CRT promoted c-FLIP expression via NF-κB pathway in rheumatoid arthritis fibroblast-like synoviocytes / 天津医药

Objective To investigate the molecular mechanisms of upregulated expression of cellular Fas-associated death domain-like interleukin-1 beta converting enzyme inhibitory protein(c-FLIP)by calreticulin(CRT)in patients with rheumatoid arthritis (RA). Methods The semi-quantitative analysis and localization of c-FLIP in RA and osteoarthritis (OA)synovium were detected by immunohistochemistry.The fibroblast-like synoviocytes(FLS)were isolated by enzymatic digestion of synovial tissue specimens obtained from RA and OA patients,and cultured as an in vitro experiment model.The expressions of c-FLIP in RA and OA synovial fibroblasts were detected by immunofluorescence and Western blot assay. Whether CRT influenced c-FLIP expression and its molecular mechanism were explored by Western blot assay. Results The high expression of c-FLIP was found in RA synovium, mainly in the lining and sublining areas of FLS and vascular endothelial cells detected by immunohistochemistry.Meanwhile,weak staining of c-FLIP was observed in OA synovium.The expression of c-FLIP was significantly higher in RA synovium than that of OA synovium(t=11.717,P<0.001).Results of immunofluorescence and Western blot assay showed that c-FLIP was mainly located in cytoplasm, and which was higher expressed in FLS of RA than that of OA. The increased c-FLIP expression and phosphorylation of NF-κB were detected after being co-incubated with exogenous CRT (0, 10, 50, 100 μg/L), in dose-dependent manner. The effect of CRT upregulating c-FLIP expression was blocked by NF-κB inhibitor BAY 11-7082.Conclusion CRT can increase c-FLIP expression at least partly through NF-κB pathway in RA,which may provide therapeutic target for the treatment of RA.

Analysis of mortality among children under 5 years of age in Shenzhen from 2003 to 2013 / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the trend of the mortality rate and the leading causes of death among children under 5 years of age in Shenzhen, China, from 2003 to 2013.</p><p><b>METHODS</b>The surveillance data of mortality among children under 5 years of age in Shenzhen from 2003 to 2013 were collected, and the mortality rates among infants (IMR) and children under 5 years of age (U5MR) with different household types and the leading causes of death were determined.</p><p><b>RESULTS</b>Between 2003 and 2013 the IMR and U5MR in Shenzhen dropped by 61.56% and 60.56%, respectively from 7.83‰ and 10.04‰ in 2003 to 3.01‰ and 3.96‰ in 2013. The IMR and U5MR of the non-household population were significantly higher than those of the household population. The leading causes of death among children under 5 years of age were preterm birth/low birth weight, congenital heart disease, accidental asphyxia, septicemia, and birth asphyxia.</p><p><b>CONCLUSIONS</b>The U5MR has substantially reduced in Shenzhen. To further reduce the U5MR, it is important to improve prenatal diagnosis and neonatal resuscitation, enhance perinatal health care and accident prevention, and strengthen health care of floating population.</p>

Expression of MMR in endometrial adenocarcinoma in women under 50 years old / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression of DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6 and PMS2) in endometrial adenocarcinoma (EC) of patients under 50 years and to explore the relationship between MMR expression and clinicopathological features including body mass index (BMI), histological grade and pathological stage of EC.</p><p><b>METHODS</b>MMR gene expression was investigated by immunohistochemical S-P method in endometrial adenocarcinomas of patients under age of 50. The control groups included complexity atypical hyperplasia endometrium (CAHE), simple hyperplasia endometrium (SHE), normal endometrium (NE) of patients under age of 50 and EC of patients older than 65 years.</p><p><b>RESULTS</b>Twenty seven of 40 EC (67.5%) lost at least one MMR protein expression. Loss of at least one MMR protein expression was seen in 5/15 cases of CAHE, 1/13 SHE and 1/11 NE, respectively (P < 0.01). The rates of loss of expression of MLH1, MSH2, MSH and PMS2 proteins in EC were 52.5%, 12.5%, 35.0%, and 30.0%, respectively. The difference between MLH1 and MSH6 expression among the four groups were significant (P < 0.05), but the expression of MSH2 showed no significant difference among the groups (P = 0.295). The expression of MMR protein had no relationship with histological grade and pathological stage, although loss of MSH6 was more frequently seen in patients of higher BMI.</p><p><b>CONCLUSIONS</b>Abnormal expression of MMR proteins is correlated with the development of EC from complex atypical hyperplasia. With the exception of the correlation of MSH6 expression with higher BMI, the expression of MMR proteins in EC has no significant relationship with histological grade and pathological stage.</p>

