Objective To observe the clinical, mammographic and sonographic features of pure invasive lobular breast carcinoma (ILC), and to explore the value of combined imaging assessment of ILC. Methods Sonographic appearances of 55 patients of ILC were retrospectively reviewed in correlation with mammographic, pathologic and clinical findings, and the causes of false negative were analyzed. Results The main features found in clinical examination were mass (96.15%) and thickening in the size of breast (3.85%). The main mammographic features were spiculated or ill-defined mass (65.38%) and architectural distortion (23.08%). The most common sonographic patterns were mass (98.00%) and distortion (2.00%). The accuracy for detecting ILC of clinical examination, mammography and ultrasonography was 94.55%, 83.87% and 98.04%, respectively, while combining the three modalities, the detection rate increased to 100%. Conclusion Sonography has higher accuracy than mammography in detecting ILC. Combining clinical examination, mammography and ultrasonography can increase the pre-operative diagnostic accuracy of ILC.

Objective To evaluate the inter-observer variability of static breast sonogram final assessment among observers with different breast imaging experience, using the first edition of the Breast Imaging Reporting and Data System(BI-RADS) for ultrasound. Methods Thirty patients with 30 breast lesions were included who underwent beast lesions resection operation. A pathological diagnosis was available for all 30 lesions:16 (53%) malignant and 14 (47%) benign. Twelve radiologists independently reviewed two sonograms of each lesion, and assigned a final BI-RADS assessment category. Inter-observer variability was measured using kappa statistic. Positive predictive value(PPV) and negative predictive value (NPV) for final assessment were also calculated. Results As for the experienced observers,kappa values of categories 3,4 and 5 were 0.72,0.28 and 0.60,NPV of category 3 was 93% ,PPV of category 5 was 97% ,all of which decreased as the breast imaging experience reduced. PPVs of categories 4a,4b and 4c were 56 % ,88% and 69%, respectively. Conclusions Using BI-RADS final assessment, radiologists with sufficient breast imaging experience can provide accurate and consistent assessment for breast ultrasonography,but the agreement of diagnosis decreased as the breast imaging experience reduced. The clinical feasibility of 4a,4b and 4c subcategories is uncertain.

Objective To investigate the role of gray-scale sonography in the diagnosis of thyroid microcarcinoma(TMC).Methods The sonographic characteristics of 58 TMC and 61 benign thyroid nodules(≤1 cm)were retrospectively reviewed and compared with each other.The size,echogenicity,internal solid/cystic component,configuration,anteroposterior to transverse dimension ratio(A/T),margin,halo sign and calcification type of the nodules were studied.Statistical analysis was performed using the chi-square test.The sensitivity,specificity,positive predictive value,negative predictive value and accuracy of individual sonographic characteristics were calculated respectively.Results In ultrasonography,TMC manifested as marked hypoechoic in 48.3%,solid lesion in 98.3%,irregular-shape in 74.1%,irregular halo sign in 37.0%,with internal microcalcifications in 62.1%.There were significantly statistical differences between the benign and malignant nodules in those findings (P＜0.001).However,there was no obviously statistical difference in the obscure margin.The sensitivity,specificity and accuracy were 86.2%,77.0% and 81.5% respectively when using marked internal hypoechoic echo,A/T≥1 and microcalcification as a new combined criterior.Conclusions The gray-scale sonographic findings between the small benign and malignant thyroid nodules(≤1 cm)are different.Combining these sonographic signs can significantly improve diagnostic value of TMC.

