Objective To investigate the association between single nucleotide polymorphisms (SNPs)in cytokine IL-6, IL- 10 genes and HBV-related hepatocellular carcinoma(HCC). Methods A hospital-based case-control study was conducted in 381 cases with HBV-related HCC, 340 HBsAg carriers and 359 non-tumor controls. Genotypes of-572 site of IL-6 gene and-819, -592 sites of IL-10 gene were determined by real-time polymorphism chain reaction. Unconditional logistic regression was used to estimate the odds ratios(ORs)and 95 confidence intervals(C/s). Results For the G/C alleles of -572 loci on IL-6 gene, there were significant differences between the three groups(P＜0.05). Compared with CC genotype, GG genotype increased the risk of HBV infection (OR=2.171,95% Ch 1.068-4.415), but did not seem to be associated with HCC. For the alleles of-819 and -592 site of IL-10 gene, there were significant differences between the three groups(P＜0.05). Compared with CC genotype, TT genotype increased the risks of both HCC(OR=2.791,95%CI:1.326-5.874), and HCC in HBsAg carriers(0R=3.522,95%CI: 1.707-7.266). When compared with CC genotype on -592 site, the AA genotype reduced the risk of both HCC(OR=0.389, 95% CI:0.173-0.875), and HCC in HBsAg carriers(OR=0.336, 95% CI: 0.154-0.734). Conclusion The SNPs in -572 site of IL-6 gone might be associated with the risk of HBV infection. The SNPs in -819 site of IL-10 gene increased the risk of HCC, but -592 site of IL-10 gene decreased the risk of HCC.

Objective To explore the effects of thyroid hormone on the expression of homeobox gene Nkx6.1 in offspring of hypothyroidism rats and the relationship between gene expression and hormone level by supplying their hypothyroidism pregnant mother with thyroid hormone. Method A total of 240 Wistar rats were half nude and half female. Female rats were randomly divided into eight groups: control, hypothyroidism group, hypothyroidism groups which were supplied with thyroid hormone in high, medium and low dosage in early stage(1- 17 d) and in late stage( 18 - 20 d). According to 100 grams of body weight, the concentration of thyroid hormone were 3.5,2.0,0.5 μg/d in high, medium and low dosage group. All the rats were fed with low-iodine food. The normal control group was given KIO_3 solution and the other groups were given deionized water. After three months female rats were mated with male rats. The content of Nkx6.1 mRNA in brain tissue of 17-day fetal rats, new-born and 20- day old offspring by real-time fluorescence quantitative PCR techniques. Results①A rat model of hypothyroidism was successfully established, there were statistical significance between 8 groups in TT_3,TT_4,FT_3,FT_4(F=4.08,31.99,5.79,26.34, all P < 0.01 ). ② The expression of Nkx6.1 mRNA had significant difference(F = 758.720, 1121.589,144.716, all P < 0.01 ) between groups in 17-day fetal rats, new-bern and 20-day old offsprings and intra- groups in different time (F=2898.863,325.605,716.285,56.329,236.727,196.678,7115.752,9152.306, all P < 0.01 ). ③The time factor and dosage factor had influence on Nkx6.1 mRNA expression(F = 1176.655,246.530, all P < 0.01 ). There were interaction between time and dosage factor(F = 1249.934, P < 0.01 ). ④Comparison of Nkx6.1 mRNA expression between hypothyroidism group and normal control group had significant difference in the above three time points(all P < 0.01 ). ⑤Comparisons of Nkx6.1 mRNA expression between 6 hypothyroidism groups which were supplied with thyroid hormone and hypothyroidism group had significant difference(all P < 0.01 ) in new-bern and 20-day old offspring; comparisons of Nkx6.1 mRNA expression between hypothyroidism groups which were supplied with high and medium thyroid hormone and hypothyroidism group had significant difference in 17-day fetal rats(all P < 0.01 ). ⑥Comparison of Nkx6.1 mRNA expression between hypothyroidism groups which were supplied with medium thyroid hormone in early stage and normal control group had no statistical significance (all P > 0.05), while between the other 5 groups which were supplied with thyroid hormone and normal control group had significant difference(all P < 0.01 ) in the above three time points.⑦Multiple comparison of early stage groups which were supplied with thyroid hormone showed that the expression of Nkx6.1 mRNA had significant difference(all P < 0.01) between high, low dosage groups and medium group in 17-day fetal rats, new-bern and 20-day offspring(all P< 0.01). ⑧Multiple comparison of late stage groups supplied with thyroid hormone showed that old offspring and between high dosage groups and low dosage groups in 17-day fetal rats and 20-day the expression of Nkx6.1 mRNA had significant difference(all P < 0.01 ) between three groups in new-bern and 20- day old offspring. Conclusion The expression of Nkx6.1 in rats offspring is highly related to the supply dosage and supply time of thyroid hormone in hypothyroidism pregnant rats.

