Brown and beige adipose tissues, which contain high levels of mitochondria and UCP1, are crucial for energy expenditure and metabolic homeostasis. Previous studies have established that G protein-coupled receptors (GPCRs) play a critical role in mediating adaptive thermogenesis and browning. While the β3-adrenoceptor (β3-AR) serves as the key β-adrenergic GPCR driving adipose thermogenesis in mice, its minimal presence in human adipocytes hinders its therapeutic application. This study identifies adhesion G protein-coupled receptor L4 (ADGRL4) as a potential GPCR target for inducing adipose browning. In vitro experiments demonstrated that ADGRL4 activation promotes beige adipocyte differentiation, significantly upregulates UCP1 expression, and reduces lipid droplet accumulation. In vivo, ADGRL4 activation induces the development of beige fat in mice fed a normal chow diet without causing systemic effects. In mice fed a high-fat diet, ADGRL4 activation reduces fat deposition, decreases body weight, alleviates glucose intolerance, and ameliorated obesity and associated metabolic dysfunction. Furthermore, mechanistic investigations revealed that ADGRL4 specifically enhances AKT phosphorylation without altering total AKT levels, thereby activating a downstream signaling cascade that elevates UCP1 expression. This coordinated regulation through the p-AKT/UCP1 axis substantiates the role of ADGRL4 in driving adipose browning and identifies it as a promising molecular target for the treatment of obesity and associated metabolic disorders.

Adipose tissue exhibits remarkable plasticity, defined as its capability of adapting to various environments and energy demands by undergoing shifts in phenotypic, metabolic characteristics, and structure. However, obesity often results in diminished adipose tissue plasticity. Long non-coding RNA (lncRNA) is a class of RNA defined as being more than 200 nucleotides long and lacking protein-coding capability. With advancements in ribosome profiling, mass spectrometry, and other research technologies, an increasing number of studies have confirmed that short open reading frames (less than 300 nucleotides) within lncRNAs have the capacity to encode functional micropeptides. In our study, we initially identified a biologically active micropeptide, lncRNA Esrp2-as-ORF1(LEAO), encoded by lncRNA Esrp2-as in mice. In diet-induced obesity (DIO)mice, this micropeptide demonstrates the ability to induce fat browning, enhance adipose tissue plasticity, and subsequently improve metabolic homeostasis. Additionally, we observed that the micropeptide LEAO exerts its effects on adipocytes by stimulating IL6 secretion in adipose tissue macrophages. In summary, LEAO may have therapeutic potential for obesity-related metabolic diseases.

Background Growing evidence implicates enoyl-CoA hydratase domain-containing protein 2 (ECHDC2) in oncogenesis, yet its role in glioblastoma (GBM) remains undefined. We aimed to clarify the pathological significance and molecular mechanisms of ECHDC2 in GBM.Methods Gene-expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed. Kaplan-Meier curves were used to evaluate the prognostic value of ECHDC2. Immune cell infiltration was quantified using CIBERSORT, single-sample gene-set enrichment analysis (ssGSEA), and ESTIMATE algorithms. Spearman's correlation analysis was applied to assess the associations between ECHDC2 expression levels, immune checkpoint molecules, and immune cell subsets. To elucidate the functional relevance of ECHDC2, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene-set enrichment analyses (GSEA) were performed, while protein-protein interaction (PPI) networks were investigated using the STRING database. Subsequently, ECHDC2 was knocked down or overexpressed in GBM cell lines, and its effects on cell proliferation and migration were determined using CCK-8, EdU, wound-healing, and Transwell migration assays.Results Upregulated ECHDC2 expression was significantly correlated with unfavorable clinicopathological features and reduced overall survival (OS) in patients with GBM. High ECHDC2 expression was associated with increased infiltration of effector-memory CD8+ T cells (TEM) and plasmacytoid dendritic cells (pDCs). Enrichment analyses demonstrated that ECHDC2 is involved in tumor progression, with a particular focus on the PI3K/Akt signaling pathway. In vitro experiments showed that ECHDC2 knockdown suppressed the proliferation and migration of GBM cells. Conversely, ECHDC2 overexpression exerted the opposite effects on GBM cell proliferation and migration.Conclusion ECHDC2 overexpression promotes GBM progression and portends poor prognosis. ECHDC2 may serve as both a prognostic biomarker and a therapeutic target in GBM.

