RET gene is an important oncogene,which is closely associated with the development of various types of human tumors. The mainly mechanisms of RET gene associated tumor are mutation and over-expression of wild type. Activated RET protein participates in the proliferation,apoptosis,metastasis through some signal pathways and influences the tumorigenesis and development.

OBJECTIVE To study the effect of nano-alumina(nano-Al2 O3 )on mitophagy in primary cortical neuronal cells from Wistar newborn rats. METHODS The purity of neuronal cells was detected by immunohistochemistry,and the lactate dehydrogenase(LDH)assay was performed to determine the viability of the cells treated with 13 nm nano-Al2 O3 0.5 mmol·L-1 for 12,24 and 48 h,respectively. The mitochondrial membrane potential(MMP)was detected by flow cytometry analysis . The ultrastructure of mitochondria and mitophagy vacuoles was observed by transmission electron microscopy(TEM). Auto-phagic vacuoles were observed by dansylpentanediamine(MDC)staining and the expression of autoph-agy related protein Beclin1 and LC3Ⅱ/ Ⅰ was determined by Western blotting. Mitophagy was observed by Lysotracker and Mitotracker staining respectively. RESULTS More than 95% cells were neuronal cells. The activity of LDH in the supernatant liquid exposed to nano-Al2 O3 for 12 and 24 h groups was sig-nificantly increased compared with the control group(P﹤0.05). After exposure to nano-Al2 O3 ,the mito-chondrial membrane potential was significantly decreased compared with the control group( P ﹤0.01). The results of TEM displayed mitochondrial swelling and the formation of vacuoles and mitophagy in nano-Al2 O3 groups. MDC positive fluorescence particles were observed and the expression of autophagy related protein Beclin1 and LC3Ⅱ/ Ⅰ was increased in nano-Al2 O3 groups compared with the control group( P ﹤ 0. 05 ). The result of Lysotracker and Mitotracker colocalization showed the fusion of mitochondria and lysosomals. CONCULSION Nano-Al2 O3 may induce autophagy and mitochondria damage in neuronal cells while the damaged mitochondria may be removed by mitophagy.

Objective To detect cytokeratin in routine pathology negative regional lymph nodes postoperatively in non-small cell lung carcinoma (NSCLC). To investigate the relationship of lymph node micrometastasis in P-TNM stages NSCLC and survival rates. Methods From Jan. 1996 to Dec. 2003, 107 paraffin-embedded specimens of T1-T4N0-N1M0 NSCLC patients were collected. Anti-cytokeratin(CK) an- tibody AE1/AE3 was applied to detect cytokeratin with Envision~(TM) method in routine pathological negative re- gion lymph nodes in NSCLC, and selected negative control, positive control and blank control. The pulmo- nary hilar lymph node micrometastasis was upward regulated with stage pCK-N1, mediastinal lymph node mi- crometastatsis was upward regulated with stage pCK-N2. The result applied to SPSS11.0 software to process. Results The CK positive rate was 29.9% in all the patients. The CK positive rate was 27% (21/78), 30% (7/23), 67% (4/6)in stage p-Ⅰ, p-Ⅱand p-Ⅲ, respectively. All these data showed the tendency by which detectable rate increased and was accompanied by disease progress. Comparing the annual survival rate and median survival time of the non-micrometastasis group with the mierometastasis group in two groups, the survival rate difference was statistically significant. Comparing the annual survival rate and median sur- vival time in pCK-ⅢA stage with p-Ⅰ-Ⅱstage, pCK-ⅢA stage annual survival rate and median survival time was significantly different (P=0.020). Similarly, comparing the survival rate in pCK-ⅡB stage with p-ⅠB stage, pCK-ⅡB stage survival rate was significantly different(P=0.059). Comparing the survival time of pCK-ⅢA stage with p-Ⅲstage, pCK-ⅡB stage, with p-ⅡB stage, euther survival time difference was statistically significant (P=0.838, 0.518). Conclusions The rate of positive cytokeratin increase is ac- companied by the disease progress in NSCLC. Positive cytokeratin has disadvantagious prognosis. It is showed that pCK-N1 may be equal to p-N1 and pCK-N2 which also may be equal to p-N2. Micrometastasis may affect the UICC staging currently in use.

