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Vitamin D and Toll-like receptor-4 (TLR-4) inhibition are involved in the protection of keratinocytes. The effects of combination of 1,25(OH) 2 D 3 and TLR-4 inhibitor on the protection of keratinocytes against ultraviolet radiation B (UVB) irradiation remain unclear. This study was undertaken to explore the effects of combination of 1,25(OH) 2 D 3 and TAK-242 (TLR-4 inhibitor) on the damage to HaCaT cells caused by UVB irradiation. In vitro , HaCaT cells were treated with 1,25(OH) 2 D 3 or/and TAK-242 prior to UVB irradiation at the intensity of 20 mJ/cm2 then the production of reactive oxygen species (ROS), cell migration, apoptosis of cells, and the expression of oxidative stress, endoplasmic reticulum stress, and apoptosis related proteins were determined. Compared with the HaCaT cells treated with 1,25(OH) 2 D 3 or TAK-242, the cells treated with both 1,25(OH) 2 D 3 and TAK-242 showed, 1) significantly lower production of ROS (P < 0.05); 2) significantly less apoptosis of HaCaT cells (P < 0.05); 3) significantly lower expression of NF- κ B, Caspase-8, Cyto-C, Caspase-3 (P < 0.05). The combination of 1,25(OH) 2 D 3 and TAK-242 could produce a better protection for HaCaT cells via inhibiting the oxidative stress, endoplasmic reticulum stress and apoptosis than 1,25(OH) 2 D 3 or TAK-242 alone. [ABSTRACT FROM AUTHOR]

Objective: Vitamin D and Toll-like receptor-4 (TLR-4) inhibition are involved in the protection of keratinocytes. The effects of combination of 1,25(OH) 2 D 3 and TLR-4 inhibitor on the protection of keratinocytes against ultraviolet radiation B (UVB) irradiation remain unclear. This study was undertaken to explore the effects of combination of 1,25(OH) 2 D 3 and TAK-242 (TLR-4 inhibitor) on the damage to HaCaT cells caused by UVB irradiation., Methods: In vitro , HaCaT cells were treated with 1,25(OH) 2 D 3 or/and TAK-242 prior to UVB irradiation at the intensity of 20 mJ/cm 2 , then the production of reactive oxygen species (ROS), cell migration, apoptosis of cells, and the expression of oxidative stress, endoplasmic reticulum stress, and apoptosis related proteins were determined., Results: Compared with the HaCaT cells treated with 1,25(OH) 2 D 3 or TAK-242, the cells treated with both 1,25(OH) 2 D 3 and TAK-242 showed, 1) significantly lower production of ROS ( P < 0.05); 2) significantly less apoptosis of HaCaT cells ( P < 0.05); 3) significantly lower expression of NF- κ B, Caspase-8, Cyto-C, Caspase-3 ( P < 0.05)., Conclusion: The combination of 1,25(OH) 2 D 3 and TAK-242 could produce a better protection for HaCaT cells via inhibiting the oxidative stress, endoplasmic reticulum stress and apoptosis than 1,25(OH) 2 D 3 or TAK-242 alone., (Copyright © 2022 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Objective: Centrosome aberrations and cell-cycle deregulations have important implications for the development of endometrial carcinoma. AURKA, BRCA1, CCNE1 and CDK2 genes play pivotal roles in centrosome duplication and cell-cycle regulation. This study aimed to investigate whether genetic polymorphisms in these four genes may contribute to endometrial carcinoma susceptibility and progression in Chinese Han women., Study Design: A total of twenty-two single nucleotide polymorphisms (SNPs) were selected according to the public HapMap database (HapMap Data Release #27; Chinese Beijing population), and genotyped using TaqMan Realtime PCR method in 530 endometrial adenocarcinoma cases and 825 age-matched controls from Chinese Han women. Then, haplotype blocks were reconstructed according to our genotyping data., Results: For AURKA, the rs911162 was associated with increased risk of endometrial carcinoma [in co-dominant model: adjusted odds ratio (aOR) = 4.92, 95% CI = 1.24-19.55, P = 0.0235]. The haplotype GA (rs6064391 + rs911162) in block 1 of AURKA was also associated with increased risk of endometrial carcinoma (aOR = 1.25, 95% CI = 1.07-2.06, P = 0.0189). For BRCA1, the minor allele homozygotes of rs8067269 could decrease the risk of endometrial carcinoma (in co-dominant models: aOR = 0.52, 95% CI = 0.34-0.80, P = 0.0032), so was the haplotype CTCAG (rs8176323 + rs8176199 + rs3737559 + rs8067269 + rs2070833) (aOR = 0.69, 95% CI = 0.50-0.95, P = 0.0234). Moreover, we found several associations between genetic variations in CCNE1, BRCA1 and AURKA and clinicopathological parameters., Conclusions: This study indicates that genetic polymorphisms of AURKA, BRCA1 and CCNE1 may contribute to endometrial carcinoma susceptibility or progression in Chinese Han women., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: To study the relationship between human papillomavirus (HPV) L1 capsid protein (L1) and koilocytosis on ThinPrep cytology tests (TCTs) and the association of HPV L1 with p16 and Ki-67 expression in their corresponding biopsies., Study Design: TCTs of 75 patients with high-risk HPV infection were studied for cytologic features of koilocytosis and for HPV L1 expression using combined detection of in situ hybridization and immunocytochemistry. All TCTs had follow-up biopsies on which p16 and Ki-67 were confirmed by immunostaining., Results: Of 75 TCTs, 45 expressed HPV L1, while 23 displayed koilocytosis. All TCTs with koilocytosis expressed HPV L1. HPV L1 was lost in 23.3% of cervical intraepithelial neplasia (CIN) I, 16.7% of CIN II, and 60% of CIN III or higher (carcinoma in situ including suspected minor infiltration), categorized by biopsy, and the difference among CIN grades was statistically significant (chi2, p = 0.015). Expression scores of p16 and Ki-67 were higher in L1 negative cases than in positive cases (1.63 vs. 1.54 for p16; 1.53 vs. 1.32 for Ki-67); however, the difference was not significant (Mann-Whitney test: p = 0.57 for p16, p = 0.27 for Ki-67)., Conclusion: HPV L1 expression was significantly associated with koilocytosis on TCT, and loss of L1 was associated with increase in CIN grade but not with p16 or Ki-67 expression. Our study suggests that HPV L1 is a more sensitive method than koilocytosis for detecting active HPV infection. Detection of HPV L1 on TCTs of high-risk HPV-infected patients can be helpful in risk assessment and prognostic prediction of CIN.

