Specific molecular markers in hepatocellular carcinoma

BACKGROUND: The carcinogenesis of hepatocellular carcinoma (HCC) is a multi-factorial, multistep and complex process. Its prognosis is poor, and early diagnosis and monitoring metastasis of HCC is of the utmost importance. Circulating diagnostic and prognostic biomarkers could be used in proper postoperative treatment of patients at an early stage of HCC development. This review summarizes recent studies of the specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. DATA SOURCES: An English-language literature search was conducted using MEDLINE (June 1998 to Spetember 2006) on researches of some valuable specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. RESULTS: Hepatoma tissues can synthesize various tumor-related proteins, polypeptides, and isoenzymes, such as alpha-fetoprotein (AFP), hepatoma-specific gamma-glutamyl transpeptidase (HS-GGT), etc, and then secrete into blood. The valuable early diagnostic and prognostic biomarkers could predict the development an metastases of HCC. Recent researches have confirmed that circulating hepatoma-specific AFP subfraction, transforming growth factor (TGF)-beta 1, HS-GGT, and free insulin-like growth factor (IGF)-II may be more specific markers than total AFP level for early diagnosis for HCC. The circulating genetic markers such as AFP-mRNA, TGF-beta 1-mRNA, IGF-II-mRNA, etc from peripheral blood mononuclear cells of HCC patients have been most extensively used in monitoring distal metastasis or postoperative recurrence of HCC. CONCLUSIONS: Hepatoma tissues synthesize and secrete valuable molecular markers into blood. The analyses of circulating hepatoma-specific biomarkers are useful to early diagnosis of HCC or monitoring metastasis or postoperative recurrence of HCC.

Characteristics of general distribution of hepatitis B virus genotypes in China

BACKGROUND: Based on differences in the virus nucleotide sequence, hepatitis B virus (HBV) genotypes are presently divided into genotypes A-H. The geographic distributions of HBV genotypes differ in countries and regions. To determine the general characteristics of their distributions in the mainland of China, we reviewed articles on HBV genotypes published in China. METHODS: The Wanfang Database and the CNKI Database were searched for original articles involving HBV in China, and then the data from the articles were classified according to genotype and latitude and analyzed using SPSS 11.0. RESULTS: The main HBV genotypes were C, B and BC, and their rates were 50.99%, 35.58%, 6.07%, respectively; other genotypes were rare. There was a negative correlation between latitude and the rate of genotype B (r=-0.782, P<0.01), while a positive correlation existed between latitude and the rate of genotype C (r=0.646, P<0.01). No correlation was observed between latitude and the rates of other genotypes (r=0.294, P>0.05). CONCLUSIONS: In China, HBV genotype C predominates, followed by genotype C and mixed genotype BC; genotypes A, D and others are rare. With an increasing latitude, the distribution of genotype B decreases gradually, while that of genotype C tends to increase. The other genotypes do not show any changes.

Stapled transanal rectal resection for obstructed defecation syndrome associated with rectocele and rectal intussusception

AIM:To evaluate the safety and efficacy of stapled transanal rectal resection(STARR),and to analyze the outcome of the patients 12-mo after the operation.METHODS:From May 2007 to October 2008,50 female patients with rectocele and/or rectal intussusception underwent STARR.The preoperative status,perioperative and postoperative complications at baseline,3,6 and 12-mo were assessed.Data were collected prospectively from standardized questionnaires for the assessment of constipation[constipation scoring system,Longo’s obstructed defecation syndrome(ODS)score system,symptom severity score],patient satisfaction (visual analogue scale),and quality of life(Patient Assessment of Constipation-Quality of Life Questionnaire).RESULTS:At a 12-mo follow-up,significant improvement in the constipation scoring system,ODS score system,symptom severity score,visual analog scale and quality of life(P<0.0001)was observed.The symptoms of constipation improved in 90%of patients at 12 mo after surgery.The self-reported definitive outcome was excellent in 15(30%)patients,fairly good in 8(16%),good in 22(44%),and poor in 5(10%).CONCLUSION:STARR can be performed safely without major morbidity.Moreover,the procedure seems to be effective for patients with obstructed defecation associated with symptomatic rectocele and rectal intussusception.

