal enhancement (BPE). MATERIAL AND METHODS: Pretreatment-available gene expression profiling and different treatment timepoints MRI features were integrated for Spearman correlation analysis. MRI feature-related genes were submitted to hypergeometric distribution-based gene functional enrichment analysis to identify related Kyoto Encyclopedia of Genes and Genomes annotation. Gene set variation analysis was utilized to assess the infiltration of distinct immune cells, which were used to determine relationships between immune phenotypes and medical imaging phenotypes. The clinical significance of MRI and relevant molecular features were analyzed to identify their prediction performance of neoadjuvant chemotherapy (NAC) and prognostic impact. RESULTS: Three hundred and eighty-three patients were included for integrative analysis of MRI features and molecular information. FTV, LD, and sphericity measurements were most positively significantly correlated with proliferation-, signal transmission-, and immune-related pathways, respectively. However, BPE did not show marked correlation relationships with gene expression alteration status. FTV, LD and sphericity all showed significant positively or negatively correlated with some immune-related processes and immune cell infiltration levels. Sphericity decreased at 3 cycles after treatment initiation was also markedly negatively related to baseline sphericity measurements and immune signatures. Its decreased status could act as a predictor for prediction of response to NAC. CONCLUSION: Different MRI features capture different tumor molecular characteristics that could explain their corresponding clinical significance.

Radiomic profiling of clear cell renal cell carcinoma reveals subtypes with distinct prognoses and molecular pathways.

BACKGROUND: To identify radiomic subtypes of clear cell renal cell carcinoma (ccRCC) patients with distinct clinical significance and molecular characteristics reflective of the heterogeneity of ccRCC. METHODS: Quantitative radiomic features of ccRCC were extracted from preoperative CT images of 160 ccRCC patients. Unsupervised consensus cluster analysis was performed to identify robust radiomic subtypes based on these features. The Kaplan-Meier method and chi-square test were used to assess the different clinicopathological characteristics and gene mutations among the radiomic subtypes. Subtype-specific marker genes were identified, and gene set enrichment analyses were performed to reveal the specific molecular characteristics of each subtype. Moreover, a gene expression-based classifier of radiomic subtypes was developed using the random forest algorithm and tested in another independent cohort (n = 101). RESULTS: Radiomic profiling revealed three ccRCC subtypes with distinct clinicopathological features and prognoses. VHL, MUC16, FBN2, and FLG were found to have different mutation frequencies in these radiomic subtypes. In addition, transcriptome analysis revealed that the dysregulation of cell cycle-related pathways may be responsible for the distinct clinical significance of the obtained subtypes. The prognostic value of the radiomic subtypes was further validated in another independent cohort (log-rank P = 0.015). CONCLUSION: In the present multi-scale radiogenomic analysis of ccRCC, radiomics played a central role. Radiomic subtypes could help discern genomic alterations and non-invasively stratify ccRCC patients.

Effects of Tongmai oral liquid in femoral ateriovenous fistula.

BACKGROUND: This study was conducted to investigate the protective effect of Tongmai oral liquid on arteriovenous fistula function and to provide an effective method to promote fistula maturation. METHODS: Fifteen female and fifteen male SPF New Zealand rabbits were randomly allocated into 3 groups including control, Aspirin and Tongmai oral liquid groups. A side-to-side femoral arteriovenous fistula was established in each rabbit and then animals were treated with Aspirin or Tongmai oral liquid for 2 weeks. The concentrations of circulating ET-1 and NO were determined before and after operation (on preoperative day, operative day, post-D1, post-D3, post-D7 and post-D15), respectively. Blood flow of the fistula stoma and contralateral artery and vein was determined on the 15th postoperative day. Last, the fistula stoma was dissected to observe patency, thrombosis and adhesion with surrounding tissues. RESULTS: 28 rabbits survived during the surgical process and the following 15-day observational period. Tissue adhesion of arteriovenous fistula with surrounding tissues was improved and fistula thrombosis was reduced by treatment with Tongmai oral liquid. NO concentration decreased to a different extent after vascular surgery. Tongmai oral liquid failed to regulate the equilibrium between NO and ET-1, but it improved blood flow of fistula stoma, as compared to control and Aspirin groups. Blood flow of fistula stoma in the three groups was lower than that of the contralateral femoral artery. CONCLUSIONS: Tongmai oral liquid improved the function of femoral ateriovenous fistula in the rabbit model by increasing blood flow and reducing thrombosis, probably not by regulating the dynamic equilibrium between NO and ET-1.