Objective: To study the clinicopathological features of diabetic microangiopathy in liver and diabetic hepatosclerosis (DHS) of elderly male with type 2 diabetes mellitus (T2DM)., Methods: One hundred and twenty autopsy cases with T2DM (diabetic group) and contemporary 48 cases, non-diabetic and glucose tolerance abnormal, matched by gender and age (control group) were selected in the study. Cases with the cirrhosis and fibrosis of liver caused by other foregone etiological factors were excluded. The histopathological changes of microangiopathy in liver, hepatic portal areas and hepatic sinusoid were investigated by HE staining, histochemical and immunohistochemical stain methods. The clinical data of diagnostic DHS cases were analyzed., Results: (1) Microangiopathy was observed in 54.2% (65/120) cases of diabetic group. Histological features: microangiopathy was found in interlobular arteries (especially in arteriole, the lumen diameter < 100 µm), which included endothelial denudation, eosinophilic material deposition in the tunica intima of artery, and eccentric intimal thickening. The smooth muscle fibers of tunica media were hyperplastic or atrophy. Fibroplasia and collagen deposition were found in the tunica adventitia of artery. Arterial lumina showed stenosis and occlusion. Microangiopathy was seen in 16.7% (8/48) cases of the control group. There was statistically significant difference between the two groups (χ(2) = 19.622, P < 0.01). (2) The fibrosis and sclerosis of portal areas were detected in 55.8% (67/120) cases of T2DM group. Hyaline collagen fiber tissues was deposited around interlobular arteries, interlobular veins and interlobular bile ducts, resulting in enlargement of the portal area and the secondary atrophy and disappearance of portal triad. The fibrosis and sclerosis of portal areas were detected in 22.9% (11/48) cases of the control group. There was a statistically significant difference between the two groups (χ(2) = 14.936, P < 0.01). (3) The pathological features of 14.2% (17/120) cases were consistent with the diagnosis of DHS. The fibrous tissue extended from fibrosis or sclerosis of portal areas, or eosinophilic material deposition in the hepatic sinusoid in non-zonal pattern. The results of histochemical staining showed collagen fiber deposition in hepatic sinusoid. Stainings for Collagen IV, SMA, CD34 were found in the hepatic sinusoid. The sclerosis of hepatic sinusoid was not detected in any case in the control group.Overall, 13/17 and 11/17 DHS cases had liver microangiopathy and portal areas sclerosis respectively. Diabetic nephropathy was seen in 10 of 17 DHS cases. Among the 17 cases, 7 cases showed ALP elevation, of which there were 3 cases with ALT and AST mild elevation., Conclusions: Diabetic microangiopathy is common in the liver of elderly men with T2DM. And DHS is associated with diabetic microangiopathy. Fibrosis and sclerosis of portal areas may be the early or concomitant changes of DHS on histological ground. DHS is one of the complications of T2DM.

