The Adler grade by Doppler ultrasound is associated with clinical pathology of cervical cancer: Implication for clinical management.

OBJECTIVE: To analyze the relationship of Adler grade by transvaginal color Doppler flow imaging (TV-CDFI) and the clinical pathological parameters of patients with cervical cancer, and to identify the value of Adler grade in the diagnosis and treatment of cervical cancer. METHODS: Patients with cervical cancer diagnosed pathologically in our hospital from January 1, 2019 to December 31, 2019 were included, All patients underwent TV-CDFI examination, and the images were divided into 0 to III grades according to the Adler grades, and the correlations between the Adler classification and clinical pathological parameters (clinical stage, mass size, pathological type, squamous cell carcinoma subtype, CA125, CA199) were analyzed. RESULTS: A total of 162 patients with cervical cancer were included. With the increase of Adler severity, the clinical stage of cervical cancer increased accordingly. the cancer size differed significantly in patients with different Adler grade (p = 0.004); There were significant differences in the level of CA125, CA199 between the squamous cell carcinoma and adenocarcinoma (all p<0.05). the Adler grade was positively related with the clinical stage, pathological type and squamous cell carcinoma subtypes of cervical cancer (all p<0.05), no correlations were found among the Adler grade and the cancer size, CA125, CA199 (all p>0.05). The area under ROC curve of the cervical squamous cell carcinoma predicted by Adler grade based on FIGO results and pathological results was 0.811and 0.762 respectively (all p<0.05). CONCLUSIONS: Adler grades are closely associated with the clinical pathology of cervical cancer, which may be a convenient and effective approach for the assisting assessment of cervical cancer.

Deficiency of Pdk1 contributes to primordial follicle activation via the upregulation of YAP expression and the pro­inflammatory response.

The molecular mechanisms underlying the activation of primordial follicles are poorly understood. The serine/threonine protein kinase phosphoinositide­dependent kinase 1 (PDK1), a pivotal downstream effector of phosphatidyl inositol­3 kinase (PI3K) signaling, plays a vital role in cellular signaling. In order to identify the function of PDK1 in ovarian follicle development, this study used conditional Pdk1 deletion in mouse oocytes by crossing Pdk1loxP/loxP mice with transgenic mice carrying Gdf­9 promoter­mediated Cre recombinase and found that Pdk1flx/flxGdf9Cre mice were subfertile with increased serum follicle­stimulating hormone (FSH) and luteinizing hormone (LH) levels compared with Pdk1flx/flx mice. The deletion of Pdk1 in oocytes induced massive primordial follicle activation, leading to premature ovarian failure (POF). Further investigation revealed that enhanced Yes­associated protein (YAP) expression and an increased pro­inflammatory response also contributed to massive primordial follicle activation. PDK1 formed the complex with the core kinases of Hippo signaling and regulated the expression levels of YAP. On the whole, the findings of the present study demonstrate that PDK1 serves as an indispensable gatekeeper for maintaining the primordial follicle pool and provide a deeper understanding of POF treatment.

The effect of bisphenol a exposure onto endothelial and decidualized stromal cells on regulation of the invasion ability of trophoblastic spheroids in in vitro co-culture model.

Bisphenol A (BPA) is a kind of environmental endocrine disruptors (EEDs) that interfere embryo implantation. Trophoblast invasion plays a crucial role during embryo implantation. In this study, the effects of BPA on invasion ability of human trophoblastic Jeg-3 spheroids and regulation of endothelial and stromal cells on trophoblastic spheroids invasion, and its possible mechanism were investigated. The results showed that BPA at 10 and 100 µM can inhibit the attachment of Jeg-3 spheroid onto Ishikawa cells. BPA at 1-100 µM also activate ERE-Luc reporter expression in the transfected cells, which was through the ERα, but not ERß or GPR30 binding. Endothelial receptivity ability was harmed by BPA treatment since receptivity markers of LIF, EGF, MUC1 and integrin αVß3 were decreased after BPA treatment. The invasion ability of trophoblastic spheroids generated from Jeg-3 cell line was inhibited by BPA and this effect was mediated through canonical ERs pathway and MMP2/MMP9 down-regulation and TIMP1/PAI-1 up-regulation. Besides, BPA treated decidualized stromal cells suppressed Jeg-3 spheroid outgrowth and invasion in co-culture assay. Our study would give a better understanding on the possible mechanism of BPA effect on human embryo implantation process.

Application of transvaginal sonographic elastography to distinguish endometrial cancer from benign masses.

Transvaginal sonographic elastography can be used for the differentiation of malignant and benign lesions in different systems. Recent studies on strain elastography showed that different endometrial tissues demonstrated different stiffness characteristics. In this study, we aim to evaluate the diagnostic value of transvaginal sonographic elastography to distinguish endometrial cancer from benign masses. A prospective study was conducted on patients with suspected intracavitary uterine focal lesions, abnormal uterine bleeding for routine ultrasound examination of the pelvis. A total of 217 patients were included and underwent both conventional B-mode sonography and elastography. Endometrial lesions were categorized into 3 types for qualitative analysis and the strain ratio (SR) was measured for quantitative analysis. Pathological examinations were also conducted to establish final diagnosis. There were 104 patients diagnosed with endometrial cancer and 113 with benign lesions. All type 1 endometrial lesions were diagnosed as benign, while 95.8% of type 3 were malignant. For quantitative elastography results, the AUC for SR was 0.904 with 95% CI between 0.866 and 0.942. Using an ROC curve, the best cut-off SR value was found to be 3.02 and it could achieve a sensitivity of 81.7%, a specificity of 85%, a positive predictive value of 83.3% and a negative predictive value of 83.5%. Our results suggested that transvaginal sonographic elastography is a promising diagnostic tool for differentiating endometrial cancer from benign masses, and that SR has excellent diagnostic performance.

Oridonin effectively reverses cisplatin drug resistance in human ovarian cancer cells via induction of cell apoptosis and inhibition of matrix metalloproteinase expression.

Cisplatin is a first generation platinum­based chemotherapeutic agent, however, the extensive application of cisplatin inevitably results in drug resistance, which is a major obstacle in cancer chemotherapy. The aim of the present study was to investigate the efficiency of reversing cisplatin­resistance with the use of combination therapy with oridonin and cisplatin in human ovarian cancer cells, and attempt to reduce the side effects of the therapeutic agents when used alone. The half maximal inhibitory concentration (IC50) values of cisplatin were determined in cisplatin­sensitive and cisplatin­resistant ovarian cancer cells using an MTT assay. IC50 values of cisplatin in A2780, A2780/DDP, SKOV3 and SKOV3/DDP cells were significantly decreased in a time­dependent manner. The antitumor effect of oridonin in A2780/DDP cells was also detected by the MTT assay and the inhibitory effects of oridonin increased in a dose­ and time­dependent manner. A2780/DDP cells were treated with 20 µM oridonin in combination with increasing concentrations of cisplatin for 48 h, and the result demonstrated that oridonin synergistically increased the antitumor effects of cisplatin in A2780/DDP cells. Notably, the combination treatment of oridonin and cisplatin effectively reversed cisplatin resistance and the IC50 values were significantly decreased from 50.97 µM and 135.20 to 26.12 µM and 73.00 µM in A2780/DDP and SKOV3/DDP cells at 48 h, respectively. Furthermore, oridonin induced cell apoptosis in a dose­dependent manner and promoted cell­cycle arrest at the G0/G1 phase in ovarian cancer cells. Oridonin and cisplatin synergistically increased the cell apoptosis rate of A2780/DDP cells, which was detected by fluorescence­activated cell sorting analysis. Downregulated expression levels of Bcl­2 and upregulated the expression of Bax protein were demonstrated by western blot analysis, further indicating increased apoptosis. In addition, the expression levels of matrix metalloproteinase (MMP)­2 and MMP­9 decreased in a dose­dependent manner with oridonin treatment. The results from the present study demonstrated that oridonin exerted a synergistic effect with cisplatin to inhibit proliferation and induce cell apoptosis in cisplatin­resistant ovarian cancer cells. Thus, combination therapy with oridonin and cisplatin effectively reversed cisplatin resistance in human ovarian cancer cells, which may have useful clinical applications.

Differentiation of metastatic cervical lymph nodes with ultrasound elastography by virtual touch tissue imaging: preliminary study.

OBJECTIVES: The purpose of this study was to investigate the clinical usefulness of acoustic radiation force impulse elastography for the differential diagnosis of cervical lymph nodes. METHODS: Virtual touch tissue imaging (Siemens Medical Solutions, Mountain View, CA) was analyzed in 81 patients (mean age, 46.6 years; range, 5-82 years) with 81 lymph nodes (45 metastatic nodes and 36 benign nodes). RESULTS: Most benign lymph nodes were slightly darker or the same in brightness compared with surrounding tissue, whereas most metastatic nodes were obviously darker. The mean area ratio of benign lymph nodes ± SD (1.05 ± 0.15) was statistically lower than the mean area ratio of metastatic lymph nodes (1.39 ± 0.20; P < 0.001). The area ration cutoff level for metastatic lymph nodes was estimated to be 1.16. With the use of a receiver operating characteristic curve with this cutoff value, the area ratio predicted malignancy with sensitivity of 91.1%, specificity of 83.3%, and an area under the curve of 0.925. CONCLUSIONS: Acoustic radiation force impulse imaging is feasible for cervical lymph nodes. The Virtual Touch tissue imaging technique can complement conventional sonography, thereby making it easier to diagnose cervical lymph nodes.