Objective: To investigate the expression of miR-212 and miR-132 in the serum of patients with primary liver cancer and their targeted regulation of GP73. Methods: The patients with liver cancer, chronic hepatitis B, or liver cirrhosis who were hospitalized in Taizhou People’s Hospital from January 2015 to December 2016 were enrolled, and healthy volunteers were also enrolled as controls. Quantitative real-time PCR was used to measure the serum levels of miR-212 and miR-132, and the association between the expression of serum miR-212 and miR-132 and the clinicopathological features of patients with liver cancer was analyzed. A Spearman’s rank correlation analysis was used to analyze the correlation between serum miR-212/miR-132 and GP73. Western blot was used to measure the protein expression of GP73, and MTT assay was used to measure the survival rate of cells. The Levene’s homogeneity of variance test was used for data analysis. The independent samples t-test was used for comparison of means between two samples, and ANOVA was used for comparison of means between multiple samples. Results: A total of 90 patients with liver cancer, 60 with chronic hepatitis B, 68 with liver cirrhosis, and 100 healthy volunteers were enrolled. The relative expression levels of miR-212 and miR-132 in serum were 0.046 6 ± 0.024 7 and 0.005 9 ± 0.003 0 in the patients with liver cancer, 0.979 7 ± 0.259 5 and 1.001 8 ± 0.249 9 in the healthy volunteers, 0.588 2 ± 0.216 5 and 0.345 7 ± 0.233 8 in the patients with hepatitis, and 0.313 8 ± 0.153 3 and 0.080 1 ± 0.042 66 in the patients with liver cirrhosis. Compared with the normal controls, all patients had significant reductions in the expression of serum miR-212 (t = 10.26, 20.86, and 35.80, all P < 0.01) and miR-132 (t = 16.55, 36.09, and 39.85, all P < 0.01). In the patients with liver cancer, the relative expression of miR-212 and miR-132 was negatively correlated with alpha-fetoprotein (miR-212: t = -4.46, P < 0.01; miR-132: t = -4.83, P < 0.01), TNM stage (miR-212: t = 6.569, P < 0.01; miR-132: t = 7.31, P < 0.01), degree of tumor differentiation (miR-212: t = 5.268, P < 0.01; miR-132: t = 5.914, P < 0.01), and presence of portal vein tumor thrombus (miR-212: t = 5.16, P < 0.01; miR-132: t = 3.681, P < 0.01), while it was not correlated with tumor size (miR-212: t = 0.687, P > 0.05; miR-132: t = 0.887, P > 0.05). In addition, serum miR-212 and miR-132 were negatively correlated with GP73 in the patients with liver cancer (miR-212: r_s = -0.709, P < 0.01; miR-132: r_s = -0.877, P < 0.01). Overexpression of miR-212 or miR-132 in HepG2 cells significantly inhibited the activity and expression of 3’-UTR, and interference of miR-212 or miR-132 significantly increased the activity and expression of 3’-UTR in GP73. Overexpression of GP73 reversed the reduction in survival rate of hepatoma cells induced by the overexpression of miR-212 or miR-132. Conclusion Patients with liver cancer have a significant reduction in the expression of miR-212 and miR-132 in serum, which is closely associated with the development, progression, and metastasis of liver cancer, and miR-212 and miR-132 in hepatoma cells inhibit the growth of liver cancer by targeted regulation of GP73 expression.

OBJECTIVETo explore the strategy for the treatment of chronic hepatitis B with YMDD mutation.

METHODSA total of 120 chronic hepatitis B patients with YMDD mutation were randomly assigned into four groups. In group A, patients received adefovir dipivoxil for 48 weeks. In group B, patients received adefovir dipivoxil in combination with lamivudine during the first 12 weeks and adefovir dipivoxil only for the following 36 weeks. In group C, patients received adefovir dipivoxil in combination with lamivudine for 48 weeks. In group D, patients received entecavir for 48 weeks.

RESULTSThe rate of rebound of alanine aminotransferase (ALT) was 30.0% (9/30), 10.0% (3/30), 6.7% (2/30), 10.0% (3/30) (P < 0.05) during the first 12 weeks, and one patient with severe hepatitis was found in group A. The positive rate of YMDD mutation was 17.9%, 0, 0, 0 at week 12. There was no significant difference in the level of ALT and the rate of HBeAg seroconversion after 48-week treatment (P > 0.05). At week 48, there was significant difference in the ALT normalization rate and undetectable HBV DNA rate between group C and group A, and also between group D and group A, and the rate of drug resistant genotype was 6.9%, 6.7%, 0, 0. Two patients had rtN236T mutation in group A, and one patient had rtN236T mutation and another one had rtA181V mutation in group B.

