Interpretation of BRAF gene mutation detection by real-time PCR: a study of 8 644 thyroid fine-needle aspiration specimens / 中华病理学杂志

Objective@#To study common problems in BRAF gene mutation detection, and conditions for repetition testing using thyroid fine needle aspiration specimens.@*Methods@#A total of 8 644 cases of thyroid fine-needle aspiration specimens at China-Japan Friendship Hospital were collected between February, 2012 and July, 2018. BRAF gene mutation was detected by real-time PCR. Repeat testing was performed in 237 cases when the results were inconsistent with clinical or cytological diagnosis or when uncertain results were obtained.@*Results@#The final positive rates of BRAF mutation was 22.0% (1 897/8 625). Nineteen cases were excluded due to inadequate DNA samples. The average Ct value of internal quality control was 16.061, and the average Ct value of the positive samples was 19.147. Among 237 repeat tests, 51.4% (19/37) continued to have poor DNA quality and 48.6% (18/37) had adequate DNA resulting in 1 positive case and 17 negative cases. In 40 repetition of initial negative cases, results were unchanged. In initial positive cases, 40.4% (40/99) with a difference of Ct value (between BRAF gene and internal quality control) between 8 to 12 turned negative after repetition, 69.8% (37/53) of these cases with a difference of more than 12 turned negative after repetition. The sensitivity and specificity of BRAF mutation were 83.97% and 96.94%, respectively.@*Conclusions@#Difference between BRAF gene Ct value and internal quality control Ct value is recommended as a reliability index for the test result. Cases with a difference greater than 8 should be subjected to repeat testing.

Clinicopathologic features of atypical type A thymoma / 中华病理学杂志

Objective@#To study the clinicopathologic features, immunophenotype and differential diagnosis of atypical type A thymoma.@*Methods@#Clinicopathologic and follow-up data of three cases of atypical type A thymoma from 2004 to 2016 were reviewed. Immunohistochemical staining was performed.@*Results@#All three patients were male with average age of 59 years. Clinically, the lesions presented as anterior mediastinal masses. Grossly, the tumor ranged in size from 4 to 6 cm in greatest dimension and partially enclosed within fibrous capsule. The cut surface was homogenously fleshy, tan to brown in color, with multinodular and lobulated configurations. Cystic changes and necrosis were seen. Microscopically, the tumor was composed of plump spindle or oval-shaped cells arranged in storiform, microcystic, glandular, rosettes-like and hemangiopericytoma-like histological patterns. The tumor cells showed mild cytological atypia and mitotic activity ranged from 4 to 5/10HPF. Necrosis was present in all tumors. All tumors showed diffuse CK(AE1/AE3), CK19, p63 and vimentin expression. TdT, CK20, CD20, CD5 and CD117 were negative. The proliferative index, as measured with Ki-67, was 15.2% to 26.4%. None of the cases had recurrence or metastases during the follow-up period (9 to 27 months).@*Conclusions@#Atypical type A thymoma presents atypical features including tumor necrosis and increased mitotic activity. However, the implications of such atypical features to the biological behavior of the tumor remain to be determined.

Diagnosis value of TTF-1, Napsin A and Ki-67 index in primary salivary gland-type lung carcinomas / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic characteristics of primary salivary gland-type lung carcinomas, and the immunophenotypic value of TTF-1, Napsin A and Ki-67 in their differential diagnosis.</p><p><b>METHODS</b>Totally 48 special type lung cancer surgical removal specimens were collected in China-Japan Friendship Hospital during September 2009 to December 2014. A panel of immunohistochemical markers (TTF-1, Napsin A, Ki-67, CK5/6, CK7 and p63) were conducted on these specimens.</p><p><b>RESULTS</b>The 48 cases of special type lung cancer included 25 cases of primary salivary gland-type lung carcinoma (18 cases of adenoid cystic carcinoma and 7 cases of mucoepidermoid carcinoma), 5 cases pulmonary adenocarcinoma with mucoepidermoid carcinoma-like or adenoid cystic carcinoma-like structure, and 18 cases of pulmonary adenosquamous carcinoma. Compared with pulmonary adenocarcinoma with mucoepidermoid carcinoma-like or adenoid cystic carcinoma-like structure and pulmonary adenosquamous carcinoma, primary salivary gland-type lung carcinomas have special characteristics in median age, sex, location, tumor size, LN involvement and pleura invasion, with negative TTF-1 and Napsin A expression as well as lower Ki-67 index detected by immunohistochemistry. Primary salivary gland-type lung carcinomas usually have an indolent behavior.</p><p><b>CONCLUSIONS</b>Primary salivary gland-type lung carcinomas are low-aggressive entities. The origins of primary salivary gland-type lung carcinomas were different from that of pulmonary adenocarcinoma with mucoepidermoid carcinoma-like or adenoid cystic carcinoma-like structure and pulmonary adenosquamous carcinoma. Negative TTF-1 and Napsin A expression as well as Ki-67 index lower than 20% have special value for primary salivary gland-type lung carcinomas in their differential diagnosis.</p>

