Combined MRI-TRUS fusion targeted and systematic biopsy versus systematic biopsy alone for the detection of prostate cancer: protocol for a prospective single-centre trial.

INTRODUCTION: The classic way of diagnosing prostate cancer (PCa) is by conducting the 12-core systematic biopsy (SB). However, it has a low detection rate for clinically significant PCa (csPCa) and can lead to the detection of clinically insignificant PCa (cisPCa). Although MRI-transrectal ultrasound (MRI-TRUS) fusion targeted biopsy (TB) can effectively improve the detection rate of csPCa, it may still miss some cases. Therefore, we propose using a combination of TB and SB methods to enhance the detection rate of csPCa while minimising the detection rate of cisPCa. METHODS AND ANALYSIS: This study is a prospective, single-centre investigation that aims to assess and compare the detection rate of csPCa using MRI-TRUS fusion TB combined with SB versus TRUS 12-core SB alone. Biopsy-naïve men with suspected PCa will be subjected to multiparametric MRI. Patients with Prostate Imaging Reporting and Data System (V.2.1) score ≥3 will be enrolled in the TB-SB combination group. The sample size is established as 660 participants, considering a 10% drop-out rate. The primary outcome is the detection rate of csPCa in men without prior biopsy using MRI-TRUS fusion TB combined with the standard TRUS-guided 12-core SB method. CsPCa will be defined as International Society of Urological Pathology Grade ≥2. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee at the Shanghai Tenth People's Hospital, an affiliated hospital of Tongji University School of Medicine. The research results will be published in a peer-reviewed international journal. TRIAL REGISTRATION NUMBER: ChiCTR2000036089.

Multi-omics analysis-based macrophage differentiation-associated papillary thyroid cancer patient classifier.

BACKGROUND: The reclassification of Papillary Thyroid Carcinoma (PTC) is an area of research that warrants attention. The connection between thyroid cancer, inflammation, and immune responses necessitates considering the mechanisms of differential prognosis of thyroid tumors from an immunological perspective. Given the high adaptability of macrophages to environmental stimuli, focusing on the differentiation characteristics of macrophages might offer a novel approach to address the issues related to PTC subtyping. METHODS: Single-cell RNA sequencing data of medullary cells infiltrated by papillary thyroid carcinoma obtained from public databases was subjected to dimensionality reduction clustering analysis. The RunUMAP and FindAllMarkers functions were utilized to identify the gene expression matrix of different clusters. Cell differentiation trajectory analysis was conducted using the Monocle R package. A complex regulatory network for the classification of Immune status and Macrophage differentiation-associated Papillary Thyroid Cancer Classification (IMPTCC) was constructed through quantitative multi-omics analysis. Immunohistochemistry (IHC) staining was utilized for pathological histology validation. RESULTS: Through the integration of single-cell RNA and bulk sequencing data combined with multi-omics analysis, we identified crucial transcription factors, immune cells/immune functions, and signaling pathways. Based on this, regulatory networks for three IMPTCC clusters were established. CONCLUSION: Based on the co-expression network analysis results, we identified three subtypes of IMPTCC: Immune-Suppressive Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (ISMPTCC), Immune-Neutral Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (INMPTCC), and Immune-Activated Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (IAMPTCC). Each subtype exhibits distinct metabolic, immune, and regulatory characteristics corresponding to different states of macrophage differentiation.

The RNA m6A-Binding Protein YTHDC1 Is Downregulated and Associated With M2 Macrophage Infiltration in Muscle-Invasive Bladder Cancer.

Background: Dysregulation of RNA N6-methyladenosine (m6A) modification is indispensable in tumorigenesis. However, in muscle-invasive bladder cancer (MIBC), the key regulators and mechanisms involved in this process remain largely unknown. This study aimed to screen the key m6A regulators and explore its possible role in MIBC. Methods: Aberrantly expressed m6A regulator genes were screened in The Cancer Genome Atlas (TCGA) MIBC cohort (n = 408) and validated using fresh-frozen and formalin-fixed paraffin-embedded (FFPE) specimens collected during this study. Clinicopathological relevance and association with tumor immune infiltration was further assessed. Results: We identified that the expression of YT521-B homology-domain-containing protein 1 (YTHDC1), an m6A RNA-binding protein, was downregulated in tumor tissues compared with adjacent noncancerous tissues in the TCGA MIBC cohort and our clinical samples. Low YTHDC1 expression correlated with short patient survival, advanced pathologic stage, lymph node metastasis, basal-squamous molecular subtype, non-papillary histological type, and certain genetic mutations important to MIBC. Remarkably, YTHDC1 expression exhibited negative association with tumor-infiltrating M2 macrophage abundance in MIBC. Conclusion: Among m6A regulators, we identified that YTHDC1 was downregulated in MIBC and might play an important role in the pathological process in MIBC, especially tumor microenvironment regulation.

