高密度脂蛋白功能改变可能是动脉粥样硬化形成的危险因素

高密度脂蛋白(HDL)是由1000多种脂质和几十种脂蛋白组成的复合体,因此,功能复杂、容易变异。正常HDL具有保护心血管的作用,可以抑制动脉粥样硬化形成。但近年来发现在某些疾病下,正常HDL可以转变为趋炎(或氧化)HDL,失去保护心血管的作用,甚损害心血管功能。因此,HDL可能成为心血管疾病的形成原因和治疗靶点。

Role of cytokines and chemokines in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat content within the liver. The accumulation/deposition of fat within the liver is essential for diagnosis of NAFLD and might be associated with alterations in the hepatic and systemic inflammatory state. Although it is still unclear if each histological entity represents a different disease or rather steps of the same disease, inflammatory processes in NAFLD might influence its pathophysiology and prognosis. In particular, non-alcoholic steatohepatitis (the most inflamed condition in NAFLDs, which more frequently evolves towards chronic and serious liver diseases) is characterized by a marked activation of inflammatory cells and the upregulation of several soluble inflammatory mediators. Among several mediators, cytokines and chemokines might play a pivotal active role in NAFLD and are considered as potential therapeutic targets. In this review, we will update evidence from both basic research and clinical studies on the potential role of cytokines and chemokines in the pathophysiology of NAFLD.

Prediction of severe acute pancreatitis:Current knowledge and novel insights

Acute pancreatitis (AP) is a common and potentially lethal acute inflammatory process with a highly variable clinical course. It is still unclear why some patients progress to organ failure and others do not. Physicians, ability to predict which patients will develop severe disease is limited. Routine clinical and laboratory data and multi-factorial clinical scores measured on admission and during the first 48 h of hospitalization are currently the standards of care used to estimate the magnitude of the inflammatory response to injury. Current literature highlights several common environmental, metabolic and genetic factors that increase the risk of AP development and subsequent adverse sequelae. Several cytokines have been found to play a critical role in the pathogenesis of AP by driving the subsequent inflammatory response, to include tumor necrosis factor-α (TNF-α), Interleukin-1 (IL-1), IL-6 and monocyte chemotactic protein-1 (MCP-1). Large, prospective studies are still needed to address these questions by identifying AP risk factors and serum biomarkers of severe disease.

Involvement of CXCR3-associated Chemokines in MHV-3 Induced Fulminant Hepatic Failure

The role of chemokines in murine hepatitis virus strain 3 (MHV-3) induced fulminant hepatic failure (FHF) is not well defined. In this study, we investigated the role of the CXC chemokine receptor 3 (CXCR3)- associated chemokine [monokine induced by IFN-gamma (Mig/CXCL9) and interferon-gamma-inducible protein 10 (IP-10/CXCL10)] in the recruitment of intrahepatic lymphocytes and subsequent fulminant hepatic failure induced by MHV-3. Balb/cJ mice (6-8 weeks, female) were intraperitioneally injected with 100 PFU MHV-3.The proportions and numbers of T cells and NK cells as well as the expression of CXCR3 on T cells and NK cells in the liver, spleen and blood were analyzed by flow cytometry. The hepatic mRNA level of the CXCR3-associated chemokines (CXCL9 and CXCL10) was detected by realtime PCR. A transwell migration assay was used to assess the chemotactic effect of MHV-3-infected hepatocytes on the splenic lymphocytes. Following MHV-3 infection, the number of hepatic NK cells and T cells and the frequencies of hepatic NK cells and T cells expressing CXCR3 increased markedly; however, in the spleen and peripheral blood, they both decreased significantly. Moreover, the hepatic mRNAs levels of CXCL9 and CXCL10 were significantly elevated post infection. The transwell migration assay demonstrated that MHV-3-infected hepatocytes have the capacity to attract and recruit the splenic NK cells and T cells, and CXCL10 plays a key role in lymphocyte mobilization from the spleen. These results suggest that the CXCR3- associated chemokines (CXCL9 and CXCL10) may play animportant role in the recruitment of intrahepatic lymphocytes and subsequent necroinflammation and hepatic failure in MHV-3 infection.

