Reduction of inflammation response and transition of M1 toward M2 phenotypes of macrophages in response to SiO2 challenge by inhibition of TLR4 / 环境与职业医学

Background The mechanisms of silicon dioxide (SiO2)-induced inflammation and cell injury in pulmonary macrophages are not fully characterized. Objective To investigate the potential roles of inhibition of toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling in inflammation and macrophage polarization in mouse Raw264.7 cells in response to SiO2 stimulation. Methods Sixteen 6- to 8-week-old C57BL/6 mice, half male and half female, were intratracheally instilled with 50 µL of SiO2 (50 mg·mL−1 in saline) or normal saline via oropharyngeal route, and the lungs of mice were harvested at 14 d and 28 d post the first challenge of SiO2. HE staining of mouse lung was used for histopathological analysis. The expressions of TLR4 signaling-related proteins were detected by Western blotting (WB) and immunofluorescent (IF) assay, including TLR4, myeloid differentiation factor 88 (Myd88), and TNF receptor associated factor 6 (TRAF6). Raw264.7 cells were stimulated with SiO2 (100 μg·cm2) for 12 h in absence or presence of TLR4 inhibitor M62812 for 13 h before the culture supernatants and cell lysates were harvested for analysis. The expressions of key components of TLR4 signaling cascade including TLR4, Myd88, and phosphorylated nuclear factor-kappa B P65 (P-NF-κB P65), P-1NF-kappa-B inhibitor α (P-1κbα), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), M1 phenotype markers inducible nitric oxide synthase (iNOS) and cluster of differentiation 86 (CD86), as well as M2 phenotype arginase-1 (Arg-1) were accessed by WB and IF. The expressions of inflammation factors IL-6 and TNF-α in supernatants were determined by enzyme-linked immunosorbent assay (ELISA). Results After SiO2 intratracheal instillation for 14 d, the HE staining results showed obvious fibrotic nodules in the lung tissues of mice. The results of WB analysis revealed more abundant TLR4, Myd88, and TRAF6 in the silicosis mouse lung samples than in the controls. The results of IF assay showed an increased abundance of TLR4 and Myd88 proteins in the lung samples of silicosis mice at 14 d post the silica challenge, compared to the controls, indicating TLR4 signaling activation. As seen in the in vitro experiment, significant upregulations after the exposure to 100 μg·cm2 SiO2 were observed in TLR4 and P-1κbα at 6, 12, and 24 h (P<0.05); Myd88 at 12 and 24 h (P <0.05); and P-NF-κB P65 at 12 h (P<0.05). The inhibitor significantly suppressed the expressions of TLR4, Myd88, TRAF6, P-NF-κB P65, TNF-α, and IL-6 in Raw264.7 cells. In addition, the SiO2-induced M1 phenotype marker iNOS was significantly suppressed, but the M2 phenotype marker Arg-1 was increased in the Raw264.7 cells. Conclusion The inhibition of TLR4/NF-κB signaling could result in a reduction of the inflammation response and the transition of M1 toward M2 phenotypes of macrophages in response to SiO2 challenge.

Elastosonography and Routine Ultrasonography in Diagnosis of Thyroid Nodules:A Meta-analysis / 中国医学影像学杂志

Purpose Meta-analysis was performed to compare elastosonography and routine ultrasonography in the diagnosis of thyroid nodules. Materials and Methods Extensive literature search of CNKI, Wanfang data, OVID, the Cochrane Library, PubMed and Embase from 1980 to 2013 was performed using elastosonography, ultrasonography and thyroid nodules as key words. Clinical trials utilizing elastosonograpy and routine ultrasonography were selected. The quality and heterogeneity were evaluated. Specificity and specificity were summarized to generate receiver operating characteristic curves. Results Fourteen studies were selected including 10 literature in Chinese and 4 in English. There was significant heterogeneity in the sensitivity. The sensitivity for routine ultrasound, elastosonography and two techniques combined was 0.82 (95%CI 0.79-0.85), 0.61 (95%CI 0.57-0.64) and 0.93 (95%CI 0.90-0.95), respectively;with specificity of 0.70 (95%CI 0.68-0.72), 0.84 (95%CI 0.82-0.86) and 0.69 (95%CI 0.67-0.72). The summery area under curve was 0.8549, 0.8925 and 0.9614, respectively. Conclusion Evaluation of thyroid nodules using elastosonography is more sensitive and specific than routine ultrasonography. Combining elastosonography and routine ultrasonography provides better diagnostic accuracy.

