Antidepressant-like effect of schisandrin in mice / 中国药理学与毒理学杂志

OBJECTIVE To explore the antidepressant effect and the underlying mechanisms of schisandrin (SCH), a component of the fruits of Schizandra chinesis. METHODS The forced swimming test (FST) and tail suspension test (TST) in mice were used to evaluate the antidepressant activity of SCH (5, 10, and 30 mg · kg-1) following single administration intragastrically, and the locomotor activity was investigated to exclude its neural excitatory effects. Effects of SCH on neural monoamine systems were studied in two pharmacological models, including reserpine induced monoamine depletion test and yohimbine toxicity potentiation test. RESULTS In behavioral despair models, SCH (30 mg·kg-1) signif?icantly decreased the immobility time in the TST and FST (P<0.05) compared with normal control group. Results of the locomotor activity experiment showed that SCH had no excitatory or inhibitory actions on the central nervous system. In the reserpine reversal experiment, SCH (30 mg · kg-1) antagonized thepalpebral ptosis and akinesia symptoms caused by reserpine(2.5 mg · kg-1) treatment (P<0.05) compared with model group, but had little effect on the drop of the anal temperature. Moreover, SCH did not increase the lethality caused by subcutaneous injection of yohimbine (30 mg · kg-1)at the threshold lethal dosage. CONCLUSION SCH exerts potential antidepressant-like effect in mice.

Effect of glycogen synthase kinase 3β overexpression in hippocampus on antidepressant and anxiolytic activity of total flavoids from Xiaobuxin Tang in mice / 中国药理学与毒理学杂志

OBJECTIVE To study the influence of glycogen synthase kinase3β (GSK3β) over expres?sion in the hippocampus on the antidepressant and anxiolytic effects of total flavoids from Xiaobuxin Tang (XBXT-2). METHODS Adeno-associated virus containing GSK3β(S9A) mutation was microinjected into the hippocampus. After three weeks of recovery, GSK3βand p-GSK3βwere detected by Western blotting, and open field test (OFT) was used to evaluate the locomotor activity. Then, AAV group and GSK3β over expression group were divided into administration group and solvent group, respectively. XBXT-2 (100 mg · kg-1) and solvent were ig administered chronically. After 14 d and 16 d of administra?tion, the tail suspension test (TST) and forced swimming test (FST) were used to investigate the influence of GSK3βover expression on the antidepressant effect of XBXT-2, respectively. After 18 d and 20 d of administration, the elevated plus maze test (EPMT) and staircase test (ST) were used to investigate the influence of GSK3β over expression on the anxiolytic effects of XBXT-2, respectively. RESULTS Western blotting analysis showed that the protein level of GSK3βincreased significantly in GSK3βover expression group (P<0.01) compared with AAV group, but there was no significant difference in p-GSK3β. In OFT, the number of crossings and rearings showed no difference between AAV group and GSK3β over expression group. The results of TST and FST showed that compared with AAV group, the immobility time was significantly reduced in AAV+XBXT-2 group (P<0.05, P<0.01), but compared with GSK3β over expression group, the immobility time showed no difference in GSK3β over expression+XBXT-2 group. In EPMT, compared with AAV group, the percentage of entrances and time into open arms in AAV+XBXT-2 group was significantly increased (P<0.01, P<0.05), but compared with GSK3βover expression group, these indexes showed no difference in GSK3βover expression+XBXT-2 group. In ST, compared with AAV group, the number of rearings was significantly reduced in AAV+XBXT-2 group (P<0.05), but there was no difference between GSK3β over expression+XBXT-2 group and GSK3βover expression group. CONCLUSION GSK3βover expression in the hippocampus can reverse the antidepressant effects of XBXT-2 in the TST and FST, and the anxiolytic effects in the EPM and ST.