CONCLUSIONAdefovir dipivoxil in combination with lamivudine or entecavir are safe and effective therapies for chronic hepatitis B patients with YMDD mutation.

Adenine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Adult ; Alanine Transaminase ; blood ; Antiviral Agents ; administration & dosage ; therapeutic use ; DNA, Viral ; blood ; Drug Resistance, Viral ; Drug Therapy, Combination ; methods ; Female ; Follow-Up Studies ; Guanine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; drug effects ; genetics ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Lamivudine ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Mutation ; Organophosphonates ; administration & dosage ; therapeutic use ; Reverse Transcriptase Inhibitors ; administration & dosage ; therapeutic use ; Young Adult

OBJECTIVETo investigate bcl-6 protein expression and gene rearrangement patterns in diffuse large B-cell lymphoma (DLBCL) and their clinicopathologic significance.

METHODSImmunohistochemical studies for bcl-6 and CD10 proteins were performed on 51 cases of DLBCL paraffin-embedded tissues (including 22 nodal samples and 29 extranodal samples) and 10 cases of reactive lymphoid hyperplasia (RLH) paraffin-embedded tissues. Interphase fluorescence in-situ hybridization (FISH) with dual color breakapart probe was also used to identify rearrangement of bcl-6 gene in 32 cases of nodal DLBCL tissues (including 22 paraffin-embedded samples and 10 fresh samples) and 5 cases of RLH paraffin-embedded tissues.

RESULTS(1) The rates of bcl-6 protein expression in nodal DLBCL, extranodal DLBCL and RLH were 72.7% (16/22), 75.9% (22/29) and 100.0% (10/10) respectively. The rates of CD10 expression were 40.9% (9/22), 41.4% (12/29) and 100.0% (10/10) respectively. All lymphoma samples which expressed CD10 also showed co-expression of bcl-6 protein. (2) The co-expression of bcl-6 and CD10 was observed in 40.9% (9/22) nodal DLBCL and 41.4% (12/29) extranodal DLBCL. Low clinical stage (stage I and II) was more frequently observed in cases with co-expression of bcl-6 and CD10 (P < 0.05). (3) The rates of bcl-6 gene rearrangement in nodal DLBCL was 28.1% (9/32), with 27.3% (6/22) in paraffin-embedded tissues and 30.0% (3/10) in fresh tissues. There was no statistically significant difference found between the two groups (P > 0.05). Bcl-6 gene rearrangement was not found in all the 5 cases of RLH, and there was a significant difference between RLH and DLBCL (P < 0.05).

CONCLUSIONSThe rate of bcl-6 protein expression is high in DLBCL cases, and the detection of bcl-6 and CD10 protein co-expression may help in the diagnosis and differential diagnosis of DLBCL. Those DLBCL cases with co-expression of bcl-6 and CD10 may also have a better prognostic implication. On the other hand, bcl-6 gene rearrangement can be identified by interphase FISH with dual color breakapart probe in both paraffin-embedded and fresh lymphoma tissues.

Diagnosis, Differential ; Female ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Lymphoma, B-Cell ; genetics ; metabolism ; pathology ; Lymphoma, Large B-Cell, Diffuse ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Neprilysin ; metabolism ; Proto-Oncogene Proteins c-bcl-6 ; genetics ; metabolism ; Pseudolymphoma ; genetics

OBJECTIVETo investigate BCL-6 gene mutations in B-cell non-Hodgkin lymphomas (B-NHL) and their implications in lymphoma pathogenesis.

METHODSPolymerase chain reaction (PCR) and direct DNA sequencing methods were used to identify mutations in the 5'-noncoding region of BCL-6 gene in 135 cases of B-NHL, 5 cases of T-NHL, 5 cases of nodular lymphocyte predominance Hodgkin's lymphoma (NLPHL) and 10 cases of reactive hyperplasia of lymph node.

RESULTSMutations were identified in 6 cases of nodal DLBCL (27.3%), 4 cases of FL (22.2%), 4 cases of MALT lymphoma (22.2%), 4 cases of extranodal DLBCL (20.7%) and 2 cases of LRH (20%). No mutations were detected in T-NHL and NLPHL (P < 0.05). There were no significant differences in incidences of BCL-6 gene mutations between nodal and extranodal DLBCL (P > 0.05). All mutations were base substitutions and the frequency of single-base change was 0.14 x 10(-2)/bp approximately 0.68 x 10(-2)/bp.

