The up-regulation mechanism of membrane type I matrix metalloproteinase (MT1-MMP) in macrophages stimulated by silica in vitro and the contribution of early growth response 1 (Egr-1) transcription factor in the gene expression pathway were investigated. Macrophages stimulated by silica were treated with Egr-1 antibody or Egr-1 decoy oligodeoxynucleotides (ODN). The levels of MT1-MMP proteins were determined by Western blot and the expression of MT1-MMP mRNAs was detected by RT-PCR. The results showed as compared with control macrophages, silica-stimulated group showed up-regulated gene expression of MT1-MMP via Egr-1 (P<0.01). Compared with silica-stimulated macrophages untreated with antibody, the cells treated with 5 microg/mL Egr-1 antibody were associated with reduced expression of MT1-MMP protein (P<0.01) and mRNA (P<0.01). Compared with silica-stimulated untransfected group, the Egr-1 "decoy" ODN group was associated with reduction in the expression of MT1-MMP protein and mRNA (P<0.01). It was concluded gene expression of MT1-MMP which may play a critical role in silicosis was up-regulated by silica in macrophages. Egr-1 participated in the expression of MT1-MMP and positively regulated the expression. Both Egr-1 antibody and Egr-1 decoy ODN suppressed the expression of MT1-MMP through the Egr-1 pathway and may become a potential therapeutic tool in the management of silicosis in the future.

Objective To study the value of using endoscopy iodine staining combined detecting the expression of p53, survivin and telomerase in the diagnosis of early esophageal carcinoma and precancerous lesions. Methods Three hundred patients who received routine gastrescopy and had high risk of esophageal carcinoma were examined by the iodine dyeing on their esophageal mucosa with 2. 5% Lugol solu-tion. Multiple biopsies were taken from the unstained or light-stained areas when their diameters were over 5mm for pathology diagnosis. The expression of p53, survivin and telomerase were detected by immunohistochemical staining. Results With the Lugol staining method, the incidences of light, moderate and high grade dysplasia and early esophageal carcinoma were 16. 3% ,9. 7% ,3.7% and 4. 3% respectively. The expression of p53, survivin and telomerase were related and the unstained were related to the expression of p53, survivin and telomerase in dysplasia and early esophageal carcinoma. Using endoscopy iodine staining combined testing p53, survivin and telomerase showed sensitiv-ity of 100%, specificity of 92. 3% and accuracy of 91.8% to diagnose of early esophageal carcinoma and high grade dysplasia. Conclusion Lugol solution chromoendscopy combined assay of p53, survivin and telomersse might be useful in the diagnosing early esophageal carcino-ma and precancerous lesion.

Objective Pemetrexed and β-elemene can inhibit the growth of tumor cells .This study was to investigate the effect of pemetrexed combined with β-elemene on the proliferation and apoptosis of cervical cancer HeLa cells. Methods Cervical cancer HeLa cells were treated with pemetrexed at the concentrations of 38, 76, 152, 228, and 304μg/mL, and at 24 and 48 hours of treatment subjected to MTT for detection of their proliferation .The experiment included four groups , with the cells treated with β-elemene ( 125μg/mL) , pemetrexed ( 76 μg/mL ) , β-elemene ( 125 μg/mL ) +pemetrexed (76μg/mL), and nothing (blank control) for 24 hours, followed by determination of their proliferation and apoptosis by MTT and flow cytometry, respectively. Results Pemetrexed at 38, 76, 152 and 228μg/mL inhibited the proliferation of the HeLa cells in a concentration-dependent manner, with the inhibition rates of (7.24 ±3.78), (7.94 ±4.37), (11.10 ±2.86) and (15.88 ± 3.38)%at 24 hours, and (16.69 ±0.95), (22.54 ±1.53), (24.48 ±0.92) and (25.54 ±3.61)%at 48 hours, both with statis-tically significant differences between any two groups (P<0.05).Significant differences were also found in the proliferation rate of the same concentration of pemetrexed at the two time points (P<0.05).The combination of pemetrexed and β-elemene showed an inhibi-tion rate of (49.95 ±5.76)%at 24 hours, remarkably higher than (24.36 ±5.59)%in theβ-elemene group and (10.69 ±1.37)%in the pemetrexed group (P<0.01). Conclusion Pemetrexed combined with β-elemene can significantly inhibit the proliferation and synergistically accelerate the apoptosis of HeLa cells .