Abstract Background The resolution of inflammation is actively driven by omega‐3 polyunsaturated fatty acids (PUFAs) via their specialized pro‐resolving mediator (SPM) derivatives, including resolvin E1 (RvE1), whose role has been well established. However, clinical application of these mediators is hampered by inherent instability and elevated production costs. Methods To surmount these obstacles, we have engineered a biosynthetic platform based on the probiotic Escherichia coli Nissle 1917 (EcN) that enables controlled, sustained RvE1 production through inducible expression of COX2 and 5‐LOX, designated EcN‐RvE1. The catalytic capacity, intestinal persistence, and therapeutic efficacy of the platform were evaluated in vitro and in LPS‐induced acute inflammation and DSS‐induced colitis murine models. Results In this study, we validate the capacity of EcN‐RvE1 to catalyse the conversion of eicosapentaenoic acid (EPA) to RvE1 and confirm its ability to achieve long‐term intestinal persistence. In murine models of acute inflammation and colitis, EcN‐RvE1 exerts marked anti‐inflammatory and tissue‐protective effects, which are mediated by the regulation of inflammatory cytokine expression and the amelioration of gut microbiota dysbiosis. Moreover, EcN‐RvE1 using Euglena gracilis as a photosynthetic protist‐based source of PUFAs also exhibits protective anti‐inflammatory activity. Conclusion Collectively, we report a probiotic engineering platform for the biosynthesis of RvE1, offering a novel strategy for harnessing the anti‐inflammatory potential of PUFAs derivatives in clinical settings.

Cardiovascular diseases (CVDs) remain the leading global cause of death, with hyperlipidemia being a critical risk factor. Current lipid-lowering therapies (e.g., statins, PCSK9 inhibitors) effectively reduce LDL-C but have limitations like side effects or residual cardiovascular risk, necessitating novel therapeutic targets. In this study, we aimed to explore the role of chemerin, an adipokine, in the pathogenesis of dyslipidemia. Clinical analysis of 42 treatment-naive participants showed significant positive correlations between serum chemerin and triglycerides (TG, R2 = 0.5073, p < 0.0001), total cholesterol (TC, R2 = 0.1464, p = 0.0124), and LDL-C (R2 = 0.1600, p = 0.0087), independent of HDL-C. In C57BL/6J mice, exogenous chemerin administration in high-fat diet (HFD)-induced obesity models significantly increased serum TG, TC, and LDL-C levels. Moreover, we found that the expression of chemerin was upregulated in liver (but not adipose tissues) of obese mice, which indicates that the liver is the primary source of obesity-associated chemerin. The animal experiments showed that liver-specific Rarres2 (chemerin-encoding gene) knockout via AAV9-CRISPR reduced HFD-induced elevations of serum TG, TC, and LDL-C levels. Furthermore, the results showed that liver-specific Rarres2 knockout also ameliorated hepatic injury (ALT, AST) and systemic inflammation (TNF-α, IL-6). Collectively, these findings establish chemerin as a hepatic mediator of obesity-related hyperlipidemia, supporting its potential as a therapeutic target for hyperlipidemia.