Objective To compare diagnostic values of the 2015 American Thyroid Association (ATA) Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer with the thyroid imaging reporting and data system (TI-RADS) for sonographic malignancy risk stratification of thyroid nodules.Methods From November 2011 to December 2015,485 thyroid nodules in 331 patients (mean age,42.9 years± 10.4)were included in this study.Characteristics includingsize,composition,shape(nonparallel or parallel),margin,echogenicity,calcifications and extrathyroidal extension of thyroid nodules were evaluated.Every nodule was stratificated by criteria set by TI-RADS and ATA guidelines,and malignant rate of each risk stratification were calculated and analysed.With pathology as the gold standard,different cutoff were taken to diagnose malignant nodules,and the sensitivity,specifity,positive predictive value,negativepredictive value and accuracy of the two methodologies were calculated at each cutoff.And the two methodologies were evaluated and measured by ROC curve.Finally their Kappa value were calculated at the best cutoff.Results Of the 485 thyroid nodules,96 were benign and 389 were malignant.The malignancy rates under TI-RADS category 2,3,4a,4b,4c,and 5 nodules were 0,12.0％ (3/25),22.2％ (10/45),29.8％ (14/47),99.2％ (261/363) and 100％ (101/101).Malignancy rates under ATA guidelines of benign,very low,low,intermediate,and high suspicion for malignancy were 0,12.5％ (1/8),16.1％ (10/62),27.7％ (13/47),and 99.2％ (365/368).There were significant differences inside each patterns (P ＜ 0.01) respectively and high correlation between risk stratification with TI-RADS (r=0.70) and ATA guidelines (r=0.83).Areas under the ROC curve of the TI-RADS and ATA guidelines classifications were 0.966 and 0.959.Best cut-off point for diagnosing malignant by TI-RADS and ATA guideline classifications were ≥ 4c and ≥ high suspicion,and at that point,diagnostic value of TI-RADS and ATA guidelines were nearly the same(sensitivity,93.1％vs 93.8％;specificity,97.9％ vs 96.9％;PPV,99.5％ vs 99.2％;NPV,75.7％vs 79.5％;and accuracy,94.0％vs94.4％),and there was no significant differences (P=0.50,P=0.50,P=0.50,P=0.53,P=0.55),Kappa=0.97.Conclusions Both TI-RADS and the ATA guidelinesprovide effective malignancy risk stratification for thyroid nodules.The diagnosticvalue of TI-RADS when considering ≥ 4c and ATA guidelines when considering ≥ high-suspicion nodules as malignant were nearly the same and both high.

Objective To investigate the neurodevelopmental toxicity of ACR by studying the expression of DCX and GAP-43 in the hippocampal dentate gyrus of rats after maternal exposure to acrylamide. Methods Pregnant rats were randomly divided into low-dose ACR(4.5 mg/kg),medium-dose(9 mg/kg),high dose groups(18 mg/kg)and the control group(0 mg/kg),8 in each group,and were exposed to toxicant from gestation-al day 15 to postnatal day 13. All rats and their pups were killed on postnatal day 14. ABC immunohistochemistry was used to detect the expression of GFAP in the hippocampus of mother rats and offspring. Results Compared with the control group,the expression of DCX and GAP-43 in hippocampus dentate gyrus of the pregnant rats in middle and high dose groups was significantly decreased(P < 0.05). Conclusion ACR may interfere with the growth and development of neurons by reducing the expression of DCX and GAP-43.

Objective To study the correlation between the sonographic features of papillary thyroid microcarcinoma (PTMC) and high volume lymph node metastasis. Methods Medical records of 463 PTMC patients were reviewed. Cases of all patients are completed with lymph node metastasis identified by histopathology. Sonographic features such as lesion number, lesion size, echogenicity, calcification, envelope and vascularity of papillary microcarcinoma are recorded. Univariate and multivariate analysis was performed to investigating relationship between sonographic features and high volume lymph node metastasis. Results Twenty four patients have high volume central lymph node metastasis (5.2%, 24/463), in univariate analysis,sex(11.2% in male vs 3.4% in female),age(8.3% in<45 years vs 2.4% in≥45 years),calcification(8.3% in micro vs 0.0% in coarse, 3.2% in mixed and 0.7% in non) , extracapsular invasion (9.3% with vs 3.2% without)and size(9.2% in ≥7 mm vs 2.5% in <7 mm)showed significant difference;multiple logistic regression analysis showed that male(OR=3.205,P=0.009),age<45 years(OR=2.923,P=0.031), microcalcification(OR=9.380,P=0.031)and tumor size≥7mm(OR=3.272,P=0.013)is independent risk factor for high volume lymph node metastasis in the central compartment of PTMC. 10 patients have high volume lateral lymph node metastasis(2.2%,10/463),in univariate analysis,age(4.1% in<45 years vs 0.4% in≥45 years),number of lesions(5.3% in multiple vs 0.9% in single)showed significant difference;multiple logistic regression analysis showed that age < 45 years (OR=11.939,P=0.024) and multiple lesion (OR=7.247, P=0.007) is independent risk factor for high volume lymph node metastasis in the lateral compartment of PTMC. Conclusion Sonographic features of primary papillary microcarcinoma of the thyroid has correlation with high volume lymph node metastasis.