Objective To evaluate the effects of SHENG JI YU HONG herbs loading on modified gelatin sponges on the wound healing of mechanical trauma.Methods The round size of 1.8cm diameter of full thickness back skin was cut mechanically and covered with petrolatum gauzes,modified gelatin sponges,SHENG JI YU HONG plasters and SHENG JI YU HONG herbs loading on modified gelatin sponges respectively.On day3,day7 and day14 after model mading,the wound surface healing rate,the amount of hydroxyproline,hemoglobin,the number of capillaries and the cells with positive rhVEGF165 by immunochemical method inside granulation of the wound were detected individually.Results On day3,the wound surface healing rate and the number of capillaries and the cells with positive rhVEGF165 of SHENG JI YU HONG herbs loading on modified gelatin sponges were significant enhanced than those in the other groups.On day14,all the experimental indicators of SHENG JI YU HONG herbs loading on modified gelatin sponges were better than those in the other groups with P

Objective To evaluate previous gastroscopy before percutaneous coronary intervention (PCI) for the risks and benefits of concomitant use of proton pump inhibitors (PPIs) after PCI in patients with non-acute coronary syndrome (non-ACS).Methods The data of 673 non-ACS patients who underwent PCI with stenting were retrospectively analyzed.They were divided into concomitant use of PPIs group and non-PPIs group,then subdivided into high-,moderate-and low-risk groups according to risk factors associated with adverse upper gastrointestinal (GI) events.The incidences of adverse cardiovascular events and adverse upper GI events were compared among groups.Findings of previous gastroscopy were also included.Results Only 82 patients (12.2％) underwent gastroscopy within 5 years before PCI,of whom,27 (32.9％) were diagnosed as having peptic ulcer,and 55.6％ (15/27) of whom were in concomitant use of PPIs.Compared with the non-PPIs group,the rate of adverse cardiovascular events in the concomitant use of PPIs group was significantly higher (22.6％ vs.8.9％,P ＜0.01),and the highest rate (41.7％) was in the high-risk group.However,the corresponding rate of adverse upper GI events was the lowest (4.2％).In the moderate-risk group,90.5 ％ (344/380) of patients were older than 65 years with concomitant use of NSAIDs.The rate of gastroscopy within 5 years before PCI in these patients was remarkably lower than that in patients who had the history of upper GI disease with concomitant use of NSAIDs (concomitant use of PPIs group 14.1％ vs.54.5％ ; non-PPIs group 7.5％ vs.28.0％ ; P ＜ 0.01).In the concomitant use of PPIs group,the rate of adverse cardiovascular events in the former was notably higher than that in the latter (20.5％ vs.9.1％,P ＜0.01),but the rate of adverse upper GI events within 1 year after PCI were similar (9.0％ vs.9.1％).Conclusion Previous gastroscopy before PCI could provide the baseline information of upper GI disease,which may be helpful for the evaluation of concomitant use of PPIs after PCI so as to decrease the incidence of adverse cardiovascular events.Special attention should be paid to those patients older than 65 years in the moderate-risk group and concomitant use of NSAIDs.

