Predicting the risk of fetal growth restriction by radiomics analysis of the placenta on T2WI: A retrospective case-control study.

INTRODUCTION: Fetal growth restriction (FGR) is associated with placental abnormalities, and its precise diagnosis is challenging. This study aimed to explore the role of radiomics based on placental MRI in predicting FGR. METHODS: A retrospective study using T2-weighted placental MRI data were conducted. A total of 960 radiomic features were automatically extracted. Features were selected using three-step machine learning methods. A combined model was constructed by combining MRI-based radiomic features and ultrasound-based fetal measurements. The receiver operating characteristic curves (ROC) were conducted to assess model performance. Additionally, decision curves and calibration curves were performed to evaluate prediction consistency of different models. RESULTS: Among the study participants, pregnant women who delivered from January 2015 to June 2021 were randomly divided into training (n = 119) and test (n = 40) sets. Forty-three other pregnant women who delivered from July 2021 to December 2021 were used as the time-independent validation set. After training and testing, three radiomic features that were strongly correlated with FGR were selected. The area under the ROC curves (AUCs) of the MRI-based radiomics model reached 0.87 (95% confidence interval [CI]: 0.74-0.96) and 0.87 (95% CI: 0.76-0.97) in the test and validation sets, respectively. Moreover, the AUCs for the model comprising MRI-based radiomic features and ultrasound-based measurements were 0.91 (95% CI: 0.83-0.97) and 0.94 (95% CI: 0.86-0.99) in the test and validation sets, respectively. DISCUSSION: MRI-based placental radiomics could accurately predict FGR. Moreover, combining placental MRI-based radiomic features with ultrasound indicators of the fetus could improve the diagnostic accuracy of FGR.

The expression and clinical significance of secretory leukocyte proteinase inhibitor (SLPI) in mammary carcinoma using bioinformatics analysis.

BACKGROUND: Secretory leukocyte protease inhibitor (SPLI) was a secreted protein which belongs to a member of whey acidic protein four-disulfide core family. In breast cancer (BC) it may inhibit cell proliferation and promote cancer metastasis. In this study, a comprehensive bioinformatics analysis was performed to identify the expression and prognostic value of SLPI in breast cancer. METHODS: SLPI expression in breast cancer was analyzed in Oncomine online database, which was subsequently confirmed by quantitative PCR (qPCR) in 18 BC samples and western blotting in 26 BC samples. Breast cancer gene-expression miner v4.1 was used to access the expression level with clinicopathological parameters in breast cancer patients. The prognostic values of SLPI in breast cancer were evaluated using the PrognoScan database. RESULTS: Our results indicated that SLPI was downregulated in breast cancer than in normal tissues. SLPI expression was found to be negatively correlated with estrogen receptor (ER) and progesterone receptor (PR) status. SLPI expression level was decreased in negative basal-like status patients compared with positive basal-like status. Meanwhile, triple-negative breast cancer status positive correlated with SLPI. We confirmed a positive correlation between SLPI and interleukin 17 receptor B (IL17RB) express in breast cancer tissues via oncomine co-expression analysis. Ten proteins: Elastase, Granulin, Lipocalin, Defensin beta 103B, Defensin beta 103A, Tubulin, Heparin-binding EGF-like growth factor, Interleukin 6, Epidermal growth factor, Phospholipid scramblase 1 were determinate interactions with SLPI by STRING. CONCLUSION: SLPI could as a biomarker to predict the prognosis values of breast cancer. However, further comprehensive study and mining more evidence are needed to clarify our results.

An Innovative Ultrasound Strain Elastographic Method for the Differential Diagnosis of Breast Tumors.

In this monocentric perspective study examining 64 lesions (19 benign and 45 malignant), we tested an innovative ultrasound elastographic method for diagnosing breast tumors. A new region of control and a new index designating the strain ratio (SR) were used. A traditional ultrasound elastographic method was used as the control. The results indicated that the SR ratios of the benign and malignant groups were 0.25 ± 0.22 and 1.10 ± 1.53, respectively, and this difference was statistically significant. The area under the receiver operating characteristic curve of the SR ratio method was 0.95, the cutoff point was 0.37 and the sensitivity and specificity were 95.56% and 94.74%, respectively. The two receiver operating characteristic curves of the traditional method and the SR of the proposed method were significantly different, at a p value of 0.02. Compared with that of the traditional method, the SR obtained with the new method had a larger area under the receiver operating characteristic curve, sensitivity, specificity and objectivity.

Metacarpal Bone Plane Examination by Ultrasonography for the Diagnosis of Fetal Forearm and Hand Deformity.

We explored the value of the metacarpal bone plane in screening for serious fetal forearm and hand deformities, excluding simple polydactyly and dactylion deformity, by ultrasonographic examination. Observed the second to fifth metacarpal bone plane of fetuses in 20,139 pregnant women at a gestational age of 16 to 30 weeks in The International Peace Maternity &Child Health Hospital of China Welfare Institute (IPMCH). There was a total 138 cases of fetal forearm and/or hand deformity among the 20,139 pregnant women. Of these, 134 cases were diagnosed, 4 cases were not diagnosed, and 1 case was misdiagnosed. Among the 134 diagnosed cases, there were 19 cases of hand absence, 5 cases of cleft hand, 13 cases of ectrodactyly, 26 cases of radius absence, 9 cases of forearm and hand dysplasia, 55 cases of thanatophoric dysplasia, 6 cases of wrist joint dysplasia, and 1 case of forearm amputation deformity. The deformity rate was 0.76%, the diagnostic coincidence rate was 99.97%, the sensitivity was 97.10%, the specificity was 99.99%, and the false negative rate was 2.9%. As such, careful observation of the metacarpal bone plane can be used increase the diagnosis rate of fetal forearm and hand deformity.

MiR-506 Over-Expression Inhibits Proliferation and Metastasis of Breast Cancer Cells.

BACKGROUND: This study aimed to investigate the relationship between miR-506 and proliferation and migration of breast cancer cells. MATERIAL AND METHODS: MiR-506 mimics, inhibitor, and negative control (NC) were transfected into MDA-MB-231 breast cancer cells. Cell proliferation, cell counting, colony formation assay, and Transwell assay were applied to evaluate the proliferation and migration of breast cancer cells. Data are shown as mean ± standard deviation and the experiment was performed 3 times. Statistical analyses were performed with SPSS version 10.0. RESULTS: At 1 day after transfection, cell proliferation detected by CCK-8 assay was significantly promoted in miR-506 inhibitor when compared with the miR-506 mimics group and the NC group (P<0.05). At 3 days or 5 days after transfection, cell proliferation was markedly inhibited in the miR-506 mimics group, and miR-506 inhibitor was still significantly promoted. Cell counting with a hemocytometer showed similar results to cell proliferation. Colony formation assay showed that the number of colonies in the miR-506 mimics group was significantly smaller than that in the miR-506 inhibitor group and NC group. Transwell assay revealed that the number of migrated cells in miR-506 mimics was markedly smaller than that in the miR-506 inhibitor group and NC group. CONCLUSIONS: MiR-506 over-expression significantly inhibits the proliferation, colony formation, and migration of breast cancer cells. miR-506 over-expression may thus be able to improve the malignant phenotype of breast cancer cells.

miR-26a and its target CKS2 modulate cell growth and tumorigenesis of papillary thyroid carcinoma.

BACKGROUND: While many studies have shown that levels of miR-26a are lower in papillary thyroid carcinoma (PTC), the role and mechanism of miR-26a in PTC are unclear. METHOD: We used database searches to select potential mRNA targets of miR-26a. Anti-miR-26a, miR-26a mimic, siRNA for CKS2 and their effects on cell growth, cell-cycle distribution and colony formation were evaluated. We also evaluate the over-expressed miR-26a in TPC-1 cells in severe combined immune-deficient mice. We used luciferase reporter assays, real-time PCR and western blot analysis to measure the expression and activity of miR-26a, CKS2, and related factors such as cyclin B1, cyclin A, cdk1, bcl-xl and Akt. Finally, we measured the relationship between the levels of miR-26a and CKS2 in PTC and normal thyroid tissues. RESULTS: Relative to normal thyroid tissues, miR-26a is consistently down-regulated in TPC specimens, and CKS2 was identified as a potential target. Up-regulated miR-26a expression or down-regulated CKS2 expression in TPC-1 and CGTH W3 cells lines caused G2 phase-arrest. Decreased miR-26a expression or increased CKS2 expression could have inverse function on PTC cell lines. CyclinB1, cyclinA, bcl-xl and AKt are indirectly regulated by miR-26a in a CKS2-dependent manner. Finally, CKS2 is overexpressed in PTC specimens relative to normal thyroid tissue, and a significant inverse correlation exists between miR-26a and CKS2 expression in clinical PTC specimens. CONCLUSION: Our data indicate that miR-26a functions as a growth-suppressive miRNA in PTC, and that its suppressive effects are mediated mainly by repressing CKS2 expression.

Genetic polymorphism of glucokinase on the risk of type 2 diabetes and impaired glucose regulation: evidence based on 298,468 subjects.

BACKGROUND: Glucokinase (GCK) is the key glucose phosphorylation enzyme which has attracted considerable attention as a candidate gene for type 2 diabetes (T2D) based on its enzyme function as the first rate-limiting step in the glycolysis pathway and regulates glucose-stimulated insulin secretion. In the past decade, the relationship between GCK and T2D has been reported in various ethnic groups. To derive a more precise estimation of the relationship and the effect of factors that might modify the risk, we performed this meta-analysis. METHODS: Databases including Pubmed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. RESULTS: A total of 24 articles involving 88,229 cases and 210,239 controls were included. An overall random-effects per-allele OR of 1.06 (95% CI: 1.03-1.09; P<10(-4)) was found for the GCK -30G>A polymorphism. Significant results were also observed using dominant or recessive genetic models. In the subgroup analyses by ethnicity, significant results were found in Caucasians; whereas no significant associations were found among Asians. In addition, we found that the -30G>A polymorphism is a risk factor associated with increased impaired glucose regulation susceptibility. Besides, -30G>A homozygous was found to be significantly associated with increased fasting plasma glucose level with weighted mean difference (WMD) of 0.15 (95%: 0.05-0.24, P = 0.001) compared with G/G genotype. CONCLUSIONS: This meta-analysis demonstrated that the -30G>A polymorphism of GCK is a risk factor associated with increased T2D susceptibility, but these associations vary in different ethnic populations.

Therapeutic effect of 188Re-MAG3-depreotide on non-small cell lung cancer in vivo and in vitro.

OBJECTIVE: To investigate the in vivo and in vitro therapeutic effect of 188Re-MAG3-depreotide on non-small cell lung cancer (NSCLC). METHODS: MTT was done to measure the cell proliferation; flow cytometry to detect cell apoptosis; Transwell invasion assay to determine the invasiveness of NSCLC. In addition, HE staining, TUNEL staining and immunohistochemistry for CD34 were employed to investigate the influence of 188Re-MAG3-depreotide on the growth of NSCLC. RESULTS: 1) Within 2-6 days, the inhibitory effect of 188Re-MAG3-depreotide on the proliferation of A549 cells and SPC-A1 cells increased over time. 2) At 48 h after treatment with 188Re-MAG3-depreotide, the apoptosis rate of A549 cells and SPC-A1 cells was 23.1% and 22.6%, respectively. 3) After 188Re-MAG3-depreotide treatment, the number of invasive A549 cells and SPC-A1 cells was reduced by about 3 times when compared with control group. 4) The cancer in the control group presented with unlimited growth. The cancer growth continued after treatment with 188Re or MAG3-depreotide alone, while the cancer growth was markedly inhibited after 188Re-MAG3-depreotide treatment when compared with control group. CONCLUSION: 188Re-MAG3-depreotide can inhibit the proliferation and invasion of A549 cells and SPC-A1 cells. Treatment with 7.4MBq 188Re-MAG3-depreotide via tail vein can significantly suppress the in vivo cancer growth and induce the apoptosis of cancer cells. These findings demonstrate that 188Re-MAG3-depreotide can induce the apoptosis of NSCLC cells and directly kill the NSCLC cells, which provide evidence for the radiotherapy of NSCLC.

Effects of indoleamine 2,3-dioxygenases in carbon tetrachloride-induced hepatitis model of rats.

Indoleamine 2,3-dioxygenase (IDO) converts tryptophan to l-kynurenine, and it is noted as a relevant molecule in promoting tolerance and suppressing adaptive immunity. In this study, to investigate the effects of IDO in carbon tetrachloride (CCl(4) )-induced hepatitis model, the levels of IDO enzymic activities in the mock group, the control group and the 1-methyl-D-tryptophan (1-MT)-treated group were confirmed by determination of l-kynurenine concentrations. Serum alanine aminotransferase levels in 1-MT-treated rats after CCl(4) injection significantly increased compared with those in mock and control groups. In CCl(4)-induced hepatitis models, tumour necrosis factor-α (TNF-α) is critical in the development of liver injury. The mRNA expression and secretion levels of TNF-α in the liver from 1-MT-treated rats were more enhanced compared with those in the mock and the control groups. Moreover, the levels of cytokine and chemokine from mock, control group and 1-MT-treated rats after treated with CCl(4) were analyzed by ELISA, and the level of interleukin-6 was found to increase in 1-MT-treated rats. It was concluded that the deficiency of IDO exacerbated liver injury in CCl(4)-induced hepatitis and its effect may be connected with TNF-α and interleukin-6.

Cytokines as prognstic tool in breast carcinoma.

Serum cytokines are promising biomarkers of cancer staging and outcome prediction, including response to treatment. Serum samples were collected from 200 breast carcinoma patients prior to chemotherapy treatment. Luminex liquid protein chip technology was used to analyze 25 cytokines in serum. Linear regression was used to analyze the relationship of cytokine levels and tumor size. The independent sample T-test and Chi-square test methods were used to analyze the difference of cytokine levels between two groups. IL-12p40, sIL-2R, MMP-2 levels showed linear correlation with tumor size. Eotaxin, IL-10, IL-12p70, IL-7, IL-1ra, IP-10, MCP-1beta, MP-2 and MIP-1beta levels showed significant difference between different lymph node groups, but only Eotaxin, IP-10 and MCP-1 levels had an inverse correlation with the number of positive nodes. Fractalkine, G-CSF, MIP-1alpha, MIP-1beta levels showed significant differences between different ER+ groups. Eotaxin, Fractalkine, IL-6, IL-7, IL-10, MCP-1 and VEGF levels had significant differences between different HER-2 groups. Our study resulted in the identification of a serum cytokine profile with the potential to be clinically applicable to predict disease outcome and in monitoring of efficacy of treatment.