Down-regulation of the Smad signaling by circZBTB46 via the Smad2-PDLIM5 axis to inhibit type I collagen expression / 老年心脏病学杂志（英文版）

BACKGROUND@#Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood.@*METHODS@#Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5.@*RESULTS@#In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development.@*CONCLUSIONS@#CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.

Expression and effect of roundabout guidance receptor 1 during valproate induced neural stem cells differentiation / 解剖学报

Objective To investigate the expression and role of roundabout guidance receptor 1 (Robo1) in the neuronal differentiation of neural stem cells (NSCs) induced by valproate (VPA). Methods The hippocampus NSCs of SD rats were isolated and cultured. Normal NSCs and VPA-treated NSCs were extracted from 10 SD rats. After VPA treatment, the proportion of neuron-specific marker β-tubulin III (Tuj1) positive neurons differentiated from NSCs were detected by immunofluorescence. The differentially expressed mRNA in normal NSCs and VPA-induced NSCs were detected by gene chip technology. After VPA treatment, the expression levels of Robo1 mRNA and protein were detected by Real-time PCR and Western blotting. The dynamic changes of Robo1 mRNA were detected by Real-time PCR after the differentiation of NSCs. After the expression of Robo1 was down-regulated in NSCs by small interfering RNA, the expression of Robo1 protein was detected by Western blotting, and the expression levels of neuron-specific markers Tuj1 and microtubule associated protein-2 (MAP-2) were detected by Real-time PCR and immunofluorescence. Results VPA induced NSCs to differentiate into neurons. Compared with the control group, the expression levels of Robo1 mRNA and protein in the differentiation of NSCs were significantly up-regulated during valproate treatment. After interference of Robo1 expression, not only Robo1 upregulation was inhibited during the differentiation of NSCs induced by VPA, but also the proportion of NSCs differentiated into neurons decreased. Conclusion VPA may promote the differentiation of NSCs into neurons by up-regulating the expression of Robo1.

Effects of astrocytes on the proliferation of neural stem cells in the hippocampal microenvironment of old and young adults / 解剖学报

Objective To investigate the effect and mechanism of astrocytes on the proliferation of neural stem cells (NSCs) in adult and juvenile hippocampus microenvironment. Methods Hippocampal astrocytes were isolated and cultured from 5 female SD rats at day 1 and week 30 postnatal, respectively; Embryonic hippocampus NSCs was isolated and cultured from 1 SD rat at day 15 of gestation; Conditioned astrocyte culture medium(CM) was collected for NSCs culture; Flow cytometry and CCK-8 were used to detect the proliferation of NSCs cultured in CM. Colony stimulating factor 1 (CSF-1) with differential expression was screened by mass spectrometry after cultured astrocyte CM. Western blotting and ELISA were used to verify the result of mass spectrometry. Immunofluorescence, flow cytometry and CCK-8 were used to detect the proliferation of NSCs treated with different concentrations of CSF-1 recombinant protein (20 μg/ L, 100 μg/ L, 1 mg/ L and 5 mg/ L). Results Compared with the adult group, the CM of hippocampal astrocytes in the young group could promote the proliferation of NSCs(P<0. 01); Compared with the conditioned medium of hippocampal astrocytes in the juvenile group, the expression of CSF-1 in the hippocampus of the elder group was significantly up-regulated(P<0. 01); At 20 μg/ L, CSF-1 promoted the proliferation of NSCs(P<0. 01), and 5 mg/ L CSF-1 inhibited significantly the proliferation of NSCs(P<0. 01). Conclusion The secretion of CSF-1 by astrocytes in hippocampal microenvironment can regulate the proliferation of NSCs with the development of the times.

Genomewide DNA Methylation Responses in Patients with β-Thalassemia Treated with Yisui Shengxue Granules () / 中国结合医学杂志