To study the relationship between the interleukin (IL)6 -572G/C polymorphism and risk of hepatocellular carcinoma (HCC) in men.A hospital-based case-control study was conducted with 500 male HCC patients without tumor history in other organs and 590 healthy male controls without history of tumors or chronic diseases. All HCC cases were diagnosed by histopathology. The controls were recruited from the Department of Orthopedic Trauma and Ophthalmology at the same hospital. The IL-6 promoter -572G/C polymorphism and its genotype variants were detected by real-time fluorescence quantitative PCR. The Chi-squared test and unconditional logistic regression analyses were applied to determine the risk of HCC among men carrying the different genotype variants.The frequencies of alleles and distribution of genotypes in the -572G/C loci were not significantly different between the HCC cases and controls (P more than 0.05). The Chi-squared test indicated that the polymorphisms of the loci were not associated with HCC in our male population. However, after adjusting by multivariate logistic regression, the odds ratio (OR) of HCC for the G allele (CG + GG genotypes) carriers was 1.31 (95% confidence interval (CI): 1.00 - 1.71) compared with the CC genotype. Among the male HBV carriers, the CG genotype increased HCC risk significantly (OR = 1.60, 95% CI: 1.14 - 2.24) compared with the CC genotype. A trend test indicated that HCC risk was significantly increased with the numbers of G alleles (P trend less than 0.05). Breslow-Day tests of homogeneity of the ORs indicated an interaction between hepatitis B virus (HBV) infection and polymorphisms of IL-6 (P less than 0.05). The synthetic odds ratio (OReg) of HBV infection and harboring a G allele was 5.95 (95% CI: 3.99-8.87), which represented a super multiplication interaction.Polymorphism of the IL-6 promoter -572 loci may be associated with HCC occurrence in men. Moreover, there is a super multiplication interaction for HCC risk between HBV infection and harboring the IL-6 G allele.
Adult ; Alleles ; Carcinoma, Hepatocellular ; genetics ; pathology ; Case-Control Studies ; Genotype ; Humans ; Interleukin-6 ; genetics ; Liver Neoplasms ; genetics ; pathology ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Risk Factors

OBJECTIVETo explore the half life and retention of Imipenem in the third space.

METHODSEight severely burned patients and eight healthy volunteers were enrolled as the burn group (B) and normal control group (C), respectively. HPLC (high performance liquid chromatography) was employed to determine the contents of Imipenem in the plasma, subeschar tissue fluid (STF) and the changes in its pharmacokinetics. Furthermore, the Imipenem content in the third space was calculated according to the systemic edema degree.

RESULTSThe half life of Imipenem in STF (2.53 h) was longer than that in plasma (1.73 h), P < 0.05). The Imipenem content in STF increased gradually along with the lapse of time after repeated intravenous infusion of Imipenem, and at the same the total content of imipenem was increased significantly in the third space.

CONCLUSIONThere was antibiotic retention in the third space after severe burn injury, and a prolonged action of the drug could be expected when the drug re-entered the blood stream.

Adolescent ; Adult ; Anti-Bacterial Agents ; pharmacokinetics ; therapeutic use ; Burns ; drug therapy ; metabolism ; Case-Control Studies ; Exudates and Transudates ; metabolism ; Female ; Half-Life ; Humans ; Imipenem ; pharmacokinetics ; therapeutic use ; Male ; Young Adult

OBJECTIVETo investigate the value of serum soluble CD40 ligand (sCD40L) detection in risk evaluation of acute coronary syndromes (ACS).