Value of contrast-enhanced ultrasound in the evaluation of neoadjuvant chemotherapy for breast cancer / 中华超声影像学杂志

Objective To explore the application value of contrast-enhanced ultrasound(CEUS) in evaluating the effect of neoadjuvant chemotherapy(NAC) on breast cancer.Methods Image features of 80 breast cancer patients with neoadjuvant chemotherapy were observed and analyzed by CEUS.In the process,the changes of primary foci before and after neoadjuvant chemotherapy and the changes of qualitative and quantitative indexes of blood perfusion were evaluated.The correlation between qualitative change and pathological response was also studied.Results The change of focus size measured by CEUS was higher than that of conventional ultrasound before and after neoadjuvant chemotherapy(P ＜0.05).However,there was no significant difference between the two measurements before NAC(P ＞ 0.05).All the qualitative observation indexes of the ultrasound contrast after NAC revealed obviously benign conversion(P ＜0.05).Among them,the pathological response was closely related to the changes of the enhancement degree,the distribution of the contrast agent,the order of the contrast and the contrast mode.After NAC,the perfusion parameters of the lesions showed slowly crawl and slowly retreat,low enhancement and the diminished total amount of microcirculation perfusion.Conclusions Before and after neoadjuvant chemotherapy,the changes of the lesion size deteted by CEUS were more close to the pathological evaluation than those detected by conventional ultrasound.The benign outcome of qualitative and quantitative indexes of the CEUS was more obvious than the changes of the lesion size,which had practical value for guiding the neoadjuvant chemotherapy for breast cancer,especially the CEUS indexes related to pathological assessment.

Relationship between perfusion defect and contrast-enhanced ultrasound features,clinical pathological parameters of breast cancers / 中华超声影像学杂志

Objective To study the ultrasonic imaging of breast cancer with or without filling defect with contrast-enhanced ultrasound and clinical pathologic correlation.Methods The suspicious breast lesions underwent contrast-enhanced ultrasound examination, the imaging of 1 1 9 breast cancer with pathological results were retrospectively analyzed,and the contrast enhanced ultrasound effect,distribution of contrast agent,sequence of contrast agent into the tumor,contrast enhanced ultrasound mode,perforator vessel,filling defect and flow classification were observed.Then clinical and pathological data were collected including the tumor size,clinical stage,pathological grade and the situation of micro calcification.The perfusion defect as the grouping factor,there were 37 cases of perfusion defect and 82 cases without perfusion defect.A mono-pactor and multi factor analysis was performed by the logistic regression models to the relationship between perfusion defect and contrast-enhanced ultrasonography,clinical pathological parameters.Results Both mono factor and multifactor analysis displayed that whether to display the filling defect in contrast enhanced ultrasound was associated with ultrasound contrast distribution,the sequence of contrast agent into the tumor and histological grade(χ2=19.5050,21.1210,10.3640,OR =6.977,0.261, 2.509,all P <0.05).Multivariate analysis showed that tumor size and whether to display the filling defect in contrast enhanced ultrasound were close(OR =1.692,P <0.05).Clinical stage,whether the blood flow signal penetrates was meaningful in univariate analysis but excluded in multivariate analysis.Both mono factor and multifactor analysis displayed that contrast enhanced ultrasound mode,contrast enhanced ultrasound effect,flow classification and pathological micro calcification were not associated with whether to display the filling defect.Conclusions Whether to display the filling defect and the related factors of contrast-enhanced ultrasound in diagnosis of benign and malignant were not completely consistent.Breast cancers with filling defects of contrast-enhanced ultrasound tend to present large masses,contrast agent distribution of peripheral enhancement,centripetal filling of ultrasound contrast agents and the higer histological grading.