OBJECTIVE@#To examine the clinical effects of Yisui Shengxue Granules () in the treatment of β-thalassemia and explore its mechanism on DNA methylation levels.@*METHODS@#A randomized placebo-controlled double-blinded trial was conducted. Forty patients with β-thalassemia were recruited and distributed randomly by envelope method into an experimental group and a control group, 20 patients in each group. The patients were given Yisui Shengxue Granules in the experimental group and placebo in the control group (12 g/bag three times a day) during a 3-month intervention. Before and after 1, 2, and 3 months of treatment, peripheral intravenous blood was sampled, and blood parameters such as hemoglobin (Hb), red blood cells (RBCs), reticulocytes (Ret), and fetal hemoglobin (HbF) were analyzed. Mononuclear cells from 5 patients, who showed an obvious treatment effect, were isolated by density gradient centrifugation. DNA methylation was analyzed using an Affymetrix USA GeneChip Human Promoter 1.0 Array and Input-promoter 1.0.@*RESULTS@#Compared with pre-treatment, there was an obvious increase in Hb and RBCs counts after 1, 2, and 3 months in the experiment group (P<0.01 or P<0.05). Meanwhile, HbF increased from the 2nd to the 3rd month (P<0.05). In the control group, Hb and RBCs showed no obvioas change. After 3-month treatment, DNA methylation results from 5 patients revealed that there were 24 hypomethylated genes and 3,685 hypermethylated genes compared with pre-treatment. Genes of insulin-like growth factor 1 receptor (IGF1R) and Janus kinase 3 (JAK3) revealed the most relations with other genes (degree: 21) and genes of 1-phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma 2 (PLCG2) and mitogen-activated protein kinase 10 (MAPK10) showed a stronger intermediary role (betweenness centrality=0.04).@*CONCLUSIONS@#JAK3 and MAPK10 are two key genes in bone marrow and the lymphatic system, and JAK3 is likely to be related to hematopoietic cytokines in the process of early hematopoiesis. (Registration No. NCT01549080).

Association of DAZL A260G and A386G polymorphisms with oligozoospermia- or azoospermia-induced male infertility: A meta-analysis / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the association of A260G and A386G polymorphisms of the DAZL gene with male infertility caused by oligozoospermia or azoospermia.</p><p><b>METHODS</b>We searched the PubMed, Science Direct, Wiley Online Library, CNKI, VIP, and CDDB databases up to November 30, 2013 for case-control studies evaluating the relationship of SNP260 and SNP386 polymorphisms of the DAZL gene with male infertility, and meanwhile conducted manual sourcing of the references in the identified studies and relevant articles. Two reviewers independently screened the title, abstract and keywords of each article retrieved. The StataSE12. 0 software was used for meta-analysis and other statistical analyses.</p><p><b>RESULTS</b>Totally, 13 case-control studies were included (10 about A260G and 11 about A386G), involving 2 715 infertile patients (2 500 with oligozoospermia or azoospermia) and 1 835 normozoospermic men. DAZL A260G showed no statistical significance in the allele, dominant, recessive, co-dominant, or super-dominant gene model (P >0. 05). DAZL A386G exhibited a strong correlation with oligozoospermia or azoospermia in Asians in the allele gene model (OR = 0. 15, 95% CI 0.07 -0.34, P <0.05), dominant gene model (OR =0. 16, 95% CI 0.07 - 0. 35, P <0.05), co-dominant gene model (AA/AG) (OR = 0. 15, 95% CI 0. 06 - 0. 33, P < 0. 05), and super-dominant gene model (OR = 0. 15 (95% CI 0.06 - 0.33, P <0.05) , and so did it in Chinese in the four gene models ( OR = 0. 11, 95% CI 0.04 - 0. 28, P <0.05; OR =0. 11, 95% CI 0.04 - 0.28, P<0.05; OR = 0.09, 95% CI 0.03 - 0.26, P<0.05; OR = 0.09, 95% CI 0.03 - 0.26, P< 0.05).</p><p><b>CONCLUSION</b>Our study manifested that the DAZL polymorphism A386G, but not A260G, was correlated with reduced sper- matogenesis or sperm count specifically in Chinese males. More high-quality trials are required for a deeper insight into the exact relationship of DAZL A260G and A386G polymorphisms with oligozoospermia- or azoospermia-induced male infertility.</p>

Clinicopathological features and prognosis of young patients with gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To summarize the clinicopathological characteristics and analyze the prognostic factors of young patients with gastric cancer.</p><p><b>METHODS</b>A total of 99 patients with the age less than or equal to 40 were admitted in The First Affiliated Hospital of Sun Yat-sen University from August 2001 to December 2009. Their clinicopathological and follow-up data were compared with middle-aged and elderly patients with the age more than 40.</p><p><b>RESULTS</b>There were statistically significant differences in gender, tumor location, Borrmann type, histological type, differentiated histology, depth of invasion, peritoneal metastasis between young patients and elder ones. The 5-year survival rates of young and elder patients were 49.1% and 44.4% respectively, and the difference was not statistically significant (P>0.05). Univariate and multivariate analyses showed that TNM stage (P=0.014) and surgical methods (P=0.012) were independent predictive factors of survival for young patients. For the young patients, the 5-year survival rate was 56.7% after curative resection, 11.1% after palliative resection. Those who underwent palliative surgery or biopsy alone died within 1 year after surgery. The difference between difference surgical procedures in survival were statistically significant (P<0.05).</p><p><b>CONCLUSIONS</b>As compared to elder patients, young patients with gastric cancer have special clinicopathological features. However, no significant difference of survival rate is found between the young and the elder patients. TNM stage and surgical methods are independent prognostic factors of young patients with gastric cancer. Radical resection appears to confer the only chance of prolonged survival.</p>