ObjectiveTo observe the clinical efficacy and safety of treating mediate-risk pure ground glass pulmonary nodules （pGGNs） based on the state theory. MethodsA prospective clinical randomized controlled trial was used. Totally 141 cases of mediate-risk pGGNs were divided into treatment group （92 cases） and control group （49 cases） according to the random table method. The treatment group was given the basic Sanjie Formula （基础散结方） orally with modification according to the identification of traditional Chinese medicine （TCM） state， 1 dose per day， 3 months as a course of treatment.Three months after the treatment patients were checked by CT. Patients who were clinically judged as cure， moderate to low risk， and turned to surgical resection do not carry out a second course of treatment，and the rest of the patients continued to complete the second courses. Patients in the control group did not receive any treatment and were only followed up periodically. Patients in both groups received a CT review 3 months and 6 months after enrolled. Comprehensive curative effect was evaluated according to the reduction rate of the area of pulmonary nodules shown in chest CT， to further explore the clinical effective difference for patients at different TCM state； the risk of malignancy index （Mayo score） was calculated by Mayo model at enrollment and 3 months and 6 months after enrolled. Adverse events were monitored continuously during the study. ResultsDuring the follow-up， 8 cases in the treatment group and 7 cases in the control group were lost. A total of 126 cases completed the whole process， including 84 cases in the treatment group and 42 cases in the control group. The total effective rates at 3 months and 6 months of the treatment group were 46.15% （30/65） and 45.71% （32/70） in the treatment group， while the total effective rates at 3 months and 6 months in the control group were 12.5% （4/32） and 10.00% （4/40）. Compared with the control group， the comprehensive curative effect of 3 months and 6 months of enrollment in treatment group was significantly better than that in corresponding control group （P＜0.01）. The pulmonary nodule area and Mayo score in the treatment group decreased after 3 and 6 months of enrollment （P＜0.01）. In contrast， there was no statistically significant difference in nodule area between pre- and post-enrollment time points in the control group （P＞0.05）， and probability of Mayo risk increased in the control group after 6 months of enrollment compared to pre-enrollment （P＜0.05）. Among the 84 patients in the treatment group， there were 15 cases of qi deficiency state， 7 cases of yin deficiency state， 5 cases of yang deficiency state， 20 cases of qi depression state， 32 cases of damp-heat state， and 5 cases of harmonious state； the difference in the distribution of the total clinical effective rate of the patients with different TCM states after treatment was statistically significant （P＜0.05）， and the total effective rate of two-by-two comparison of qi depression state was higher （13/20，65.00%） than that of the total effective rate of damp-heat state （8/32，25.00%， P＜0.00833）. There were no significant changes in blood routine， urine routine， liver function and kidney function in both groups， and no adverse events occurred. ConclusionTreating mediate-risk pGGNs based on the state theory can effectively reduce the area of pulmonary nodules and inhibit the growth of malignant risk of pulmonary nodules.

Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) is one of important kinases in inflammation to phosphorylate inhibitor of nuclear factor kappa-B (IκBα) and then activate nuclear factor kappa-B (NF-κB). Inhibition of IKKβ has been a therapeutic strategy for inflammatory and autoimmune diseases. Here we report that IKKβ is constitutively activated in healthy donors and healthy Ikkβ ^C46A (cysteine 46 mutated to alanine) knock-in mice although they possess intensive IKKβ-IκBα-NF-κB signaling activation. These indicate that IKKβ activation probably plays homeostatic role instead of causing inflammation. Compared to Ikkβ ^WT littermates, lipopolysaccharides (LPS) could induce high mortality rate in Ikkβ ^C46A mice which is correlated to breaking the homeostasis by intensively activating p-IκBα-NF-κB signaling and inhibiting phosphorylation of 5' adenosine monophosphate-activated protein kinase (p-AMPK) expression. We then demonstrated that IKKβ kinase domain (KD) phosphorylates AMPKα1 via interacting with residues Thr183, Ser184, and Thr388, while IKKβ helix-loop-helix motifs is essential to phosphorylate IκBα according to the previous reports. Kinase assay further demonstrated that IKKβ simultaneously catalyzes phosphorylation of AMPK and IκBα to mediate homeostasis. Accordingly, activation of AMPK rather than inhibition of IKKβ could substantially rescue LPS-induced mortality in Ikkβ ^C46A mice by rebuilding the homeostasis. We conclude that IKKβ activates AMPK to restrict inflammation and IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα.