Objective:To explore clinical and histopathological characteristics of primary biliary cirrho-sis-autoimmune hepatitis overlap syndrome.Methods:Clinical data and pathological findings of 10 pa-tients were reviewed.Results:Serum glutamine transpeptidase,alkaline phosphatase levels,alaninetransaminase,aspartate transaminase,serum IgG and IgM were elevated in all the patients.They were allpositive for anti-mitochondrial antibody and AMA-M2.Nine patients were positive for anti-nuclear anti-body and one patient was positive for anti liver-kidney microsome antibody.Liver biopsies in these pa-tients revealed:ten patients had bile duct lesion,hepatitis activities ranged from moderate to severe,andfibrosis ranged from S1 to S3.Conclusion:PBC-AIH overlap syndrome is mostly found in middle-agedwomen.It has the clinical and histopathological characteristics of both PBC and AIH.Accurate andprompt diagnosis of overlap syndrome patients should be based on the clinical presentation,biochemicaland immune indexes,and hepalic pathological changes.

Objective To explore the relationship between some single nucleotide polymorphisms (SNP)loci of interferon regulatory factor 6(IRF6)gene,transforming growth faetor-?(TGFA)gene and nonsyndromic cleft lip with or without cleft palate(NSCL/P)in nuclear families consisting of fathers, mothers and affected offspring with NSCL/P from southeast China.Methods Some SNloci of IRF6 and TGFA were detected by applying microarray technology in nuclear families,and then haplotype relative risk (HRR)and transmission disequilibrium test(TDT)were performed.Results There were no significant difference in genotypes and alleles distribution between patients and their parents.The SNP locus——V274I of IRF6 was associated with NSCL/P(HRR:?~2=4.5816,P

Objective To detect the mutations of ATP2C1 gene in patients with Hailey-Hailey dis- ease (HHD).Methods PCR and direct sequencing were performed in 17 patients and 120 healthy controls to screen the mutations in the exons of ATP2C1 gene.Results Eight mutations were identified in nine probands, including three deletion mutations (nt1464-1487 del/nt1462-1485del,1523delAT,2375delTTGT),three splice site mutations (360—2A→G,1415—2A→T,2243+2T→C) and two missence mutations (C920T and G1942T).None of the above mutations was found in the controls.Conclusion Eight specific novel mutations were identified in nine probands of HHD,which could be causative factors of the disease.

Reproductive toxicity research takes an important place in traditional Chinese medicine pre-clinical safety evaluation. Modern reproductive toxicity experiment includes drug-related miscarriage, fetal death, teratism, and adverse effects on fertility, genital system, embryonic development and fetus, which is different from contraindicated in pregnancy in traditional Chinese medicine theory. Now the three-phases reproductive toxicity study is the method mainly applied in traditional Chinese medicine reproductive toxicity evaluation. Besides that, alternative methods of whole embryos culture and embryonic stem cell test are also used in traditional Chinese medicine embryo toxicity evaluation. This article reviews research progress and pre-clinical evaluation on reproductive toxicity of traditional Chinese medicine.
Animals ; Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal ; toxicity ; Embryonic Development ; drug effects ; Embryonic Stem Cells ; drug effects ; Female ; Humans ; Medicine, Chinese Traditional ; Pregnancy ; Reproduction ; drug effects ; Toxicity Tests

Objective To investigate the main components of inner ear antigens inducing autoimmune Meniere's disease(AIMD) in guinea pigs. Methods The guinea pigs were immunized with isologous crude inner ear antigens (ICIEAg). Then, the hearing function was measured with auditory brainstem response (ABR), the vestibular function was measured with electronystagmography (including spontaneous nystagmus and caloric test), and inner ear histopatholoical changes were observed by inner eareelloidin section with haematoxylin-eosin staining and observed under light microscope. According to these results, the AIMD-model animals from non-AIMD-model ones were distinguished. The special antibodies against ICIEAg in sera were measured with ELISA. The antigen-antibody reactions against different components of ICIEAg were detected by Western blotting with sera of AIMD and non-AIMD guinea pig srespectively. Then, we analysed the contrast between them and found the main components of the ICIEAgthat were positive reaction in AIMD guinea pigs and negative reaction in non-AIMD guinea pigs. Results The result of ELISA demonstrated that the sera of both the AIMD and non-AIMD guniea pigs contained thespecial antibodies against ICIEAg after immunized with ICIEAg. The difference of the amount of antibodyagainst ICIEAg between AIMD guinea pig group and non-AIMD guinea pig group was not significant. Western blotting assay showed only the sera of AIMD guinea pig contained the antibodies against the specific antigens with the molecular of 68 000, 58 000, 42 000 and 28 000. Conclusions ICIEAg contain many different components, the AIMD might only happen in the guinea pigs in which the special immunization against themain components that could induce this kind of disorder appeared. The inner ear antigens with molecular of68 000, 58 000, 42 000 and 28 000 might be the main components inducing AIMD in guinea pigs.

A simple, reliable and sensitive liquid chromatography-isotope dilution mass spectrometry (LC-ID/MS) was developed and validated for quantification of olanzapine in human plasma. Plasma samples (50 microL) were extracted with tert-butyl methyl ether and isotope-labeled internal standard (olanzapine-D3) was used. The chromatographic separation was performed on XBridge Shield RP 18 (100 mm x 2.1 mm, 3.5 microm, Waters). An isocratic program was used at a flow rate of 0.4 m x min(-1) with mobile phase consisting of acetonitrile and ammonium buffer (pH 8). The protonated ions of analytes were detected in positive ionization by multiple reactions monitoring (MRM) mode. The plasma method, with a lower limit of quantification (LLOQ) of 0.1 ng x mL(-1), demonstrated good linearity over a range of 0.1 - 30 ng x mL(-1) of olanzapine. Specificity, linearity, accuracy, precision, recovery, matrix effect and stability were evaluated during method validation. The validated method was successfully applied to analyzing human plasma samples in bioavailability study.

Drug allergy and pseudoallergic reactions are main adverse drug reactions. Allergy is mainly induced by the immunogenicity of drug, drug metabolic products or drug additive. Pseudoallergic reactions may result from the irritation or activation of inflammatory material release. Pre-clinical evaluation of drug allergy and pseudoallergic reactions is included in immunotoxicity evaluation. Now there is no in vivo or in vitro method that could predict all kinds of allergy or pseudoallergic reactions due to the different mechanisms. In the past few years, FDA, SFDA OECD, ICH and WHO have published several guidelines on per-clinical immunotoxicity evaluation, however, no agreement has been reached on allergy and pseudoallergic reactions evaluation. This article reviews the requirements of allergy and pseudoallergic reactions in pre-clinical evaluation.
Drug Hypersensitivity ; diagnosis ; Humans ; Immune System ; drug effects ; Practice Guidelines as Topic

Ischemic stroke refers to the general term of brain tissue necrosis caused by the stenosis or occlusion of the cerebral blood supply artery and the insufficiency of cerebral blood supply.It is called"stroke"in traditional Chinese medicine.It has the characteristics of high incidence rate,high disability rate,high recurrence rate,high mortality,etc.which seriously threatens the health and quality of life of patients and increases the social burden.This article reviews the research status on the etiology and pathogenesis of ischemic stroke in traditional Chinese medicine,as well as the pharmacological effects and mechanisms of traditional Chinese medicine in treating ischemic stroke.It aims to provide reference for the diagnosis and treatment of ischemic stroke in traditional Chinese medicine and further exploration of its mechanism of action in the future.

OBJECTIVETo explore the risk factors of acute lymphoblastic leukemia (ALL) recurrence in adult patients and establish a prognosis index (PI) calculation model in order to improve the prevention strategy of ALL in adults.