METHODSThis study involved 200 patients with established diagnosis of ACS, with death or nonfatal myocardial infarction as the end point of observation during the 6-month-long follow-up. Blood samples were obtained from the patients within the initial 72 h of ACS onset, and the levels of sCD40L and C-reactive protein (CRP) were determined with enzyme-linked immunosorbent assay (ELISA). Cardiac troponin I (cTnI) measurement was performed using chemiluminescent immunoassay.

RESULTSOf the 200 patients, 108 had serum sCD40L levels higher than 5.0 microg/L, and the levels of sCD40L, CRP and cTnI were found to significantly correlate with ACS.

CONCLUSIONIndependent detection of serum sCD40L, CRP and cTnI can help predict the risks of ACS, and their combined measurement may increase the sensitivity of the risk prediction and provide new cardiac makers to replace the cardiac enzymes for laboratory diagnosis and risk evaluation of cardiovascular events.

Acute Coronary Syndrome ; blood ; complications ; diagnosis ; Aged ; Biomarkers ; blood ; C-Reactive Protein ; metabolism ; CD40 Ligand ; blood ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; blood ; etiology ; Predictive Value of Tests ; Risk Factors ; Troponin I ; blood

AIMTo explore the synthetic methods of polypeptides containing new heart of kidney imaging agents.

METHODS AND RESULTSFive new target chelators--2-N-(2'-s-triphenylmethylacetyl) amino-(N'-2"-N",N"-diethylethylamine) phenylpropamide (MPNE), 2-N-(2'-s-triphenylmethyl acetyl) amino-(N'-2"-N",N"-dimethylethylamine) phenylpropamide (MPNM), 2-N-(2's-triphenylmethylacetyl) amino-3-methyl-(N'-2"-N",N"-dimethylethylamine) butyramide (MVNM), 2-N-(2'-s-triphenyl methylacetyl) amino-3-methyl-(N'-2"-N",N"-diethylethylamine) butyramide (MVNE), 2-N-(2'-s-triphenylmethylacetyl) amino-(N'-acetylglycine) phenylpropamide (MPG2)--were synthesized through five steps with mercaptoacetic acid as primitive materials, all of which were identified on the basis of spectroscopic data, such as IR, 1HNMR, MS or elementary analysis. The protection of the mercapto group was improved and the relatively new reaction condition of active ester with amino acid is developed. All the chelators were labeled with Technetium-99m and their biological activities in mice given in ID values was tested to explore new heart imaging agents, where ID is the percentage injected dose per organ. The ID was determined by in vivo biodistribution study. Tc-99m complexes 0.1 mL was injected into the laterial tail vein of 3 anaesthetised rats. At 2, 5, 10, 30, 60 min post-injection, rats were sacrificed by decapitation, bled from the neck and dissected. Organs were removed at dissection. The radioactivities in various organs were determined in an automatic twin crystal gamma counter.

CONCLUSIONThe bio-distribution results in mice indicate that 99Tcm-MVNM have higher heart uptake (ID = 8.40%/g, 2 min post-injection) and quicker blood clearance (ID = 4.3%/g, 60 min post-injection); 99Tcm-MPNE and 99Tcm-MPNM also have fairly high heart uptake and quick blood clearance; 99Tcm-MPG2 has better kidney accumulation and higher activity ratios of kidney to blood (about 4).

Amides ; chemical synthesis ; pharmacokinetics ; Animals ; Kidney ; metabolism ; Mice ; Molecular Structure ; Myocardium ; metabolism ; Organotechnetium Compounds ; chemical synthesis ; pharmacokinetics ; Peptides ; chemical synthesis ; chemistry ; pharmacokinetics ; Sulfides ; chemical synthesis ; pharmacokinetics ; Tissue Distribution

