Objective To summarize the pathological features of nonalcoholic fatty liver disease(NAFLD)in China based on a histological scoring system for NAFLD designed by the Pathology Committee of NASH Clinical Research Network(NASH-CRN).Methods The specimens of liver needle biopsy from 130 patients with NAFLD were examined with light microscopy after haematoxylin eosin,reticular fiber,and Masson trichrome staining.Immunohistochemistry staining of the sections,combined with clinical data,was used to exclude non-NAFLD cases.Results Hepatic steatosis,lobular inflammation,hepatocyte ballooning and fibrosis existed extensively in 130 cases NAFLD liver tissues.Furthermore,macrovesicular steatosis predominantly located in acinar zone 3 was the main pathological feature of NAFLD,and lobular inflammation was usually mild.Hepatocyte ballooning was observed in 94.6 percent of 130 cases.Mild perisinusoidal fibrosis and periportal fibrosis were often observed in stage 1.According to the statistic analysis,hepatic steatosis was positively correlated with lobular inflammation,hepatocyte ballooning and fibrosis(r=0.587,0.488,0.374,respectively;all P value

Objective To explore the pathological features and the causative particles of severe acute respiratory syndrome (SARS) for providing evidences of SARS prevention and clinical treatment. Methods A dead case of SARS of China was studied by light microscopy, electron microscopy, histochemical and immunohistochemical stain. Results The major pathological changes of lung in the SARS case were acute pulmonary interstitial exudative and leakage inflammation, with predominant lymphocyte infiltration. The hyaloid membranes were formed in 20%～30% pulmonary alveoli. The diffuse pulmonary epithelial injury was observed, and virus like inclusions were found in about 30% of total alveolar epithelia by histochemical stain, but chlamydia like inclusions were found occasionally. Meanwhile, the extra pulmonary organs, such as lymph nodes and spleen, showed extensive haemorrhagic necrosis inflammation, accompanied macrophage/histocyte reactive proliferation with erythrocytophage. The double adrenal glands also presented focal haemorrhagic necrosis inflammation. Under the electron microscopy observation, virus like particles with 100 ～150 nm diameter and halo or garland envelopes were found in more than 30 % alveolar epithelial cells, endothelial cells in lung tissues, and also in a part of cardiomyocytes, lymphocytes and macrophages in lymph nodes. The virus like particles were mainly located in cytoplasm and dilated reticular endoplasm. In contrast, chlamydia like particles were commonly visualized in multiple extra lung organs such as liver, but very few in the lung. Immunohistochemistry showed the positive reactions in the lung tissues with the serum IgG and/or IgM from the dead case himself and other SARS convalescent stage cases from Guangdong province of China. Conclusion In the severe SARS case, predominant acute interstitial exudative and leakage inflammation, often with the formation of hyaloid membranes in pulmonaryalveoli, and the haemorrhagic necrosis inflammation of immune organs might be pathological features of SARS. According to the structures, diameter and location of the virus like particles found in this case, combined with the pathological changes, we should consider that those virus like particles might be a new kind of coronavirus, and this kind of virus might be the main causative agent of SARS. However, the chlamydia like particles frequently observed in extra lung organs also suggested the potential new kind of coronavirus might be coexist and synergicallly cause SARS. Our findings in this study provide several evidences for SARS clinical therapy such as application of corticosteroid and enhancement of immune ability and combination of anti virus and anti chlamydium drugs.

Objective To study the pathological changes in organs remote from the lung in SARS patient. Methods The pathological changes in extra lung organs and potential coronavirus infection were studied by using light and electron microscopic examinations as well as special virus inclusion stains in the tissues obtained from an autopsy of a patient who died of SARS. Results Besides the lesions in the lung, pathological changes were found also in the central nervous system (CNS), including the cerebrum, cerebellum, thalamus, pons, and medulla oblongata, such as widening of the Virchow Robin′s space, infiltration of a few lymphocytes and macrophages in the parenchyma, vasodilatation and congestion. However, no significant neuron degeneration or necrosis was identified. Vasodilatation in the lamina propria of mucosa and submucosa of the digestive tract with some lymphocytes infiltration, and epithelial nuclear vacuolation, and occasional apoptosis were observed in the mucosal epithelial and glandular cells, as well as focal hemorrhage in segments of the small intestine. Mesenchymal edema and infiltration of a few lymphocytes in the pancreas were noted. Very mild lymphocyte infiltration, but no viral inclusions, was found in the convoluted seminiferous tubules of the testis. The patient who died of SARS was proved to have arteriosclerosis of the coronary arteries, and coronavirul particles were identified in the blood vessels under electron microscopic examination, however no coronavirul particles were found in the brain or the testis of the patient. Conclusion There were mild hypoxic changes in the tissue of CNS in the patient with severe SARS without invasion of the virus. It was confirmed that there were coronavirul particles in the blood of the patient at the acute stage of SARS. Since the patient who succumbed to the disease had a history of coronary arteriosclerosis, it was inferred that cardiovascular disease might be a contributory factor of mortality in this patient with severe SARS.