Application of high-throughput sequencing to analyze the diet of black croaker (Atrobucca nibe) in southern coastal waters of Zhejiang.

This study investigated the feeding habits of black croaker (Atrobucca nibe) to fully understand its role in the food web in southern coastal waters of Zhejiang, China. In total, 225 black croakers were collected in a bottom trawl survey, of which 195 were used for the stomach contents analysis and 30 for high-throughput sequencing (HTS). Both approaches showed that the main prey was shrimp, with Alpheus japonicus being the most predominant. In addition, black croaker also fed on other benthic species, suggesting that it was a demersal predator. Feeding intensity also varied with black croaker body length, as did prey preference, from small-sized species to larger species with increases in fish size; in addition, prey species were more diverse in the large-bodied prey group. Canonical correspondence analysis indicated that the feeding habit of black croaker was most significantly correlated with temperature and dissolved oxygen. HTS was shown to be a feasible high precision semi-quantitative analytical approach, although it must be combined with morphological methods to obtain more complete feeding data; thus, it could provide an effective scientific basis for feeding ecology studies of marine organisms.

The value of deep neural networks in the pathological classification of thyroid tumors.

BACKGROUND: To explore the distinguishing diagnostic value and clinical application potential of deep neural networks (DNN) for pathological images of thyroid tumors. METHODS: A total of 799 pathological thyroid images of 559 patients with thyroid tumors were retrospectively analyzed. The pathological types included papillary thyroid carcinoma (PTC), medullary thyroid carcinoma (MTC), follicular thyroid carcinoma (FTC), adenomatous goiter, adenoma, and normal thyroid gland. The dataset was divided into a training set and a test set. Resnet50, Resnext50, EfficientNet, and Densenet121 were trained using the training set data and tested with the test set data to determine the diagnostic efficiency of different pathology types and to further analyze the causes of misdiagnosis. RESULTS: The recall, precision, negative predictive value (NPV), accuracy, specificity, and F1 scores of the four models ranged from 33.33% to 100.00%. The area under curve (AUC) ranged from 0.822 to 0.994, and the Kappa coefficient ranged from 0.7508 to 0.7713. However, the performance of diagnosing FTC, adenoma, and adenomatous goiter was slightly inferior to other types of pathological tissues. CONCLUSION: The DNN model achieved satisfactory results in the task of classifying thyroid tumors by learning thyroid pathology images. These results indicate the potential of the DNN model for the efficient diagnosis of thyroid tumor histopathology.

Molecular testing raises thyroid nodule fine needle aspiration diagnostic value.

Thyroid fine needle aspiration biopsy (FNAB) remains indeterminate in 16%-24% of the cases. Molecular testing could improve the diagnostic accuracy of FNAB. This study examined the gene mutation profile of patients with thyroid nodules and analyzed the diagnostic ability of molecular testing for thyroid nodules using a self-developed 18-gene test. Between January 2019 and August 2021, 513 samples (414 FNABs and 99 formalin-fixed paraffin-embedded (FFPE) specimens) underwent molecular testing at Ruijin Hospital. Sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. There were 457 mutations in 428 samples. The rates of BRAF, RAS, TERT promoter, RET/PTC, and NTRK3 fusion mutations were 73.3% (n=335), 9.6% (n=44), 2.8% (n=13), 4.8% (n=22), and 0.4% (n=2), respectively. The diagnostic ability of cytology and molecular testing were evaluated in Bethesda II and V-VI samples. For cytology alone, Sen, Spe, PPV, NPV, and accuracy were 100%, 25.0%, 97.4%, 100%, and 97.4%; these numbers were 87.5%, 50.0%, 98.0%, 12.5%, and 86.2% when considering positive mutation, and 87.5%, 75.0%, 99.0%, 17.6%, and 87.1% when considering positive cytology or and positive mutation. In Bethesda III-IV nodules, when relying solely on the presence of pathogenic mutations for diagnosis, Sen, Spe, PPV, NPV, and AC were 76.2%, 66.7%, 94.1%, 26.8%, and 75.0%, respectively. It might be necessary to analyze the molecular mechanisms of disease development at the genetic level to predict patients with malignant nodules more accurately in different risk strata and develop rational treatment strategies and definite management plans.

