Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5–24 Hours of Onset (ROSE-TNK): A Phase 2, Randomized, Multicenter Study / 대한뇌졸중학회지

Background@#and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. @*Methods@#In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). @*Results@#Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. @*Conclusion@#This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

The Cellular Toxicity of PM2.5 Emitted from Coal Combustion in Human Umbilical Vein Endothelial Cells / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To explore the relationship between different components of fine particulate matter (PM2.5) emitted from coal combustion and their cytotoxic effect in the vascular endothelial cells.</p><p><b>METHODS</b>Coal-fired PM(2.5) was sampled using a fixed-source dilution channel and flow sampler. The sample components were analyzed by ion chromatography and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The PM(2.5) suspension was extracted using an ultrasonic water-bath method and then human umbilical vein endothelial cells (EA.hy926) were treated with various concentrations of the PM(2.5) suspension. Cell proliferation, oxidative DNA damage, and global DNA methylation levels were used to measure the cellular toxicity of PM(2.5) emitted from coal combustion.</p><p><b>RESULTS</b>Compared to other types of coal-fired PM(2.5) preparations, the PM2.5 suspension from Yinchuan coal had the highest cytotoxicity. PM(2.5) suspension from Datong coal had the highest toxic effect while that from Yinchuan coal had the lowest. Exposure to coal-fired PM(2.5) from Jingxi coal resulted in lower 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. At the same dose, PM(2.5) emitted from coal combustion could produce more severe DNA impairment compared to that produced by carbon black. Cell survival rate was negatively correlated with chloride and potassium ions content. The 5-methylcytosine (5-mC) level was positively correlated with Mn and negatively correlated with Zn levels. The 8 OHdG% level was positively correlated with both Mn and Fe.</p><p><b>CONCLUSION</b>PM(2.5) emitted from coal combustion can decrease cell viability, increase global DNA methylation, and cause oxidative DNA damage in EA.hy926 cells. Metal components may be important factors that influence cellular toxicity.</p>

Construction of shRNA-Bmi-1 plasmid and its effect on proliferation of ECA109 cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the role of Bmi-1 gene in the proliferation of squamous carcinoma cells and whether the silencing Bmi-1 can inhibit the growth of squamous cell carcinomas cells.</p><p><b>METHODS</b>The expressions of Bmi-1 in primary cultured Fibroblasts, karatinocyte cell line Hacat,squamous carcinoma cell line A431, and ECA109 were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Recombinant plasmid inserted with Bmi-1 gene short hairpin RNA (shRNA) expression vector PGPU6/GFP/Neo-shBmi-1 was constructed and transfected into ECA109 cells with control set. After transfection for 48 and 72 hours,the mRNA and protein levels of Bmi-1 were examined with RT-PCR and Western blot analysis, respectively. The proliferation of the ECA109 cells was evaluated by MTT method and flow cytometry.</p><p><b>RESULTS</b>Bmi-1 was highly expressed in A431 and ECA109 cells than in Fibroblast cells and Hacat cells. The mRNA and protein expressions of Bmi-1 were significantly silenced in ECA109 cells after recombinant expression vector PGPU6/GFP/Neo-shBmi-1 transfection (P<0.05). Compared with the control groups,the proliferation of ECA109 transfected with PGPU6/GFP/Neo-shBmi-1 was significantly inhibited (P<0.05), and cells in G1 phase increased while in S phase decreased (P<0.05).</p><p><b>CONCLUSIONS</b>Bmi-1 is involved in the proliferation of squamous carcinoma cells. After the silencing of Bmi-1 expression,the proliferation ECA109 cells is suppressed due to the altered cell cycle.</p>

SCHWABE Company's patent portfolio of Ginkgo biloba preparation / 中国中药杂志

SCHWABE Company in German is the first and largest manufacturer of Ginkgo biloba preparation. The company not only has leading technology in this field, but also protects its own market effectively through the high quality of patent drafting and exactly patent layout. Based on multi-angle analysis for patent portfolio of G. biloba preparation at application time, legal status, globally layout, Chinese layout, the article provides technical reference of research and development of G. biloba, also provides valuable experience of traditonal Chinese medicine patent portfolio layout for Chinese enterprises.

Preliminary study on main impacting factors on brand equity of listed traditional Chinese medicine companies / 中国中药杂志

The brand equity is valuable intangible assets of traditional Chinese medicine companies, who are excellent representatives of traditional Chinese medicine enterprises and the most promising ones to good international medicine brands. However, there is still no systematic study on how to correctly evaluate the brand equity of listed traditional Chinese medicine companies at present. To make it clear, the main impacting factors on brand equity of listed traditional Chinese medicine companies, both structured open outline pre-research and closed questionnaire research were adopted for the field survey, and some suggestions for how to protect and enhance the brand equity were also presented on the basis of survey and analysis, in the hope of improving the brand management level of listed traditional Chinese medicine companies, and making a beneficial exploration for the development of brand theory of the traditional Chinese medicine industry.