Type II enteropathy-associated T-cell lymphoma: a clinicopathologic study / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunohistochemical findings, differential diagnosis and prognosis of type II enteropathy-associated T-cell lymphoma (EATL).</p><p><b>METHODS</b>Fourteen cases of type II EATL encountered in Department of Pathology, Nanjing General Hospital were retrospectively reviewed. The clinical data, histologic features, immunohistochemical findings and follow-up information were analyzed, with literature review.</p><p><b>RESULTS</b>There were altogether 12 males and 2 females. The median age of patient was 49 years. The sites of involvement included jejunum (10 cases) and ileum/colon (4 cases). The patients often presented with an abdominal mass, abdominal pain, diarrhea and constitutional symptoms such as fever, night sweating and cachexia. There was no clinical evidence of gluten-sensitive enteropathy. Histologically, the lymphoma cells showed full-thickness infiltration of the intestinal wall. They contained round hyperchromatic nuclei and pale cytoplasm. The stroma was minimally inflamed, with or without associated coagulative necrosis. A remarkable finding was the presence of villous atrophy, cryptal hyperplasia and intraepithelial lymphocytosis. Immunohistochemical study showed that the tumor cells expressed CD3, CD43 and CD8 (14/14). Some of them were also positive for CD56 (11/14) and CD30 (2/14). The staining for CD4, CD20, CD79a and myeloperoxidase was negative. A high proliferation index was demonstrated by Ki-67 immunostain. In-situ hybridization for EBER was negative. Follow-up data were available in 9 cases. The duration of follow-up ranged from 6 months to 36 months. Seven patients died within 14 months.</p><p><b>CONCLUSIONS</b>EATL is a rare type of lymphoma with intestinal involvement. Associated enteropathy is not demonstrated, in contrast to cases encountered in Nordic countries. A correct diagnosis requires evaluation of clinical manifestations, pathologic features and ancillary study results.</p>

Clinicopathological features of colorectal neuroendocrine neoplasms and prognostic significance of WHO staging system / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics of colorectal neuroendocrine neoplasms (NENs) and the prognostic significance of the new WHO classification and staging system about gastroenteropancreatic NENs.</p><p><b>METHODS</b>The clinical and pathological records were reviewed in 73 patients with colorectal NENs (carcinoids). All slides were retrieved and reviewed, immunohistochemical staining (EnVision method) was performed and follow-up information retrieved.</p><p><b>RESULTS</b>Forty-one men and thirty-two women were included with a median age of 53 years (19 - 79 years). The location of the primary tumors in 65 patients was within 10 cm from the anorectal line. In 45 cases, the tumor diameter was ≤ 1 cm (no metastasis occurred); in 11 cases, the tumor diameter was > 1 cm but ≤ 2 cm (two patients had metastatic tumors); in 17 cases, the tumor diameter was > 2 cm (12 patients had metastatic tumors). The metastatic rate was significantly correlated with tumor size (P = 0.000). All tumors were immunoreactivity for synaptophysin and/or chromogranin A. According to the criteria of WHO classification and staging system about gastroenteropancreatic NENs, there were 65 cases of neuroendocrine tumors, including 51 cases of grade 1 (G1), 14 cases of grade 2 (G2), 4 cases of neuroendocrine carcinoma (G3) and 4 cases of mixed adenoneuroendocrine carcinoma. Following-up data showed that of the 34 patients with G1 tumor, there were no tumor-related death, but two patients showed metastases, and the remaining patients were disease free for 6 to 179 months. Of the 12 patients with G2 tumors, five developed metastasis, there were two tumor-related deaths, and the nine surviving patients were alive for 17 to 118 months. Of the four G3 patients, all developed metastasis and there were three tumor-related deaths. Of the four mixed adenoneuroendocrine carcinoma there were two tumor-related deaths. The difference of metastatic rate, tumor-related mortality, and overall survival among different grading groups in this series was statistically significant (P = 0.000).</p><p><b>CONCLUSIONS</b>Colorectal neuroendocrine neoplasm is a group of tumors with distinct prognostic difference, and most of these tumors show an indolent clinical behavior. There is a good correlation between the new WHO classification and staging system of gastroenteropancreatic NENs and their clinical behaviors.</p>

