OBJECTIVE:To prepare the norcantharidin (NCTD) nano-micelle and study its antitumor effect. METHODS:NCTD nano-micelle was self-formed in water using Triblock copolymers distearyl phosphatidylethanolamine-polyethylene glycol-ma-leimide;its shape was observed,the drug-loading rate,entrapment efficiency,particle size,Zeta potential were investigated. MTT was used to investigate the cell survival rate of human lung cancer A549 cells in negative control group (Phosphate buffer solu-tion),carrier group (blank nano-micelle),positive control group (NCTD APIs,5-320 μg/mL) and NCTD nano-micelle group (NCTD,5-320 μg/mL) after acting different time (24,48,72 h). Tumor nude mice were randomly divided into blank control group,NCTD injection group(1 mg/kg),NCTD low-dose,high-dose groups(0.5,1 mg/kg),6 in each group. All mice were in-travenously injected relevant medicines in tail,once a day,for 8 weeks. Tumor size was measured every week,and tumor quality was detected after the second day of finishing administration. RESULTS:NCTD nano-micelle was round,drug-loading rate was (2.82±0.05)%,entrapment efficiency was(83.67±1.78)%,particle size was(138.6±45.8)nm,Zeta potential was -(12.75± 0.34)mV(n=6). Cell survival rate of A549 cells in carrier group had no obvious changes,and was obviously decreased in posi-tive control group and NCTD nano-micelle group,which was positively correlated with concentration and time. And the decrease degree of cell survival rate in NCTD nano-micelle group was stronger than positive control group(P<0.01). Compared with blank control group,the tumor quality of mice in 3 administration groups was reduced (P<0.05),the reduction degree in NCTD na-no-micelle high-dose group was stronger than NCTD nano-micelle injection group (P<0.05). CONCLUSIONS:NCTD nano-mi-celle is successfully prepared,which has good in vitro and in vitro anti-tumor effect on A549 cells.

Objective To study the homocysteine induced gene(HCY-2) expression in human fetus arterial smooth muscle cells(hASMCs) in culture and explore the effects of homocysteine(HCY) and folic acid on HCY-2 expression and cell proliferation of hASMCs. Methods Immunohistochemistry ABC staining method was used to observe and analyze HCY-2 expression in hASMCs in culture.The image analysis system was used to research of hASMCs quantificationally.The effect of different HCY concentration on the proliferation of hASMCs was investigated by the cell counting. Results Immunoreactive substance of HCY-2 was chiefly found in cytoplasm of hASMCs.The expression of HCY-2 could be affected by HCY concentrations.There was a positive dose-dependent correlation with HCY concentrations in the culture medium.Folic acid increased the expression of HCY-2.The different concentration of HCY enhanced the proliferation of hASMCs,and this enhancement was maximal at the concentration of 1.25 mmol/L of HCY,while the proliferation was decreased when the concentration of HCY was over 1.25 mmol/L.Conclusion HCY increases the expression of HCY-2,and affects the proliferation of hASMCs.HCY is inhibited by folic acid.

Objective To investigate the effect of different ventilation modes on the ventilation rate and prognosis in patients with cardiac arrest after advanced airway placement. Methods Based on the national database of emergency cardiac arrest treatment, patients treated with advanced airway placement during cardiopulmonary resuscitation (CPR) were enrolled in PUMCH Emergency Department from December 2013 to June 2018. The physiological parameters, such as electrocardiograph waveform, pulse oximetry plethysmographic waveform and capnography, were recorded at least 18 minutes. The demographic data and resuscitation parameters were collected. Waveform capnography was used for calculating ventilation rate (VR) and the VR between 8 to 12 breaths/min was defined as the qualified ventilation rate (QVR). According to the ventilation modes, patients were divided into the bag-mask group (BMG) and mechanical ventilation group (MVG). According to the VR, patients in the mechanical ventilation group were divided into two subgroups, the high-frequency ventilation subgroup (HFV subgroup) with the VR more than 20 breaths/min and the low-frequency VR subgroup (LFV subgroup) with the VR less than 20 breaths/min. VR, the qualified ventilation rate ratio (QVRR), the return of spontaneous circulation (ROSC), and 24-h and 7-day survival were compared between the two groups and subgroups. Result A total of 90 patients were enrolled in the analysis with 22 patients in the bag-mask group and 68 patients in the mechanical ventilation group. The total rate of ROSC was 35.6％, 24-h survival was 1.1％ and 7-day survival was 0. The first 18 minutes ventilation data were collected and added up to 1620 min. The median VR was 16.5 (12.0, 26.0) breaths/min and the QVRR was 30％. Compared with the mechanical ventilation group, the VR in the bag-mask group were lower (10 breaths/min vs 21 breaths/min) and the QVRR was higher (88.9％ vs 11.5％). The ROSC, 24-h survival and 7-day survival had no statistical differences between the two groups. In the mechanical ventilation group, the ratio of VR more than 20 breaths/min was 52.6％. Between the two subgroups, there was no statistical difference in ROSC, 24-h survival and 7-day survival. Conclusions Compared with the mechanical ventilation during CPR, the VR is lower with bag-mask ventilation, and the QVRR is higher. But there was no statistical difference on the outcomes. There was no difference on the outcomes between the two mechanical ventilation subgroups.