RIG-I contributes to keratinocyte proliferation and wound repair by inducing TIMP-1 expression through NF-κB signaling pathway.

Epithelial keratinocyte proliferation is an essential element of wound repair, and chronic wound conditions, such as diabetic foot, are characterized by aberrant re-epithelialization. In this study, we examined the functional role of retinoic acid inducible-gene I (RIG-I), a key regulator of epidermal keratinocyte proliferation, in promoting TIMP-1 expression. We found that RIG-I is overexpressed in keratinocytes of skin injury and underexpressed in skin wound sites of diabetic foot and streptozotocin-induced diabetic mice. Moreover, mice lacking RIG-I developed an aggravated phenotype when subjected to skin injury. Mechanistically, RIG-I promoted keratinocyte proliferation and wound repair by inducing TIMP-1 via the NF-κB signaling pathway. Indeed, recombinant TIMP-1 directly accelerated HaCaT cell proliferation in vitro and promoted wound healing in Ddx58-/- and diabetic mice in vivo. In summary, we demonstrated that RIG-I is a crucial factor that mediates epidermal keratinocyte proliferation and may be a potential biomarker for skin injury severity, thus making it an attractive locally therapeutic target for the treatment of chronic wounds such as diabetic foot.

Differential Performances in Lesions and Radiotracer of 18F-FDG PET/CT between Multiple Myeloma and Unknown Osteolytic Metastasis.

PURPOSE: The aim of the study was to investigate the differential performances in lesions and 18F-FDG radiotracer distribution detected by PET/CT between multiple myeloma and unknown osteolytic metastasis. METHODS: A retrospective study was performed on 18F-FDG PET/CT imaging of 63 patients with multiple bone destructions without extraosseous primary malignant tumors. By pathological diagnosis, 20 patients were confirmed to have multiple myeloma and 43 patients to have unknown osteolytic metastasis. The whole body was categorized into 8 sites: skull, spine, ribs, pelvis, sternum, clavicle, scapula and limb bone. The length of lesion cross-sections, cortical bone damage, SUVmax and radiotracer distribution were comprehensively compared to differentiate these two diseases. RESULTS: The cross-section lengths and SUVmax of the lesions in 5 sites (e.g., skull, spine, ribs, pelvis, and limb bone) were significantly shorter and lower in the multiple myeloma group than those of the unknown osteolytic metastasis group (P < 0.05). The 18F-FDG was more uniformly distributed in the lesion sites of the skull, spine, ribs, pelvis, scapula, and limb bone in the multiple myeloma group (P < 0.05). In the spine and rib lesion sites, the multiple myeloma group was more likely to show noncortical bone damage than the unknown osteolytic metastasis group (P < 0.05). CONCLUSION: Differential observations in lesions and 18F-FDG distribution between multiple myeloma and unknown osteolytic metastasis were detected by comprehensively comparing the length of lesion cross-sections, cortical bone damage, SUVmax, and the distribution of radiotracer on18F-FDG PET/CT imaging.

Hypomethylation of Thyroid Peroxidase as a Biomarker for Hepatocellular Carcinoma with Tumor Thrombosis.