Clinicopathologic features of intestinal natural killer/T-cell lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, diagnosis and differential diagnosis of intestinal natural killer (NK)/T-cell lymphoma.</p><p><b>METHODS</b>The clinical features, histopathology, immunohistochemical findings and follow-up data of 14 cases of intestinal NK/T-cell lymphoma were retrospectively reviewed.</p><p><b>RESULTS</b>The male-to-female ratio was 9:5. The medium age of patients was 45 years. The sites of involvement included small intestine (6 cases), colon (6 cases) or both (2 cases). The main clinical manifestations were an abdominal mass, other gastrointestinal symptoms such as abdominal pain, as well as systemic symptoms such as fever and cachexia. Intestinal perforation complicated by acute peritonitis might occur in advanced disease. Histologically, the intestinal wall showed full-thickness infiltration by medium-sized atypical lymphoid cells with pleomorphic nuclei, prominent inflammatory background, angiocentric/angiodestructive growth pattern and coagulative necrosis. Immunohistochemical study showed that the tumor cells were positive for CD3ε, CD43, CD56, granzyme B and perforin. They were negative for CD20, CD79α and MPO. In-situ hybridization for Epstein-Barr virus encoded RNA (EBER) showed negative signals. A high proliferative index was demonstrated by Ki-67 immunostaining. Follow-up data of 8 cases were available, with duration of follow up ranging from 0.5 to 36 months. Five patients died within 20 months.</p><p><b>CONCLUSIONS</b>Extranodal NK/T-cell lymphoma, nasal-type primarily involving intestine is rare and tends to carry an aggressive clinical course. The relatively non-specific clinical manifestations of intestinal NK/T-cell lymphoma may result in misdiagnosis in some cases. A comprehensive evaluation of clinical manifestations, pathologic features and immunohistochemical findings is essential for definitive diagnosis.</p>

Impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer (EGC) patients.</p><p><b>METHODS</b>A total of 142 EGC cases screened from database of gastric cancer of Sun Yat-sen University, from Aug. 1994 to Jan. 2010, were included in this study. According to the lymph node metastasis status, they were divided into lymph node negative (n = 116) and lymph node positive (n = 26) groups. The clinicopathological features of the two groups and the impact of extent of lymph node dissection on the prognosis were analyzed.</p><p><b>RESULTS</b>There were no significant differences in age, gender, tumor size and location, Borrmann typing, WHO TNM staging, histological typing, and CEA value between the two groups (P > 0.05). The TNM stages in the lymph node positive group were higher than that in the lymph node negative group (P < 0.001). Between the cases who underwent D1 (n = 21) and D2 (n = 121) dissection, there were no significant differences in postoperative hospital days, blood transfusion volume, and operation time (P > 0.05). The median numbers of LN dissected in D1 and D2 cases were 4 (0 to 16) and 20 (12 to 30), with a significant difference (P = 0.000), but the number of positive LN without significant difference (P = 0.502). The postoperative complication rates were 9.5% in the D1 and 3.3% in the D2 dissection groups, without a significant difference (P = 0.128). The median survival time of the lymph node negative and positive groups was 156 vs. 96 months (P = 0.010). In cases who received D2 and D1 lymph node dissection, the median survival time (MST) was 156 vs. 96 months (P = 0.0022). In the lymph node positive group, D2 dissection prolonged survival time significantly than D1 dissection (96 vs. 27months) (P = 0.001). Cox regression analysis showed that the extent of lymph node dissection and LN metastasis were independent prognostic factors for EGC patients.</p><p><b>CONCLUSIONS</b>It is not able to accurately assess the LN metastasis status preoperatively according to the routine clinicopathological features. For the patients with unknown LN metastasis status, D2 dissection should be the first choice. Comparing with D1 dissection, the morbidity of D2 dissection are not increased, but survival time is prolonged.</p>