Objective: To evaluate the value of cytomorphologic and immunocytochemical approaches in the diagnosis of hematologic neoplasms in serous effusion., Methods: The cytospin and Thinprep smears of effusion specimens were prepared from 23 cases of lymphoid malignancies with histological confirmation and 30 cases of benign effusions used as control. Morphological assessment of the cellular components was conducted, including the ratio of mesothelium to lymphocyte, karyomorphism of lymphoid cell and the presence of apoptosis and mitosis. Immunocytochemical study was performed in all the cases, with flow cytometry in one case., Results: Among the 23 tumor cases, 14 represented disease relapse, and in the remaining nine cases, the serous effusion was the primary manifestation. The proportion of mesothelium was low in the tumor group, being less than 10% in 20 cases (87.0%, 20/23). It was more than 10% in most of benign cases (20/30, 66.7%). Lymphoid cells were prominent (> 80% cells) in 69.6% of the tumor cases, and the cellular component in some control cases (63.3%, 19/30) showed fewer lymphocytes. Nipple-like projection of lymphocytic nuclei could be detected in almost all the tumor cases (91.3%, 21/23), but was occasionally found in the control group (26.7%, 8/30). Apoptosis and mitosis were obvious in lymphomatous effusion, but observed in only 6.7% of the control cases. Significant difference of the previously mentioned cytomorphologic features existed between the tumor and control groups (P < 0.01). The results of immunocytochemical staining in cell block were identical to the corresponding immunohistochemistry, and one case of mantle cell lymphoma was confirmed by flow cytometry. The cytologic findings seen in all the 23 studied cases were in agreement with the corresponding histologic diagnosis., Conclusions: Some cytomorphologic features, including decreased number of mesothelium, increased number of lymphoid cells, nuclear nipple-like projection, and the presence of apoptosis and mitosis, are very useful for diagnosing lymphoid malignancy in serous effusion. Immunocytochemistry is an important approach to the cytodiagnosis and classification of lymphoma.

Objective: To enhance the understandings of clinical, radiological and pathological features of hypersensitivity pneumonitis (HP)., Methods: Six HP cases with pathological data, clinical and radiological data were retrospectively analyzed during the period from February 2009 to September 2011 at Beijing Hospital of Ministry of Health. There were 2 males and 4 females with a mean age of 51.5 years (range: 38-61). Clinically, the patients presented with chronic cough, shortness of breath and dyspnea (n = 2). The disease course was 1-8 months. Five cases had fed pigeons and other contact histories. Specimens obtained by transbronchial lung biopsy (n = 3) and open lung biopsy (n = 3) were paraffin embedded and stained by hematoxylin and eosin, special stains and immunohistochemistry., Results: Four cases had subacute HP and 2 cases chronic HP. Three cases of subacute HP underwent transbronchial lung biopsy. One case of subacute HP and 2 cases of chronic HP were diagnosed by open lung biopsy. High-resolution computed tomography of lungs showed diffuse ground glass and patch shadow along the bronchial and centrilobular distributions. There was a predominance of upper half zone. Typical visible mosaic syndrome was present. There was poorly formed granuloma without cheesy necrosis. With an insidious medical history and complicated radiological features, chronic HP cases were characterized by pulmonary interstitial fibrosis. There were usual interstitial pneumonitis (UIP)-like fibrosis and fibrosis with an airway-centered distribution type. The lesions were distributed around bronchioles. Continuous bridge fibrosis might be present. There were bronchiolar metaplasia of peribronchiolar alveoli, poorly formed granuloma and multinucleated giant cells in interstitium. Schaumann body was identified in 1 case., Conclusions: Because of its diverse clinical, radiological and pathological features, HP may be easily confused with other interstitial lung diseases. Aggregate analyses yield a definite diagnosis.

