Objective: In recent years,an increasing number of drugs have been proved to be associated with the induction of anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).This article reviews the latest research progress on drug-induced AAV.Data sources: We conducted a comprehensive and detailed search of the PubMed database.The search terms mainly included drug-induced,ANCA,and vasculitis.Study selection: We summarized the original articles and reviews on drug-induced AAV in recent years.The extracted information included the definition,epidemiology,associated drugs,pathogenesis,clinical features,diagnosis,treatment,and prognosis of drug-induced AAV.We also focused on the differences between drug-induced AAV and primary vasculitis.Results: The offending drugs leading to drug-induced AAV are almost from pharmacologic categories and we need to be vigilant when using these drugs.The pathogenesis of drug-induced AAV might be multifactorial.The formation of neutrophil extracellular traps is an important mechanism for the development of drug-induced AAV.The clinical features of drug-induced AAV are similar to those of primary AAV.Understanding the difference between drug-induced AAV and primary AAV is helpful to identify drug-induced AAV.Stopping the offending drug at once after diagnosis may be sufficient for those patients with mild symptoms.Immunosuppressive therapy should only be used in patients with vital organs involvement.Conclusions: Patients with drug-induced AAV usually have a good prognosis if they stop using the offending drug immediately.Recent advances in research on AAV are expected to help us better understand the pathogenesis of drug-induced AAV.

Objective To observe the clinical manifestation and the mode of RET proto-oncogene mutation in a pedigree of mutiple endocrine neoplasia type 2A (MEN2A). Methods Genomic DNA was extracted from the peripheral blood lymphocytes in 18 family members including 3 patients, then PCR was performed to amplify seven exons of the RET proto-oncogene, i. e. exon 8,10,11,13-16. The PCR products were directly sequenced to identify the RET mutation and then sequenced after subcloning to identify their heterozygosity. Results The male proband suffered from pheochromocytoma and medullary thyroid carcinoma since the age of 30; while his sibling sister was ill with pheochromocytoma, and his brother with medullary thyroid carcinoma. A novel heterozygous mutation, 1893-1895delCGA, was detected in exon 11 of the RET proto-oncogene in the 3 patients and the other 2 family members. Conclusion A novel heterozygous mutation of RET proto-oncogene, 1893-1895delCGA, seems to be the disease-causing mutation in the studied MEN2A family.

Objective: To observe the efficacy of Astragalus-Polygonum Anti-Fibrosis decoction (APAFD)and Jinshuibao capsule (JSBC) in treating liver fibrosis of chronic hepatitis B. Methods: Ninety-two cases of liver fibrosis of chronic hepatitis B were randomly divided into group A and group B. Patients in group A received APAFD for 48 weeks, and in group B, they received JSBC for 48 weeks. The effects on the level change of hyaluronic acid (HA), laminin (LN), pro-collagen Ⅲ (PCⅢ) and collagen Ⅳ (CⅣ) as well as liver functional tests and liver biochemical parameters before and after treatment were observed.Results: Level of serum HA, LN, PCⅢ and CⅣ in group A declined more obviously than that of group B, the difference was significant (P<0.01). The liver functional tests such as total bilirubin (TB), alanine aminotransferase (ALT), albumin/globulin (A/G) ratio, hepatitis related serum biochemical parameters such as cholylglycine (CG), serum ferritin (SF), prealbumin (PC) of group A were all improved more significantly than that of group B (P<0.01).Conclusion: APAFD is more effective than JSBC in treating liver fibrosis of chronic hepatitis B and in the inhibition of hepatic inflammation, hence it is a good composite Chinese herbal preparation against liver fibrosis.

This study aims to explore the efficacy of interferon-α (IFN-α) combined with either entecavir (ETV) or adefovir (ADV) therapy versus IFN-α mono-therapy for chronic hepatitis B (CHB) patients,and to identify the factors associated with treatment outcomes.Totally,159 CHB patients receiving interferon-based treatment for 48 weeks were enrolled in this retrospective study,including IFN-α mono-therapy group (group A,n=44),IFN-α plus ADV group (group B,n=53) and IFN-α plus ETV group (group C,n=62).The primary measures of efficacy assessments were the changes in HBsAg.Cox regression analysis was used to identify the predictors of treatment outcomes.The predictive values of the factors were assessed by ROC analysis.For patients with baseline hepatitis B surface antigen (HBsAg) level ＜1000 IU/mL,the reductions in mean HBsAg levels at week 48 were greater in group C than that in group A (P＜0.05).Higher rate of HBeAg seroconversion was achieved in the combined therapy group than in IFN-α mono-therapy group at week 48 (P＜0.05).Two factors were independently associated with HBeAg seroconversion:baseline HBeAg level ＜2.215 log10 index/mL and △HBeAg (.decline in HBeAg from baseline) ＞0.175 log10 at week 12.In conclusion,interferon-α plus ETV therapy can accelerate HBsAg decline as compared with interferon-α mono-therapy in CHB patients with lower baseline HBsAg levels,and the combination therapy was superior to IFN-α mono-therapy in increasing the rate of HBeAg seroconversion.Baseline HBeAg and △HBeAg at week 12 can independently predict HBeAg seroconversion in patients subject to interferon-based therapy for 48 weeks.

