Objective To study clinical value of percutaneous intrabiliary expandable metallic biliary stenting (EMBS) for treatment of malignant obstructive jaundice. Methods One hundred and sixty patients with malignant obstructive jaundice were treated with EMBS ( EMBS group) . Thirty patients underwent only external drainage by PTCD were recruited as control. The patency rate of stent,decline of bilirubin and the complication were analyzed retrospectively. Both groups were followed up for three months. The Kaplan-Meier method (log-rank test) was used to compare the survival period between the two groups. Results Anorexia,skin pruritus and color of urine alleviated at a certain degree in both groups.In the EMBS group,plasma total bilirubin was(218. 78 ±2. 29) μmol/L pre-stent,and decreased to (134. 90 ±2. 34), (83. 18 ±2.40) , (40. 74 ±2. 29) μmol/L at the 7,14,21 days after the stenting, respectively; direct bilirubin was (128.82 ±2.40) μmol/L pre-stent, and decreased to (81.28 ± 2. 34), (51. 29 ±2. 45) and (25. 70 ±2.40)μmol/L at the 7,14,21 days after the stenting ( P =0. 000). In the PTCD group,plasma total bilirubin was (223. 57 ± 2. 58) μmol/L pe-stent, and decreased to ( 145. 68 ± 2. 57 ) ,(87.57 ±2.58) ,(38.65 ±2. 20) μmol/L at the 7,14,21 days after the stenting,respectively;direct bilirubin was (127. 6 ±2. 59)μmol/L pre-stent,and decreased to (79. 78 ±2. 70) ,(58. 36 ±2. 46) and (29.46 ±2. 20)μmol/L at the 7,14,21 days after the stenting,respectively ( P <0.001 ). No significant difference was found between the two groups at any time point ( P > 0. 05). Complications occurred in 34 patients in the EMBS group and the incidence rate was 20. 62% . Two or more complications occurred in 9 patients. In the PTCD group, complications occurred in 60.00% of the patients. In the EMBS group, 14 patients were failed to follow up, and 136 died. The median length was 214 days. In the PTCD group,all patients were followed up and all died,with a median length of survival of 75. 5 days. The survival analysis showed that the EMBS group survived longer than the PTCD group (P =0. 000). Conclusions EMBS placement showed better effect than PTCD. Compared to PTCD, internal drainage of metallic stents lead few complications and faster recover, and can improve the life quality and prolong survival time of patient with malignant obstructive jaundice. The placement of metallic stents is recommended as a preference for palliative therapy of malignant biliary obstruction.

Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Molecular Docking Simulation ; Molecular Structure ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; Quinazolinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

Objective To make a comparison for the neutrophils prepared either by induction of differentiation of myeloid leuke-mia cell line,or by separation and purification of peripheral blood cells,or by induction of myeloid differentiation of peripheral blood stem cells.Methods NB4 cells were induced differentiation by 1μmol/L all-trans retinoic acid (ATRA)to mature granulo-cytes;neutrophils were separated and purified from peripheral blood by lysis of red blood cells followed by negative selection using magnetic bead-labeled antibodies;hematopoietic stem cells were separated and purified from peripheral blood by Percoll gradient centrifugation followed by negative selection using magnetic bead-labeled antibodies,and were induced to myeloid differentiation by GM-CSF and G-CSF.Morphology and purity of neutrophils prepared by these three methods were studied by means of MGG stai-ning.CD18 protein expression and subcellular distribution were studied by means of immunofluorescence staining.Results Purity of neutrophil was above 40% by induction of differentiation of NB4 cells,and was about 90% if purified from peripheral blood,and was above 70% if induced by myeloid differentiation of peripheral blood stem cells.There was no obvious difference for CD18 ex-pression in neutrophils prepared by these three methods,and staining of CD18 had a dotted pattern distributed in these cells.Con-clusion Peripheral blood neutrophils prepared by lysis of red blood cells followed by negative selection using magnetic bead-labeled antibodies are with high purity and viability which is suitable for immediate test of neutrophils from fresh blood.Neutrophils pre-pared by myeloid differentiation of hematopoietic stem cell are with high viability and last for days,which can be used in long test for neutrphils.

Objective To evaluate the effectiveness of single balloon enteroscopy (SBE) in diagno-sing of suspected lesions in small intestine. Methods Data of 23 patients with suspected small intestinal disease, who underwent SBE (Olympus) between February 2009 and August 2009, were retrospectively studied. A total of 34 procedures were performed in 23 patients. The indications for the examination were suspected obscure gastrointestinal bleeding (n = 9), abdominal pain (n = 7), suspected intestinal tumor re-vealed by capsule endoscopy (n = 4), and Crohn disease (n = 3). Results The average preparation time of SBE was less than 5 minutes. The mean procedure time was 61±25 minutes and 67±28 minutes for the oral and anal routes, respectively. Examination of whole length of small intestine was achieved in 6 patients. The diagnostic rate of small-intestinal lesions was 60. 9%, and no severe complications including perforation occurred. Conclusion SBE is safe and easy to prepare and perform, which can be a useful diagnostic and therapeutic tool for suspected small bowel disease.