Objective: To observe the expression of PECAM-1 and E-selectin in the vulnerable plagues and their relationships to myocardial Leu125Val polymorphism of PECAM-1 and Ser128Arg polymorphism of E-selectin in autopsied samples of patients with acute coronary syndrome (ACS)., Methods: We detected the expressions of PECAM-1 and E-selectin in the vulnerable plaques by immunohistochemistry on 50 autopsy samples of patients with ACS, 30 autopsy samples from non-cardiac disease patients served as control. Genetic Leu125Val polymorphism of PECAM-1 was detected by PCR-SSCP in myocardial paraffin blocks of 37 ACS cases and 43 control cases, and Ser128Arg polymorphism of E-selectin was detected by PCR-RFLP in myocardial paraffin blocks of 39 ACS cases and 43 control cases, respectively., Results: Immunohistochemical features: (1) the incidence of positive expression in the intima of coronary artery of PECAM-1 [76.0% (38/50) vs. 26.7% (8/30)] and E-selectin [26.0% (13/50) vs. 0] was significantly higher in ACS group than in control group (all P < 0.01). (2) Expressions of PECAM-1 [58.0% (29/50) vs. 28.0% (14/50)] and E-selectin [22.0% (11/50) vs.12.0% (6/50)] were significantly higher at neovascular endothelial cells in plaques than expressions at coronary arterial endothelial cells in ACS group (all P < 0.01). (3) In 41 plaques with inflammatory infiltration, the expression rates of PECAM-1 and E-selectin in inflammatory cell density of < 10, 10 - 30 and > 30/HPF were 33.3%, 68.2%, 92.3% and 16.7%, 31.8% and 23.1%, respectively. Genotype detection results: There is significant difference in frequencies of allele in Leu125Val polymorphism (P < 0.05), but the genotype distributional frequencies were similar (P > 0.05) between ACS group and control group. There are significant differences in frequencies of allele and genotype in Ser128Arg of E-selectin polymorphism between ACS group and control group (all P < 0.05)., Conclusions: The immunohistochemical expressions of PECAM-1 and E-selectin were significantly increased at intima in vulnerable plaques of ACS group, especially in neovascular endothelial cells, and positively correlated with inflammatory cell density, suggesting that PECAM-1 and E-selectin might play an important role in inflammatory reaction and development of vulnerable plaque. E-selectin Ser128Arg polymorphism is associated with ACS, and it might be a risk factor for ACS.

Objective: To observe pathohistological features of vulnerable plaques in coronary arteries., Methods: Autopsy coronary samples from 67 patients died of acute coronary syndrome (ACS) and 60 patients of non-cardiac death from 1992 to 2006 in Beijing Hospital were examined. Morphological features of vulnerable plaques of ACS cases were evaluated in terms of thrombus, ratio of lipid core, the minimal thickness of fibrous cap and the density of inflammatory infiltration., Results: (1) There are 305 plaques in ACS group and the incidence of big lipid core is 153 (50.16%), thin fibrous cap is 187(61.31%), inflammatory infiltration is 263 (86.23%), neovasculature conformation is 217 (71.15%), severe stenosis is 26 (8.52%), calcification is 238 (78.03%), superficial calcified nodule is 26 (8.52%), fissured plaque is 12 (3.93%), endothelial denudation is 3 (0.98%) and intraplaque hemorrhage is 54 (17.70%), which are significantly higher than control samples except endothelial denudation (P < 0.01). (2) The incidence of vulnerable plaques in ACS group is significantly higher than in the control group (89.51% vs. 21.98%, P < 0.01). There are 4.07 sections of vulnerable plaques with high density of inflammatory infiltration out of 4.55 sections reviewed in ACS patients, while there are 0.85 sections of vulnerable plaques with mild inflammatory infiltration out of 3.87 sections reviewed in the control cases., Conclusions: Formation of vulnerable plaque was an important pathological factor for the development of ACS. The major morphological characteristics of vulnerable plaque are big lipid core, thin fibrous cap, inflammatory infiltration, neovascularization, severe stenosis, plaque rupture, and endothelial denudation suggesting inflammation performed an important role in the formation of vulnerable plaque.