Objective To investigate the flexibility of both the covered stents specially designed for use in intracranial vasculature and the delivering system in passing through the bone tube and the physiological curves of the cranial internal carotid artery(CICA)to reach the targeted area,the performance (adherence)of the covered stents in occluding vascular wall diseases and the impact on the vascular branches of the covered segment.Methods The covered stents specially designed for use in intracranial vaseulature were used to treat 13 patients with CICA diseases using endovascular techniques.There were 4 huge pseudoaneurysms,4 giant aneurysms,3 small wide-necked aneurysms,1 giant pseudoaneurysm with concurrent internal carotid cavernous fistula(CCF),and 1 CCF.Prior to the detachment of the covered stents,balloon occlusion test(BOT)of the internal carotid artery on the diseased side and whole-brain digital subtraction angiography(DSA)were performed in all the patients.Three to 16 months following procedure,DSA and clinical follow-ups were performed.Results Thirteen patients all tolerated the BOT well with the DSA demonstrating well-opened anterior and posterior communicating arteries.The covered stents and the delivering systems all successfully passed CICA to reach the targeted diseased area,with the diseased segments of the internal carotid artery including C3—C4 in 4 cases,C4—C5 in 4 and C6—C7 in 5.Immediately following the detachment of the covered stents,DSA demonstrated that 7 aneurysms were completely occluded,4 aneurysms had slight endoleak,and 1 CCF had markedly-decreased blood flow through the fistula.In the patient with concurrent pseudoaneurysm and CCF,the pseudoaneurysm disappeared and the blood flow through the fistula was markedly-reduced immediately following the stenting procedure.Apart from one patient with aneurysmal subarachnoid hemorrhage who died due to extensive vascular spasm on the 9th day following the stenting procedure,all the other 12 patients had unobstructed stented vessels on the follow-up DSA images,with 2 demonstrating slight stenosis.In the 6 patients with post-procedure endoleak,DSA showed that the endoleak in 4 patients had disappeared,one endoleak disappeared following the second stenting,and one CCF remained low-flow fistula.There was no sequela related to the occlusion of branches in the covered arterial segment.Conclusion The covered stents specially designed for use in the intracranial vasculature and the delivering system are both flexible enough to pass the tortuous CICA to reach the intracranial diseased artery,and are effective in managing CICA diseases.Further follow-up is still needed to determine the long-term effect of the covered stents,and the adherence of the covered stents needs further investigation.

Objective:To obtain a high specificity and high affinity anti-PcrV protein monoclonal antibody which can be used for the treatment of Pseudomonas aeruginosa infected.Methods: The PcrV gene was amplified by PCR using P.aeruginosa PAO1 genome DNA as the template.The expression vector(pET-28a-PcrV) was constructed and transformed into E.coli BL21(DE3).The re-combinant PcrV protein was expressed by IPTG induction and purified by Ni2+affinity chromatography.The specific binders of PcrV were screened by phage display.The genes encoding VH and VL were amplified respectively by PCR using the plasmid of positive clone as the template.Then the recombinant expression vectors were constructed and transfected into 293E cells.Monoclonal antibody were purified by the Protein A affinity resin from the culture supernatants.The affinity of antibody was detected by ELISA and the function of YG5 was verified in murine pneumonia model caused by P.aeruginosa.Results: Recombinant PcrV protein was expressed and purified.A full human monoclonal antibody(named as YG5) against PcrV was obtained by phage display.The results of ELISA showed that YG5 had a high affinity with EC50=61 ng/ml.Furthermore,it was found that YG5 could protect mice from infection caused by P.aeruginosa.Conclusion:Our findings present a novel human monoclonal antibody YG5 against PcrV,which inhibits the infection casued by P.aeruginosa and may be a potential drug for treatment of P.aeruginosa infection.

OBJECTIVETo study the morphologic and immunohistochemical features of gastrointestinal B-cell lymphomas.

METHODSOne hundred and ninety-four cases of gastrointestinal B-cell lymphoma were retrieved from the archival file. The clinical features and pathologic findings were reviewed. Immunohistochemical study for B-cell markers, T-cell markers, bcl-6, CD10, bcl-10, cyclin D1, TdT, MUM1 and Ki-67 was carried out.