Delayed hepatocarcinogenesis through antiangiogenic intervention in the nuclear factor-kappa B activation pathway in rats

BACKGROUND: The active form of nuclear factor-kappa B (NF-kappa B) is involved in the initiation, generation, and development of hepatocellular carcinoma (HCC), and is up-regulated in inflammation-associated malignancies. We investigated the dynamic expression of NF-kappa B and its influences on the occurrence of HCC through antiangiogenic (thalidomide) intervention in NF-kappa B activation. METHODS : Hepatoma models were induced with 2-fluorenylacetamide (2-FAA, 0.05%) in male Sprague-Dawley rats, and thalidomide (100 mg/kg body weight) was administered intragastrically to intervene in NF-kappa B activation. The pathological changes in the liver of sacrificed rats were assessed after hematoxylin and eosin staining. NF-kappa B mRNA was amplified by RT-nested PCR. The alterations of NF-kappa B and vascular endothelial growth factor (VEGF) expression were analyzed by enzyme-linked immunosorbent assay, immunohistochemistry, and Western blotting. RESULTS: Rat hepatocytes showed denatured, precancerous, and cancerous stages in hepatocarcinogenesis, with an increasing tendency of hepatic NF-kappa B, NF-kappa B mRNA, and VEGF expression, and their values in the HCC group were higher than those in controls (P<0.001). In the thalidomide-treated group, the morphologic changes generated only punctiform denaturation and necrosis at the early or middle stages, and nodular hyperplasia or a little atypical hyperplasia at the final stages, with the expression of NF-kappa B (chi(2)=9.93, P<0.001) and VEGF (chi(2)=8.024, P<0.001) lower than that in the 2-FAA group. CONCLUSION: NF-kappa B is overexpressed in hepatocarcinogenesis and antiangiogenic treatment down-regulates the expression of NF-kappa B and VEGF, and delays the occurrence of HCC. (Hepatobiliary Pancreat Dis Int 2010; 9: 169-174)

鼠伤寒沙门氏菌群体感应复苏oxyR基因缺失引起的VBNC状态

探讨鼠伤寒沙门氏菌oxyR基因缺失株引起的VBNC状态及其与群体感应的关系。运用同源重组的方法构建oxyR基因无痕缺失的鼠伤寒沙门氏菌并检测该菌株对H_2O_2的敏感性;将oxyR基因缺失株和亲本株(WT)涂布或滴于LB固体培养基,观察其是否生长及其浓度依赖性生长情况;用swimming和swarming平板检测oxyR基因缺失株和WT的运动能力;检测固体培养基和液体培养基中沙门氏菌分解H_2O_2的能力。成功构建了oxyR无痕缺失菌株;oxyR基因缺失株在0.1 mmol/L H_2O_2的LB平板上形成的菌苔发生了变形,在1 mmol/L H_2O_2的LB平板上不能生长,而WT均能生长;6×10~6和6×10~5 cfu/mL的WT涂布于LB平板上能长满菌苔,而等量的oxyR缺失株不能生长菌落;不同浓度的WT滴于LB平板均能形成菌苔,而oxyR缺失株仅在OD_(600)≥10^(-1)浓度时才能形成菌苔;oxyR缺失株泳动距离无显著性变化,而群集运动距离显著性大于WT;固体培养的沙门氏菌比液体培养的沙门氏菌有更强的分解H_2O_2的能力。鼠伤寒沙门氏菌的群体感应系统通过调控其群集运动和H_2O_2分解能力来复苏由oxyR基因缺失引起的VBNC状态。

Construction and characterization of calreticulin-HBsAg fusion gene recombinant adenovirus expression vector