METHODS104 adult ALL patients from Blood Diseases Hospital & Chinese Academy of Medical Sciences between August 2008 and November 2011 were enrolled. COX proportional hazards regression stratified by Dummy variable was used to set up the prediction model; Kaplan-Meier method and Log-rank test were used to estimate and compare the survival. After calculated individual PI value, patients' expected survival should be estimated by groups.

RESULTSThe overall median survival of adult ALL patients was 22.00 months (95% CI 17.00-27.00). COX regression analysis showed that chemotherapy group patients had a higher risk of recurrence than of ASCT group while setting treatment as the dummy variable (RR=2.052, 95%CI 0.877-4.799, P=0.007). Stratified Analysis showed that the risk factors of B-ALL recurrence in adult patients included HGB <100 g/L (RR=0.186, 95% CI 0.068-0.512, P=0.001), CNSL (RR=7.767,95% CI 2.951- 20.433, P=0.001), number of consolidation chemotherapy<3 (RR=0.445, 95% CI 0.211-0.940, P=0.034) and Ph chromosome positive (RR=2.771, 95% CI 1.353-5.674, P=0.005). Grouped by the PI value, the expected survival of each individual patient could be estimated as PI=0.58 base.

CONCLUSIONHGB, CNSL, number of consolidation chemotherapy and Ph chromosome were independent risk factors of B-ALL recurrence in adult patients. PI value could predict the survival of adult ALL patients and provide reference for individual therapy and prognostic evaluation.

Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; epidemiology ; pathology ; Prognosis ; Recurrence ; Risk Assessment ; Risk Factors ; Young Adult

OBJECTIVETo explore the effect of three-dimensional structure of dermal matrix on biological behavior of fibroblasts (Fb) in the microcosmic perspective.

METHODSThe three-dimensional structure of dermal tissue was analyzed by plane geometric and trigonometric function. Microdots structure array with cell adhesion effect was designed by computer-assisted design software according to the adhesive and non-adhesive components of dermal tissue. Four sizes (8 microm x 3 microm, space 6 microm; 16 microm x 3 microm, space 6 microm; 16 microm x 5 microm, space 8 microm; 20 microm x 3 microm, space 2 microm) of micropier grid used for cell culture (MPGCC) with cell-adhesive microdots, built up with micro-pattern printing and molecule self-assembly method were used to culture dermal Fb. Fb cultured with cell culture matrix without micropier grid was set up as control. The expression of skeleton protein (alpha-SMA) of Fb, cell viability and cell secretion were detected with immunohistochemistry, fluorescent immunohistochemistry, MTT test and the hydroxyproline content assay.

RESULTSThe three-dimensional structure of dermal tissue could be simulated by MPGCC as shown in arithmetic analysis. Compared with those of control group [(12 +/- 3)% and (0.53 +/- 0.03) microg/mg, (0.35 +/- 0.04)], the expression of alpha-SMA [(49 +/- 3)%, (61 +/- 3)%, (47 +/- 4)%, (51 +/- 3)%] and the content of hydroxyproline [(0.95 +/- 0.04), (0.87 +/- 0.03), (0.81 +/- 0.03), (0.77 +/- 0.03) microg/mg] were increased significantly (P < 0.05), the cell viability of Fb (0.12 +/- 0.03, 0.13 +/- 0.04, 0.14 +/- 0.03, 0.19 +/- 0.03) cultured in MPGCC was decreased significantly (P < 0.05). When the parameters of micropier grid were changed, the expression of alpha-SMA, the cell viability and the content of hydroxyproline of Fb cultured in four sizes of MPGCC were also significantly changed as compared with one another (P < 0.05).

CONCLUSIONSMPGCC may be the basic functional unit of dermal template, or unit of dermal template to call. Different three-dimensional circumstances for dermal tissue can result in different template effect and wound healing condition.

Biocompatible Materials ; Cell Adhesion ; Cell Culture Techniques ; Cells, Cultured ; Computer-Aided Design ; Dermis ; Fibroblasts ; cytology ; Tissue Engineering ; methods