CONCLUSIONSMutations of the 5'non-coding region of BCL-6 gene may be involved in the pathogenesis and progression of B-NHL. Molecular demonstration of such mutations may provide a marker of lymphomas derived from the germinal center-related B cells.

5' Untranslated Regions ; genetics ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Base Sequence ; Child ; DNA-Binding Proteins ; genetics ; Female ; Humans ; Lymphoma, B-Cell ; genetics ; pathology ; Lymphoma, Non-Hodgkin ; genetics ; pathology ; Male ; Middle Aged ; Molecular Sequence Data ; Point Mutation ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins c-bcl-6 ; Transcription Factors ; genetics

BACKGROUNDA few recent studies have reported that inflammation is associated with the prognosis of acute aortic dissection (AD). There is, however, no systemic investigation regarding the role of plasma C-reactive protein (CRP) and white blood cell (WBC) levels in predicting in-hospital clinical events of acute type A AD.

METHODSThe levels of high-sensitivity CRP and WBC counts were systemically determined after admission in 36 patients with acute type A AD. The variations of plasma CRP and WBC levels in different time windows (admission, 1, 2, 3, 4, 6, 8 days) in patients with acute type A AD were analyzed between patients with events and without events.

RESULTSDuring hospitalization, five patients died, and increased levels of CRP and WBC were found in patients died with acute type A AD compared with patients survived (P < 0.01, respectively). Medical treatment may significantly decrease inflammatory response in survived patients with acute type A AD. Additionally, patients with complication of pleural effusion showed higher CRP and WBC levels (P = 0.046, P = 0.018, respectively). Lower WBC levels were found in survived patients treated medically (P = 0.001). Moreover, mean CRP and WBC levels had positive correlations with aortic diameter (r = 0.364, P = 0.000; r = 0.333, P = 0.000, respectively) and age (r = 0.270, P = 0.000, respectively), while negative correlations with the time from onset of symptoms to hospital admission (r = -0.229, P = 0.000, r = -0.200, P = 0.002, respectively). Univariate analysis showed that age ≥ 65 years, CRP ≥ 12.05 mg/L, WBC ≥ 12.16 × 10(9)/L, aortic diameter ≥ 48 mm, pleural effusion and diastolic blood pressure ≥ 105 mmHg were associated with hospital mortality. While CRP ≥ 12.05 mg/L, WBC ≥ 12.16 × 10(9)/L, aortic diameter ≥ 48 mm were strongly associated with hospital mortality in multiple Logistic regression analysis.

CONCLUSIONSThe results suggested that CRP and WBC were preferred markers for predicting the clinical events in patients with acute type A AD, especially death during hospitalization. Therefore, further study enrolling larger cohort, prospective study would be warranted.

Adult ; Aneurysm, Dissecting ; blood ; diagnosis ; Aortic Aneurysm, Thoracic ; blood ; diagnosis ; C-Reactive Protein ; metabolism ; Female ; Humans ; Leukocyte Count ; methods ; Logistic Models ; Male ; Middle Aged

OBJECTIVESTo explore the clinical and pathological features and the pathogenesis of primary biliary cirrhosis (PBC) in Chinese Mainland.

METHODS30 PBC patients were divided into the early group (Scheuer stage I and II, 19 patients) and the late group (Scheuer stage III and IV, 11 patients). The data of clinics and serology were analyzed, and the pathological features of the liver tissues were characterized. The changes of dendritic cells (DCs) and hepatic stellate cells (HSCs) were studied by immunohistochemistry.

RESULTSIn all the PBC patients, the rate of the male to the female was 1 to 5, and the average age was 40.6 years. The mean levels of TBiL, ALP and GGT in the sera were (95.9+-88.5) micromol/L, (537.2+-339.2) U/L, and (582.0+-351.2) U/L, respectively. 73.3% patients showed AMA positive, and the level of GGT was positively correlated with the AMA level according to the result of statistical analysis (r=0.778, P=0.000). The symptoms of jaundice and hepatomegaly were presented more commonly in the late group than those in the early group (chi2=5.182, P<0.05; chi2=13.659, P<0.01, respectively). The main changes of morphology of PBC located in portal tracts. The liver tissues in the early stage of PBC showed the damage of bile ducts and obvious proliferation of small bile ducts. The granulomas, the lymphoid follicles and the foamy cells were found in the liver tissues of PBC (2/19 patients, 12/19 patients, and 10/19 patients in the early stage respectively, while 0/11 patients, 4/11 patients, and 3/11 patients in the late stage respectively). There was significant difference between the early stage and the late stage in presence of the lymphoid follicles and the foamy cells (t=4.489, P<0.05; t=4.019, P<0.05, respectively). The biliary pigmentary particles were mainly accumulated in the liver cells around the portal tracts in 90.0% PBC patients, and the accumulation of copper and iron increased, compared with that in normal specimens. The DCs and HSCs located mainly in the portal tracts, especially around the damaged bile ducts.