AIM: To generate recombinant adenoviral vector con-taining calreticulin (CRT)-hepatitis B surface antigen (HBsAg) fusion gene for developing a safe, effective and HBsAg-specific therapeutic vaccine.METHODS: CRT and HBsAg gene were fused using polymerase chain reaction (PCR), endonuclease diges-tion and ligation methods. The fusion gene was cloned into pENTR/D-TOPO transfer vector after the base pairs of DNA (CACC) sequence was added to the 5′ end. Adenoviral expression vector containing CRT-HBsAg fusion gene was constructed by homologous recombinan-tion. The human embryo kidney (HEK) 293A cells were transfected with linearized DNA plasmid of the recombi-nant adenoviral vector to package and amplify recombi-nant adenovirus. The recombinant adenovirus titer was characterized using the end-dilution assay. The expres-sion of the CRT/HBsAg fusion protein in Ad-CRT/HBsAg infected 293A cells was detected by Western blotting.RESULTS: The CRT-HBsAg fusion gene was char-acterized by PCR and sequencing and its length and sequence were confirmed to be accurate. The CRT-HB-sAg fusion gene recombinant pENTR/D-TOPO transfer vector was constructed. The recombinant adenoviral vector, Ad-CRT/HBsAg, was generated successfully. The titer of Ad-CRT/HBsAg was characterized as 3.9 × 1011 pfu/mL. The CRT-HBsAg fusion protein was ex-pressed by HEK 293A cells correctly. CONCLUSION: CRT/HBsAg fusion gene recombinant replication-defective adenovirus expression vector is constructed successfully and this study has provided an experimental basis for further studies of Hepatitis B vi-rus gene therapy.

Multisite mutations of the PRSS1 gene in a Chinese patient with chronic pancreatitis

BACKGROUND: Chronic pancreatitis shows alterations in the trypsinogen gene (protease serine 1, PRSS1) in some individuals. The conversion of trypsinogen to trypsin in the pancreas is believed to be one of the causes of pancreatitis. This study was to identify the mutation of the PRSS1 gene in a Chinese patient with chronic pancreatitis and to analyze the clinical features of the disease. METHODS: In 6 patients with chronic pancreatitis and 120 normal controls, PRSS1 genes were amplified by the polymerase chain reaction and the products were analyzed by sequencing. RESULTS: Multisite mutations of PRSS1 were found in a patient with chronic pancreatitis. C to A mutation occurred in exon 3 of PRSS1, and T to A mutation in the same exon. These mutations were not found in normal controls or the patients with chronic pancreatitis. CONCLUSION: These are novel mutations in PRSS1.

Correlation study on Chinese medical syndrome types of chronic atrophic gastritis patients,Hp,and IL-1β polymorphism

Objective To explore the correlation between Chinese medical(CM)syndrome types of chronic atrophic gastritis(CAG)patients and Helicobacter pylori(Hp)infection,polymorphisms of IL-1B,and IL-1β.Methods Totally 192 CAG patients and 202 healthy subjects(as healthy control group)were recruited in this

The role of a novel protein ligand hMSH 2 in Vγ9δ2 T cell-mediated anti-cervix cancer immunity

Objective To explore the role of hMSH2,a novel endogenous tumor-associated protein ligand recognized by Vγ9δ2 T cells,in innate anti-cervix cancer immunity.Methods hMSH2 that expressed on the surface of cervical cancer cell line HeLa cells was blocked by specific antibody.Then the differences in their effects on Vγ9δ2T cells before and after antibody blockage were evaluated by cytotoxicity of Vγ9δ2 T cells and cytokines secretion.

Clinical features analysis of B-cell acute lymphoblastic leukemia with KMT2A::AFF1 gene expression

Objective To analyze the correlation between clinical features and prognosis or prognostic risk factors in patients with KMT2A::AFF1 gene positive B-ALL.Methods Retrospective cohort study was conducted.167cases of B-ALL admitted to the Shanghai General Hospital and the Naval Medical University Affiliated First Hospital from April 1,2011 to July 31.

Relationship between serum HER2 extracellular domain levels, tissue HER2 expression, and clinico-pathological parameters in early stage breast cancer

Background Measurement of human epidermal growth factor receptor 2 （HER2） protein in the serum of metastatic breast cancer patients has previously been reported, but there are no consistent data to support the clinical utility of serum HER2 extracellular domain for patients with early stage breast cancer. We aimed to evaluate the correlation between serum extracellular domain levels and tissue HER2 expression, and analyzed their relationship with clinico-pathological parameters in patients with early stage disease. Methods A prospective study was conducted on 232 breast cancer patients with stage I-III prior to treatment. Preoperative serum samples were measured by enzyme-linked immunosorbent assay. Tissue HER2 status was analyzed by immunohistochemistry and fluorescence in situ hybridization assays. Results The median serum extracellular domain concentration was 6.8 ng/ml. The best diagnostic cut-off value was 7.4 ng/ml, with 62.9% sensitivity and 85.3% specificity. High serum extracellular domain levels were reported in 89 patients （38.3%）, and HER2-positive expression was observed in 77 patients （33.2%）. Multivariate analysis showed that elevated serum extracellular domain correlated with postmenopausal status （P 〈0.001）, high histological grade （P 〈0.001）, negativity of both estrogen （P=0.012） and progesterone receptors （P 〈0.001）, and high levels of carcinoembryonic antigen 153 （P=-0.048）. Conclusions We recommend that 7.4 ng/ml should be used as the cut-off value when evaluating serum extracellular domain levels in early stage of breast cancer. Patients with high serum extracellular domain levels have a certain clinico- pathological characteristics, may provide a basis for clinical practice.