The correlation between lesion size and contrast-enhanced ultrasound in breast cancer / 中华超声影像学杂志

Objective To investigate whether there are differences of the characteristics of the contrast‐enhanced ultrasound among breast cancer vary in size .Methods The contrast‐enhanced ultrasound perfusion mode were retrospectively analyzed in 113 cases of breast cancer patients with 119 lesions .They were divided into two groups according to the maximum diameter of the lesion based on ultrasound measured ,one group (≤2 0. cm ) 47 cases ,the other group (> 2 0. cm ) 72 cases .The characteristics and mode of contrast‐enhanced ultrasound of the lesion were analyzed ,including whether is greater than the two‐dimensional ultrasound in enhanced range ,enhanced strength ,the distribution of the contrast agent ,contrast agent perfusion sequence in lesions ,contrast mode ,and the existence of perforator vessels and perfusion defects .Results Enhanced strength ,the existence of perforator vessels and perfusion defects associated with the size of the lesions .The breast cancer lesions more than 20 cm were apt to higher enhance strength ,the presence of perfusion defects ,perforator vessels ( P 0 0.5) .Regardless of breast lesions size ,the enhanced range tended to larger than two‐dimensional ultrasound range ,and contrast‐enhanced ultrasound present inhomogeneous ,centrality and integrity filling and perfusion mode of quickly rising and falling .Conclusions Within breast tumor angiogenesis is gradual .With the increase of tumor volume ,more significant vascular heterogeneity ,breast cancer lesion are more prone to uneven high perfusion ,accompanied by perfusion defects and perforating vessels ,but the main sign of differentiating benign and malignant showed consistency between different sized lumps in breast cancer ,which included whether or not contrast mode and enhanced range greater than two‐dimensional ultrasonic range .

The expressions of decoy receptors of TRAIL in carcinoma of endometrium / 医学研究生学报

Objectives:To determine the expressions of decoy receptors (DcR1 and DcR2) of TRAIL in carcinoma of endometrium. Methods:The expressions of DcR1 and DcR2 in endometrium tissues from 13 carcinoma of endometrium and 7 normal endometrium were detected by immunohistochemical staining.Results: The expressions of DcR1 and DcR2 in carcinoma of endometrium were much lower than in normal endometrium. Conclusions:The decreasing of DcR1 and DcR2 in carcinoma of endometrium may be concerned with its pathogenesis, which may be related to the prevention of endometrium from carcinomatous change.

Review of Cutaneous Malignant Melanoma from Two General Hospitals in Western China, 1981-2000 / 中华皮肤科杂志

Objective To review the clinical-pathological features, the tendency of incidence over 20 years, the predisposing factors, and the differences between the cases of cutaneous malignant melanoma from two hospitals. Methods A collection of 305 cases diagnosed as cutaneous malignant melanoma, among which 185 cases had complete clinical-pathological data, during 1981-2000 was analyzed. Results Acral malignant melanoma accounted for 63.3%, and the cases associated with congenital small nevi at the primary site accounted for 15.8% of 305 patients. During the period 1981-1990 and 1991-2000, cutaneous malignant melanoma constituted 0.053% and 0.094%, respectively, of all diagnoses with pathological sections, with an growth rate of 3.9% yearly. There was a tendency of the increased lesions located on face and neck, and decreased lesions on acra, over 20 years. Conclusion A rise of diagnosis of cutaneous malignant melanoma has been noticed from two hospitals over 20 years. Acra, especially planta, is the predominant anatomical site of cutaneous malignant melanoma.

Effects of zanthoxylum seed oil_(A2) on NF-?B signaling pathway and inflammatory factor in lung tissue of asthmatic mice / 中国病理生理杂志

AIM: To investigate the dynamic influence of zanthoxylum seed oilA2(ZSOA2) on NF-?B signaling pathway and inflammatory factor in pulmonary tissue of asthmatic mice.METHODS: The suspensoid(0.2 mL containing 20% albumin hydroxide and 10% ovalbumin) was administered by intraperitoneal injection to sensitize the BALB/c mice on day 1,then 0.4% ovalbumin solution(50 ?L in phosphate buffer fluid) was dripped into the respiratory tract through nasal cavity to establish the asthmatic mouse model.After dripped ovalbumin for 24 h,48 h,3 d,7 d and 14 d,the mice were killed at specified time points.The contents of interleukin-4(IL-4),interleukin-5(IL-5) and interferon-?(IFN-?) in bronchoalveolar lavage fluid(BALF) were determined by ELISA.The pathological changes of the lung tissues were observed with HE staining.The inflammatory cell counts were conducted by Eosin staining.The protein levels of adhesion molecule and the molecules of NF-?B signaling pathway in lung tissues were determined by Western blotting.RESULTS: In ZSOA2 treated mice,the pathological injury of the lung was significantly attenuated as compared to the model mice,the counts of eosinophils and lymphocytes were reduced obviously in lung bronchial area of asthmatic mice at all observed time points(P