OBJECTIVE: Thyroid hormones (THs) regulate multiple physiological activities in the liver, including cellular metabolism, differentiation, and cell growth, and play important roles in the pathogenesis of hepatocellular carcinoma (HCC). Thyroid peroxidase (TPO) is a key molecule involved in the THs synthesis and signaling pathway. As an epigenetic modification, DNA methylation has a critical role in tumorigenesis with diagnostic potential. However, the connection between THs and DNA methylation has been rarely investigated. METHODS: The methylation of key TH-related genes was analyzed by in-house epigenome-wide scanning, and we further analyzed the methylation levels of the TPO promotor in 164 sample pairs of HCC and adjacent non-cancerous tissues by Sequenom EpiTYPER assays, and evaluated their clinical implications. RESULTS: We identified that the methylation of the TPO promoter was downregulated in the HCC tissues (P<0.0001) with a mean difference ranging from 18.5% to 22.3%. This methylation pattern correlated with several clinical factors, including a multi-satellite tumor, fibrous capsule, and the presence of tumor thrombus. The receiver operator characteristic (ROC) curve analysis further confirmed that the percent methylated reference (PMR) values for TPO were predictive of the tumor [the area under the curve (AUC) ranged from 0.755 to 0.818] and the thrombosis in the HCC patients (the AUC ranged from 0.706 to 0.777). CONCLUSION: These findings demonstrated that epigenetic alterations of TPO, as indicated by the PMR values, were a potential biomarker for HCC patients with tumor thrombosis.

[Feeding ecology of Decapterus maruadsi in the southern coastal area of Zhejiang based on stomach contents and stable isotope analysis.] / åŸºäºŽèƒƒå«ç‰©å’Œç¢³ã€æ°®ç¨³å®šåŒä½ç´ ç ”ç©¶æµ™æ±Ÿå—éƒ¨è¿‘æµ·è“åœ†é²¹çš„æ‘„é£Ÿç”Ÿæ€.

Decapterus maruadsi is an important economic pelagic fish in the southern coastal area of Zhejiang. According to the bottom trawl surveys conducted in May, August, November 2020 and January 2021, the feeding habits of D. maruadsi in the southern coastal area of Zhejiang were examined by both stable isotope (carbon, δ13C, and nitrogen, δ15N) and stomach content analyses. Results showed that the δ13C value of D. maruadsi ranged from -17.76‰ to -15.25‰, with a mean of (-16.55±0.60)‰, while the δ15N value ranged from 9.06‰ and 13.03‰, with a mean of (11.76±0.88)‰. There was a significant negative correlation between the δ13C values and fork length, and a positive relationship between the δ15N with fork length. Results from stomach content analysis showed that the main prey groups of D. maruadsi were fish, shrimp, crabs, Cephalopod, Polychaete, and small crustaceans. As for the stable isotope analysis, the nutritional contribution rate of shrimp was the highest (40%-84%) among all prey groups, followed by Polychaete, small crustaceans, crabs, Cephalopods and fish. Significant ontogenetic dietary changes were found for D. maruadsi. As the fork length of D. maruadsi increased, it tended to eat prey from higher trophic levels.

Differential diagnostic value of the ResNet50, random forest, and DS ensemble models for papillary thyroid carcinoma and other thyroid nodules.

Objective To explore the differential diagnostic efficiency of the residual network (ResNet)50, random forest (RF), and DS ensemble models for papillary thyroid carcinoma (PTC) and other pathological types of thyroid nodules.Methods This study retrospectively analyzed 559 patients with thyroid nodules and collected thyroid pathological images and auxiliary examination results (laboratory and ultrasound results) to construct datasets. The pathological image dataset was used to train a ResNet50 model, the text dataset was used to train a random forest (RF) model, and a DS ensemble model was constructed from the results of the two models. The differential diagnostic values of the three models for PTC and other types of thyroid nodules were then compared.Results The DS ensemble model had the highest sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (85.87%, 97.18%, 93.77%, and 0.982, respectively).Conclusions Compared with Resnet50 and the RF models trained only on imaging data or text information, respectively, the DS ensemble model showed better diagnostic value for PTC.

miR-185-3p targets Annexin-A8 to inhibit proliferation in cervical cancer cells.