ObjectiveTo study the expression changes of Lon protein and mitochondrial dynamics-related protein in the hippocampus of SAMP8 mice and provide a theoretical basis for the treatment of Alzheimer's disease by invigorating the spleen and supplementing Qi. MethodEight 3-month-old SAMR1 mice were used as the normal group， and 32 3-month-old SAPM8 mice were divided into model group， western medicine group （0.013 g·kg^-1）， low-dose Si Junziwan group （3.24 g·kg^-1）， and high-dose Si Junziwan group （12.56 g·kg^-1）， with 8 mice in each group. The western medicine group was gavaged with donepezil， and the Si Junziwan low- and high-dose groups were gavaged with Si Junziwan for 30 days. The positioning navigation experiment of the water maze was started on the 25^th day， and the space exploration experiment of the water maze was started on the 30^th day. On the 30^th day， the protein expression of mitofusin 2 （MFN2） was detected by immunohistochemistry， the expression of adenosine 5'-monophosphate （AMP）-activated protein kinase （AMPK） was detected by enzyme-linked immunosorbent assay （ELISA）， the content of ATP was detected by colorimetry， the microstructure of neuron mitochondria was detected by electron microscope， and the expressions of Aβ protein， Lon protein， dynamin-related protein 1 （DRP1） protein， and MFN1 protein were detected by Western blot. ResultAs compared with the normal group， the latency escape period increased， the number of crossings decreased， the expression of AMPK increased， and the content of ATP decreased in the model group. The expressions of Aβ protein and DRP1 protein increased （P<0.01）， whereas the expressions of Lon protein， MFN1 protein decreased in the model group （P<0.05，P<0.01）， and MFN2 protein decreased. The vacuolation of mitochondria increased and the cristae broke in the model group. As compared with model group， the time of the latent escape period decreased （P<0.01）， and the number of crossings increased in the low-dose and high-dose Si Junziwan groups （P<0.05）. The expression of AMPK （P<0.01） decreased， the content of ATP increased （P<0.01）， the expression of Aβ and DRP1 protein decreased （P<0.05， P<0.01）， and the expression of MFN1 protein was up-regulated （P<0.05） in high-dose Si Junziwan groups. The vacuolation was more obvious in the low-dose Si Junziwan group， whereas the vacuolation was restored and the ridge was clear in the high-dose Si Junziwan group. ConclusionSi Junziwan treats Alzheimer's disease by up-regulating the protein expression of Lon， correcting the disorder of mitochondrial division and fusion protein， and changing the memory function of SAMP8 mice.

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults, with increasing incidence with age and a generally poor prognosis. Almost 20% of AML patients express mutant isocitrate dehydrogenase 2 (mIDH2), which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate (2-HG), resulting in poor prognosis. Thus, global institutions have been working to develop mIDH2 inhibitors. SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised. We have conducted a comprehensive study on its pharmacodynamics, pharmacokinetics and safety. First, SH1573 exhibited a strong selective inhibition of mIDH2 R140Q protein, which could effectively reduce the production of 2-HG in cell lines, serum and tumors of an animal model. It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models. Then, it was confirmed that SH1573 possessed characteristics of high bioavailability, good metabolic stability and wide tissue distribution. Finally, toxicological data showed that SH1573 had no effects on the respiratory system, cardiovascular system and nervous system, and was genetically safe. This research successfully promoted the approval of SH1573 for clinical trials (CTR20200247). All experiments demonstrated that, as a potential drug against mIDH2 R140Q acute myeloid leukaemia, SH1573 was effective and safe.