Clinical study of molecular markers and COL1A1/PDGFB fusion gene in dermatofibrosarcoma protuberans / 中国肿瘤临床

Objective:To investigate the values of immunophenotype and the Collagen type1 alpha1/Proto-oncogene Proteins c-sis (COL1A1/PDGFB) fusion gene in the diagnosis of dermatofibrosarcoma protuberans (DFSP). Methods:IHC markers and the COL1A1/PDGFB fusion gene were detected by IHC staining and interphase fluorescence in situ hybridization (FISH) in 73 cases previously diagnosed as DFSP. A total of 85 and 10 non-DFSP cases were also included as controls for IHC staining and FISH, respectively. Results:In the 73 DFSP cases, the positive detection rates for immunohistochemical marker vimentin, CD34, CD99, S100, desmin and SMA were 100%, 91.78%, 61.64%, 0, 0, and 6.85%, correspondingly. Protein expression levels in these cases varied from the control group, and CD34 ex-pression was significantly different among the differential diagnoses. The positive detection rate for the COL1A1/PDGFB fusion gene was 86.96%(60/69), whereas the gene expression in the control group was negative. Conclusion:The COL1A1/PDGFB fusion gene is a highly specific and sensitive marker in the diagnosis of DFSP. CD34 is a suitable marker for DFSP.

Delay in formalin fixation and HER2 testing in gastric cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluated HER2 status using immunohistochemistry (IHC) assay and fluorescence in situ hybridization (FISH) at two different time points of tissue fixation after surgical resection of gastric cancer, emphasizing the importance of standard operation and quality control in HER2 testing.</p><p><b>METHODS</b>Forty-one resection specimens of advanced gastric cancer were collected with tissue fixation periods of < 30 min or > 30 min after surgical resection. HER2 status was evaluated by immunohistochemistry (IHC) assay and fluorescence in situ hybridization (FISH).</p><p><b>RESULTS</b>The frequency of HER2 expression by IHC in the samples with fixation time of < 30 min was higher than that in those of > 30 min (P < 0.05). However, no significant difference was observed by FISH (P > 0.05) between the two groups. Samples of < 30 min fixation time had high concordant results between IHC and FISH (100.0% for both positive and negative cases, Rho = 0.724, P < 0.05). In addition, HER2 expression by IHC was significantly correlated with Lauren classification, histologic differentiation, TNM stage and gender (P < 0.05).</p><p><b>CONCLUSION</b>The time to tissue fixation after surgical resection of more than 30 min has deleterious effect on the detection of HER2 by IHC although FISH testing is not affected.</p>

Chromosomal translocation involving USP6 gene in nodular fasciitis / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the frequency of USP6 gene rearrangement in nodular fasciitis (NF) and to evaluate its clinical application.</p><p><b>METHODS</b>Twenty nine cases of previously diagnosed NF were screened for the presence of the USP6 gene rearrangement by interphase fluorescence-in-situ hybridization (FISH) on formalin-fixed paraffin-embedded tissue. Fifteen of these cases, which had available tissue, were also analysed for MYH9-USP6 fusion transcripts by reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Twenty four of the 29 cases (83%) were positive for the USP6 gene rearrangement by interphase FISH. The 15 cases with RT-PCR showed the following results: 11 positive, one deletion and three negative for USP6 gene rearrangement. Of these 15 cases, eight (8/15) showed MYH9-USP6 fusion transcript by RT-PCR. Of these eight cases, seven were positive for USP6 gene rearrangement and one showed USP6 deletion by FISH.</p><p><b>CONCLUSIONS</b>USP6 gene rearrangement is a recurrent genetic event in NF. It is a valuable ancillary tool for the pathological diagnosis of these lesions.</p>

A20 and TNF genes aberration in ocular adnexal MALT lymphomas / 白血病·淋巴瘤

Objective To investigate the copy number changes of A20 and TNF genes,and determine the contribution of the two genes in the development of ocular adnexal MALT lymphoma.Methods Forty-one cases of archive paraffin-embedded ocular adnexal MALT lymphoma tissues were detected by interphase fluorescence in situ hybridization (FISH) using the commercial chromosome 6 centromere probe (CEP6),and house-made site-specific probe of A20 and TNF. Results Of the 41 ocular adnexal MALT lymphoma cases,loss of heterozygosity (LOH)in A20 locus was detected in 2 cases (4.88 ％).TNF extra copies were found in 5 cases (12.20 ％),of which three cases simultaneously had extra CEP6 signals.No A20 deletion were found coexistence with TNF extra copies in any case.Conclusion A20 gene deletion is present in the small part of ocular adnexal MALT lymphoma, and might contribute to the development of Chinese ocular adnexal MALT lymphoma.A20 deletion is not associated with extra copies of TNF locus.