Effects of Wenjing Tongluo Formula on GFAP Level in Perpheral Neuropathy Rats / 中国中医药信息杂志

Objective To discuss the treatment action and mechanism of Wenjing Tongluo Formula on oxaliplatin-induced perpheral neurotoxicity in rats. Methods Intraperitoneal injection was used to inject oxaliplatin 4 mg/kg to establish oxaliplatin-induced peripheral neurotoxicity rat models. Female Wistar rats were randomly divided into normal group, model group, and TCM group. TCM group was given Wenjing Tongluo Formula to soak rats’ limbs and tails. Rats in the model group were soaked with deionized water for comparison. Rats in the normal group received intraperitoneal injection with 5%glucose. Algesia hypersensitivity and anaphylaxis were detected under the mechanical stimulation and temperature. Immunohistochemical method was used to detect the expression of GFAP in L4-L6 spinal dorsal horn of rats. Explore the level of GLT-1 in L4-L6 dorsal root ganglia by RT-PCR. Results Rats in model group showed obvious behavioral changes compared with normal group (P<0.05);Rats in the TCM group improved in behavioristics compared with model group (P<0.01);number of positive cells in GFAP of rats in the model group increased compared with normal group (P<0.05);the increase in the TCM group was not obvious. Compared with normal group, astrocytes in spinal dorsal horn of model group were enlarged, protuberances increased, became coarse, and GLT-1 mRNA is decreased (P<0.05, P<0.01). Compared with model group, active cells and protuberances in the TCM group decreased (P<0.01), GLT-1 mRNA is increased (P<0.01). Conclusion Wenjing Tongluo Formula can improve behavioral changes of model rats under temperature and mechanical stimulation, probably related to harmful signal transmission induced by inhibition of astrocyte in spinal dorsal horn.

The prognostic impact of preoperative PET-CT on postoperative recurrence for completely resected stage I non-small cell lung cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the prognostic impact of preoperative (18)F-fluorodeoxyglucose (FDG) PET-CT on postoperative recurrence in patients with completely resected stage I non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>The clinic data of 182 patients with stage I NSCLC who underwent (18)F-FDG PET-CT scan before surgical resection between June 2005 and June 2012 were reviewed retrospectively. There were 121 male and 61 female patients, with an average age of 68 years (range from 34 to 85 years). The pathological stage was I A in 98 patients, I B in 84 patients; the histology were adenocarcinoma in 137 patients, squamous cell carcinoma in 35 patients, and others in 10 patients. Clinicopathological factors including gender, age, smoking history, SUV(max), surgical procedure, pathological features and adjuvant chemotherapy were evaluated to identify the independent factors predicting postoperative recurrences by univariate and multivariate analysis. The survivals were calculated by the Kaplan-Meier method and differences in variables were analyzed by the Log-rank test.</p><p><b>RESULTS</b>The postoperative recurrence rate was 15.9%. The univariate analysis identified that the SUV(max) (t=3.278, P<0.001), p-stage (χ² =5.204, P=0.026), blood vessel invasion (χ² =5.333, P=0.027) and visceral pleural invasion (χ² =7.697, P=0.009) are factors for predicting postoperative recurrence. Only SUV(max) was found to be a significant independent factor according to multivariate analysis (HR=1.068, 95%CI: 1.015 to 1.123, P=0.001). The study population was stratified into three groups by SUV(max), patients with SUV(max) > 5.0 had significantly higher risk of recurrence (23.9%) than those with 2.5 < SUV(max) ≤ 5.0 (15.0%) and SUV(max) ≤ 2.5 (7.3%) (P=0.043); patients with SUV(max) ≤ 2.5 had significantly better 5-year recurrence-free survival rate (90.9%) than those with 2.5 < SUV(max) ≤ 5.0 (82.7%) and SUV(max) ≤ 2.5 (71.0%) (P=0.030). There was a trend toward higher probability of blood vessel invasion (χ² =20.267, P < 0.001), visceral pleural invasion (χ² =6.185, P=0.045) and pathological stage I B (χ² =13.589, P=0.001) with increased SUV(max).</p><p><b>CONCLUSIONS</b>Preoperative SUV(max) of primary tumor is a predictor of postoperative relapse for stage I NSCLC after surgical resection. Therefore, it can contribute to the risk stratification for patients with the same pathological stage and selecting the optimal postoperative follow-up and therapeutic strategy.</p>