Family-based association study of a variable number of tandem repeat polymorphism of DAT1 gene with Tourette syndrome in a Chinese Han population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of a 40 bp variable number of tandem repeat (VNTR) polymorphism within 3 untranslated region of dopamine transporter gene (DAT1) with Tourette syndrome (TS) in a Chinese Han population.</p><p><b>METHODS</b>A total of 160 TS patients and their parents were recruited. The VNTR polymorphism was detected with polymerase chain reaction-VNTR analysis, and its association with TS and its subtypes were assessed through a family-based association study comprising transmission disequilibrium test (TDT) and haplotype relative risk (HRR) analysis.</p><p><b>RESULTS</b>The repeat numbers at the DAT1 40 bp locus were 11, 10, 9, 7.5 and 7 among the patients and their parents, with the most common type being a 10-repeat allele. No significant association was detected between the polymorphism and TS (TDT: X ² = 0.472, df = 1, P = 0.583; HRR: X ² = 0.313, P = 0.576, OR = 0.855, 95%CI: 0.493-1.481).</p><p><b>CONCLUSION</b>Our data suggested that the VNTR polymorphism of DAT1 gene is not associated with susceptibility to TS in Chinese Han population. However, our results are to be validated in larger sets of patients collected from other populations.</p>

Evaluation of heart and liver iron deposition status in patients with β- thalassemia intermedia and major with MRI T2* technique / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the status of iron deposition in patients with β-thalassemia intermedia and major in mainland China.</p><p><b>METHODS</b>The status of transfusion and chelation was examined in 39 patients with β-thalassemia intermedia or major. Serum ferritin levels were measured. MRI T2* technique was used to detect cardiac and hepatic iron deposition.</p><p><b>RESULTS</b>Serum ferritin levels ranged from the minimum of 1500 ng/mL up to a maximum of 11491 ng/mL. From liver MRI T2* measurement, 15 cases had severe hepatic iron deposition (38%) and moderate deposition was found in 15 cases (38%), mild in 7 cases (18%), and normal in 2 cases (5%). Heart MRI T2* showed severe heart iron deposition in 7 cases (18%), mild in 5 cases (13%), and normal in 27 cases (69%). One case had cardiac arrhythmia. Four cases were over 20 years of age, and presented with gonadal function hypoplasia. The majority of patients did not receive regular transfusion and they had delayed, suboptimal chelation due to financial problems. Serum ferritin level was closely related with timing and dosage of chelation.</p><p><b>CONCLUSIONS</b>In patients with β-thalassemia who do not receive early regular transfusion and iron chelation therapy, iron deposition may occur at an early age. Important organs and tissue functional lesions and related complications also result. Relevant agencies and family members should be aware of this trend and develop appropriate strategies to improve the medical condition and quality of life of patients with this disorder.</p>

Effect of Yisui Shengxue Granule () on the oxidative damage of erythrocytes from patients with hemoglobin H disease / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Yisui Shengxue Granule (, YSSXG), a complex Chinese medicine, on the oxidative damage of erythrocytes from patients with hemoglobin H (HbH) disease.</p><p><b>METHODS</b>Twenty-two patients with HbH disease and 22 healthy volunteers were observed. YSSXG was given to patients with HbH disease for 3 months. Before and after the 3-month treatment, blood parameters [hemoglobin (Hb), red blood cells (RBCs), and reticulocyte percent (Ret)] were examined; inclusion bodies in erythrocytes were observed by transmission electron microscopy (TEM); activities of antioxidant defense enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (Cat)] and erythrocyte membrane malondialdehyde (MDA) concentrations were determined.</p><p><b>RESULTS</b>In patients with HbH disease, measured values of RBC and Hb obtained from the first to the third months after treatment with YSSXG were significantly higher than before treatment (P<0.01). Measured values of Ret from the second to the third months after treatment were significantly lower than before treatment (P<0.05 and P<0.01, respectively). Prior to treatment with YSSXG, TEM images of RBCs showed the presence of numerous inclusion bodies. After treatment with YSSXG, the amount and volume of inclusion bodies decreased. Treatment with YSSXG also led to a significant increase in SOD activity (P<0.01), a decrease in Cat activity (P<0.01), and no significant differences in GSHPx activity (P>0.05) or MDA concentration (P>0.05). However, compared with the healthy counterparts, SOD, GSH-Px, and Cat activities presented at high levels (P<0.01) both before and after treatment.</p><p><b>CONCLUSIONS</b>YSSXG could improve the degree of hemolysis and anemia in patients with HbH disease. The mechanism may be related to its antioxidative effects, which could elevate the activity of total SOD in erythrocytes and efficiently inhibit the oxidative precipitation of β-globin chains.</p>