The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bile Acids and Salts ; metabolism ; Bilirubin ; blood ; Chemical and Drug Induced Liver Injury ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Fallopia multiflora ; chemistry ; HMGB1 Protein ; metabolism ; Hepatocytes ; drug effects ; Interleukin-1beta ; metabolism ; Liver ; drug effects ; pathology ; Plant Extracts ; pharmacology ; Rats ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo observe the occurrence and progression of liver fibrosis induced by pig serum exposure and bile duct ligation, and analyze the relationship between hepatic inflammation and liver fibrosis.

METHODSChronically immune-mediated liver fibrosis was induced in rats by weekly injection of pig serum (IPS) into the peritoneal cavity at 3 ml/kg for 12 weeks. Cholestatic fibrosis was induced by common bile duct ligation (BDL). The Knodell score was used to evaluate the histological changes in the liver, and immunohistochemistry was performed using anti-SMA, anti-ED1, anti-CK7, and anti-CD45 antibodies. Quantitative real time PCR (qPCR) analysis was employed to quantify the mRNA expression of the genes related to inflammation, including interleukin-1beta (IL-1beta), IL-6, monocyte chemotactic protein-1, tumor necrosis factor-alpha, regulated upon activation normal T cell expressed and secreted (RANTES), transforming growth factor-beta, platelet-derived growth factor A, as well as the genes associated with fibrogenesis, namely collagen 1, alphaSMA, MMP-9 and TIMP-1.

RESULTSKnodell scores for periportal necrosis, intralobular degeneration and focal necrosis, and portal inflammation were all significantly higher in the BDL group than in the IPS group (P<0.01), whereas the scores for fibrosis was higher in the IPS group (P<0.05). Immunohistochemistry showed obvious inflammation with numerous alphaSMA-positive cells in the liver of the rats in BDL group; the liver of the rats in IPS group showed numerous alphaSMA-positive myofibroblasts with limited inflammatory cell infiltration. qPCR demonstrated a significant up-regulation of the genes related to extracellular matrix remodeling such as collagen 1 (P<0.01), alphaSMA (P<0.01), MMP-9 (P<0.01) and TIMP-1 (P<0.01) in the rat liver in IPS group compared with those in the normal control group, and the mRNA expressions of the inflammation-related cytokines, except for RANTES, were comparable with those in the control. In contrast, the BDL group showed a significant up-regulation of all the pro-inflammatory genes examined with also increased expression of the fibrogenesis-related genes (P<0.05).

CONCLUSIONLiver fibrosis induced by IPS is characterized by active ECM remodeling in the absence of obvious inflammation, indicating that chronic development of liver fibrosis can be independent of active hepatic inflammation. BDL-induced liver fibrosis highlights obvious inflammation and fibrous proliferation in the liver.

Animals ; Bile Ducts ; surgery ; Cholestasis ; complications ; physiopathology ; Ligation ; Liver Cirrhosis, Experimental ; etiology ; immunology ; pathology ; Male ; Rats ; Rats, Inbred F344 ; Serum ; immunology ; Swine

OBJECTIVETo study the antigenic properties of mutant hepatitis B virus surface antigen, to understand the sensitivity of the commercially available HBsAg assays to the variants and to reduce the undetectability of the variants.

METHODSRecombinant eukaryotic expression plasmids for HBsAg. The recombinant eukaryotic expression plasmids pSS1adr, pSS1adw2, pSS1adw2- 145Arg, pSS1adr-126 Asn and pSS1adr-126Ser were transfected into COS-7 cells. HBsAg in the supernatants of transfected cells was detected by using different commercial ELISA kits.

RESULTSThe absorbance value of pSS1adr-126 Asn and pSS1adr-126Ser plasmids were similar to that of the wild type HBsAg, the absorbance value of pSS1adw2-145Arg plasmids was lower than that of the wild type HBsAg.

CONCLUSIONIt is estimated that the antigenicity of HBsAg mainly depended on the amino acid sequence of "a" antigen determinant and its conformation, so 145 amino acid substitutions led to the change of conformation and the antigenicity of variant HBsAg was lower than that of the wild type.

Animals ; COS Cells ; Cercopithecus aethiops ; Culture Media, Conditioned ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Genetic Vectors ; genetics ; metabolism ; Hepatitis B Surface Antigens ; analysis ; genetics ; immunology ; Mutation ; Transfection ; Viral Envelope Proteins ; genetics

OBJECTIVETo study the incidence, clinical features and related factors of propylthiouracil (PTU)-induced hepatic injury in patients with hyperthyroidism.

METHODSA prospective study were carried out in 70 patients of hyperthyroidism with normal liver function. Every patient was treated with PTU 300 mg/d until the thyroid functions recovered to normal, following by decease and maintenance PTU dose in period of six months. Liver function, including serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin (TBIL) and direct bilirubin (DBIL), thyroid function (serum thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine and thyrotropin) and blood routine items were measured before therapy and once a month for six months after PTU therapy was begun.