Objective: To study the significance of cytokine IL-1α and S100β expression in formation and evolution of different types of plaques in Alzheimer's disease., Methods: Thirty-four autopsy cases of Alzheimer's disease encountered during the period from 1982 to 2008 were retrieved from the archival files of Department of Pathology, Beijing Hospital. Tissue blocks were taken from hippocampus for dual immunostaining for IL-1α/Aβ and S100β/Aβ., Results: Immunohistochemical studied for IL-1α/Aβ and S100β/Aβ delineated four different types of senile plaques: diffuse non-neuritic plaques, diffuse neuritic plaques, dense-core neuritic plaques and dense-core non-neuritic plaques. The numbers of IL-1α-positive microglias and S100β-positive astrocytes associated with diffuse neuritic plaques were (7.29 ± 3.04) per mm(2) and (6.49 ± 2.20) per mm(2), respectively. In contrast, the numbers of IL-1α-positive microglias and S100β-positive astrocytes associated with diffuse non-neuritic plaques, dense-core neuritic plaques and dense-core non-neuritic plaques were (3.24 ± 1.53) per mm(2) and (4.14 ± 1.77) per mm(2), (2.09 ± 1.37) per mm(2) and (2.25 ± 0.83) per mm(2), and (1.38 ± 0.90) per mm(2) and (0.58 ± 0.36) per mm(2), respectively. The numbers of IL-1α-positive microglias and S100β-positive astrocytes associated with diffuse neuritic plaques were significantly higher than those of the other three types of plaques (P < 0.05)., Conclusion: The IL-1α-positive microglias and S100β-positive astrocytes may be of certain significance in transformation of diffuse non-neuritic plaques to diffuse neuritic plaques in Alzheimer's disease.

Objective: To study the values of immunohistochemistry staining and cytological diagnosis by using cell block sections prepared with the effusion fluid cytology specimens., Methods: Ninety-nine effusion cytology specimens with the diagnoses of reactive mesothelial hyperplasia, atypical cells and metastatic carcinoma were enrolled into the study. The cytospin preparations/smears, cell block sections and immunohistochemical study were performed and correlated with the clinical findings and follow-up data., Results: Amongst the 99 cases studied, the percentage with positive diagnosis using cytospin preparations/smears was 68.7% (68/99). The percentages with negative and equivocal diagnoses were 16.2% (16/99) and 15.1% (15/99), respectively. As for cell block sections, the percentages were 71.7% (71/99), 16.2% (16/99) and 12.1% (12/99), respectively. On the other hands, the percentages became 76.8% (76/99), 20.2% (20/99) and 3.0% (3/99), respectively, when coupled with immunohistochemical findings. The overall percentages of positive, negative and equivocal diagnoses were 77.8% (77/99), 17.2% (17/99) and 5.0% (5/99), respectively, upon clinicopathologic correlation. The difference between cytospin preparations/smears and cell block sections was not statistically significant (P > 0.05). When coupled with immunohistochemical findings or clinicopathologic correlation, the difference in rates of equivocal diagnosis however carried statistical significance (P < 0.05). The false-negative rate of immunohistochemical study applied on cell block sections was 1.0% (1/99)., Conclusions: Immunohistochemistry, when applied on cell block sections, is useful in delineation of the primary origins of the tumor cells in effusion fluid cytology specimens. Combination of morphologic examination, immunohistochemical findings and clinicopathologic correlation can further improve the rate of positive diagnosis.

Objective: To explore the value of electrocardiographic (ECG) Cornell criteria for detecting left ventricular hypertrophy (LVH) in elderly Chinese men., Methods: Since 1990, 244 autopsies were performed in our hospital in elderly men, LVH was determined in these autopsy hearts and correlated to ECG LVH signs recorded within 3 months before death according to Cornell (SV3+RaVL) and Sokolow-Lyon criteria (SV1+RV5 or RV6). The reference value of Cornell criteria was obtained based on values from autopsied healthy hearts, the sensitivity and specificity of Cornell and Sokolow-Lyon criteria for detecting left ventricular hypertrophy in these elderly men were calculated., Results: There were significantly correlations between QRS amplitudes of Cornell and Sokolow-Lyon criteria and autopsy left ventricular wall thickness in these hearts. The reference value of Cornell criteria (SV3+RaVL) was 2.9 mV. The sensitivity of Sokolow-Lyon and Cornell criteria for detecting LVH was 25.4% and 34.3% (P<0.05 vs Sokolow-Lyon criteria), respectively., Conclusion: Voltage (SV3+RaVL)>or=2.9 mV might be a suitable diagnostic value for detecting left ventricular hypertrophy in Chinese elderly men.

Objective: To study the histopathologic features, differential diagnosis and pathogenesis of diabetic cardiomyopathy., Methods: The clinicopathologic features of 40 autopsy cases of diabetes mellitus were studied. The hearts from another 40 cases of non-diabetic elderly deceased were used for comparison., Results: In the 40 cases of diabetes studied, 36 cases (90.0%) showed microscopic myocardial cell death. Focal interstitial fibrosis was observed in 37 cases (92.5%). On the other hand, similar myocardial cell death and patchy interstitial fibrosis was seen in 8 cases (20.0%) and 9 cases (22.5%) of non-diabetic hearts, respectively. The difference between the two groups was statistically significant (P < 0.01). The mural thickness of intramyocardial blood vessels was significantly increased in diabetic group (20.6 microm +/- 4.2 microm) than in non-diabetic group (7.2 microm +/- 5.2 microm), P < 0.01.The myocardial changes in diabetic group however were similar to those in non-diabetic group with systemic hypertension., Conclusions: Pathologic diagnosis of diabetic cardiomyopathy relies on detailed histologic examination of heart tissue and clinical correlation of a long history of diabetes mellitus. Exclusion of other possible etiologies is also essential. The myocardial cell death observed may be due to the ischemic effect induced by diabetic microangiopathy in cardiac muscle.

Objective: To investigate the relation between atrial fibrillation (AF) and coronary heart disease according to the pathological data., Method: Total 540 out of 1012 anatomic older cases were admitted to our study, according to the clinical and pathological data in our hospital., Results: (1) The incidence of AF increased significantly with aging (Cochran-Armitage trend test, P<0.01). (2) The AF patients were more likely to accompany coronary heart disease (P=0.0028) based on the anatomical documentation; the incidence of myocardial infarction in the AF group was statistically significant higher than that in the sinus rhythm group (P=0.0144). The level of coronary artery lesion in AF group was statistically significant severe than that in the sinus rhythm group. (3) Age (OR=1.34, 95% CI 1.11 - 1.60), male (OR=5.71, 95% CI 1.87 - 17.39) and chronic heart failure (OR=1.87, 95% CI 1.27 - 2.76) were independent risk factors of AF based on multivariant logistic analysis, while coronary heart disease (OR=1.47, 95% CI 0.91 - 2.39) was not an independent risk factor., Conclusions: The incidence of AF increases significantly with aging in the elderly. The AF patients seem more likely to accompany coronary heart disease but coronary heart disease may be not the independent risk factor of AF in the elderly.

Objective: To explore cytological parameters that may identify the primary sites of metastatic adenocarcinomas in serous fluid., Methods: Serous fluid specimens from 89 cases of metastatic adenocarcinomas (40 metastatic adenocarcinomas of lung, 6 metastatic adenocarcinomas of breast, 21 metastatic ovary adenocarcinomas, 22 metastatic gastrointestinal and pancreatic adenocarcinomas) were studied by using multiple morphologic parameters. Immunocytochemical S-P method was used to detect the expression of CA125, CA199, SPB and TTF-1 in 75 cases., Results: Metastatic adenocarcinomas of different primary sites displayed certain different morphologic features, including the total amount of tumor cells, size of clusters, ratio of clusters over single cells, configuration of tumor clusters and the background of the smear. Cell clusters of small to medium sizes represented 95% and 100% in the metastatic adenocarcinomas of lung and breast, respectively. Most of the ovarian metastatic adenocarcinomas (85.7%) presented some large cell clusters and larger amount of cells, whereas certain metastatic gastrointestinal and pancreatic adenocarcinomas (45.5%) presented smaller number of cells and predominantly to be single cell in distribution (40.9%). Psammoma bodies were found in metastatic adenocarcinomas of lung and ovary. SPB and TTF-1 expression supported the diagnosis of adenocarcinoma of pulmonary origin. CA125 expression supported an ovarian origin. Although CA199 was seen in all groups of metastatic adenocarcinomas, nevertheless, its appearance in tumor cells in ascitic fluid specimens supported gastrointestinal and pancreatic origins., Conclusion: Morpho-logic features of the cytological smear, immunohistochemical staining and clinical history are equally important in determining the primary sites of metastatic adenocarcinomas in serous fluid.