Analysis of hematological characteristics on the 79 co-inheritance of α-thalassemia and β-thalassemia carriers in Guangxi / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the hematological characteristics of co-inheritance of α-thalassemia (α-thal) and β-thalassemia (β-thal) and to survey the incidence of co-inheritance of α-thal and β-thal in Guangxi.</p><p><b>METHODS</b>DNA samples from 370 primary and middle school students who were β-thal carriers in Guangxi were further processed for the α-goblin gene mutation screening, and were grouped based on the genotype of β- and α-goblin gene. The hematological indexes to the different groups were compared by One-way ANOVA.</p><p><b>RESULTS</b>Of the total 370 β-thal carriers, 79 were found to carry α-thal, which gave a frequency of 21.35% for β-thal carriers and 1.36% for coincidence of these two common disorders in the local population. As expected, the 79 patients presented very variable α-globin alterations in combination with β-globin mutations, showing 31 genotype combined with the coincidence of both Hb disorders. Except the genotypes of 3 β-thal heterozygotes combined with ααα(anti3.7) triplication and 2 β-thal carriers with IVS-II-654(C→T)/N combined-α(3.7)/αα presented the phenotype of thalassemia intermedia, and other 74 carriers with co-inheritance of α-thal and β-thal all presented the phenotype of β-thal trait. There were significant differences between β-thal heterozygotes and the carriers with a co-inheritance of both β+α(0) thal in MCH, MCV and Hb. In addition, there existed significant difference between the carriers with a co-inheritance of both β+α(+) thal and a co-inheritance of both β+α(0) thal in MCV, MCH and Hb.</p><p><b>CONCLUSION</b>Compared to that of β-thal heterozygotes, the carriers with a co-inheritance of α-thal and β-thal had slighter phenotype with hematological characteristics. It's difficult to distinguish the double heterozygotes with the co-inheritance of α-thal and β-thal from β-thal heterozygotes by hematological indexes, the molecular diagnosis should be performed.</p>

Relevance of molecular alterations in histopathologic subtyping of lung adenocarcinoma based on 2011 International Multidisciplinary Lung Adenocarcinoma Classification / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the relevance of molecular alterations and histopathological subtypes of lung adenocarcinoma according to 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Lung Adenocarcinoma Classification.</p><p><b>METHODS</b>Mutations of epidermal growth factor receptor (EGFR) 18-21 exons (E18-21), KRAS 12/13 codons and EML4-ALK fusion in 212 cases of lung adenocarcinoma which underwent complete tumor resection, were detected by immunohistochemistry, PCR-amplifying and gene sequencing. The relevance of the molecular alterations to histopathological subtypes based on the new classification and 2004 WHO classification were further characterized.</p><p><b>RESULTS</b>Mutations of EGFR were observed in 49.6% of lung adenocarcinomas, involving mainly E21 (52.4%, 55/105) and E19 (36.2%, 38/105). Mutations of KRAS were detected in 8% cases of adenocarcinoma, involving mainly codon 12 (15/17). EML4-ALK fusions were found in 6.1% of lung adenocarcinoma, the most common fusion mutation was type V1 (E13; A20) (7/13), followed by type V3a/b (E6a/b; A20) (4/13). Based on the new classification, 7/10 lepidic, 63.2% (48/76) papillary, and 5/8 micropapillary predominant adenocarcinomas harbored EGFR mutations. EGFR mutations showed significant difference among different histological subtypes (P = 0.008). KRAS mutations were most frequently found in invasive mucinous adenocarcinoma (1/2), followed by colloid predominant adenocarcinoma (3/7). There was significant difference of KRAS mutations among different histological subtypes (P = 0.003). EML4-ALK fusions were most frequently found in the solid predominant with mucin production subtype (15.4%, 6/39), followed by colloid predominant adenocarcinoma (1/7), and no significant difference of EML4-ALK fusions was found among different histological subtypes (P = 0.181). Significant TTF-1 overexpression was observed in adenocarcinomas harbored EGFR mutations (P = 0.008), and no or significantly lower level expression of TTF-1 was observed in adenocarcinomas harbored KRAS mutations (P = 0.000). However, there was no association between TTF-1 expression and EML4-ALK fusions (P = 0.274). Based on the 2004 WHO classification, mutations of KRAS (P = 0.002) and EML4-ALK (P = 0.000), rather than EGFR (P = 0.502), showed significant differences among different subtypes. According to both classification systems, the difference of "triple negative" adenocarcinomas was not significant among different subtypes (P = 0.684, P = 0.449, respectively).</p><p><b>CONCLUSIONS</b>The new classification, combined with TTF-1 immunomarker, can help to predict the molecular alterations of EGFR and KRAS genes, but can not indicate the EML4-ALK fusion in lung adenocarcinoma. Lepidic, papillary, and micropapillary predominant adenocarcinomas with TTF-1 expression are closely related to the presence of EGFR mutation, and invasive mucinous adenocarcinoma, while colloid predominant adenocarcinoma without TTF-1 expression is closely related to the presence of KRAS mutation.</p>