Immunohistochemical evaluation of mutant p53 protein over-expression in non-mucinous adenocarcinoma in-situ and invasive adenocarcinoma, NOS of lung / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the over-expression of mutant p53 protein in non-mucinous adenocarcinoma in-situ (NMAIS) and invasive adenocarcinoma, NOS of lung.</p><p><b>METHODS</b>Immunohistochemical study for p53 protein was performed on 17 cases of NMAIS and 70 cases of invasive adenocarcinoma, NOS of lung. The difference in p53 over-expression between the two tumor subtypes was analyzed.</p><p><b>RESULTS</b>The over-expression of mutant p53 protein was observed in 0 case (0%) of NMAIS and 37 cases (52.9%) of invasive adenocarcinoma, NOS of lung. The difference was of statistical significance (P = 0.000).</p><p><b>CONCLUSION</b>Mutant p53 protein over-expression may play a role in the progression of NMAIS to invasive adenocarcinoma, NOS.</p>

Correlation study on virtual touch tissue quantification and the pathological stages of liver fibrosis in chronic hepatitis B / 中华超声影像学杂志

Objective To investigate the correlation between virtual touch tissue quantification (VTQ) and the pathological grading of liver fibrosis in chronic hepatitis B.Methods 64 chronic hepatitis B patients (the chronic hepatitis group) and 40 healthy volunteers (the controlled group) were collected.The patients in the chronic hepatitis group were underwent liver biopsy.According to the hepatic fibrosis degree,the patients in the test group were classified into stage 0,1,2,3 and 4.The liver shear wave velocities (SWV) of all the participant were measured by VTQ.The cut-off values were determined by an analysis of receiver operating characteristic (ROC) curve.Results The mean SWV was (1.04± 0.13)m/s in the controlled group.The SWV in stages 0,1,2,3,and 4 were (1.17 ± 0.08)m/s,(1.33 ± 0.32)m/s,(1.53 ±0.32) m/s,(2.09 ± 0.54) m/s,(2.18 ± 0.70) m/s,respectively.There was a significantly difference in SWV between the controlled group and the chronic hepatitis group (F =34.97,P =0.00).The SWV were significantly different not only between stages 0-2,and 3,but also between 0-2 and 4 (F =8.87,P =0.00).A positive correlation was observed between the liver fibrosis and the SWV in the chronic hepatitis group (r =0.67,P =0.00).When a cut off value was set at 1.43 m/s,area under ROC curve was 0.875.The sensitivity and specificity were 100 ％ and 62.5 ％.Conclusions SWV has a better correlation with liver fibrosis.VTQ can make an accurate assessment for stage 3 and stage 4 of the chronic hepatitis B.Therefore,VTQ can be used as a noninvasive and reliable diagnostic indicator for chronic hepatitis B.

Research Advance of Muir-Torre Syndrome / 中国普外基础与临床杂志

Objective To review recent studies on Muir Torre syndrome (MTS) and to improve the knowledge about MTS.Methods The literatures in recent years on clinic and gene research of MTS were reviewed.Results MTS was is a rare autosomal dominant disorder characterized by the predisposition to both sebaceous tumors (or multiple keratoacanthomas) and internal malignancies. Gastrointestinal cancers were the most common kind of internal malignancies in MTS patients(61%),followed by genitourinary cancers(22%). In most cases(56%),sebaceous tumors appeared after the emergence of internal maliganancy. Both hereditary nonpolyposis colorectal cancer(HNPCC) and MTS were caused by germline mutations in the DNA mismatch repair genes. MTS patients exhibit significantly more mutations in the hMSH2 than in the hMLH1. In these cases , both internal and skin tumors showed the characteristic of high microsatellite instability(MSI).Conclusion The presence of sebaceous tumors(or multiple keratoacanthomas) necessitates the search for internal malignancies. It is mandatory that patients with MTS, as patients with HNPCC, should be regularly followed up to search new malignancies. Evaluation and monitoring of the family members of patients are also necessary. The patients and their families should be counseled for genetic test. Sequencing the hMSH2 gene should be the prior selection of further examinations when clinical manifestations, history and laboratory tests suggest MTS.