Analysis of GJB2 gene coding sequence in patients with nonsyndromic hearing loss / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the coding sequence of GJB2 gene in six pedigrees with nonsyndromic hearing loss in order to find deafness-causing mutations in the GJB2 gene, and to explore the inherent pattern of deafness-causing mutations in the GJB2 gene.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood for the probands and their family members. Coding sequence of the GJB2 gene was amplified by polymerase chain reaction, sequence variations were determined by DNA sequencing. Amplified fragments with overlapping peaks on sequencing chromatogram were sequenced by TA cloning in order to determine whether the mutations originated from the same allele.</p><p><b>RESULTS</b>Mutations in the GJB2 gene were found in 4 out of the 6 pedigrees with nonsyndromic hearing loss. Four types of mutations were detected in the GJB2 gene, which were 235delC, 299-300delAT, 79G>A+341A>G, and 109G>A. Compound heterozygous polymorphisms 79G>A and 341A>G, and mutations 109G>A and 235delC had deafness-causing effects.</p><p><b>CONCLUSION</b>Heterogeneous mutations of the GJB2 gene are frequently seen in patients with nonsyndromic hearing loss. Sometimes, polymorphisms may cause deafness when they are combined. Environmental factors and other genes may contribute to hearing loss caused by the GJB2 gene mutations.</p>

Mutation of thyroid peroxidase gene in 35 patients with congenital hypothyroidism / 中华儿科杂志

<p><b>OBJECTIVE</b>To identify thyroid peroxidase (TPO) gene mutations in 35 patients with congenital hypothyroidism.</p><p><b>METHOD</b>Genomic DNA was isolated from peripheral blood samples of 35 patients with congenital hypothyroidism. All of the 17 exons and flanking introns of TPO gene were amplified by PCR, then the PCR products were sequenced bi-directionally and were analyzed by restriction endonucleases.</p><p><b>RESULT</b>One patient had compound heterozygous mutations c.961A>G/c.2422delT, one was c.2268insT/c.1477G>A, and three was homozygous mutation c.2268insT. The TPO gene mutation c.961A>G [p. Thr321Ala] was one novel mutation.</p><p><b>CONCLUSION</b>High frequency mutation in TPO gene was detected in patients with congenital hypothyroidism.</p>

A study on vasculogenic mimicry in hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore if vasculogenic mimicry (VM) exists in hepatocellular carcinoma (HCC) and to explain the clinical significance of VM.</p><p><b>METHODS</b>Ninety-nine HCC resection specimens with complete clinical and prognostic data were collected. Immunohistochemical staining of CD31 and CD105, hepatocyte and PAS staining of the histological preparations were conducted to explore if VM exists in those HCC.</p><p><b>RESULTS</b>12.12% (12 specimens) of the 99 specimens exhibited evidence of VM. One of 40 HCC specimens (2.5%) which belong to Edmondson pathologic grade I-II exhibited VM; 11 of 59 HCC specimens which belong to Edmondson pathologic grade III-VI (18.64%) exhibited VM, the low differentiated HCC (grade III-VI) exhibited more VM specimens than the high differentiated HCC (grade I-II) (chi2=4.416, P < 0.05). The biological behavior of VM was assessed and the stages of the cancers, using the TNM (tumor, node, metastases) classification criteria, were analyzed. These parameters of the VM and non-VM groups were compared. The mean TNM stage of the VM group was not more advanced than that of the non-VM group. The hematogenous metastases ( lung, bone, peritoneum et al) between the 2 groups were compared, and in the VM group the hematogenous metastasis rate was higher (chi2=8.873, P < 0.01). Kaplan-Meier actuarial survival curves were used to compare the VM group (n = 12) with the non-VM group (n = 87). Median survival time of the VM group was 9 months and that of the non-VM group was 31 months. The VM group had a lower survival rate than the non-VM group (P < 0.01).</p><p><b>CONCLUSION</b>VM exists in HCC, and the higher invasive HCCs exhibit more VM than the less invasive HCCs. The HCC patients in the VM group had a higher rate of hematogenous metastases, a lower survival rate, and a poorer prognosis.</p>

Expressions and significance of E-cadherin and beta-catenin in synovial sarcoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the expression and significance of E-cadherin (E-cad) and beta-catenin (beta-cat) in synovial sarcoma.</p><p><b>METHODS</b>Expression of E-cad and beta-cat in 72 cases of synovial sarcoma were detected by tissue microarray technique and immunohistochemistry. The relationships between E-cad and beta-cat expression and clinicopathological data and survival rate were analyzed.</p><p><b>RESULTS</b>(1) 95.1% of dots on the tissue microarrays were observable morphologically. The background was clear and the contrast was vivid after immunohistochemistry. (2) The expression of E-cad was reduced in 56 patients (77.8%) and that of beta-cat was reduced in 51 patients (70.8%). (3) In patients with synovial sarcoma of monophasic fibrous type, grade III, and in patients with recurrence or metastasis, CK-negative and EMA-negative the rates of reduced expression of E-cad and beta-cat were significantly higher than those with primary sarcoma of biphasic type, grade II, CK-positive and EMA positive (P < 0.05 for all). (4) The survival of synovial sarcoma patients with E-cad and beta-cat expressions preserved was significantly better than those with reduced expressions (P = 0.012, P = 0.047).</p><p><b>CONCLUSION</b>The expression of E-cad and beta-cat is correlated with cell differentiation. Reduced expression of E-cad and beta-cat may indicate a high potential of recurrence or metastasis and poor prognosis. Tissue microarray technique is applicable for retrospective studies of large sample size.</p>