Numerous studies have found that microRNAs (miRNAs) are involved in regulating various tumor-related biological functions. The downregulation of miR185-3p have been identified in various types of cancer but the effect and its underlying molecular mechanism in cervical cancer have not been elucidated. Therefore, it is important to investigate the role of miRNAs associated with cervical cancer and its corresponding molecular mechanism to develop new therapeutic targets. The cell counting kit (CCK-8) assay was performed to measure the cell viability. The quantitative real-time PCR (qRT-PCR) and western blot analyses were carried out to identify mRNA and protein expression levels, respectively. Besides, a luciferase activity assay was conducted to confirm the target miRNA gene predictions. In this study, it is found that miR185-3p expression was potentially downregulated in cervical cancer tissues when compared with normal tissues. The CCK-8 results indicated that miR185-3p overexpression suppressed the cancer cell proliferation and the downregulation of miR185-3p enhanced the cancer cell growth. Further, enhanced miR185-3p expression led to a reduction in Annexin-A8 (Anx-A8) expression but miR185-3p inhibition promoted ANX-A8 levels in cervical cancer cells. The luciferase reporter assay indicated that ANX-A8 was a direct target of miR185-3p in cervical cancer cells.

SET1A-Mediated Mono-Methylation at K342 Regulates YAP Activation by Blocking Its Nuclear Export and Promotes Tumorigenesis.

YAP, a key effector of Hippo pathway, is activated by its translocation from cytoplasm to nucleus to regulate gene expression and promote tumorigenesis. Although the mechanism by which YAP is suppressed in cytoplasm has been well-studied, how the activated YAP is sequestered in the nucleus remains unknown. Here, we demonstrate that YAP is a nucleocytoplasmic shuttling protein and its nuclear export is controlled by SET1A-mediated mono-methylation of YAP at K342, which disrupts the binding of YAP to CRM1. YAP mimetic methylation knockin mice are more susceptible to colorectal tumorigenesis. Clinically, YAP K342 methylation is reversely correlated with cancer survival. Collectively, our study identifies SET1A-mediated mono-methylation at K342 as an essential regulatory mechanism for regulating YAP activity and tumorigenesis.

Anoctamin5 regulates cell migration and invasion in thyroid cancer.

Anoctamin/TMEM16 family members have recently been identified as novel calcium-activated chloride channels, and dysregulation of many family members participates in tumorigenesis and progression. However, the exact role of anoctamin5 (ANO5), one member of this family, in thyroid cancer is still not clarified. In this study, we firstly found that the expression levels of ANO5 was significantly downregulated in thyroid cancer compared to adjacent normal tissue by mining the public GEO database. Subsequently, we further demonstrated that the expression levels of ANO5 was significantly downregulated in 69.5% (57/82) clinical thyroid cancer tissues using real-time PCR assay. Moreover, western blot assay also showed that ANO5 was downregulated in papillary thyroid cancer and follicular thyroid cancer compared to adjacent noncancerous tissues. Furthermore, some biological and functional in vitro experiments proved that ANO5 knockdown promotes thyroid cancer cell migration and invasion but overexpression of ANO5 inhibits these phenotypes. By analyzing gene set enrichment, we found that lower ANO5 expression was positively associated with JAK/STAT3 signaling pathway. Collectively downregulation of ANO5 promotes thyroid cancer cell migration and invasion by affecting JAK/STAT3 pathway.

Genomic expression profiling and bioinformatics analysis of pancreatic cancer.

Pancreatic cancer is a polygenic disease and the fourth leading cause of cancer-associated mortality worldwide; however, the tumorigenesis of pancreatic cancer remains poorly understood. Research at a molecular level, which includes the exploration of biomarkers for early diagnosis and specific targets for therapy, may effectively aid in the diagnosis of pancreatic cancer in its early stages and in the development of targeted molecular­biological approaches for treatment, thus improving prognosis. By conducting expression profiling in para­carcinoma, carcinoma and relapse of human pancreatic tissues, 319 genes or transcripts with differential expression levels >3­fold between these tissue types were identified. Further analysis with Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes demonstrated that the translation, nucleus assembly processes and molecular functions associated with vitamin B6 and pyridoxal phosphate binding in pancreatic carcinoma were abnormal. Pancreatic cancer was additionally identified to be closely associated with certain autoimmune diseases, including type I diabetes mellitus and systemic lupus erythematosus.

Effect of Huanshuai Recipe Oral Liquid ([characters: see text]) on renal dysfunction progression in patients with atherosclerotic renal artery stenosis.