Unusual cause of acute renal failure from acute pyelonephritis due to Klebsiella pneumoniae in a young woman

To the editor： Acute pyelonephritis is a common kidney disease in female adult, but an unusual cause of acute renal failure（ARF）. We reported one woman suffered from acute pyelonephritis due to Klehsiella pneumoniae infection presented with ARF and unremarkable abdominal signs, however with a favorable prognosis after appropriate antibiotic treatment.A 23-year-old woman was admitted to the First Affiliated Hospital of Sun Yat-sen University with a 10-day history of abdominal bloating, lower flank pain; 3-day history of fatigue, without fever, urinary urgency, frequency, dysuria or oliguria. She had a history of taking the herbs medicine lbr removing urinary calculi （Wu Lin Hua Shi Dan and other unknown herbs） by herself for one week.

A retrospective study on the diagnostic value of bone marrow megakaryocyte micronuclei morphology for the hematological diseases

Objective To evaluate the value and significance o testing megakaryocyte micronuclei in bone marrow smear for hematopathy diagnosis.Methods Bone marrow smears from a total of 863 cases of patients with hemopa thy were collected from 2002 to 2009 at the second affili ated hospital of Zhejiang university school of medicine.Smears from 25 healthy individuals were used as control.

Joint detection of troponin T,high sensitivity C-reactive protein,N-terminal probrain natriuretic peptide applied in the diagnosis of acute coronary syndrome for elderly patients

Objective To investigate the value of the joint detection of Troponin T(TnT) ,highsensitivity C-reactive protein (hs-CRP) and N-terminal probrain natriuretic peptide(NT-proBNP) for the clinical diagnosis of acute coronary syndrome(ACS) in elderly patients.

The diagnostic value and clinical relevance of thrombelastography and light transmission aggregometry based identification of low response to clopidogrel in ACS patients after percutaneous coronary intervention

Objective To obtain the incidence of"clopidogrel low response"(CIR)of acute coronary syndrome(ACS)patients after percutaneous coronary intervention(PCI)by Thrombelastography(TEG)and Light transmission aggregometry(LTA),and explore the correlation of CLR with clinical related factors and major adverse cardiac e-

Application of fecal calprotectin and myeloperoxidase in evaluation of disease activity of ulcerative colitis

Objective To explore the clinical value of fecal calprotectin and myeloperoxidase in evaluation of ulcerative colitis(UC) activity.Methods Specimens of serum and feces over the same period were collected

Clinical application of whole blood red cell distribution width in lung cancer metastasis

Objective To investigate the clinical value of whole blood red cell distribution width(RDW)in discriminating lung cancer metastasis.Methods A retropective analysis was conducted on the patients who were initially diagnosed as primary lung cancer.A total of 525 patients were included for analysis between January 2012 and July2013,stratified by different stages and metastasis scenarios.RDW data was investigated.Kruskal-Wallis H

NJ001 specific antigen expression in lung adenocarcinoma and its clinical significance

Objective To evaluate the expression of NJ001 specific antigen in lung adenocarcinoma,and the relationship between the antigen and clinicopathological features.Methods A case-control study was conducted.Tumor tissues of 113 lung adenocarcinoma and 46 benignlung disease were collected from the First Affiliated Hospital of Nanjing Medical University.The expression of NJ001 specific antigen was examined by means of immunohistochemistry,and the results were scored by semi-

The relationship between plasma soluble receptor tyrosine kinase Mer /Tyro3 and acute coronary syndrome

Objective To investigate the concentrations of plasma Gas6 and its receptor in acute coronary syndrome patients and their dynamic changes after PCI.Methods In this case control study,we enrolled 66 ACS patients[(63.5±14.5)years age,40 males and 26 females]and 42 age and gender matched stable coronary heart disease patients