An epidemiological investigation on a food-born outbreak of noroviru caused by Sydney 2012 G II.4 strain / 中华流行病学杂志

<p><b>OBJECTIVE</b>To identify the source of infection, route of transmission and risk factors related to a cluster of acute gastroenteritis cases in a university of Guangzhou.</p><p><b>METHODS</b>Cases were identified according to the definition. Descriptive epidemiological approaches and case-control study designs were employed in the analysis. All the samples were tested for norovirus by RT-PCR. Positive samples were subjected to both nucleotide sequence and homology analysis.</p><p><b>RESULTS</b>A total of 141 cases related to norovirus gastroenteritis were identified in January 8 to 21, 2013, with the attack rate as 8.5 per thousand (141/16,600). The peak in morbidity was seen on January 8 to 9. No clustering was found in different classes or dormitories. Results from the case-control study revealed that early cases were infected in Restaurant A (OR = 3.46, 95% CI: 1.07-11.16) and the cold shredded chicken set meal (OR = 17.82, 95% CI: 4.46-78.17) served at lunch (OR = 4.34, 95% CI: 1.18 -17.37) on January 7 was under suspicion. A total of 266 samples, including rectal swabs from the patients and kitchen wokers, leftover food and environmental swabs, were collected. Twenty-one samples (collected from 17 persons) were positive for norovirus by RT-PCR. About 29.6% (8/27) of the kitchen workers in the Restaurant A were tested positive for the virus. The pathogen was identified as the new norovirus genotype II.4 variant, termed Sydney 2012. The virus strains isolated from the patients among student and staff and the kitchen workers were 100% identical in their nucleotide sequence.</p><p><b>CONCLUSION</b>This was the first reported acute gastroenteritis outbreak caused by the new norovirus genotype II.4 variant, Sydney 2012, which showed that the food was contaminated by the asymptomatic kitchen workers who carried the virus.</p>

Valproic acid exerts differential effects on cytokine synthesis in human peripheral lymphocytes / 中国病理生理杂志

AIM: Valproic acid (VPA) is a histone deacetylase inhibitor and is believed to have anti-tumor activity. The present study aims to investigate the effect of VPA on the, apoptosis and cytokine synthesis of human peripheral lymphocytes. METHODS: The activation and cytokine synthesis in lymphocytes in whole blood stimulated with phorbol dibutyrate (PDB) and ionomycin were evaluated with flow cytometry after fluorescent staining. The mitochondrial membrane potential was examined using 3, 3-dihexyloxacarbocyanine iodide [DiOC6(3)]staining. RESULTS: VPA at low doses (1 and 5 mmol/L) promoted CD69 expression in activated lymphocytes, whereas it turned to inhibit the expression of CD69 at a high dose (25 mmol/L). Meanwhile, VPA at low doses increased the mitochondrial membrane potential, while a high dose of VPA decreased it in activated lymphocytes. Furthermore, interleukin-2 (IL-2) synthesis was enhanced by low doses of VPA but inhibited by a high dose. However, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) synthesis were dose-dependently enhanced by VPA as compared with those of PDB plus ionomycin-treated cells. CONCLUSION: VPA exerts biphasic effect on the further activation and apoptosis of human peripheral lymphocytes stimulated with mitogens and exhibits differential activity on the synthesis of several important cytokines in human lymphocytes.

Expression of integrin beta1 in squamous cell carcinoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the expression of integrin beta1 in squamous cell carcinoma (SCC) and explore the relationship between stem cell marker and SCC.</p><p><b>METHODS</b>The expressions of integrin beta1 in SCC tissues and SCC cell strain A431 were detected with immunohistochemical methods and cell staining method. The differentiation of SCC cells were induced with all-trans-retinoic acid (ATRA). The changes of integrin beta1 levels before and after induction were detected with RT-PCR.</p><p><b>RESULTS</b>In highly differentiated SCC tissues, integrin beta1 was constantly expressed in the basal-like cells in the edge of tumor; some cells inside arranged as island also showed positive integrin beta1 expression. In poorly differentiated SCC tissues, island-like integrin beta1-positive cells remarkably increased and distributed in a diffuse way. In SCC A431 cells, integrin beta1 was expressed unevenly in tumor cells. After treatment by ATRA, level of integrin beta1 mRNA in A431 cells significantly decreased compared with untreated control (P < 0.05), and the ratios between the intensity values of integrin beta1 to beta-actin were 0.071 +/- 0.025 and 0.029 +/- 0.018 at 24 h and 48 h, respectively, whereas in controls were 0.148 +/- 0.027 and 0.136 +/- 0.011 (P < 0.05).</p><p><b>CONCLUSIONS</b>Integrin beta1 is heterogeneously expressed in both SCC tissues and SCC A431 cells. The expression of Integrin beta1 decreases when the differentiation level of tumor cells increase, indicating that integrin beta1 is closely related with the initiation of SCC and potential cancer stem cells in SCC.</p>

A retrospective analysis of combined chemoradiotherapy for locally advanced esophageal carcinoma / 肿瘤