Prognostic significance of a newly proposed grading and scoring system in stage I pulmonary adenocarcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the prognostic significance of a new grading and scoring system (based on the new IASLC/ATS/ERS classification) in stage I pulmonary adenocarcinoma, as compared with the WHO grading system.</p><p><b>METHODS</b>The clinicopathologic characteristics of 125 patients with stage I pulmonary adenocarcinoma primarily treated by surgical resection were reviewed retrospectively. All cases were classified according to the new IASLC/ATS/ERS classification and graded into three prognostic groups based on the new classification, the Sica scoring system and the WHO grading system, respectively. The differences in prognosis of the three groups were analyzed.</p><p><b>RESULTS</b>There was a statistically significant correlation between the new grading system and the WHO grading system (P = 0.000). Both of them showed negative correlation with overall survival. The new scoring system however better correlated with disease recurrence and/or metastasis (P = 0.855, P = 0.073 versus P = 0.011). According to univariate Log-rank test, the prognosis correlated with tumor size (P = 0.004), clinical stage (P = 0.000), the WHO grading (P = 0.020), the new grading system (P = 0.000), the new scoring system (P = 0.000), vascular invasion (P = 0.021), and recurrence and/or metastasis (P = 0.000). The Cox regression analysis demonstrated that clinical stage (P = 0.014), the new grading system (P = 0.047), the new scoring system (P = 0.043), and recurrence and/or metastasis (P = 0.018) were significantly independent poor prognostic factors.</p><p><b>CONCLUSIONS</b>The new grading and scoring system shows good correlation with the WHO grading system. Compared with the WHO grading system, the new scoring system based on the new IASLC/ATS/ERS classification provides valuable information in categorizing stage I pulmonary adenocarcinoma cases with different risks of disease recurrence, tumor metastasis and prognosis.</p>

Impact of different gastrectomy and reconstruction methods on prognosis and quality of life in proximal gastric cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the impact of different gastrectomy and reconstruction method on prognosis and quality of life in proximal gastric cancer.</p><p><b>METHODS</b>The 265 cases of proximal gastric cancer received radical resection, according to gastrectomy or reconstruction method, were divided into proximal gastrectomy/gastroesophagostomy group (PG) (n = 63) and total gastrectomy/esophagojejunostomy group (TG) (n = 202). The clinical pathologic features, prognosis, postoperative quality of life in 2 groups were compared.</p><p><b>RESULTS</b>There had no significant differences in age, gender, CEA value between two groups (all P > 0.05). In PG and TG group, tumor size (cm), ratio of organic invasion, lymph nodes metastasis, distal metastasis, TNM IV stage, Borrmann typing, poor or undifferentiated carcinoma was 2.9 ± 1.9 vs. 4.8 ± 2.8, 9.5% vs. 32.2%, 64.7% vs. 70.6%, 0 vs. 8.4%, 6.9% vs. 31.8%, 44.4% vs. 69.2%, 31.7% vs. 53.7%, respectively, all with significant difference (t = -6.260, χ(2) = 29.473, 14.559, 5.665, 32.483, 12.588, 10.954, all P < 0.05). In PG and TG group, the ratio of D3 and D3(+) resection, multi-visceral resection, complications was 0 vs. 13.8%, 9.5% vs. 38.6%, 7.9% vs. 1.5% respectively, showed increasing range of resection and decreasing complications significantly in TG group (all P < 0.05). The median survival time (months) was 62.5 vs. 78.9 in TG and PG group respectively, without significant difference (P > 0.05). In 2 groups, the evaluation index of post-operative quality of life without significant differences (P > 0.05).</p><p><b>CONCLUSIONS</b>For proximal gastric cancer, although the cases received TG with worse clinicopathological features, which prognosis was similar to that received PG. The postoperative quality of life without significant difference between the cases received gastroesophagostomy and esophagojejunostomy.</p>

Effects of ursolic acid on NADPH oxidase subunit p47Phoxexpression and ERKL/2 pathway activation in rat hepatic stellate cells / 第二军医大学学报