BACKGROUND:Obesity has emerged as a global health challenge. Although GLP-1 receptor agonists are showing considerable promise in weight loss, their clinical utility is partly limited by gastrointestinal adverse reactions and non-fat weight loss side effects. UCP1-mediated adipose thermogenesis is a critical process for body temperature maintenance and weight management. However, the lack of effective and specific adipose thermogenesis therapies has restricted its clinical application. We aimed to explore the potential of inducing adipose-specific UCP1 overexpression via modified plasmids as an innovative therapeutic approach for obesity. METHODS:We replaced the cytomegalovirus (CMV) promoter in the plasmids with two types of adipose-specific promoters: mouse adiponectin (mADP) promoter and human adiponectin (hADP) promoter, to selectively overexpress UCP1 in adipocytes. The expression level of UCP1, weight loss, metabolic homeostasis and adipose thermogenesis effects were evaluated by immunohistochemistry, western blot, weight measurements, thermography, and comprehensive lab animal monitoring system. RESULTS:The experiments demonstrated that the mADP promoter-modified plasmids failed to drive UCP1 overexpression. In contrast, the hADP promoter-modified Ucp1 overexpression (hADP-Ucp1 OE) plasmids achieved robust adipose-specific UCP1 protein expression both in vitro and in vivo. In vitro experiments revealed that delivery of the hADP promoter-modified UCP1 overexpression (hADP-UCP1 OE) plasmids reduced lipid droplet size and enhanced energy consumption in human adipocytes. In obese mice, administration of the hADP-Ucp1 OE plasmids resulted in significant weight loss and improved metabolic homeostasis. CONCLUSIONS:These findings highlight the therapeutic potential of hADP-UCP1 OE plasmids in obesity management. KEY POINTS:The hADP promoter-modified plasmids selectively overexpress protein in adipose tissue. Overexpression of UCP1 driven by hADP promoter induces thermogenesis in mouse and human adipocytes in vitro. The hADP-Ucp1 OE treatment promotes thermogenesis and energy expenditure in mice. The hADP-Ucp1 OE treatment restrains the development of obesity and glucose intolerance in mice.

The induction of adipose thermogenesis plays a critical role in maintaining body temperature and improving metabolic homeostasis to combat obesity. β3-adrenoceptor (β3-AR) is widely recognized as a canonical β-adrenergic G-protein-coupled receptor (GPCR) that plays a crucial role in mediating adipose thermogenesis in mice. Nonetheless, the limited expression of β3-AR in human adipocytes restricts its clinical application. The objective of this study was to identify a GPCR that is highly expressed in human adipocytes and to explore its potential involvement in adipose thermogenesis. Our research findings have demonstrated that the adhesion G-protein-coupled receptor A3 (ADGRA3), an orphan GPCR, plays a significant role in adipose thermogenesis through its constitutively active effects. ADGRA3 exhibited high expression levels in human adipocytes and mouse brown fat. Furthermore, the knockdown of Adgra3 resulted in an exacerbated obese phenotype and a reduction in the expression of thermogenic markers in mice. Conversely, Adgra3 overexpression activated the adipose thermogenic program and improved metabolic homeostasis in mice without exogenous ligand. We found that ADGRA3 facilitates the biogenesis of beige human or mouse adipocytes in vitro. Moreover, hesperetin was identified as a potential agonist of ADGRA3, capable of inducing adipocyte browning and ameliorating insulin resistance in mice. In conclusion, our study demonstrated that the overexpression of constitutively active ADGRA3 or the activation of ADGRA3 by hesperetin can induce adipocyte browning by Gs-PKA-CREB axis. These findings indicate that the utilization of hesperetin and the selective overexpression of ADGRA3 in adipose tissue could serve as promising therapeutic strategies in the fight against obesity.

Induction of beige fat for thermogenesis is a potential therapy to improve homeostasis against obesity. β3-adrenoceptor (β3-AR), a type of G protein-coupled receptor (GPCR), is believed to mediate the thermogenesis of brown fat in mice. However, β3-AR has low expression in human adipose tissue, precluding its activation as a standalone clinical modality. This study aimed at identifying a potential GPCR target to induce beige fat. We found that chemerin chemokine-like receptor 1 (CMKLR1), one of the novel GPCRs, mediated the development of beige fat via its two ligands, chemerin and resolvin E1 (RvE1). The RvE1 levels were decreased in the obese mice, and RvE1 treatment led to a substantial improvement in obese features and augmented beige fat markers. Inversely, despite sharing the same receptor as RvE1, the chemerin levels were increased in obesogenic conditions, and chemerin treatment led to an augmented obese phenotype and a decline of beige fat markers. Moreover, RvE1 and chemerin induced or restrained the development of beige fat, respectively, via the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. We further showed that RvE1 and chemerin regulated mTORC1 signaling differentially by forming hydrogen bonds with different binding sites of CMKLR1. In conclusion, our study showed that RvE1 and chemerin affected metabolic homeostasis differentially, suggesting that selectively modulating CMKLR1 may be a potential therapeutic target for restoring metabolic homeostasis.

Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.