Objective To explore the status of immune responses in the lungs and the changes in lymphocyte subgroups in the immune organs in a patient having been suffered from severe acute respiratory syndrome (SARS). Methods The distribution and number of lymphocyte subgroups in the lungs and immune organs from an autopsy case of SARS were analyzed by using immunochemical staining with an array of monoclonal antibodies including CD3, CD4, CD8, CD20, CD57, CD68, S-100 and HLA-DR. Healthy spleen and lymph nodes were used as normal controls. Results CD8 + T lymphocytes constituted the major component of infiltration of inflammatory cells in the pulmonary interstitium. A semi-quantitative analysis of lymphocyte subgroups revealed that the percentage of CD3 +, CD4 +, CD8 + or CD20 + lymphocyte in a total of 31 thoracic lymph nodes of the SARS case were decreased by 74.2%, 67.7%, 74.2%, and 83.9%, respectively, compared with healthy controls. However, the percentages of lymphocyte subgroups in the celiac lymph nodes were less decreased than those in thoracic lymph nodes. The numbers of CD20 + , CD3 +, CD4 + and CD8 + lymphocytes were also decreased. CD20 + lymphocyte were notably decreased in the spleen, while CD57 +, CD68 +, S-100 + and HLA-DR + cells were increased relatively in the lymph nodes and spleen. Conclusions The results suggested that cellular immune responses were predominant in the lung of SARS patient, and it might play an important role in getting rid of coronaviruses in the infected cells and inducing immune mediated injuries to the lungs. There might be a decrease in number and imbalance in various degrees in the proportion of lymphocyte subgroups in the immune organs of the patients with severe SARS, and these changes might have a tendency to be more remarkable in lymphatic tissue situated closer to the lungs.

Objective To explore the target cells of SARS coronavirus infection in vivo and to provide the evidence of multi organ injuries produced by SARS coronavirus infection. Methods Three biotin labeling oligonucleotide probes were synthesized according to the published gene sequence of SARS coronavirus. The location, distributtion and quantity of SARS coronavirus in 2 autopsy cases of SARS were studied by in situ hybridization and electron microscopic examination. Results SARS coronavirus particles were identified in multiple organs. In lungs, SARS coronaviruses were located predominantly in the cytoplasm of bronchiolar and alveolar epithelial cells, in a part of macrophages and endothelial cells as well as a few infiltrated lymphocytes. In situ hybridization showed that in target cells SARS coronavirus distribution presented a cytoplasmic or inclusive pattern, and the mean number of positive cells in the pulmonary tissue was 80?25 per 200? field. Electron microscopic examination showed that the coronaviral particles were 100～150 nm in diameter, with low density electron cores with halo or garland envelopes. About 15% of renal tubular epithelial cells harbored SARS coronavirus, and a few parenchymal cells and sinusoid capillary endothelial cells of adrenal glands were hybridization positive. In the gastro intestinal tract, SARS coronaviruses were seen in the cytoplasm of mucosal and crypt epithelial cells, mostly in 2/3 of superficial mocosa. Under both electron microscopy and in situ hybridization observation, SARS coronaviruses were found focally distributed in some cardiomyocytes. The SARS coronavirus positive particles were also noted in macrophages/histocytes, sinusoid endothelial cells, as well as a few lymphocytes in thoracic and celiac lymph nodes. In addition, coronavirus particles were also seen in a few testicular epithelial cells and Leydig's cells. Conclusion SARS coronavirus could attack multiple target cells, implicating that SARS might cause multi organ damages, with lungs as the predominant organ of injury.

Objective To explore the effects of severe acute respiratory syndrome coronavirus (SARS-CoV) on heart and its conduction system in SARS patients. Methods Six specimens of heart tissue and one specimen of heart condunction system from patients who died from SARS were studied histologically, and by histochemical and in situ hybridization examinations. Results The pathological changes showed that a part of cardiomyocytes manifested slight vacuolar degeneration, atrophy and cytoplasmic lysis, stromal edema, mild mononuclear infiltration, and vasculitis. SARS-CoV was identified within some cardiomyocytes and specialized cardiomyocytes which belonged to the conduction system of the heart by in situ hybridization in combination with Macchiavello's viral inclusion stain. Conclusions The results showed that SARS-CoV could invade not only cardiomyocytes, but also the specialized cells of heart conduction system, thus resulting in mild viral myocarditis-like pathological changes. The results provided the evidence in explaining the clinical manifestations of cardiac dysfunction in patients with SARS.