Objective To investigate the effects of ursolic acid (UA) on leptin-induced NADPH oxidase (NOX) subunits p47Phox expression and ERKl/2 pathway activation of rat hepatic stellate cells (HSC-T6), and to observe the cells proliferation and collagen I synthesis. Methods Culture-activated HSC-T6 cells were divided into six groups: normal control group received no treatment; leptin group received recombinant rat leptin (100 ng/ml); the four intervention groups were pretreated with UA(50 μmol/L), JAK inhibitor AG490 (50 μmol/L), NOX inhibitor DPI(20 μmol/L), and ERK inhibitor PD98059 (30 μmol/L) for 30 min, and then stimulated with leptin for different time periods. Western blotting analysis was used to examined the expression of p47Phox protein translocation to the cell membrane, total cellular p47Phox protein and phosphorylated ERKl/2 (p-ERKl/2) protein. Collagen I mRNA expression was detected by RT-PCR and cell proliferation was examined by MTT assay. Results Expression of p47Phox membrane protein was significantly increased compared with the normal control 30 min after leptin stumulation (P<0. 01), and p-ERKl/2 protein expression was also significantly increased correspondingly (P<0. 05). UA, AG490, DPI and PD98059 inhibited the p47Phox protein translocation to membrane and ERKl/2 protein phosphorylation in HSC-T6 cells. Compared with normal control group, leptin stimulation for 12 h significantly up-regulated collagen I mRNA expression in HSC-T6 cells (P<0. 01); UA, AG490, DPI and PD98059 treatment inhibited collagen I mRNA expression in HSC-T6 cells compared with the leptin group (P<0. 01). Proliferation rates of HSC-T6 cells were significantly higher at 12, 24 and 48 h after leptin stimulation compared with the control group (all P<0. 01); UA, AG490, DPI and PD98059 treatment inhibited leptin-induced cell proliferation at different time points (all P<0. 01), with the inhibitory effect of UA being significantly weaker than that of DPI (P<0. 01). Conclusion UA can inhibit leptin-induced proliferation of HSC-T6 cells and collagen I expression, which might be associated with the inhibition of NOX subunit p47Phox translocation to the cell membrane and the ERK1/2 pathway activation.

Clinical analysis of imatinib in patients with advanced gastrointestinal stromal tumor / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and influencing factors of imatinib in patients with advanced gastrointestinal stromal tumor(GIST).</p><p><b>METHODS</b>From April 2004 to January 2010, clinicopathological data of 73 adult patients with advanced GIST treated with imatinib at the First Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. The treatment outcomes and associated factors were investigated.</p><p><b>RESULTS</b>Treatment outcomes included complete response in 1(1.4%) patients, partial response in 53(72.6%), stable disease in 14(19.2%), and primary resistant in 5(6.8%). All the patients had routine followed up, the length of which ranged from 12 to 76 (median 32) months. The median progression-free survival was 45.0 months(95% confidence interval, 34.2-55.8). The progression-free survival(PFS) rate was 87.7% in 1 year, 63.6% in 3 year, and 39.6% in 5 years. On multivariate analysis, both mutation status and patient performance were independent factors influencing the efficacy of imatinib treatment(both P<0.01). PFS was significantly better in patients with c-kit exon 11 mutations than those with exon 9 mutations, and better in lower ECOG scales than in higher ones.</p><p><b>CONCLUSION</b>Imatinib is effective in treating patients with advanced GIST, c-kit exon 9 mutations and poor performance status predict an adverse survival benefit of imatinib therapy.</p>

Association of methylenetetrahydrofolate reductase A1298C polymorphisms with non-syndromic cleft lip with or without cleft palate / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the association between a polymorphism of methylenetetrahydrofolate reductase with Non-syndromic cleft lip with or without cleft palate (NSCL/P) in Chinese population.</p><p><b>METHODS</b>The polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) technique was used to detect a single nucleotide polymorphism (SNP), rs1801131, at the methylenetetrahydrofolate reductase (MTHFR) gene in both 158 patients with NSCL/P and 192 healthy individuals. The Hardy-Weinberg equilibrium for genotypic distributions was estimated by the goodness-of-fit test. The UNPHASED program was applied to perform the association analysis.</p><p><b>RESULTS</b>The genotypic distribution of A1298C was not deviated from the Hardy-Weinberg equilibrium in both controls and patients. No association was found between cleft lip with or without palate (CL/P) and controls. There was significant difference of cleft palate only (CPO) and the healthy individuals (χ(2) = 4.256, P = 0.039). The frequency of AC + CC genotype was higher in control group than that in CPO group (OR = 0.8, 95%CI = 0.381 - 1.683), 26 among 100 healthy individuals carried AC + CC genetypes, which were carried by 22% of CPO patients.</p><p><b>CONCLUSIONS</b>The polymorphism of MTHFR A1298C may be involved in the occurrence of non-syndromic cleft palate only in Chinese population.</p>