Objective: To study the association between Alzheimer' s disease (AD) and apolipoprotein E (apoE) polymorphism and apoE epsilon4 allele; and to investigate the role of apoE in senile plaque formation., Methods: During the period from 1982 to 2003, 27 portmortem cases of AD from the archival files of Department of Pathology of Beijing Hospital, diagnosed according to the consortium to establish a registry for Alzheimer's disease (CERAD) criteria, were enrolled into this study. Among the 27 cases studied, there were 23 cases of definite AD and 4 cases of probable AD. Postmortem brain tissues from 67 neurologically unremarkable deceased were used as age-matched controls. Immunohistochemical study for beta-amyloid (Abeta) and Tau protein, as well as immunohistochemical study for Abeta/apoE, were performed in all AD cases using streptavidin-peroxidase (SP) and double immunostaining ( SP/ABC) methods, respectively. Senile plaques and neurofibrillary tangles in the 23 cases of definite AD were further quantified. The apoE genotypes in all cases were analyzed by polymerase chain reaction and restriction fragment length polymorphism technologies., Results: Immunohistochemical study for Abeta distinguished 4 different types of senile plaques: diffuse non-neuritic plaques, diffuse neuritic plaques, dense-core neuritic plaques and dense-core non-neuritic plaques. Double immunohistochemistry for Abeta/apoE showed that some senile plaques were positive for both Abeta and apoE. The expression rates for Abeta and apoE in these 4 different types of senile plaques were 4. 28%, 84. 71%, 8.50% and 2.51%, respectively. The positivity rate for Abeta/apoE in diffuse neuritic plaques were significantly higher than those in other 3 types (P < 0.01). The frequency of occurrence of apoE epsilon4 allele in AD was significantly higher than that in the control group (P < 0.01). The numbers of senile plaques and neurofibrillary tangles in AD cases with apoE epsilon4 allele were also significantly higher than those in AD cases without apoE epsilon4 allele (P < 0.01)., Conclusions: ApoE polymorphism is associated with AD. The presence of apoE epsilon4 allele carries a higher risk for the development of AD. ApoE may also play an important role in the transformation of diffuse non-neuritic plaques to diffuse neuritic plaques.

Objective: To assess the relationship between microglia activation and apoptosis of neurons, and the significance of activated microglias in the formation and progression of senile plaques in Alzheimer's disease., Methods: IL-1alpha and beta-amyloid immunohistochemistry, combined with TUNEL assay were used to assess brain tissue samples from 10 patients with Alzheimer's disease and 4 negative control cases without neurological disease., Results: The number of resting microglias in the brains of Alzheimer's disease patients was similar to that of the control group (P > 0.05), but the number of activated microglias was significant greater in the Alzheimer's disease patients than that of the controls (P < 0.01). The activated microglias displayed altered size and morphology, and was therefore, categorized into three subtypes as primed, enlarged and phagocytic microglias. The numbers of primed, enlarged and phagocytic microglias were 5.4 +/- 0.87, 11.5 +/- 1.25, and 3.4 +/- 0.32 microglia/mm2 and represented 26.6%, 56.65%, and 16.75% of all activated microglias respectively. The number of TUNEL positive apoptotic neurons was significantly greater in Alzheimer patients than that in the control group (P < 0.05). There was a close relationship between the apoptosis of neurons and the activation of microglias (P < 0.01). The activated microglias were differentially distributed among four different plaque types in Alzheimer patients. Many primed (42.3%) and most of the enlarged and phagocytic microglias (56.2% and 70.6%) were present in the diffuse neuritic plaques., Conclusions: Hyperplasia and activation of microglias are a common phenomena in AD and may play an important role in its pathogenesis. There is a close relationship between the apoptosis of neurons and activation of microglias. The activation of microglias may play a key pathogenic role in senile plaque formation and progression of Alzheimer disease.