OBJECTIVE To explore the potential neurotoxicity of nano-alu mina (<50 n m)in vivo, we treated the ICR mouse with the nano-alu mina to investigate the mitochondrial da mage of nerve cells on morphology and function.METHODS Adult male mice were exposed to nano-alu mina (<50 n m)of 0,25,50 and 75 mg·kg -1 by nasal instillation for 1 month.Then we observed the mitochondrial ultra-structure of the nerve cells in CA3 region of hippoca mpus,and measured the mean dia meter in every group.The activities of Na +-K +-ATPase and Ca2 +-Mg2 +-ATPase were tested by the determination of the inorganic phosphorus,which was the deco mposition product of ATPase.Western blot analysis was used to detect the expression of COX-Ⅳ,Beclin1 ,LC3Ιand LC3Ⅱ.RESULTS Co mpared with 0 and 25 mg·kg -1 groups exposed to Al2 O3 nanopartilces (Al2 O3 NPs),the mitochondria of CA3 region in hip-poca mpus in 50 mg·kg -1 group beca me ede matous and swollen with sparse and broken cristae sur-rounding the nuclear,and the mean dia meter was higher(0.49 ±0.02 μm,P <0.05).But co mpared with 50 mg·kg -1 group,the mitochondria in 75 mg·kg -1 group beca me s maller with inner cristae of high density,and the mean dia meter was lower(0.36 ±0.02 μm,P<0.05).The enzy me activity of the mito-chondria in cerebral cortex decreased dose-dependently with exposure,the activities of Na +-K +-ATPase in 50 and 75 mg·kg -1 groups(6.37 ±0.22 kU·g -1 protein,5.48 ±1 .53 kU·g -1 protein)and Ca2 +-Mg2 +-ATPase in 50 and 75 mg·kg -1 groups (3.21 ±0.99 kU·g -1 protein,3.28 ±0.15 kU·g -1 protein)were lower than the 0 mg·kg -1 group(P<0.05).Meanwhile,the Ca2 +-Mg2 +-ATPase in 50 and 75 mg·kg -1 groups showed lower activities in co mparison with the 25 mg·kg -1 group.The 75 mg·kg -1 group expressed higher level of the COX-Ⅳ protein 1 .35 ±0.66(P<0.05)than other groups.Both expression of Beclin1 protein and rate of LC3Ⅱ/LC3Ⅰin 75 mg·kg -1 group were more than the 0 mg·kg -1 group. CONCLUSION The mitochondrial dysfunction may be the potential neurotoxicity of nano-alu mina,and the da maged mitochondria were cleared by autophagy.

Objective To investigate the difference between Asia-Pacific Colorectal Screening (APCS) scoring system and colorectal cancer sequential screening criteria issued by the Health Ministry of China (China sequential criteria) in the evaluation of high-risk colorectal neoplasm in patients undergoing coronary artery angiography (CAG) examination.Methods The data of 870 patients aged from 40 to 74 who underwent CAG examination were retrospectively analyzed.The measurement data were analyzed by t test and the count data were aralyzed by x2 test.Results There were 72 patients aged from 40 to 49 years old.Among them,eight patients were stratified as high-risk population according to the Chinese sequential criteria; however there was no high-risk population by APCS.There were 798 patients aged from 50 to 74 years old.There were 460 patients stratified as high-risk population by APCS.The percentage of CAG negative group (34.7％) was significantly lower than that of the coronary artery disease (CAD) group (68.0％,x2 =77.74,P＜0.01).According to the Chinese sequential criteria,and there were 134 patients stratified as high-risk population,and there was no significant difference between the CAG negative group (17.7 ％) and the CAD group (16.4％,P＞0.05).Among the patients aged from 50 to 74 years old without family history of colorectal cancer in first-degree relatives,72 cases (29.0％) of the CAG negative group and 316 cases (57.5％) of the CAD group were stratified as high-risk according to APCS,however not stratified as high-risk by the Chinese sequential criteria.About 90.5 ％ (351/388) of them were male smokers.According to APCS,30 cases (12.1％) of the CAG negative group and 32 cases (5.8％) of the CAD group were stratified as middle-risk population,however stratified as high-risk population by the Chinese sequential criteria.About 75.8％ (47/62) of them were female non-smokers.Conclusions The percentage of patients stratified as high-risk population by APCS was higher than that by the Chinese sequential criteria.In patients aged from over 50 to 74 years old and without family history of colorectal cancer in first-degree relative,APCS maybe overestimated the risk degree of colorectal neoplasm in male smokers and underestimated the risk degree in female non-smokers.

