A case of pseudomyogenic hemangioendothelioma misdiagnosed as low-grade malignant fibrous histiocytoma and review of literature / 中南大学学报(医学版)

Pseudomyogenic hemangioendothelioma (PHE) is a rare angiogenic tumor. Histologically, the morphological characteristics of neoplastic vessels and endothelial differentiation are not obvious, and it is easy to be confused with epithelioid sarcoma, epithelioid hemangioendothelioma and myogenic tumor. PHE usually occurs in arms and legs in young people and has a significant male predominance. The tumor has a predilection for the distal extremities and its typical manifestation is multiple center invasion of a single limb, which can involve all layers of skin and subcutaneous tissues,and is often accompanied by abvious pain. Histologically, PHE is characterized by infiltrative growth of tumor. Most tumor lesions are composed of sheets and loose fascicles of plump spindle or epithelioid cells within a background of variably prominent inflammatory infiltration, which was commonly composed of neutrophils. Some cells may resemble rhabdomyoblasts, and nuclear atypia and mitosis were rare. The tumor cells generally expressed positive cytokeratin (CK), ETS-related gene (ERG), Friend leukemia virus integration 1 (FLI1) and integrase interactor 1(INI1). In some cases, the tumor cells expressed CD31. A case of a young woman was reported in this paper, who presented with a subcutaneous mass with severe pain and was chronologically misdiagnosed with herpes zoster, low-grade malignant fibrous histiocytoma and epithelioid hemangioendothelioma. In this study, the clinical and pathological features, differential diagnosis and the latest progress in therapy of PHE were analyzed based on relevant literature.

Consistency of ALK Ventana-D5F3 immunohistochemistry interpretation in lung adenocarcinoma among Chinese histopathologists / 中华病理学杂志

Objective@#To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy.@*Methods@#This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS.@*Results@#There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109).@*Conclusion@#There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.

Difference of silicon dioxide-stimulated macrophage-derived exosomal miRNA expression profile / 中南大学学报(医学版)

To analyze the differential expression of RAW264.7 macrophage-derived exosomes miRNA stimulated by free silicon dioxide (SiO2).
 Methods: RAW264.7 was stimulated with SiO2 (200 mg/L) for 48 h (exo_48 h group), and the supernatant was collected. The exosomes in the supernatant were extracted by ultracentrifugation. Transmission microscopy, nanoparticle tracking analysis (NTA) and Western blotting were used to identify exosomes. High-throughput sequencing was performed to compare the differential expression of exosome miRNAs between the exo_control group (RAW264.7 cultured for 48 h without SiO2) and the exo_48 h group; miRanda, TargetScan and starBase were used to predict target genes of differential miRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed on target genes to further analyze the biological functions of genes.
 Results: The transmission microscopy showed that the exosomes were lipid membrane coated vesicles, which were heterogeneously distributed, with a diameter ranging from 30 to 100 nm, and the shape was round or elliptical. The volume kurtosis was concentrated between 40 and 100 nm and the exosome marker protein TSG101 was positive. High-throughput sequencing screened 148 differentially expressed exosomal miRNAs. MiR-219c-3p, let-7d-3p, let-7a-1-3p, miR-328-3p, miR-365-3p, and miR-7219-3p were significantly up-regulated, and miR-378d and miR-5106 were significantly down-regulated compared with the control group. Target genes were mainly enriched in mTOR signaling pathway, Wnt signaling pathway, TGF-β signaling pathway, and so on.
 Conclusion: The exosomes secreted by SiO2-induced macrophages contain abundant miRNAs, and their expressions are significantly different. These differential miRNAs may be involved in the activation of lung fibroblasts and epithelial-mesenchymal transition.

Discovery of novel protein biomarkers in early silicosis by proteomics and identification of alpha B-crystallin / 中南大学学报(医学版)

OBJECTIVE@#To establish 2-dimensional gel electrophoresis (2-DE) image for the early lung injury rats induced by silica dioxide and to identify differentially expressed protein biomarkers during the early stage of silicosis.
@*METHODS@#The animal models of silicosis were established and morphology changes were observed by HE staining, and then the key protein biomarkers in silicosis were identified by 2-DE and matrix-assisted laser desorption/ionization time of flight tandem mass spectrometry (MALDI-TOF-MS) and verified by Western blot.
@*RESULTS@#The well qualified 2-DE gel images for experimental and control lung tissues were successfully established, and 40 different protein spots was observed when comparing the gel images between the experimental and control groups. Twenty of them were analyzed by MALDI-TOF-MS. A total of 13 altered proteins were identified, including alpha B-crystallin, mast cell protease 6, annexin 1, etc. The expression of alpha B-crystallin in lung was further verified by Western blot.
@*CONCLUSION@#The protein expression of alpha B-crystallin was increased significantly, suggesting that it might play an important role in the progress of silicosis.

Manual reduction for external fixation of distal radius fractures / 中国组织工程研究

BACKGROUND:Manual reduction for external fixation of distal radius fractures can achieve good outcomes. OBJECTIVE:To carry out the bibliometric analysis on manual reduction for external fixation of distal radius fractures. METHODS:Literatures concerning reduction for external fixation of distal radius fractures were retrieved in CNKI database from 2003 to 2012. The keywords were“external fixation;distal radius fractures”. Duplicate and irrelevant articles were eliminated, and a total of 408 articles were retrieved. A bibliometric analysis of these 408 articles was performed in terms of publishing time and number, subject categories, source journals, research institutions, times cited and download frequency. RESULTS AND CONCLUSION:Literatures concerning manual reduction for external fixation of distal radius fractures exhibit an upward trend in number. In 2012, there were 85 relevant articles. In the past 10 years, 18 relevant articles have been published in Chinese Journal of Traditional Medical Traumatology&Orthopedics, which is the most. There are not many relevant studies in various research units, only 1-7 articles published per unit, and five articles are funded.