Objective To establish a convenient,accurate and practical method for detection of adefovir dipivoxil resistance-as- sociated mutation in hepatitis B virus:rtA181V/T/S and rtN236T mutations.Methods According to HBV complete sequences in GenBank,two pairs of primers were designed to amplify the region of HBV reverse transcriptase in order to introduce a BglI restriction site upon PCR product of wild type (wt) and a BseDI restriction site upon PCR product of rt236 mutant type.After amplification,the PCR products were digested with BglI and BseDI separately.We used this method to detect wild,rt181 mu- tant,rt236 mutant plasmids and 3 chronic hepatitis B patients' serum with obvious ADV resistance-associated mutations.We also tested the sensitivity of this method by mixing the wild and mutant plasmids in different proportions.Results The method could detect rt181 and rt236 mutations simultaneously.The result of RFLP analysis was in accordance with that of DNA se- quencing and cloning analysis.This method could detect the mutants even when they comprised only 10% of the total virus population.Conclusions The PCR-RFLP method with high sensitivity can detect rt181 and rt236 mutations simultaneously.It can be used for early detection of ADV resistance-associated mutation in hepatitis B virus.

OBJECTIVETo study the pattern of RET proto-oncogene mutations in two pedigrees affected with multiple endocrine neoplasia type 2A (MEN2A).

METHODSPeripheral blood samples were collected from members of the two pedigrees, with total genomic DNA extracted for polymerase chain reaction (PCR). PCR products of 7 exons of the RET proto-oncogene (including exons 8, 10, 11, 13, 14, 15, 16) which have higher mutation rates were purified and subjected to direct sequencing. Suspected mutations in the 2 probands were verified in other members of the pedigrees. To exclude other mutations, PCR products of remaining 14 exons were sequenced in the proband from pedigree 1.

RESULTSA novel heterozygous mutation, 1893-1895delCGA, was detected in exon 11 of the RET proto-oncogene among 3 patients and 2 unaffected members from pedigree 1, while a heterozygous mutation, Cys634Arg, was detected in exon 11 among 2 patients and 1 unaffected family member from pedigree 2.

CONCLUSIONThe heterozygous 1893-1895delCGA and Cys634Arg mutations of the RET proto-oncogene probably underlie the disease in the two pedigrees. Above discovery has enriched the human gene mutation database.

BACKGROUNDTo investigate whether high-dose toremifene can enhance the efficacy of chemotherapy in non small cell lung cancer.

METHODSUntreated stage IIIB/IV non-small cell lung cancer patients were randomly devided into group A (high-dose toremifene combined with the platinum-based chemotherapy) or group B (the same platinum-based chemotherapy alone).

RESULTSA total of 30 eligible patients had been recruited. Hemotologic and nonhemotologic toxicities were similar with no statistic difference. The median survival for group A was 8 months, 95% CI (6.63-9.37) versus 7.5 months, 95% CI (4.75-10.25) for group B ( P =0.9). One year-survival rate was 31% for group A versus 28% for group B ( P =0.87). The response rate was 25% for group A versus 21% for group B ( P =0.99).

CONCLUSIONSThe results suggest that high-dose toremifene does not enhance the efficacy of platinum-based chemotherapy for IIIB/IV non-small cell lung cancer but toxicities are well tolerated.

OBJECTIVETo investigate the therapeutic efficiency of antiviral treatment with pegylated-interferon (Peg-IFN) for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) and to explore whether liver histopathological features or other factors influence the HBeAg seroconversion treatment response.

METHODSEighty HBeAg-positive CHB patients with diagnosis confirmed by liver puncture were treated with Peg-IFN(2a or 2b)body weight dose, once weekly). At treatment week 48, the rate of HBeAg seroconversion was determined and used to analyze the influence of liver histopathological features (liver biopsy assessment of: inflammation, graded G0 to G4; fibrosis stage, graded S0 to S4), sex, age, differential levels (pre-treatment baseline vs. week 48 post-treatment) of serum alanine transferase (ALT), and HBV DNA, by binary logistic analysis.