Breast cancer is one of the most common malignant tumors with high mortality and poor prognosis in women. There is an urgent need to discover new therapeutic targets for breast cancer metastasis. Herein, we identified that Apolipoprotein C1 (APOC1) was up-regulated in primary tumor of breast cancer patient that recurrence and metastasis by immunohistochemistry (IHC). Kaplan-Meier Plotter database showed that high levels of APOC1 in breast cancer patients were strongly associated with worse overall survival (OS) and relapse-free survival (RFS). Mechanistically, APOC1 silencing significantly inhibits MAPK/ERK kinase pathway and restrains the NF-κB to decrease the transcription of target genes related to growth and metastasis in vitro. Based on this regulatory mechanism, we developed these findings into potential therapeutic drugs, glutathione (GSH) responsive nano-particles (NPs) were used for systemic APOC1 siRNA delivery, NPs (siAPOC1) silenced APOC1 expression, and subsequently resulted in positive anti-tumor effects in orthotopic and liver metastasis models in vivo. Taken together, GSH responsive NP-mediated siAPOC1 delivery was proved to be effective in regulating growth and metastasis in multiple tumor models. These findings show that APOC1 could be a potential biomarker to predict the prognosis of breast cancer patients and NP-mediated APOC1 silencing could be new strategies for exploration of new treatments for breast cancer metastasis.

目的 糖尿病是一种慢性疾病,身体各个系统都有不同程度的损伤.大量研究指出糖尿病患者在新型冠状病毒肺炎(COVID-19)流行期间更加容易感染COVID-19并且更容易出现重症.本研究拟通过Meta分析来探明糖尿病与COVID-19严重程度和死亡率的关联性.方法 使用关键词(1)"COVID-19"OR"SARS-CoV-2"OR"Coronavirus"OR"novel coronavirus"AND"clinical characteristics"(2)"COVID-19"OR"SARS-CoV-2"AND"Diabetes"检索PubMed,Embase和中国知网的数据,筛选截至2021年2月发表的英文和中文期刊论著,提取数据后使用RevMan 5.4进行Meta分析,并使用Stata 12.0评估发表偏倚.结果 共纳入82篇文献,合计35715例患者.Meta分析结果显示,患糖尿病与COVID-19预后较差有关[OR 2.29(2.14,2.46),P<0.01;I2:52％,P<0.01].COVID-19患者中糖尿病患者相对非糖尿病患者发生重症[OR 2.40(2.20,2.62),P<0.01;I2:49％,P<0.01]和死亡[OR 2.08(1.70,2.56),P<0.01;I2:60％,P<0.01]的风险均升高.结论 糖尿病是影响COVID-19患者的重症率和死亡率升高的一个重要因素,而针对糖尿病如何影响COVID-19预后的确切作用机制亟需进一步研究阐明.

Cholestasis caused by bile secretion and excretion disorders is a serious manifestation of hepatopathy. Interleukin (IL)-25 is a member of the IL-17 cytokine family, which involves in mucosal immunity and type 2 immunity via its receptor—IL-17RB. Our previous studies have shown that IL-25 improves non-alcoholic fatty liver via stimulating M2 macrophage polarization and promotes development of hepatocellular carcinoma via alternative activation of macrophages. These hepatopathy are closely associated with cholestasis. However, whether IL-25 play an important role in cholestasis remains unclear. IL-25 treatment and IL-25 knockout (Il25-/-) mice were injected intragastrically with α-naphthyl isothiocyanate (ANIT) to determine the biological association between IL-25 and cholestasis. Here, we found that IL-25 and IL-17RB decreased in ANIT-induced cholestatic mice. Il25-/- mice showed exacerbated ANIT-induced parenchymal injury and IL-25 treatment significantly alleviated cholestatic liver injury induced by ANIT. We found that IL-25 reduced the level of hepatic total bile acids and increased the expression of multidrug resistance-associated protein 2 (MRP2) and multidrug resistance-associated protein 3 (MRP3) in liver. In conclusion, IL-25 exhibited a protective effect against ANIT-induced cholestatic liver injury in mice, which may be related to the regulation on bile acids secretion. These results provide a theoretical basis for the use of IL-25 in the treatment of cholestatic hepatopathy.