CONCLUSIONSThere are some clinical and pathological characteristics in the patients with PBC. The level of AMA has no direct relationship with the level of transaminase or bilirubin. The proliferated bile ductules may express the antigens which maybe the target of immune attack. As an antigen-presenting cell, DCs may play an important role in the pathogenesis of PBC.

Adolescent ; Adult ; Antibodies, Antinuclear ; blood ; Antigen-Presenting Cells ; immunology ; pathology ; Dendritic Cells ; pathology ; Female ; Humans ; Liver ; pathology ; Liver Cirrhosis, Biliary ; etiology ; immunology ; pathology ; Male ; Middle Aged ; Mitochondria ; immunology

OBJECTIVETo compare screw's inserting angle through the 11th and 12th rib in treating L1 burst fracture, explore effects on inserting screw and postoperative angle.

METHODSFrom October 2007 to October 2010, 108 patients with L1 brust fracture treated through anterior approach were analyzed,including 68 males and 40 females, aged from 21 to 64 years (mean 38.22 years). All patients were divided into the 11th (A, 51 cases) and 12th (B, 57 cases) approach. The data of operation time,blood loss, duration of incision pain, JOA score, Oswestry score, VAS score, quality of life (SF-36), recovery of nervous function, coronal Cobb angle, included angle between screw and plate were observed.

RESULTSAll patients were followed up for 9 to 37 months, mean 23 months. The operation time, blood loss, duration of incision pain, in group A were lower than group B (P<0.05), JOA score, Oswestry score, VAS score, SF-36, recovery of nervous function had no significant differences (P>0.05). There were no differences in Cobb angle before operation, but had significance after operation (P=0.000). There were statistically significance between two group in angle between screw and plate (P=0.000, P=0.003).

CONCLUSIONThe 11th rib approach for the treatment of L1 burst fracture has less effects on screw, less trauma and less angle between screw and plate.

Adult ; Bone Screws ; Female ; Fracture Fixation, Internal ; adverse effects ; instrumentation ; Humans ; Male ; Middle Aged ; Postoperative Complications ; Recovery of Function ; Rib Fractures ; diagnostic imaging ; physiopathology ; surgery ; Ribs ; surgery ; Spinal Cord ; physiopathology ; Tomography, X-Ray Computed ; Young Adult

With the enormous resources having been invested in oncology drugs development in China in recent years, the Center for Drug Evaluation (CDE) of National Medical Products Administration has been issuing a number of technical guidelines to further standardize the requirements on implementation and registration of domestic oncology clinical trials. As data is the cornerstone of clinical trials, data integrity and quality will directly decide the outcome of clinical studies. Given the specific characteristics of oncology therapeutic clinical trials, and combined with the clinical data standards established by the Clinical Data Interchange Standards Consortium (CDISC) and the issued industrial guidelines, this article introduces the general considerations of clinical data management for oncology clinical trials, with the aim of emphasizing normative data collection and timely data monitoring to ensure the data quality and reliability of results of the study. This article discusses the impact of complex study design on CRF, design CRF according to CDASH, develop DVP scientifically, rolling submissions and data cut-off.

BACKGROUNDTo explore the pathological features and pathogenesis of severe acute respiratory syndrome (SARS) to provide evidence for the clinical treatment and prevention of SARS.

METHODSPathological features of 2 cases of full autopsy and 4 cases of needle biopsy tissue samples from the patients who died from SARS were studied by light and electron microscopy. The distribution and quantity of lymphocyte subpopulations in the lungs and immune organs from SARS patients were analyzed by immunohistochemistry. The location and semi-quantitative analysis of SARS coronavirus in the tissue specimens were studied by electron microscopy, in situ hybridization and immunohistochemistry.

