BACKGROUND: 3-nitropropionic acid(3-NP) can inhibit the process of oxidative phosphorylation and injure the energy metabolism of the cell and thereby induce cell injury. However, small dose of 3-NP can excite intrinsic cellular protective factor to protect neurons and increase the tolerance of neurons to ischemic hypoxia through mild inhibiting the process of oxidative phosphorylation. It is unclear whether it also has the similar effect on dopaminergic neurons.OBJECTIVE: To investigate whether 3-NP preconditioning could enhance the tolerance of dopaminergic neurons to MPP+(1-methyl-4-phenylpyridine)toxicity.DESIGN: A randomized controlled exploring research based on neuroblastoma SH-SYSY cell that could secrete dopamine.SETTING: Department of neurology of a university hospital.MATERIALS: The study was conducted in the Laboratory of Pathophysiology of Tongji Medical College between March 2003 and November 2003. SH-SYSY cell was obtained from the Cell Center of Peking Union Medical University.INTERVENTIONS: Cells were randomly divided into 6 groups. MPP+ was added into the cultured dopaminergic neuron SH-SY5Y cells for the establishment of the cell model for Parkinson disease. Before the admission of MPP+ (0.25 mmol/L), 3-NP(0. 2 mmol/L) was added once or repetitive times to form preconditioning. Microculture tetrozolium(MTT) was used to detect cell survival rate, and[3H] DA uptake rate was used to test the anterior synaptic function of dopaminergic neurons.MAIN OUTCOME MEASURES: Major consequence: Cell survival rate;Minor consequence: [3H] DA uptake rate.RESULTS: Cell survival rate of MPP+ group was 54.3%, which was significantly lower than that of blank control group( P ＜ 0.01) . After 3-NP preconditioning, cell survival rate significantly elevated, which was 71.8%(single) or 85.2% (repetitive) . There was significant difference between single preconditioning and repetitive preconditioning( P ＜ 0.05 ). The results of[3H] DA uptake rate were similar to that of cell survival rate. [3H] DA uptake rate was 65.8% (single) or 80. 3% (repetitive), which was significantly higher than 50. 1% of MPP+ group. And moreover, repetitive preconditioning had more favorable effect than single preconditioning. Simple admission of 3-NP had no impact on cells.CONCLUSION: 3-NP preconditioning can significantly enhance the tolerance of dopaminergic neuron to MPP+ toxicity, which has significant protective effects on dopaminergic neuron. Repetitive preconditioning have more significant protective effects.

BACKGROUND: Mainly pathological changes of Parkinson disease (PD)are related to irreversible degeneration and reduction of dopamine neurons of substantia nigra in midbrain; however, oxidative stress reaction plays an important role in onset of PD. 3-nitropropionie acid (3-NP) is an inhibitor of mitochondria compound I, and it can inhibit oxidative phosphorylation so as to restrain energy metabolism. However, professor Riepe from Germany found that small dose of 3-NP can increase the tolerance of neurons to ischemic hypoxia. It is unclear whether it can also strengthen the tolerance of dopamine neurons to neurotoxin.OBJECTIVE: To investigate the possible mechanism and prevention of repetitively preconditioning 3-NP for treating PD.DESIGN: Controlled observational animal study. SETTING: Department of Neurology, Union Hospital affiliated to TongjiMedical College, Huazhong University of Science and Technology. MATERIALS: The experiment was carried out at the Neurological Lab oratory, Union Hospital affiliated to Tongji Medical College, Huazhong U niversity of Science and Technology from March to July 2004. A total of48 C57BL mice, weighing 18-20 g, aged 2-3 months, of both genders, were randomly divided into 6 groups with 8 in each group. ① Blank con trol group: Mice were not medicated. ② 3-NP single administrationgroup: Mice were intraperitoneally injected with 3-NP once. ③ 3-NPrepetitively administrations group: Mice were intraperitoneally injectedwith 3-NP every 5 days for 5 times in total. ④ Neurotoxin group: Micewere intraperitoneally injected with neurotoxin once every day for 5 timesin total. ⑤ 3-NP single preconditioning group: Mice were intraperitoneal ly injected with 3-NP once, and 3 days later, they were intraperitoneallyinjected with neurotoxin once every day for 5 times in total. ⑥ 3-NPrepetitively preconditionings group: Mice were intraperitoneally injectedwith 3-NP and repetitively every 5 days for 5 times in total; 3 days later, mice were intraperitoneally injected with neurotoxin once every day for5 times in total. Dosages of 3-NP and neurotoxin were 20 mg/kg and30 mg/kg, respectively. METHODS: Motor coordination of mice was scored with pole test andtraction test before experiment and at 3 days after the last injection ofneurotoxin. Three days after complete injection, mice were sacrificed rapid ly to measure the contents of malondialdehyde (MDA) and reduced glu tathione (GSH) in the substantia nigra of midbrain. MAIN OUTCOME MEASURES: ① Motor and behavior scores; ② con tent of MDA; ③ content of GSH.~ULTS: All 48 mice were involved in the final analysis. ① Scores of pole test and traction test were decreased in neurotoxin group as compared with those in control group (P＜0.01); but the scores were increased after 3-NP single/repetitively preconditionings, and there were significant difference (P＜0.05, P＜0.01). Meanwhile, there was also significant differencebetween 3-NP repetitively preconditionings group and 3-NP single preconditioning group (P＜0.05). ② Content of MDA was increased in neurotoxin group as compared with that in control group, and there was significant difference (P＜0.01); content of MDA was decreased after 3-NP single preconditioning as compared with that in neurotoxin group, and there was significant difference (P＜0.05); content of MDA was remarkably decreased after 3-NP repetitively preconditionings as compared with that in neurotoxin group, and there was greatly significant difference (P＜0.01); meanwhile, there was also significant difference between 3-NP repetitively preconditionings group and 3-NP single preconditioning group (P＜0.05). ③As compared with that in blank control group, content GSH in 3-NP single administration group was not changed; content of GSH in 3-NP repetitively administrations group was increased (P＜0.05); content of GSH in neurotoxin group was decreased as compared with that in blank control group (P＜0.01); content of GSH in 3-NP single preconditioning group was not changed as compared with that in neurotoxin group (P＞0.05); content of GSH was increased after 3-NP repetitively preconditionings, and there was significant difference (P＜0.05); meanwhile, there was significant difference between 3-NP repetitively preconditionings group and 3-NP single preconditioning group (P＜0.05).CONCLUSION: 3-NP repetitively preconditionings can activate synthesis of GSH, protect dopamine neurons through decreasing production of MDA.