RESULTSThe male-to-female ratio was 1.4:1. The age of patients ranged from 8 to 85 years. Amongst the 194 cases studied, 128 (66.0%) were diagnosed as diffuse large B-cell lymphoma, including 16 cases of large cell lymphoma associated with mucosa-associated lymphoid tissue (MALT) lymphoma component. There were also 40 cases (20.6%) of MALT lymphoma, 8 cases (4.1%) of follicular lymphoma, 5 cases of (2.6%) of lymphoplasmacytic lymphoma, 3 cases (1.6%) of mantle cell lymphoma, 1 case of (0.5%) of B-lymphoblastic lymphoma and 9 cases (4.6%) of indefinite type (including 5 biopsy cases). The site of involvement included stomach (100 cases, 51.5%), small intestine (43 cases, 22.2%), ileocecal junction (26 cases, 13.4%), appendix (1 case, 0.5%), colon (21 cases, 10.8%) and rectum (3 cases, 1.6%). Amongst the 163 cases which had undergone surgical resection, 20 cases (12.3%) cases had invasion down to the mucosa, 20 cases (12.3%) down to the superficial muscular layer, 19 cases (11.6%) down to the deep muscular layer and 104 cases (63.8%) with full-thickness involvement. Histologic examination showed lymphoepithelial lesions in 52 cases, residual lymphoid follicles in 29 cases, coagulative necrosis in 66 cases and nodular growth pattern in 30 cases. The lymphoma cells in all cases were immunoreactive for B-cell marker CD20. There was also various degrees of positivity for bcl-6, CD10, bcl-10, cyclin D1, TdT, MUM1 and Ki-67.

CONCLUSIONSGastrointestinal B-cell lymphomas can be subdivided into two main groups: large B-cell lymphomas and small B-cell lymphomas. The latter group often poses diagnostic pitfalls. Accurate pathologic typing requires correlation with histologic and immunohistochemical findings.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD20 ; metabolism ; Child ; DNA-Binding Proteins ; metabolism ; Female ; Gastrointestinal Neoplasms ; metabolism ; pathology ; surgery ; Humans ; Immunohistochemistry ; Lymphoma, B-Cell ; metabolism ; pathology ; surgery ; Lymphoma, B-Cell, Marginal Zone ; metabolism ; pathology ; surgery ; Lymphoma, Follicular ; metabolism ; pathology ; surgery ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neprilysin ; metabolism ; Proto-Oncogene Proteins c-bcl-6 ; Young Adult

OBJECTIVETo observe the effects of early goal-directed fluid therapy with hydroxyethyl starch 130/0.4 on intra-abdominal hypertension (IAH), multiple organ dysfunction and fluid balance in severe acute pancreatitis (SAP) patients.

METHODSAccording to the criteria of selection and exclusion, 120 SAP patients within 72 hours after the symptom occurred from 4 study sites were recruited. They were given standard medication according to "the guideline of diagnosis and treatment of SAP in China" in SICU or PICU. The patients were randomly divided into two groups with crystalloid (control group) and colloid plus crystalloid resuscitation (research group). The objective of fluid therapy was to keep steady hemodynamics for 8 days. IAP was measured three times daily by means of urinary bladder transduction. Function of liver, renal and lung were detected daily. APACHE II score and fluid balance were calculated daily.

RESULTSTotal 120 cases were recruited into research group (n = 59) and control group (n = 61). The demography and baseline data were comparable. IAP was lower in research group than that in control group at day 4 and day 5 (P < 0.05). There was no significant difference in APACHE II scores between two groups pre- and after admission. The decline of daily IAP to baseline (DeltaIAP) in research group was significantly higher than in research group from day 2 to day 8(P < 0.05), whilst the decline of daily APACHE II score to baseline (DeltaAPACHE II score) in research group were significantly higher from day 4 to day 8 (P < 0.05). Negative fluid balance emerged much earlier in the research group (P = 0.036). Percentage of patients with negative fluid balance within 8 days was significantly higher in research group than that in control group (94.9% vs. 62.3%). The amount of positive fluid balance was significantly lower in research group (P = 0.039). IAP correlated significantly with APACHE II score (r(2) = 0.322, P = 0.000). PaO2/FiO2 was significantly higer in research group at day 4 and day 8.

CONCLUSIONSIt is very important to pay close attention to IAP in early fluid therapy of SAP patients. Early goal-directed fluid therapy with HES130/0.4 shortens the duration of positive fluid balance, decreases the amount of positive fluid balance, reduces APACHE II score, relieves IAH, and improves PaO2/FiO2.

Fluid Therapy ; Goals ; Humans ; Intra-Abdominal Hypertension ; Multiple Organ Failure ; Pancreatitis