RESULTSIn total of 6 cases, diffuse alveolar damage and alveolar cell proliferation were common. The major pathological changes of 2 autopsy cases of SARS in lung tissues were acute pulmonary interstitial and alveolar exudative inflammation, and 2 autopsy and one biopsy lung tissues showed alveolar hyaline membrane formation. Terminal bronchiolar and alveolar desquamation of lung tissues in one autopsy and 2 biopsy cases were noted. Among 6 cases, 2 biopsy cases presented early pulmonary fibrosis and alveolar organization. Meanwhile, the immune organs, including lymph nodes and spleens from 2 autopsy cases of SARS whose disease courses were less than 12 days showed extensive hemorrhagic necrosis, reactive macrophage/histocyte proliferation, with relative depression of mononuclear and granulocytic clones in the bone marrows. However, spleen and bone marrow biopsy tissue samples from 4 dead SARS cases whose clinical course lasted from 21 to 40 days presented repairing changes. SARS coronaviruses were mainly identified in type I and II alveolar epithelia, macrophages, and endothelia; meanwhile, some renal tubular epithelial cells, cardiomyocytes, mucosal and crypt epithelial cells of gastrointestinal tracts, parenchymal cells in adrenal glands, lymphocytes, testicular epithelial cells and Leydig's cells were also detected by electron microscopy combined with in situ hybridization. The semi-quantitative analysis of lymphocyte subpopulations revealed that the proportion of CD8+ T lymphocytes were about 80% of the total infiltrative inflammatory cells in the pulmonary interstitium, with a few CD4+ lymphocytes CD3+, CD4+, CD8+ or CD20+ lymphocyte subpopulations were obviously decreased and there was imbalance in number and proportion, while CD57+, CD68+, S-100+ and HLA-DR+ cells were relatively increased in lymph nodes and spleens.

CONCLUSIONSHistologically, the pulmonary changes could be divided into acute inflammatory exudative, terminal bronchiolar and alveolar desquamative and proliferative repair stages or types during the pathological process of SARS. SARS coronavirus was found in multi-target cells in vivo, which means that SARS coronavirus might cause multi-organ damages which were predominant in lungs. There were varying degrees of decrease and imbalance in number and proportion of lymphocyte subpopulations in the immune organs of the patients with SARS. However, these changes may be reversible. It was found that cellular immune responses were predominant in the lungs of SARS cases, which might play an important role in getting rid of coronaviruses in infected cells and inducing immune mediated injury.

Aged ; Female ; Humans ; Lung ; immunology ; pathology ; virology ; Lymphocyte Subsets ; immunology ; Male ; Middle Aged ; SARS Virus ; isolation & purification ; ultrastructure ; Severe Acute Respiratory Syndrome ; immunology ; pathology ; virology

BACKGROUNDTo explore the cut-off period of subclassification and pathological features of severe hepatitis (SH).

METHODSBased on combined clinical and pathological analyses, the complete clinical and biopsy or autopsy liver tissues data from 196 cases of patients with severe hepatitis were investigated. Meanwhile, proliferative hepatocytes, cholangioepithelia and collagens were identified by a panel of monoclonal antibodies such as those against albumin, cytokeratin 18,19 and collagen I, III with immunohistochemical method.

RESULTSThe clinical and pathological analyses indicated the cut-off periods of acute, subacute and chronic SH (ASH,SSH and CSH) were (13.4+/-7.2) d, (77.4+/-69.3) d and (80.5+/-63.2) d, respectively. Among all SH cases, one case of ASH patient presented clinical manifestation and pathological changes of ASH for 21 days, however, one patient with SSH was demonstrated 12 day course by histological examination. The time of cut-off period between ASH and SSH in child cases was shorter than that in adult cases. Histologically, ASH liver tissues showed massive and/or submassive necrosis caused by one attack, with congestive sinusoid frameworks and proliferative cholangioepithelium-like hepatocytes, while SSH liver tissues presented combined fresh and old submassive or massive necrosis caused by multiple attacks, accompanied by obviously proliferative bile ducts and sinusoid framework collapse.However, the pathological changes of CSH showed ASH- or SSH-like lesions on the background of chronic liver injury.

CONCLUSIONOur data indicated that the cut-off period between ASH and SSH is in accordance with the Scheme of Viral Hepatitis Prevention and Therapy, China, published in 2000, but excluded a part of child SH cases. In our study, the authors found a few pathological features in ASH and SSH.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Collagen ; metabolism ; Female ; Hepatitis ; classification ; metabolism ; pathology ; Humans ; Keratins, Type I ; metabolism ; Liver ; pathology ; Male ; Middle Aged ; Young Adult