Objective To investigate the efficacy and safety of crizotinib in patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC),and focuse on analysis of its prognostic factors.Methods Fifty patients with advanced (stage m B-Ⅳ) ALK-positive NSCLC confirmed by cytology or histology in Peking Union Medical Collage Hospital from January 2013 to September 2016 were collected.The relevant clinical imformation and treatment protocols were recorded.The efficacy and safety of crizotinib were followed up,and its prognostic factors were analyzed.Results At the end of follow-up,the median progression free survival (PFS) of progressed patients (n =24) was 9.6 months (95％ CI:8.3-10.9 months),of which five patients died.The median follow-up time of non-progressed patients (n =26) was 10.7 months.The most common adverse event was abnormal liver function (48.0％,24/50).In the single factor analysis of Kaplan-Meier,younger or equal to 40 years old patients had a longer PFS (P =0.017),and the COX regression analysis (Enter method) also had statistical significance differences (HR =6.1,95％ CI:1.4-27.5,P =0.018).However,gender (HR =0.8,95％ CI:0.2-2.6,P =0.697),smoking history (HR =1.5,95％ CI:0.4-5.6,P =0.524),pathology (HR =1.1,95％ CI:0.3-4.2,P =0.922),tumor stage (HR =1.7,95％ CI:0.4-8.4,P =0.502),epidermal growth factor receptor (EGFR) mutant type (HR =0.4,95％ CI:0.4-4.3,P =0.461),EGFR unknown (HR =1.3,95％ CI:0.3-6.1,P =0.727),Eastern Cooperative Oncology Group Performance Status (ECOG) PS score (HR =2.0,95％ CI:0.6-6.8,P =0.290),the status of previous treatment (HR =0.6,95％ CI:0.2-1.8,P =0.385) and brain metastasis (HR=0.7,95％CI:0.1-3.2,P=0.628) were not associated with disease progression Conclusion Crizotinib has good efficacy and is safe and well-tolerated to advanced ALK-positive NSCLC patients,and age is the independent prognostic factor.

Hepatocyte growth factor/c-MET (HGF/c-MET) signaling pathway can be abnormal activated by many mechanisms such asc-MET mutation, ampliifcation and the overexpression of HGF, and it plays an important role in the development of non-small cell lung cancer (NSCLC), as well as in the tolerance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in NSCLC. hTerefore, c-MET is a new molecular target for the therapy of NSCLC since EGFR and ALK. At present, although the c-MET inhibitors have shown a potential prospect in some clinical trials, its assessment of safety and effectiveness in clinical applications, and the choice of testing methods and standards still need a further discussion. In this paper, we summarized the mechanism of c-MET in NSCLC, as well as its treatment prospect and selection of testing methods.

BACKGROUND: Low dose computed tomography (LDCT) for lung cancer screening is widely employed in China as a result of increasing cancer screening awareness. Although some pulmonary lesions detected by LDCT are cancerous, most of the pulmonary nodules are benign. It is important to make effective preoperative differentiation of pulmonary lesions and to obviate the need for surgery in some patients with benign disease. METHODS: From January 1, 2017 to December 31, 2018, patients in our institution with surgical pathology confirmed benign pulmonary lesions in which malignancy could not be excluded in preoperative assessment were enrolled in this study. Retrospective analysis of clinical data was conducted. RESULTS: 297 cases were collected in this study. Prevalence of benign disease in patients underwent resection for focal pulmonary lesions is 9.8% in our institution. In 197 patients (66.3%), pulmonary lesions were detected by LDCT screening. A total of 323 assessable pulmonary lesions were detected by chest CT. The average diameter of pulmonary lesions was (17.9±12.1) mm, and 91.0% of which were greater than or equal to 8 mm. Solid nodules accounted for 65.6% of these lesions. Imaging characteristics suggesting malignancy were common, including spicule sign (71/323, 22.0%), lobulation (94/323, 29.1%), pleural indentation (81/323, 25.1%), vascular convergence sign (130/323, 40.2%) and vacuole sign (23/323, 7.1%). 292 patients (98.3%) underwent video-assisted thoracoscopic surgery (VATS). Pulmonary wedge resection was performed in 232 cases (78.1%), segmental resection in 13 cases (4.4%) and lobotomy in 51 cases (17.2%). Surgical complications occurred in 4 patients (1.3%). The most frequent findings on surgical pathology analysis were: infectious lesions in 98 cases (33.0%), inflammatory nodules in 96 cases (32.3%), and hamartoma in 64 cases (21.5%). CONCLUSIONS Solid nodules accounted for most of these benign pulmonary lesions in which malignancy could not be excluded preoperatively, and imaging characteristics suggesting malignancy were common. VATS is an important biopsy method to identify etiology and pathology for lesions. The most frequent benign pulmonary diseases that are suspected to be malignant and underwent surgical resection are: infectious lesions, inflammatory nodules and hamartoma.