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 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 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 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.

Aim Using chronic pre-pregnancy stress to establish a postpartum depression animal model, given a single YG,and acute ketamine was served as control, to explore the pathology of PPD and the anti-depressive mechanism of the YG on the PPD model on AKT/mTOR signaling pathway. Methods Thirty-two fe-male Balb / c were randomly assigned to two groups, the control group ( Control, Con) and the pre-pregnancy stressed group(Model,Mod) , which was subjected to 3 weeks chronic restraint stress. After the last stressor, the pre-pregnancy stressed group was housed with a male. After about 4 weeks later, the mice gave birth to pups. Then at 3 weeks postpartum, we tested the ma-ternal tail suspension test ( TST). Both YG and Ket-amine was single administered 24 hours before behavior test, with single saline for control group and PPD mod-el group. After TST,the mouse hippocampus were ex-tracted to detect the expression of AKT and mTOR. Results After 3 weeks postpartum, the model mice showed depression-like behaviors. Immobility in TST was significantly increased in vehicle groups(P <0. 01). Acute YG improved performance in the TST (P< 0. 01), which was similar to ketamine. And the PPD model mice group showed decreased phosphorylation of AKT and mTOR (P < 0. 01,P < 0. 01), compared to control group. A single dose of YG or ketamine normal-ized AKT/ mTOR signaling in the PPD model mice(P< 0. 01,P < 0. 01),( P < 0. 01,P < 0. 01). Conclu-sions Chronic pre-pregnancy stress can induce dams into postpartum depression and its mechanism maybe associated with down-regulating AKT/ mTOR signa-ling. Acute YG exerts fast antidepressant effect on this PPD model similar to ketamine, and its mechanism may be related to up-regulating AKT/ mTOR signaling in the hippocampus.

Objective To understand the current development situation and the existing problems and deficiencies of the exercise cardiopulmonary rehabilitation development in Level 2 and above the general hospitals in Chongqing, and to analyze and find out the factors restricting the development of cardiopul-monary rehabilitation in Chongqing, and put forward suggestions for reform and development. Methods Through literature research, field visits and questionnaire survey, the condition of 115 Level Two compre-hensive hospital's rehabilitation and exercise cardiopulmonary rehabilitation development in Chongqing was understood. Among them, 500 questionnaires were sent to 6 hospitals concerned with cardiopulmonary rehabilitation service, and 483 questionnaires were received with 351 valid questionnaires. Epidata3.1 and SPSS 13.0 statistical software were used to gather research data. Results The settings rate of 115 secondary general hospital rehabilitation was 41.7％, while only 6 hospitals carried out cardiac rehabilitation and cardio pulmonary rehabilitation. There were few rehabilitation beds, the basic staffing was inadequate and the medical staff ratio was only 2 to 2.6. Besides, there is a severe shortage of full-time health instructors.Conclusion The clinical sports cardiopulmonary rehabilitation in Chongqing is as following: The construc-tion of hospital related policies is lagging behind, the overall development of rehabilitation therapy is unbal-anced, the development is late and the level of operation is low. While the lack of professional health movement means that instructors and medical staff have cognitive impairment, residents have low accep-tance of sports rehabilitation therapy and there are insufficient pathogens, which are the main factors that restrict the development of cardiopulmonary rehabilitation.

Objective To evaluate the measurement uncertainty of the detecting procedure of amino acids and carnitines by the Waters ACQUITY TQD tandem mass spectrometer and PerkinElmer NeoBaseTM non‐derivatized MSMS kit ,and to discuss the meaning of evaluation .Methods According to the method provided by the Medical Laboratories‐Evaluation and Expression of Measurement Uncertainty ,the internal quality control was detected by using two different batch codes of kit for 20 d ,once before and after the routine sample detection on each working day ,the detector were randomly changed ,and then the measurement uncer‐tainty introduced by measurement reproducibility was calculated;the amino acid external assessment quality control data in 20 times of neonatal hereditary metabolic disease tandem mass spectrometry screening provided by the National Center for Clinical Laborato‐ry in 2014 and 2015 ,and the same and 16 times of carnitines external assessment quality control data were performed the statistics , and then the measurement uncertainty introduced by bias was calculated .Next the relative standard uncertainty and the relative ex‐panded uncertainty according to the measurement uncertainty introduced by bias and measurement reproducibility were calculated . The allowed total error indicators of amino acid and carnitines external quality assessment in the neonatal hereditary metabolic dis‐ease tandem mass spectrometry screening by the National Center for Clinical Laboratory were used as the target expanded uncer‐tainty .Results The relative expanded uncertainties of citrulline ,methionine ,phenylalanine ,propionyl carnitine ,octanoyl carnitine , dodecanoyl carnitine ,palmitoyl carnitine and octadecanoyl carnitine were 19 .1% -26 .1% (k=2) ,which were smaller than the tar‐get uncertainty .The relative expanded uncertainties of leucine ,tyrosine ,valine ,free carnitine were 31 .0% -43 .3% (k=2) ,which were greater than the target uncertainty .The uncertainty of isovaleryl carnitine needed to be estimated separately .Conclusion As‐sessing the measurement uncertainty of the detecting procedure of amino acids and carnitines by the non‐derivatized tandem mass spectrometer method can not only provide an opportunity for continuously improving the detection quality ,but also can help the ex‐perimental technique staffs to interpret the test data correctly and the clinician to use the detection reports correctly .