Chronic Disease ; Heart Failure ; therapy ; Heart Rate ; Humans

T lymphocyte immune dysfunction plays an important role in the occurrence and development of chronic obstructive pulmonary disease (COPD), but the specific mechanism is not fully understood. Programmed cell death 1 (PD-1) negatively regulates the activation and effector function of T lymphocytes by binding to its ligand PD-L1, thus participating in the maintenance of immune tolerance. Recent studies have found that blocking the PD-1/PD-L1 signaling pathway can improve T-cell depletion and enhance the ability of anti-infection in COPD patients. Therefore, understanding the regulatory effects of PD-1 on T lymphocytes is of great significance to studying the pathogenesis and clinical treatment of COPD. This article briefly reviewed the research progress in PD-1 in terms of structure, function, T cell regulation and relationship with COPD.

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

To study the mechanism of matrix degradation in alcoholic liver disease (ALD), the liver tissues from 28 patients with ALD were divided into three groups according to their fibrosis degree. The mRNA expression of matrix metalloproteinase 1 (MMP 1), matrix metalloproteinase 2 (MMP 2), membrane type metalloproteinase (MT1 MMP), and tissue inhibitors of metalloproteinase (TIMP) was detected using in situ hybridization method. The results showed that the cells with positive MMP 1, MMP 2, MT1 MMP, and TIMP mRNA staining were mainly located around the fibrotic central veins, walls of sinusoids, and portal triads. These positive cells were the cells of hepatic sinusoidal walls and a few hepatocytes, meanwhile, some cells expressed both the MMP 2 and the MT 1MMP mRNA. The positive cells of the MMP 2, MT1 MMP, and TIMP mRNA increased in parallel with the severity of fibrosis, whereas the expression of MMP 1 mRNA decreased. These changes were observed predominantly in moderate fibrosis group. There findings demonstrated that down regulation of MMP 1 expression and up regulation of TIMP expression might be involved in excessive accumulation of extracellular matrix (ECM) in ALD. MMP 2 might collaborate with MT1 MMP in degradation of ECM. thereby contributing to fibrosis of central veins.Hepatic stellate cells might be the main cellular source of MMP 1, MMP 2, MT1 MMP and TIMP in ALD.

Objective To study the disease spectrum,the features of clinical pathology,epidemiology and prognosis of liver diseases in Chinese populations from Jan.1980 to Jun.2008.Methods Twenty-five thousand nine hundred and forty-six patients with liver diseases in a wide spectrum of inhabitants(including 1 448 military patients) from 31 provinces or cities of all over mainland China in recent 28 years were involved in the present study for a retrospective study regarding their clinical,pathological and epidemiological features,including laboratory re-examinations and pathological examination.1 322 patients with liver disease(course lasted from 6 months to 18 years) were followed-up by more than 2 liver biopsies to study the outcome of chronic hepatitis B.Results For all the patients involved,the sex ratio of male to female was 3 to 1,with mean age of 32.3?14.4 years ranging from 41 days to 91 years,and the diseases occurred predominantly between the age of 18 to 37 years.Hebei,Henan,Beijing,Shandong and Shanxi provinces(city) ranked at the fore in the endemic distribution of the diseases.The spectrum of liver disease covered more than 100 kinds of liver diseases,of which 73.05% were infectious liver disease.As a whole,the incidence of both infectious and non-infectious,especially the non-infectious liver diseases became more prevalent since 2000.It was shown that the chronic hepatitis B was the most predominant factor which caused liver failure,liver cirrhosis and liver cancer,and chronic hepatitis C was the second factor.Chronic infection pathological changes were found in the liver tissues in 0.26% patients with hepatitis A and 0.51% patients with hepatitis E.For all the 1 322 followed-up patients with chronic hepatitis B,the incidence of liver cirrhosis and hepatocellular carcinoma was respectively 15.36%(203 cases) and 1.06%(14 cases),and the average progressive period for the changes in pathology was 46.37?16.93 months and 60.29?39.15 months,respectively.Meanwhile,the degree of liver fibrosis increased more than one stage in 188 patients(14.22%),decreased more than one stage in 441 patients(33.36%),and no change in 476 patients(30.01%).Conclusions The liver disease spectrum during recent 28 years in Chinese populations has been essentially identified by a retrospective analysis of a large number of clinical pathological data.The clinical features of predominant liver diseases have been illustrated,and the outcome and transition time of chronic hepatitis B has been elucidated in present study.

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.