Changes of TGF-β1 and CTGF in rats with increased blood flow-induced pulmonary artery hypertension / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the role of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) in the pathogenesis of pulmonary artery hypertension, we observed the dynamic expression of TGF-β1 and CTGF in rats with high blood flow.@*METHODS@#Fifty adult male SD rats were randomly divided into 5 groups: a sham group (group S) and groups with right pneumonectomy for 1, 2, 4 and 6 weeks (PE1, PE2, PE4 and PE6 group), 10 rats per group. The mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were measured. TGF-β1 and CTGF protein expression in the lung tissues were determined with immunohistochemistry and Western blot. The expression of TGF-β1 mRNA and CTGF mRNA in the lung tissues was evaluated by RT-PCR.@*RESULTS@#Compared with group S, the mPAP and RVHI in the rats were significantly increased in group PE1, PE2, PE4, and PE6 (P<0.05); the indicators of vascular remodeling [(MA+PMA)%, RMT, and RMA] were markedly elevated in group PE4 and PE6 (P<0.05), but not in group PE1 and PE2. Immunohistochemical staining of TGF-β1 and CTGF were more prominent in all of the right pneumonectomy groups than in the sham group. Western blot showed that the level of TGF-β1 protein was significantly increased in all of the right pneumonectomy groups (P<0.01), and the peak was observed in group PE2, whereas the level of CTGF protein was markedly elevated in group PE4 and PE6 (P<0.05), but no change was noticed in group PE1 and PE2. Compare to group S, the mRNA level of TGF-β1 was dramatically increased in all right pneumonectomy groups (P<0.01), peaked at group PE2, and remained high in group PE4 and PE6. In contrast, the elevation of mRNA level of CTGF was not significant in group PE1, but group PE2, PE4 and PE6 demonstrated significant mRNA level of CTGF (P<0.01). Correlation analysis showed that the protein and mRNA levels of CTGF were positively correlated with RMT and RMA ( r=0.743, r=0.906; P<0.05), while no correlation between the protein and mRNA level of TGF-β1 with RMT or RMA. There was no correlation between the mRNA level of TGF-β1 and CTGF.@*CONCLUSION@#TGF-β1 and CTGF play a role in the pathogenesis of increased pulmonary blood flow-induced pulmonary hypertension.

ERK signaling pathway mediated epithelial-mesenchymal transition induced by SiO₂ in human bronchial epithelial cells / 中南大学学报(医学版)

OBJECTIVE@#To determine the role of extracellular signal regulated kinase (ERK) signaling pathway in SiO₂ induced epithelial-mesenchymal transition (EMT) in human bronchial epithelial cells (HBEC) in vitro.@*METHODS@#HBEC were treated with SiO₂ (0-300 μg/mL) for 72 h or pretreated with U0126 (0-30 μmol/L) for 1 h and then treated with 200 μg/mL SiO₂ for 72 h. Western blot was used to detect the protein expression of E-cadherin and α-smooth muscle actin (α-SMA). The activity of ERK was examined by mitogen-activated protein kinase (MAPK) activity assay kit in HBEC exposing to SiO₂ (200 μg/mL) for 0-8 h.@*RESULTS@#The expression of E-cadherin decreased gradually in SiO₂ -stimulated HBEC, and the effect was most significant at 300 μg/mL (P<0.01). The expression of α-SMA increased and the effect was most evident at 200 μg/mL (P<0.01). With SiO₂ treatment, the activity of ERK was upregulated significantly. The phosphorylation of ERK increased at 30 min and decreased after 1 h. U0126 significantly inhibited SiO₂ -induced expression changes in E-cadherin and α-SMA. At 30 μmol/L, the effect was most evident(P<0.01).@*CONCLUSION@#ERK signaling pathway mediated EMT induced by SiO₂ in HBEC.

Effect of Rho signaling pathway on SiO2 induced α-SMA expression in human bronchial epithelial cells / 中南大学学报(医学版)

Objective To investigate the role of Rho in SiO2 induced α-SMA expression in human bronchial epithelial cells (HBECs). Methods HBECs were cultured and stimulated with SiO2. Immunocytochemistry and Western blot were used to detect the expression of α-SMA. The activity of Rho was determined by GST pull down assay. In the prevention experiment,SiO2-stimulated HBECs were incubated with Rho inhibitor Y27632,and the expression of α-SMA was examined by Western blot. Results With SiO2 (0-300 μg/mL) treatment,the expression of α-SMA increased gradually,and 200 μg/mL of SiO2 led to the highest expression of α-SMA which was (5.09±1.98) times of the expression of α-SMA in the control group(P＜0.01). HBECs treated with SiO2 (200 μg/mL) for indicated time (1,2,6,12,and 24 h)showed an obvious increase of Rho activity(P＜0.01). Y27632 inhibited SiO2-induced α-SMA expression significantly,and the inhibition rate of 20 and 30 μmol/L Y27632 was 68% and 75%,respectively (P＜0.01).Conclusion Rho signaling pathway may mediate SiO2 induced α-SMA expression in HBECs.

The Exploration and Practice on Open Experimental Teaching of Pathology / 中华医学教育探索杂志

Experimental teaching plays an important role in pathological teaching.We have taken effective measures to renovate the methods for experimental teaching,establishing open teaching mode.As a result,teaching quality increases and students become more active in pathological learning.