Expression of CC Chemokine Ligand 5 in Patients with Rheumatoid Arthritis and Its Correlation with Disease Activity and Medication

Objective To determine the levels of CC chemokine ligand 5 (CCL5) in serum and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and their relations with disease activity and medication. Methods CCL5 in serum and SF was quantified by enzyme-linked immunosorbent assay (ELISA) in 28 RA patients and 21 osteoarthritis (OA) patients. In RA patients, the correlations of CCL5 levels in serum and SF with disease activity were analyzed. Meanwhile, the serum CCL5 levels among RA patients treated with disease-modifying antirheumatic drugs (DMARDs), Tripterygium Glucosides, and other Chinese herbs without disease-modifying effects were also compared. Results CCL5 levels in both serum and SF of RA patients were significantly higher than those of OA patients (P<0.05). Moreover, the level of CCL5 was higher in SF than that in serum of RA patients (P<0.01). Serum CCL5 level was correlated significantly with the number of swollen joints (r=0.3329, P<0.05), erythrocyte sedimentation rate (r=0.4001, P<0.05), and C reactive protein (r=0.3735, P<0.01). In addition, the level of CCL5 had a trend of lower in patients treated with DMARDs or Tripterygium Glucosides than those treated with other Chinese herbs, although the difference was not significant among those patients due to the small number of patients in each group. Conclusions In RA patients, the expression of CCL5 increases and correlates with some clinical and laboratory parameters of RA, which indicate that CCL5 plays an important role in RA and may serve as a useful marker of disease activity. DMARDs and Tripterygium Glucosides might exert their clinical effects through reducing CCL5 production in RA.

Hepatitis B and C infection and liver disease trends among human immunodeficiency virus-infected individuals

AIM:To examine trends in and correlates of liver disease and viral hepatitis in an human immunodeficiency virus (HIV)-infected cohort. METHODS:The multi-site adult/adolescent spectrum of HIV-related diseases (ASD) followed 29 490 HIVinfected individuals receiving medical care in 11 U.S. metropolitan areas for an average of 2.4 years,and a total of 69 487 person-years,between 1998 and 2004. ASD collected data on the presentation,treatment,and outcomes of HIV,including liver disease,hepatitis screening,and hepatitis diagnoses. RESULTS:Incident liver disease,chronic hepatitis B virus (HBV),and hepatitis C virus (HCV) were diagnosed in 0.9,1.8,and 4.7 per 100 person-years. HBV and HCV screening increased from fewer than 20% to over 60% during this period of observation (P < 0.001). Deaths occurred in 57% of those diagnosed with liver disease relative to 15% overall (P < 0.001). Overall 10% of deaths occurred among individuals with a diagnosis of liver disease. Despite care guidelines promoting screening and vaccination for HBV and screening for HCV,screening and vaccination were not universally conducted or,if conducted,not documented. CONCLUSION:Due to high rates of incident liver disease,viral hepatitis screening,vaccination,and treatment among HIV-infected individuals should be a priority.

TEMPORAL TRENDS IN ETIOLOGY AND IN-HOSPITAL OUTCOME IN CHINESE PATIENTS WITH PERICARDIAL EFFUSION:10-YEAR EXPERIENCE OF A SINGLE CENTER

Objective To evaluate the evolution of etiology, clinical characteristics, and in-hospital outcomes of pericardial effusions in the recent decade. Methods All patients with a diagnosis of pericardial effusion during hospitalization were recruited from the Hospital Inpatient System between January 1996 and December 2005. Demographic and clinical characteristics, laboratory measurements, echocardiographic and treatment features, and in-hospital outcomes were retrospectively reviewed by using a standardized data collection form. Results One hundred and fifry-three consecutive patients were recruited. Mild, moderate and large pericardial effusion occurred in 61 （40%）, 52 （34%） and 40 （26%） patients, respectively. The most frequent etiologic diagnoses were tuberculous pericarditis （ n = 50, 33% ） , malignancy （ n = 36, 24% ） and idiopathic pericarditis （n = 35, 23% ）. Large effusions were more likely＇ associated with malignancy （P 〈 0. 01 ）. Compared to the initial 5 years （from 1996 to 2000） , the incidence of tuberculous effusion was decreased but neoplastic effusion increased significantly in the recent 5 ）,ears （from 2001 to 2005 ）. Forty-four patients underwent percardiocentesis （tuberculous in 23, neoplastic in 16, and others in 5） and 28 patients required pericardectomy （tuberculous in 11 and neoplastic in 17）. One patient with tuberculous and 3 patients with neoplastic pericardial effusion died during hospitalization. Conclusion Tuberculosis remains the major cause of pericardial effusion, but neoplastic pericardial effusions are on the rise. Pericardial drainage or pericardectomy are often required for symptomatic relief in those with malignancy-caused pericardial effusion.