OBJECTIVE: To investigate the effect of Huanshuai Recipe Oral Liquid ([characters: see text], HSR) on retarding the progression of renal dysfunction in patients with atherosclerotic renal artery stenosis (ARAS). METHODS: A total of 52 ARAS patients with the Chinese medicine (CM) syndrome of qi deficiency and blood stasis, phlegm and dampness retention were recruited and randomly assigned into the treatment group (36 cases) and the control group (16 cases). Both groups received a basic treatment (high-quality low-protein diet, blood pressure control, lipid-lowering, correcting the acidosis, etc.). In addition, the treatment group received 20 mL HSR and the control group received placebo, 3 times a day for 6 months. Renal function (serum creatinine, blood urea nitrogen and uric acid) and blood lipids (cholesterol, triglycerides and low density lipoprotein) were examined monthly. The estimated glomerular filtration rate (eGFR) and CM syndrome score were compared between groups. RESULTS: After treatment, compared with the control group, the serum creatinine level, uric acid level and CM syndrome score of the treatment group were significantly decreased (P<0.05 or P<0.01), and the eGFR in the treatment group were significantly increased (P<0.05). CONCLUSION: HSR can effectively improve the renal function and clinical symptoms of ARAS patients.

Hypoxia inducible factor-1α suppresses Peroxiredoxin 3 expression to promote proliferation of CCRCC cells.

Peroxiredoxin 3 (Prx3) is a mitochondrial member of the antioxidant family of thioredoxin peroxidases that uses mitochondrial thioredoxin 2 as a source of reducing equivalents to scavenge hydrogen peroxide (H2O2). Here, we report that the protein levels of Prx3 are significantly reduced in VHL-deficient clear cell renal cell carcinoma (CCRCC). Furthermore, stabilization of HIF-1α protein, caused either by VHL deficiency under normoxia, or by hypoxia, significantly reduced Prx3 expression. Luciferase-reporter and chromatin-immunoprecipitation assays indicated that HIF-1α binds to the hypoxia-responsive elements of PRDX3 promoter and represses its transcription. Finally, shRNA-based assays suggested that Prx3 downregulation is required for the HIF-1α-dependent proliferation of CCRCC cells. Taken together, our results shed new light onto the mechanism of HIF-1α-dependent proliferation in CCRCC cells.

[Feeding ecology of Amblychaeturichthys hexanema in Jiaozhou Bay, China].

From February to November 2011, four seasonal bottom trawl surveys were conducted in the Jiaozhou Bay of China. A total of 624 Amblychaeturichthys hexanema individuals were collected to analyze their stomach contents, with the feeding ecology of A. hexanema studied. The prey items of A. hexanema included more than 40 species, among which, Alpheus japonicas, Philine kinglippini, and Leptochela gracilis were the dominant prey species. The diet composition of A. hexanema had an obvious seasonal variation, with the gastropods, fish, decapods, and microcrustacean being the most important prey items in spring, summer, autumn, and winter, respectively. This phenomenon could be mainly related to the seasonal variations in the species and biomass of the preys in Jiaozhou Bay. With the increase of predator size, the prey species of A. hexanema varied from small size copepod to larger sizes P. kinglippini, Raphidopus ciliates, and A. japonicas. The canonical correspondence analysis (CCA) showed that water temperature and salinity were the most important factors affecting the feeding of A. hexanema, followed by predator size and water pH.

Cholecystokinin octapeptide significantly suppresses collagen-induced arthritis in mice by inhibiting Th17 polarization primed by dendritic cells.

Cholecystokinin octapeptide (CCK-8) is a neuropeptide, and is shown to be a potent immunomodulator with predominant anti-inflammatory effects. Although the regulatory effect of CCK-8 on macrophages and B cells has been defined, the effect of CCK-8 on dendritic cells (DCs) and T cells is not well understood. In this study, we showed that CCK-8 reduced the expression of CD80, CD86, and MHCII on DCs. Moreover, CCK-8 promoted Th1 and inhibited Th17 polarization by increasing the production of IL-12 and decreasing the production of IL-6 and IL-23 on DCs in vitro and in vivo. In addition, intraperitoneal administration of CCK-8 to mice with collagen-induced arthritis (CIA) was found to effectively reduce the incidence of arthritis, delay its onset and prevent the occurrence of joint damage. Collectively, these results suggest that CCK-8 significantly suppresses the incidence and severity of CIA in mice, through the inhibition of DC mediated Th17 polarization.