RESULTSAt week 48, the overall rate of HBeAg seroconversion was 30.0%. The rate of HBeAg seroconversion gradually advanced with increased liver inflammation (X2 = 8.435, P = 0.015): 9.09% of the 22 patients with G1; 31.58% of the 38 patients with G2; 47.30% of the 19 patients with G3; the one patient with G4. In contrast, the rate of HBeAg seroconversion showed a much weaker association with liver fibrosis (X2 = 5.917, P = 0.116). Only baseline HBeAg level, and no other baseline index, was significantly different between the patients who achieved HBeAg seroconversion and those who did not. Liver inflammation and baseline HBeAg level were identified as influencing factors of HbeAg seroconversion in response to Peg-IFN treatment.

CONCLUSIONPeg-IFN therapy induces a higher rate of HBeAg seroconversion in HBeAg-positive CHB patients with severe liver inflammation; histological analysis of pre-treatment liver biopsies may help to identify patients most likely to benefit from the antiviral regimen.

Adult ; Antiviral Agents ; therapeutic use ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; drug therapy ; pathology ; Humans ; Interferon-alpha ; therapeutic use ; Liver ; pathology ; Male ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; therapeutic use ; Serologic Tests

OBJECTIVETo study the resistant rate of hepatitis B virus (HBV) to ADV and the dynamic evolution of HBV in lamivudine (Lam)-resistant chronic hepatitis B (CHB) patients.

METHODSTwenty-three Lam-resistant CHB patients were assigned to a 10mg/d ADV monotherapy for 68-116 weeks. The baseline and different time point blood samples after ADV monotherapy were analyzed for ADV-resistant mutations using direct sequencing of PCR products; the evolution of HBV mutations was examined by clonal analysis of serial samples from one patient infected with ADV-associated resistant HBV strains.

RESULTSThe cumulative incidence of genotypic ADV resistance at weeks 48 and 96 was 4.3% and 10.5% respectively respectively. The evolution analysis of HBV mutant strains in an ADV-resistant CHB patient showed that the proportion of YMDD mutants gradually decreased with rtA181S mutants increasing over time after ADV monotherapy, and that rtA181S+N236T mutants became the predominant strains during prolonged ADV monotherapy. The addition of Lam to the ongoing ADV treatment had poorer antiviral response in the patient with rtA181S or rtA181S+N236T mutant infection; one clone with multi-drug resistant mutations was selected during Lam and ADV combination therapy.

CONCLUSIONIncreased risk of adefovir resistance and selection of multi-drug resistant mutations are associated with long-term ADV monotherapy in patients with Lam-resistant chronic hepatitis B.

Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; therapeutic use ; Drug Resistance, Viral ; Evolution, Molecular ; Female ; Hepatitis B virus ; classification ; drug effects ; genetics ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Lamivudine ; pharmacology ; Male ; Middle Aged ; Organophosphonates ; therapeutic use

This study aims to investigate the characteristics of genomic variation of pandemic A/H1N1/2009 influenza virus isolated in Fujian Province, China. Complete genome sequence analysis was performed on 14 strains of pandemic A/H1N1/2009 influenza virus isolated from Fujian during 2009-2012. All virus strains were typical low-pathogenic influenza viruses, with resistance to amantadine and sensitivity to neuraminidase inhibitors. Eight genome fragments of all strains were closely related to those of A/California/07/2009 (H1N1) vaccine strain, with > or = 98.2% homology. Compared with the vaccine strain, the influenza strains from Fujian had relatively large variation, and variation was identified at 11 amino acid sites of the HA gene of A/Fujiangulou/SWL1155/2012 strain, including 4 sites (H138R, L161I, S185T, and S203T) involved inthree antigen determinants (Ca, Sa, and Sb). In conclusion, the influenza vaccine has a satisfactory protective effect on Fujian population, but the influenza strains from Fujian in 2012 has antigenic drift compared with the vaccine strain, more attention should therefore be paid to the surveillance of mutations of pandemic A/H1N1/2009 influenza virus.
Antiviral Agents ; pharmacology ; China ; epidemiology ; Drug Resistance, Viral ; genetics ; Genome, Viral ; genetics ; Genomics ; Humans ; Influenza A Virus, H1N1 Subtype ; drug effects ; genetics ; immunology ; physiology ; Influenza, Human ; epidemiology ; prevention & control ; Pandemics ; prevention & control ; Viral Vaccines ; immunology