BACKGROUND:Gut microbiota and microbe-derived metabolites are involved in the development of HCC. Bile acids (BAs) are the most important gut microbiota-modulated endogenous signaling molecules.METHODS:We tested serum bile acid levels and gut microbiome compositions in patients with HCC, chemical-induced HCC mouse models (DEN-HCC mice) and mouse orthotopic implanted liver tumor models with vancomycin treatment (vancomycin-treated mice). Then, we screened an important kind of HCC-related BAs, and verified its effect on the growth of HCC in vivo and in vitro.RESULTS:We found that the remarkably decreasing percentages of serum secondary BAs in the total bile acids of patients and DEN-HCC mice, especially, conjugated deoxycholic acids (DCA). The relative abundance of the bile salt hydrolase (BSH)-rich bacteria (Bifidobacteriales, Lactobacillales, Bacteroidales, and Clostridiales) was decreased in the feces of patients and DEN-HCC mice. Then, in vancomycin-treated mice, vancomycin treatment induced a reduction in the BSH-rich bacteria and promoted the growth of liver tumors. Similarly, the percentage of conjugated DCA after vancomycin treatment was significantly declined. We used a kind of conjugated DCA, Glyco-deoxycholic acid (GDCA), and found that GDCA remarkably inhibited the growth of HCC in vivo and in vitro.CONCLUSIONS:We conclude that the remarkably decreasing percentages of serum conjugated DCA may be closely associated with HCC, which may be induced by the reducing gut BSH-rich bacteria. The mechanisms may be correlated with conjugated DCA directly inhibiting the growth and migration of HCC cells.

Interleukin-25 (IL17E/IL25) plays a critical role in colitis and intestinal homeostasis. However, the expression and biological role of IL25 in colorectal cancer is not properly understood. In this study, we show that IL25 is mainly expressed by cancer stem cells in the colorectal cancer microenvironment. Genetic deletion of IL25 inhibited tumor formation and growth and prolonged survival in AOM/DSS-treated mice. IL25 stimulated cancer organoid and cancer cells sphere formation and prevented the tumor from chemotherapy-induced apoptosis. Mechanistically, IL25 upregulated stem cell genes LGR5, CD133, and ABC transporters via activating the Hedgehog signaling pathway. IL25 inhibited phosphorylation of AMPK and promoted GLI1 accumulation to maintain cancer stem cells. Moreover, IL25 expression was associated with poor survival in patients with metastatic colorectal cancer. Taken together, our work reveals an immune-associated mechanism that intrinsically confers cancer cell stemness properties. Our results first demonstrated that IL25, as a new potent endogenous Hedgehog pathway agonist, could be an important prognostic factor and therapeutic target for CRC.

Tanshinone IIA (TAN2A) is a major active ingredient of Salvia miltiorrhiza used in traditional Chinese medicine and tanshinone 20 (TAN20) is a derivative of TAN2A. In this study, we examined the effects of TAN2A and TAN20 on adipogenesis, lipid metabolism, and thermogenesis. Our experiments showed that both TAN2A and TAN20 increased mitochondria content in adipose tissue, enhanced energy expenditure, reduced body weight, and improved insulin sensitivity and metabolic homeostasis in obese and diabetic mouse models. We demonstrated that TAN20 can facilitate the transformation from white to beige adipose tissue, as well as activate brown adipose tissue. In uncoupling protein 1 (UCP1) knockout mouse model, the effects of TAN2A and TAN20 on body weight and glucose tolerance were not observed, suggesting that such effects were UCP1 dependent. Furthermore, we found that TAN2A and TAN20 increased the expression of UCP1 and other thermogenic genes in adipocytes through AMPK-PGC-1α signaling pathway. Our findings indicate that TAN2A and its derivative TAN20 are potential interesting energy expenditure regulators and may be implicated in treatment of obesity and other metabolic disorders.

Beige fat dissipates energy and functions as a defense against cold and obesity, but the mechanism for its development is unclear. We found that interleukin (IL)-25 signaling through its cognate receptor, IL-17 receptor B (IL-17RB), increased in adipose tissue after cold exposure and β3-adrenoceptor agonist stimulation. IL-25 induced beige fat formation in white adipose tissue (WAT) by releasing IL-4 and IL-13 and promoting alternative activation of macrophages that regulate innervation and up-regulate tyrosine hydroxylase (TH) up-regulation to produce more catecholamine including norepinephrine (NE). Blockade of IL-4Rα or depletion of macrophages with clodronate-loaded liposomes in vivo significantly impaired the beige fat formation in WAT. Mice fed with a high-fat diet (HFD) were protected from obesity and related metabolic disorders when given IL-25 through a process that involved the uncoupling protein 1 (UCP1)-mediated thermogenesis. In conclusion, the activation of IL-25 signaling in WAT may have therapeutic potential for controlling obesity and its associated metabolic disorders.