Objective To know the quality of iodized salt and the current situation of the salt coverage in Tibet,and to provide scientific basis for proposing proper prevention and control measures to Iodine dificiency disorders(IDD). Methods In 2008, according to the "Sampling Methods of the Main Products in the Salt Industry",one batch fifteen salt samples were collected in iodized salt processing factory in Tibet. Five townships were chosen in each county based on 5 different directions of east, south, west, north and center. If the monitoring county has less than five townships, then all of the townships were sampled. In each township, four villages were selected withrandom sampling and importance sampling. In each township, 15 households were selected for salt collection. Results A batch of 15 salt samples in a salt processing plant were tested, and all of them were qualified with salt iodine(34.6±1.58) mg/kg. A total of 21 107 edible salt samples were tested, and 11 203 of them were qualified iodized salt. These results meant that the provincial iodized salt coverage rate was 53.08%. Shannan iodized salt coverage rate was 94.31% (3395/3600) which was the highest in Tibet. Those of Nagqu, Changdu, Ngari were lower, they were 29.84% (897/3006), 24.94% (823/3300) and 17.08% (205/1200), respectively. Conclusions The quality of iodized salt in Tibet is up to the national standard, but the coverage rate of iodized salt is very low.We suggest that the strategy should be carried out according to the national overall program strategy and supplement iodized oil capsule for special groups.

The up-regulation mechanism of membrane type Ⅰ matrix metalloproteinase (MT1-MMP) in macrophages stimulated by silica in vitro and the contribution of early growth response 1 (Egr-1) transcription factor in the gene expression pathway were investigated. Macrophages stimulated by silica were treated with Egr-1 antibody or Egr-1 decoy oligodeoxynucleotides (ODN). The levels of MT1-MMP proteins were determined by Western blot and the expression of MT1-MMP mRNAs was detected by RT-PCR. The results showed as compared with control macrophages, silica-stimulated group showed up-regulated gene expression of MT1-MMP via Egr-1 (P＜0.01). Compared with silica-stimulated macrophages untreated with antibody, the cells treated with 5 μg/mL Egr-1 antibody were associated with reduced expression of MTI-MMP protein (P＜0.01) and mRNA (P＜0.01). Compared with silica-stimulated untransfected group, the Egr-1 "decoy" ODN group was associated with reduction in the expression of MT1-MMP protein and mRNA (P＜0.01). It was concluded gene expression of MT1-MMP which may play a critical role in silicosis was up-regulated by silica in macrophages. Egr-1 participated in the expression of MT1-MMP and positively regulated the expression. Both Egr-1 antibody and Egr-1 decoy ODN suppressed the expression of MT1-MMP through the Egr-1 pathway and may become a potential therapeutic tool in the management of silicosis in the future.

Objective To investigate the relationship between plasma homocysteine on admission and the outcome at discharge of acute ischemic stroke.Methods A non-concurrent cohort study was performed and a total of 1 3 1 9 patients with acute is-chemic stroke were continuously included in this study.According to tertile range of plasma homocysteine,patients were di-vided into three group.Logistic regression analysis was used to assess the independent association between plasma homocys-teine on admission and poor outcome at discharge of acute ischemic stroke.Results The difference of plasma homocysteine on admission between the poor outcome and those with good outcome had statistical significance (P<0.000 1).Without the adj ustment of multiple factors,when comparing to the first group,the second and third tertile seemed to have a tendency of increasing the risk of poor outcome at discharge,the OR (95%CI)was 2.111 (1.297~3.437,P<0.05),2.113 (1.361~3.279,P<0.05).After adjustment for multivariate,the second and third tertile also seemed to have a tendency of increasing the risk of poor outcome at discharge,the OR (95%CI)was 1.876 (1.160~3.036,P<0.05),2.396 (1.414~4.062,P<0.05).Conclusion The current study indicated that higher plasma homocysteine level was an independent risk factor for poor outcome at discharge in ischemic stroke patients.It would increase the risk of the outcome at discharge in patients with acute ischemic stroke,and suggests that there is a dose-response relationship between plasma homocysteine level on admis-sion and the poor outcome at discharge.