Objective To explore the mechanism of Fufangbiejiaruanganpian(FFBJRGP) treating liver fibrosis. Methods Needle biopsies before and after treatment with FFBJRGP were done in 65 patients with chronic viral hepatitis B, and the liver tissues were studied with Ishak scoring system to evaluate the effects of treatment. The activation, proliferation and apoptosis of hepatic stellate cells (HSCs) in the liver specimens were determined by using the double immunohistochemical staining of in situ terminal deoxynucleotidyl transferase mediated dUTP nick end labelling method (TUNEL) and smooth muscle actin (SMA). Results Compared with the specimens before treatment, the stages of liver fibrosis and histological activity grades in liver tissues were significantly improved after treatment with FFBJRGP for 6 months (mean value: P

Objective To study the effect of the traditional Chinese medicinal herbs, Fufangbiejiaruanganpian (FFBJRGP), in an experimental model of hepatic fibrosis and its pharmacodynamics. Methods An experimental model of hepatic fibrosis induced by carbon tetrachloride in rat was reproduced, and FFBJRGP was given in high, moderate, and low dosage for 0, 1, 3 and 6 months respectively. Six months after the treatment, matrix metalloproteinase MMP-2, MMP-13, MT-MMP-1, MT-MMP-2 and their inhibitor TIMP-1 and TIMP-2, total extracellular matrix and collagen I, Ⅲ and Ⅳ, and active hepatic stellate cells in the fibrotic livers were qualitatively and quantitatively examined at the protein and/or mRNA expression levels by using immunohistochemistry, in situ hybridization, image analysis and Chevallier's scoring system. Meanwhile, enzyme-degrading activities of MMP-2 and MMP-13 were assessed with gelatin or collagen substrate zymography respectively. Results Compared with the control group, in which rats with hepatic fibrosis were not treated with FFBJRGP, the histological examination of rat livers in the treatment groups showed that the total scores of hepatic fibrosis in treatment groups with varions dosage were significantly decreased 3,6 months after the treatment and 3,6 months after the termination of treatment (P

Objective To study the apoptotic changes in hepatocytes and the expression of apoptosis-associated proteins Bax and Bcl-2 in the liver tissue of a rat nonalcoholic steato-hepatitis (NASH) model, and explore the relationship between hepatocyte apoptosis and the degree of NASH pathological changes. Methods A rat model of NASH was reproduced with feeding a fat-rich diet for a period of 2, 4, 6, 8 and 12 weeks. Cells apoptosis was evaluated by TdT-mediated dUTP nick end labeling (TUNEL), and the expression of Bax and Bcl-2 proteins was detected by immunohistochemistry in rat liver tissue of control and model groups respectively. Results The number of TUNEL-positive cells was increased in the second week, peaking at the 8th week, and it was significantly correlated with steatosis and hepatic fibrosis (r=0.707 and 0.750, respectively, P0.05). The expressions of Bax and Bcl-2 proteins were mainly located in cytoplasm of hepatocytes, some of which contained lipid droplets. Bax and Bcl-2 positive cells increased gradually with the progression of NASH. In early stage of modeling, the number of Bax positive cells was greater than that of Bcl-2, but the number of the both proteins tended to be about same in the late stage of modeling. Conclusion The cell apoptosis is a main pattern of liver damage in the process of NASH, and it is closely associated with the pathological changes. Proapoptosis protein Bax and antagonisitic protein Bcl-2 might participate in the modulation of hepatocytes apoptosis in the early stage of NASH, and they also have a marked effect in the whole process of NASH.

0.05).For the cases when discharge,the ratio of curing,improve,inefficiency and death were 67.47%,29.01%,2.00% and 1.52%,respectively;for the cases followed up,the ratio of restoration,improve,aggravation and death were 74.31%,23.84%,1.11% and 0.74,respectively.Conclusions It has been revealed that the main liver diseases affecting the Chinese soldier's health in the past three decades include viral liver diseases,fatty liver diseases and liver injuries induced by drug and environmental factors,and the incidence of non-viral liver diseases has gone up in the last decade.Some epidemiological characteristics have emerged in Chinese soldier with liver disease in age,sex,army service branch,rank and original place.The epidemiological data have shown that the main infectious routs of liver diseases in Chinese soldier include inter-soldiers in group live,family members to soldier,and food and beverage.To make a definite diagnosis,the liver biopsy examination should be a very useful choice to the majority of hardly diagnosed liver diseases on clinic.The serological examinations for several main liver diseases have shown some special features,and most of the soldier with liver diseases has well improved after regular treatments.