Distant metastasis is, unfortunately, the leading cause of death in colorectal cancer (CRC). Approximately 50% of CRC patients develop liver metastases, while 10–30% of patients develop pulmonary metastases. The occurrence of metastasis is considered to be almost exclusively driven by cancer stem cells (CSCs) formation. However, the key molecules that confer the transformation to stem cells in CRC, and subsequent metastasis, remain unclear. Far upstream element‐binding protein 1 (FUBP1), a transcriptional regulator of c‐Myc, was screened in CSCs of CRC by mass spectrometry and was examined by immunohistochemistry in a cohort of CRC tissues. FUBP1 was upregulated in 85% of KRAS‐mutant and 25% of wild‐type CRC patients. Further, whether in KRAS‐mutant or wild‐type patients, elevated FUBP1 was positively correlated with CRC lymph node metastasis and clinical stage, and negatively associated with overall survival. Overexpression of FUBP1 significantly enhanced CRC cell migration, invasion, tumor sphere formation, and CD133 and ALDH1 expression in vitro, and tumorigenicity in vivo. Mechanistically, FUBP1 promoted the initiation of CSCs by activating Wnt/β‐catenin signaling via directly binding to the promoter of DVL1, a potent activator of β‐catenin. Knockdown of DVL1 significantly inhibited the transformation to stem cells in, as well as the tumorigenicity of, CRC. Activation of Wnt/β‐catenin signaling by DVL1 increased pluripotent transcription factors, including c‐Myc, NANOG, and SOX2. Moreover, FUBP1 was upregulated at the post‐transcriptional level. Elevated FUBP1 levels in KRAS wild‐type CRC patients is due to the decrease in Smurf2, which promotes ubiquitin‐mediated degradation of FUBP1. In contrast, FUBP1 was upregulated in KRAS‐mutant patients through both inhibition of caspase 3‐dependent cleavage and decreased Smurf2. Our results demonstrate, for the first time, that FUBP1 is an oncogene, initiating the development of CSCs, as well as a new powerful endogenous Wnt‐signaling agonist that could provide an important prognostic factor and therapeutic target for metastasis in both KRAS‐mutant and wild‐type CRC.

INTRODUCTION:Although ultrasonography has been reported to have similar diagnostic accuracy to magnetic resonance imaging, it is not a standard imaging modality for cervical cancer. We aimed to summarize the ultrasonographic features of rare primary cervical cancer.METHODS:This was a retrospective study of patients with cervical cancer who were diagnosed between June 2014 and October 2019. They were divided into common-type cervical cancer (ie, cervical squamous cell carcinoma) and rare-type cervical cancer groups including adenocarcinoma, adenosquamous carcinoma, and small cell carcinoma. All patients were staged according to the tumor, nodes, and metastases criteria.RESULTS:Of the 64 patients, the diagnosis was suspected on ultrasonography in 61 (95.3%) patients and missed on ultrasonography in three patients. The tumor size was smaller in the rare-type cervical cancer group (p<0.05). Hypoechoic lesions in common-type cervical cancer and isoechoic lesions accounted for 74.4% (32/43) and 61.9% (13/21) of patients in the rare-type cervical cancer group, respectively (p<0.001). Meanwhile, 67.4% (29/43) of tumors in common-type cervical cancer were exophytic, while 66.7% (14/21) in rare-type cervical cancer were endophytic (p=0.01). Color Doppler blood signals, as compared with normal cervical tissue, were found in all patients. There was good consistency between ultrasonographic and pathologic diagnosis of rare-type cervical cancer (weighted kappa=0.87).CONCLUSIONS:Most patients with rare-type cervical cancer present with isoechoic lesions. The coincidence rate between ultrasonographic and pathologic diagnosis of rare-type cervical cancer is 87%.