Neuroglobin (Ngb) is a respiratory protein that is preferentially expressed in brain of mouse and man. In this article, Tibetan antelope, living at altitude of 3 000-5 000 m for millions of years, was selected as the model of hypoxia-tolerant adaptation species. Using reverse transcription polymerase chain reaction (RT-PCR) and Western blot techniques, expression of Ngb gene was amplified and analyzed in antelope brain tissue. Our results showed that Ngb homology protein in Tibetan antelope was identified with more sequence similarity with cattle (96%), sheep (95%), and human (95%). We detected that there were some mutations occurred in the Open Reading Frame of Ngb in Tibetan antelope compared with sheep. Phylogenetic analysis of Ngb chain showed that it was closer to cattle than the others. This study suggests possible roles of central nervous system enriched Ngb in adaptation of Tibetan antelope to extremely high altitude.
Acclimatization ; genetics ; Altitude ; Animals ; Antelopes ; genetics ; Cattle ; Globins ; genetics ; Humans ; Hypoxia ; genetics ; Mice ; Nerve Tissue Proteins ; genetics ; Phylogeny ; Sheep

OBJECTIVETo detect the infection of human papillomavirus (HPV) 16/18 in patients with head and neck squamous cell carcinoma and explore the relationship between HPV infection and expressions of Ki-67 and P53 proteins in tumor tissue.

METHODThe level of HPV 16/18 DNA was measured by real time polymerase chain reaction, and Ki-67 and P53 proteins were measured by immunohistochemistry in tissues from head and neck squamous cell carcinoma.

RESULTSHPV 16/18 DNA was detected in 62.8% of our patients. In each cancer tissue sample, Ki-67 protein was expressed between 2% to 70%. P53 protein was expressed in 46.15% of our patients. No significant relation was found between HPV 16/18 DNA level and sex, smoking, drinking, and tumor clinical stages. However, level of HPV 16/18 DNA was found to have positive relation with tumor pathological grades and negative relation with P53 protein expression. No relation with Ki-67 protein expression was found.

CONCLUSIONHead and neck squamous cell carcinoma may be initiated by HPV 16/18 infection and the mechanism in carcinogenesis involves abnormal expression in P53 protein.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; virology ; DNA, Viral ; analysis ; Female ; Human papillomavirus 16 ; isolation & purification ; Human papillomavirus 18 ; isolation & purification ; Humans ; Ki-67 Antigen ; metabolism ; Male ; Middle Aged ; Tumor Suppressor Protein p53 ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; virology

OBJECTIVESTo study the pathologic feature of sudden cardiac death in Yunnan province and to investigate the role of myocarditis.

METHODSDuring the period from 1991 to 2006, there were 29 cases of sudden cardiac death with autopsy performed. Fourteen of these cases were diagnosed to have myocarditis based on Dallas criteria and World Heart Federation's consensus. The clinical and pathologic findings were reviewed. The cardiac conduction system was examined in details by serial sectioning in 3 cases.

RESULTSFourteen cases suffered with myocarditis, which accounted for 48% of all cases of sudden cardiac death studied. The age of the deceased ranged from 8 to 68 years (mean = 30 years), with male-to-female ratio equaled to 9:5. Lymphocytic myocarditis and neutrophil myocarditis were the two major types, affecting 11 and 3 cases, respectively. The inflammatory infiltrates were often patchy rather than diffuse. The inflammatory foci were detected only in 8% to 42% (average = 20%) of the paraffin sections of the heart tissue. These lesions were usually located in the lateral wall of left ventricle and occasionally in interventricular septum and right ventricular wall. Myocardial injury was mild in most cases while patchy myocytolysis or coagulation necrosis was observed only in a few cases. Most of the lesions were relatively new and histologic evidence of myocardial repairing sometimes coexisted. Pericarditis and subacute endocarditis were also identified in 4 and 1 cases, respectively. Atrioventricular node was involved by myocarditis in 1 of the 3 cases examined for cardiac conduction system. Two cases showed gross evidence of cardiac dilatation (either left ventricle or biventricular). Respiratory tract and pulmonary infection was present in 5 cases.

CONCLUSIONSMyocarditis represents one of the major pathologic changes of sudden cardiac death occurring in Yunnan province. The inflammation is usually focal. Further studies are required for delineation of possible etiologies which may include virus, bacteria or exogenous toxin.

Adolescent ; Adult ; Aged ; Atrioventricular Node ; pathology ; Child ; China ; epidemiology ; Death, Sudden, Cardiac ; epidemiology ; pathology ; Dilatation, Pathologic ; pathology ; Endocarditis ; pathology ; Female ; Humans ; Inflammation ; pathology ; Lymphocytes ; pathology ; Male ; Middle Aged ; Myocarditis ; diagnosis ; epidemiology ; mortality ; pathology ; Myocardium ; pathology ; Pericarditis ; pathology

Background: Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promis-ing anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC. Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality-of-life (QoL), and safety. Results: Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were rand-omized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41–0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3–4 adverse events were hypertension (11.1%), hand-foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657). Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability. Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal Symposium