Objective: To explore the clinical response and prognosis of patients with locally advanced esophageal carcinoma after being treated with combined chemoradiotherapy. Methods: Thirty-five patients with locally advanced esophageal carcinoma were treated with radiotherapy (total radiation dosage, 45.0-50.4 Gy) and chemotherapy (5-FU plus cisplatin). Clinical response and survival time were analyzed according to their clinicopathological features. Results: The response rate was significantly higher in the patients who had the opportunity of surgery after chemoradiotherapy than those without opportunity of surgery (83.33% vs 47.83%, P = 0.023). Survival analysis confirmed that short-term efficacy and clinical staging were the important factors for progression-free survival (PFS) of patients (P <0.01, P <0.05). The efficacy of chemoradiotherapy affected overall survival (OS) statistically. The median OS for the patients with complete and partial response, stable disease, and progressed disease were 18 months, 15 months, and 6 months, respectively (P = 0.003). Conclusion: Combined chemoradiotherapy is effective in the treatment of locally advanced esophageal carcinoma. The efficacy of chemoradiotherapy is an important prognostic factor for progression-free survival and overall survival of patients.

In vitro chemo-sensitivity MTT assay guided intraperitoneal chemotherapy for malignant ascites / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility and efficacy of intraperitoneal chemotherapy for malignant ascites caused by different types of abdominal cancers guided by chemo-sensitivity methyl tetrojolium coloremetric (MTT) assay in vitro.</p><p><b>METHODS</b>Cancer cells in the malignant ascites were collected for MTT assay to determine the chemo-sensitivity. The drug producing the highest or the second highest inhibition rate was selected for intraperitoneal chemotherapy. The correlation between the results of MTT assay and the response of malignant ascites, the clinical features, Karnofsky performance score (KPS) and prognosis were analyzed.</p><p><b>RESULTS</b>MTT assay indicated that Taxotere (TXT) and Hydroxycamptothecin (HCPT) were the most effective to cancer cells in malignant ascites, and HCPT was mostly frequently used for intraperitoneal chemotherapy (56.9%). Twenty-four patients showed response by intraperitoneal chemotherapy (complete response: 7; partial response: 17) with a slightly significant correlation between the results of MTT assay and response of malignant ascites (P = 0. 014). The KPS of the responders was improved significantly (P < 0.001), and the response of malignant ascites to intraperitoneal chemotherapy was demostrated as an independent prognostic factor by multi-variate analysis in this series.</p><p><b>CONCLUSION</b>In vitro chemo-sensitivity MTT assay guided intraperitoneal chemotherapy for malignant ascites is simple, effective and safe, which can improve the KPS and prognosis of the responders.</p>

Localization and differentiation of hair follicle stem cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To identify the localization of hair follicles stem cell (HFSC) in different stages of hair and explore the differentiating capacity of HFSC into epidermis in vitro.</p><p><b>METHODS</b>HFSC were detected by K19 immunostaining in normal human skin. Then, the isolated HFSC through enzyme digestion were seeded on dermal equivalent (DE) and cultured between the air-liquid interfaces for 14 days. Skin-equivalents was harvested and used for evaluation.</p><p><b>RESULTS</b>HFSC mainly located in outer root sheet in hair follicle and human anagen hair follicles containing two distinct reservoirs for K19-positive cells located in the bulge and bulb of the follicle. These two reservoirs fused in line of outer root sheets during the catagen-telogen transition phase and individualized again in the newly forming anagen hair follicle. Based on DE, growing HFSC built a multilayered and confined epidermis.</p><p><b>CONCLUSION</b>HFSC located in outer root sheets can promote hair cycle and differentiate into epidermis in vitro.</p>

Malignancy with immune thrombocytopenia / 中国癌症杂志

Purpose:To study whether immune factors are involved in the occurrence of immune thrombocytopenia in some malignancy. Methods:Platelet associated antibodies and immune function were examined in 30 cases of malignancy with thrombocytopenia in our hospital. Results:Platelet associated antibodies(pAIgG,pAIgA,pAIgM)increased significantly in 11 of 30 patients with malignancy,especially those with metastatic adenocarcinoma and in the middle or advanced stage. Bleeding is common in these patients. After being treated with corticosteroid, immunosuppressive drugs or immunoglobulin,the platelet count of the patients increased and the bleeding syndrome improved. Conclusions:Thrombocytopenia in malignancy is partly due to the abnormal immune reaction of the patients.

THE THERAPEUTIC EFFECT OF MONOCLONAL ANTI EGFR ANTIBODY LEADING CHEMOTHERAPY TO HUMAN TUMOR / 肿瘤研究与临床

Objective:To explore the therapeutic effect of monoclonal anti EGFR antibody leading chemotherapy to human tumors.Methods:To prepare immunoconjugate of chemotherapy drugs with anti EGFR antibody and apply to clinic,and to observe it′s therapeutic effect and side effect. Results: This conjugated method could relief clinic symptoms and reduce side effect of tissues and organs significantly.Conclusion:Conjugates of monoclonal therapy of anti EGFR antibody and drug attached chemotherapy is a new and effective way for treatment of human tumors, and it can reduce side effect of the drugs meanwhile.