Monocyte chemoattractant protein 1 expression in renal tissue is associated w ith monocyte recruitment and tubulo-interstitial lesions in patients with lup us nephritis

Objective To investigate the pattern of monocyte chemoattractant prolein-1 (MCP-1) distribution in the renal interstitium and evaluate its pathogenic role in tubulo-interstitial lesions in patients with lupus nephritis, the distribution of MCP-1 in renal tissue was observed.Methods Eighteen female patients with biopsy-proven lupus nephritis were enrolled in this study. No intensive immunosuppresive therapy was used in these patients during the 3 months prior to renal biopsy. The distribution of MCP-1, infiltration of CD68+ (macrophage/monocyte), CD4+ and CD8+ cells in the tubulo-interstitium of patients with lupus nephritis was detected using immunohistochemical staining with specific antibodies. Renal specimens from patients with minimal change glomerulonephritis were used as controls. Results MCP-1 protein was widely distributed in the renal tissue of patients with lupus nephritis, mainly located at the baso-lateral surface of tubular epithelial cells (16/18 biopsies), and on the wall of interstitial blood vessels (9/18 biopsies). In contrast, tubular MCP-1 staining was weak and rare in renal tissue from controls (7.4±6.2% vs 26.7±22.8%, P<0.01). Tubulo-interstitial infiltration of CD68+, CD4+ and CD8+ cells was markedly increased in patients with lupus nephritis as compared to controls. The tubular expression of MCP-1 was strongly associated with the amount of CD68+ cell infiltration in the interstitium (r=0.5420, P<0.05) and the extent of interstitial fibrosis. There was no correlation between MCP-1 production in tubules and the degree of urinary protein excretion in patients with lupus nephritis (r=0.0547, P>0.05).Conclusions The expression of MCP-1 in the renal tubules and vascular wall was markedly increased in patients with lupus nephritis. The overproduction of MCP-1 in renal tissue may contribute to monocyte recruitment in the interstitium and thus result in tubulo-interstitial damage in lupus nephritis.

Nationwide trends of hospital admissions for acute cholecystitis in the United States

Background and aims:Acute cholecystitis is a fairly common inpatient diagnosis among the gastrointestinal disorders.The aim of this study was to use a national database of US hospitals to evaluate the incidence and costs of hospital admissions associated with acute cholecystitis.Method:We analyzed the National Inpatient Sample Database(NIS)for all patients in which acute cholecystitis(ICD-9 codes:574.00,574.01,574.30,574.31,574.60,574.61 or 575.0)was the principal discharge diagnosis from 1997 to 2012.The NIS is the largest all-payer inpatient database in the United States and contains data from approximately 8 million hospital stays each year.The statistical significance of the difference in the number of hospital discharges,lengths of stay and associated hospital costs over the study period was determined by using the Chi-square test for trends.Results:In 1997,there were 149661 hospital admissions with a principal discharge diagnosis of acute cholecystitis,which increased to 215995 in 2012(P<0.001).The mean length of stay for acute cholecystitis decreased by 17% between 1997 and 2012(i.e.from 4.7 days to 3.9 days);(P<0.05).During the same time period,however,mean hospital charges have increased by 195.4% from US$14608 per patient in 1997 to US$43152 per patient in 2012(P<0.001).Conclusion:The number of inpatient discharges related to acute cholecystitis has increased significantly in the United States over the last 16 years,along with a great increase in the associated hospital charges.However,there has been a gradual decline in the mean length of stay.Inpatient costs associated with acute cholecystitis contribute significantly to the total healthcare bill.Further research on cost-effective evaluation and management of acute cholecystitis is required.