A clinical study of chromosome translocations in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in Chinese patients / 中华内科杂志

Objective To investigate the genetic aberrations in extranodal marginal zone lymphoma of mueosa-associated lymphoid tissue (MALT) lymphomas from different sites of the body in Chinese patients. Methods Two hundred and seventeen paraffin-embedded MALT lymphoma specimens from 11 major sites were studied with interphase fluorescence in situ hybridization (FISH) to detect t(11; 18) (q21;q21)/API2-MALT1, t(1; 14) (p22; q32)/IGH-BCL10, (14; 18) (q32; q21)/IGH-MALT1 and BCL6 gene involved chromosome translocations. Results These translocations were mutually exclusive and detected in 21% (46/217) of the cases, including t(11;18) (q21;q21) API2-MALT1 13% (29/217), t (1;14)(p22 ;q32) IGH-BCLIO in 1% (3/217), t(14;18) (q32;q21) IGH-MALT1 1% (2/217), BCL6 involved translocation in 2% (4/217) and IGH-unknown translocation partner in 4% (8/217). t(11; 18) (q21;q21)API2-MALT1 was found with the highest frequency in MALT lymphoma from lungs (47% , 8/17) and small intestine (29%, 4/14), followed by salivary gland (17%, 1/6), stomach (14%, 12/84) and ocular adnexae (6% , 4/68). t(1 ;14) (p22;q32) was only detected in lungs (12%, 2/17) and stomach (1%, 1/84). t(14;18) (q32;q21) was mainly detected in lungs (6%, 1/17) and ocular adnexae (2%, 1/68). BCL6 gene involved translocation was detected in salivary gland (17% , 1/6) and stomach (4%, 3/84). Conclusions It is demonstrated that the four translocatidns occur with markedly variable frequencies in MALT lymphoma of different sites in Chinese patients. The distributions of these chromosome translocations in Chinese patients are slightly different from those reported in western patients.

Recent advances in aetiology and molecular genetics of MALT lymphoma / 白血病·淋巴瘤

Mucosa-associated lymphoid tissue (MALT} lymphoma is a low grade B-cell lymphoma arising from MALT of extra-nodal. A link of Helicobacter pylori (HP) infection with gastric MALT lymphoma was confirmed in the early years. Currently, growing evidence indicates that development of non-gastric MALT lymphoma is also associated with infections by microbial pathogens. t(l1;18)(q21;q21)、t(l;14)(p22;q32) and t (14;18)(q32;q21) are specifically associated with MALT lymphoma, which occur at variable incidences in MALT lymphoma of different sites. The oncogenic activity of these three chromosome translocations is linked by antigen receptor-mediated NF-κB activation.In addition, a number of novel genetic abnormalities have been recently identified in MALT lymphoma. The findings of these microbial pathogens and molecular genetics would be helpful in better understanding the pathogenesis of MALT lymphoma and also useful for the diagnosis at early stage and proper treatments of MALT lymphoma.

Lymphomas with CARMA1, BCL10, MALT1 and NF-?B signaling pathway / 中国癌症杂志

CARMA1, BCL10 and MALT1 are lymphocyte-specific signaling molecules of NF-?B pathway.The abnormalities of those molecules such as gene mutation, rearrangement, translocation or amplification often connect with the lymphoma genesis. This article reviewed the physiological function of those molecules and the relationship between genetic abnormalities and lymphoma genesis, also with present target-treatment research and new gene medicine development.