Combining SSH and cDNA microarray for identification of lung cancer related genes / 中国肺癌杂志

<p><b>BACKGROUND</b>To screen and identify differentially expressed genes among lung cancer tissues, paracancerous pulmonary tissues and some other kinds of tumor tissues using suppression subtractive hybridization (SSH) and cDNA Microarray.</p><p><b>METHODS</b>One cDNA chip was made by gathering clones of three differentially expressed cDNA libraries which came from BEP2D cell lines during three different malignant transformed phases. Then the clones were hybridizated with cDNA probes which extracted from 15 cases of lung cancer tissues, 5 cases of paracancerous pulmonary tissues and 24 cases of other 8 kinds of tumor tissues respectively.</p><p><b>RESULTS</b>Twenty-six cDNAs were obtained which expressed higher in lung cancer tissues than that in paracancerous pulmonary tissues. Thirty-one cDNAs expressed remarkably higher in paracancerous tissues than those in cancer tissues. Compared with other 8 kinds of tumors, paracancerous tissues had 63 overexpressed cDNAs and lung cancer tissues had 87 overexpressed cDNAs.</p><p><b>CONCLUSIONS</b>The combination of SSH and cDNA microarray is rapid and effective for screening and identification of differentially expressed genes in different samples. It may be potentially useful for diagnosis of lung cancer to further study the differentially expressed genes among lung cancer tissues, paracancerous pulmonary tissues and other tumor tissues.</p>

Research of the correlation with pathology and kinetics of TH1/TH2 cells and expression of iNOS in animals of tuberculosis / 中华微生物学和免疫学杂志

Objective　To investigate the correlation of pathology to immunology in animals with tuberculosis by molecular pathology. Methods　BALB/c mice were randomly divided into two groups: tuberculosis model (A) and control mice (N). Immunohistochemistry technology was used to investigate the correlation between the expression of IFN-γ, IL-4 and iNOS and the type as well as magnitude of tissue injury. Results　Two phases were observed during the 2nd week characterized by inflammatory infiltration in the alveolar-capillary interstitium and the tissues surrounding blood vessels. A predominance of TH1 cells was shown by a higher percentage of IFN-γ positive cells and a lower percentage of IL-4 positive cells in the inflammatory infiltrate identified by immunohistology. From the 4th week after infection to the end of experiment, we observed a chronic advanced phase characterized by pneumonia and local necrosis with a TH0 balance due to an equivalent proportion of IFN-γ and IL-4 positive cells in the lung lesions. The iNOS expression was increased in acute phase and decreased in chronic phase. Conclusion　There is a closely correlation on the kinetics of TH1/TH2 cells and iNOS expression with the type and magnitude of tissue injury during the infection of tuberculosis.

Effects of rapid decompression on ultrastructure of lung in rabbits / 解放军医学杂志

Objective To study the effect of rapid decompression on ultrastructure of the lung in rabbits. Methods Thirty healthy New-Zealand rabbits were randomly divided into low decompression group and rapid decompression group. The pulmonary ultrastructure of rabbits was observed with transmission electron microscope (TEM). Results In rabbits of the rapid decompression group, a number of pathological changes were found, such as disruption of cell membrane structure of types Ⅰ and Ⅱ alveolar cells, loosening of intercellular linkage, edematous mitochondria, expanded rough endoplasmic reticulum, engorged capillary of alveolar wall, edematous capillary endothelium cells, and increased capillary permeability. These changes became especially obvious when the decompression peak value was above 9.8 kPa. Conclusion Rapid decompression could inflict injury to the lung, which was aggravated with the increase of the decompression peak value.

A study on expression of KGF mRNA in human NSCLC and its role in the development of lung cancer / 中国癌症杂志

Purpose:To investigate expression of keratinocyte growth factor(KGF) messenger ribonuclunc acid in human NSCLC and to study the role of KGF in the development of NSCLC. Methods:The expression of KGF mRNA in 50 cases with NSCLC was detected by in situ hybridization (ISH). Results:On ISH slides, positive KGF mRNA was mainly shown as fusiform stain in plasma of fibroblast and blood vessel smooth muscle cell in mesenchymal of NSCLC, also, some parenchyma cell plasma was stained. The positive rate of KGF mRNA in tumor(86%) is statistically higher than that in normal tissue(24%)(P