RESULTSSixty-four cases of 70 patients completed the therapy for 6 months. Hepatic injury developed in 33 patients (51.6%). Asymptomatic, transient hepatic injury was shown in 22 patients (34.4%). Slight symptomatic hepatic injury occured in 6 cases (9.4%) and overt hepatic injury in 5 patients (7.8%) after PTU administration. However, all the patients who developed overt hepatic injury did not stop PTU. Hepatic function returned normal one month after stopping PTU. No one finally suffered from viral hepatitis and autoimmune hepatitis in patients of symptomatic and overt hepatic injury.

CONCLUSIONSPTU-induced symptomatic hepatic injury is not rare and usually develops within the first few months of PTU administration. Its clinical course is relatively benign. However, it may be difficult to predict its development, so all patients should be monitored for liver function test during the administration in early stage.

Adolescent ; Adult ; Aged ; Antithyroid Agents ; adverse effects ; therapeutic use ; Chemical and Drug Induced Liver Injury ; Female ; Follow-Up Studies ; Humans ; Hyperthyroidism ; drug therapy ; Liver ; pathology ; physiopathology ; Liver Diseases ; physiopathology ; Liver Function Tests ; Male ; Middle Aged ; Propylthiouracil ; adverse effects ; therapeutic use ; Prospective Studies

OBJECTIVETo evaluate the relationship between the incidence of abnormal thyroid function of newborns and maternal hyperthyroidism with antithyroid drug therapy.

METHODThe clinical data of 35 neonates born to mothers with hyperthyroidism from 1983 to 2003 in Peking Union Medical College Hospital were retrospectively analyzed. According to the maternal thyroid function and the antithyroid drugs taken during pregnancy, subjects were divided into different groups.

RESULTSThe proportion of abnormal thyroid function in newborn was 48.6% (17/35). The prevalences of primary hypothyroidism, subclinical hypothyroidism, hypothyroxinemia, and central hypothyroidism were 29.4%, 29.4%, 35.3%, and 5.9%, respectively. The incidence of abnormal thyroid function of neonates whose mothers did not take the antithyroid drugs (ATDs) until the third trimester of pregnancy was significantly higher than those without and with ATDs during the first or second trimester (P < 0.01). The incidence of abnormal thyroid function significantly increased in premature neonates, neonates whose mothers with modest or heavy pregnant hypertension, or neonates whose core serum thyroid-stimulating hormone or serum anti-thyroid peroxidase antibodies levels were abnormal.

CONCLUSIONThe risk of abnormal thyroid function of infants whose hyperthyroid mothers did not take ATDs until the third trimester of pregnancy may be increased. Prompt diagnosis and appropriate treatment of hyperthyroidism in pregnant women are essential for the prevention of neonatal thyroid functional abnormality.

Adult ; Antithyroid Agents ; adverse effects ; Female ; Humans ; Hyperthyroidism ; complications ; drug therapy ; Infant, Newborn ; Male ; Pregnancy ; Pregnancy Complications ; drug therapy ; Retrospective Studies ; Thyroid Diseases ; congenital ; epidemiology ; etiology ; Time Factors

OBJECTIVETo evaluate the clinical validity of anti-thyroperoxidase antibody (anti-TPOAb) and anti-thyroglobulin antibody (anti-TgAb).

METHODSerum levels of anti-TPOAb and anti-TgAb were assayed using chemiluminescence immunoassay in 434 subjects, including 51 patients with Hashimoto's thyroiditis, 58 with Graves' disease, 68 with nodular goiter, 56 with thyroid adenoma and carcinoma, 56 with subacute thyroiditis, 65 with euthyroid non-thyroid endocrine disease, 35 with euthyroid non-thyroid autoimmune diseases, and 45 euthyroid controls.

RESULTSThe highest level and most positive results of serum anti-TgAb and anti-TPOAb were observed in patients with Hashimoto's thyroiditis (median 373 and 6 974 U/ml, positive rate 84.3% and 86.3%), followed by patients with Graves' disease (median 84 and 1 369 U/ml, positive rate 44.8% and 72.4%). Serum anti-TgAb and anti-TPOAb were also more common in patients with subacute thyroiditis and other autoimmune diseases than in the controls.

CONCLUSIONThe assay of serum anti-TPOAb and anti-TgAb by chemiluminescence immunoassy are useful in the differential diagnosis of autoimmune thyroid disease.

Adenoma ; blood ; Adolescent ; Adult ; Aged ; Autoantibodies ; blood ; Female ; Graves Disease ; blood ; Hashimoto Disease ; blood ; Humans ; Iodide Peroxidase ; immunology ; Male ; Middle Aged ; Thyroglobulin ; immunology ; Thyroid Gland ; immunology ; Thyroid Neoplasms ; blood ; Thyroiditis, Subacute ; blood