Objective To observe the effect of telbivudine combined with adefuvir dipivoxil in the treatment of Hepatitis B patients with decompensated cirrhosis.Methods 56 Hepatitis B patients with decompensated cirrhosis were divided into two groups:treatment group (30 cases) and control group (26 cases).During 24 weeks,the control group received adefuvir dipivoxil( 10mg daily),supportive and symptomatic treatments,while the treatment group received telbivudine therapy(600mg daily) combiled with adefuvir dipivoxil ( 10mg daily) based on the regular treatments.After 24 weeks,the effect was observed and compared between the two groups.Results After treatment,the biochemical markers,Child-Pugh score of the treatment group was (33.2 ± 13.8) μmol/L,(44.5 ± 16.4) U/L,(36.1 ±1.5) g/L,(6.1 ± 1.8) points,respectively,and was better than those of the control group[ (71.8 ±18.6) μ mol/L,(89.9 ±44.9) U/L,(29.7 ± 1.3)g/L,(8.1 ±2.2) points] (t=15.32,15.20,23.37,6.09,all P＜0.05) ;HBV-DNA negative rate,HBeAg seroconversion rates of the treatment group was 93.3％ (28/30),43.3％(13/30),and was higher than that of the control group[76.9％ (20/26),7.6％ (2/26) ] (x2 =4.87,9.08,all P＜0.05).Conclusion Telbivudine combined with adefuvir dipivoxil was effective and safe for the treatment of Hepatitis B patients with decompensated cirrhosis.

Objective Rhabdomyolysis (RM) is a common disorder resulting from a large variety of causes. Acute injury is one of the main reasons. The purpose is to describe the MRI manifestations of rhabdomyolysis caused by 5.12 Wenchuan earthquake in Sichuan province and to discuss their importance in diagnosis and treatment of rhabdomyolysison in clinic practice. Methods Three patients with rhebdomyolysis caused by earthquake were studied via 1.5 T MRI. In all the patients, T, and T2 weighted sequences with and without fat suppression, and short time inversion recovery (STIR) of both lower extremities were obtained in axial, coronal and sagittal planes. All patients were given contrast material during imaging, and MRA (magnetic resonance angiography) of both lower extremity vessels were performed. The MRI characteristics of damaged extremities in 3 cases were studied. Results MRI showed swelling of the affected muscles and subcutaneous fat tissue on both T1 and T2 weighted images. The margins of involved muscles were blurred. On T1 weighted images, swollen muscles showed equal or slightly decreased intensity with small patterns of increased intensity in some local areas. On T2 weighted and STIR sequences, the affected muscles showed inhomogeneons increased signal intensity with clearer margin. Slight fluid collection in spatium intermusculare was observed. Contrast-enhanced scanning showed nonhomologous intensification of damaged muscles, the enhancement inside the muscles was decreased when compared with normal muscles. The locations of all these abnormal intensity were correlated with the injury history and clinic physical examinations. MRA showed no lower extremity vessels were affected. Conclusion MRI has very high sensitivity in detecting the injury of muscles. It's very useful in evaluating the extent and severity of muscles affected in rhabdomyolysis caused by trauma. Also it's very valuable to evaluate the condition of blood vessels in involved extremity for predicting the prognosis of the disease. Therefore MRI possesses a very important role in the diagnosis and treatment of RM.

Objective To evaluate the impact of three to four cycles of neoadjuvant chemotherapy (NACT) on the survival of patients with N2-N3 nasopharyngeal carcinoma (NPC).Methods The clinical data of 915 patients with T1-4N2-3M0 NPC from 2007 to 2010 were retrospectively analyzed.A total of 179 patients treated with 3-4 cycles of NACT (NACT≥3 group) were matched with 358 patients treated with 2 cycles of NACT (NACT=2 group) and 179 patients treated without NACT (NACT =0 group,concurrent chemoradiotherapy group) for age,N stage,pathological subtype,and NACT regimen.The Kaplan-Meier method was used to calculate overall survival (OS),disease-free survival (DFS),recurrence-free survival (RFS),and distant metastasis-free survival (DMFS) rates,the log-rank test was used for survival difference analysis and univariate prognostic analysis,and the Cox proportional hazards model was used for multivariate prognostic analysis.Results For the NACT≥ 3,NACT =2,and NACT =0 groups,the 5-year OS rates were 89.4％,81.6％,and 73.7％,respectively (P=O.000),the 5-year DFS rates were 83.2％,69.8％,and 64.2％,respectively (P=O.000),the 5-year RFS rates were 86.0％,76.0％,and 69.3％,respectively (P=0.001),and the 5-year DMFS rates were 86.6％,76.0％,and 68.3％,respectively (P=0.000).Three to four cycles of NACT was an independent protective factor for OS,DFS,RFS,and DMFS in patients with N2-N3 NPC.Conclusion Three to four cycles of NACT can significantly improve the survival of patients with N2-N3 NPC.