Advances in the study of new BCR-ABL kinase inhibitors / 药学学报

The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.

Increasing Age Associated with Higher Dipeptidyl Peptidase-4 Inhibition Rate Is a Predictive Factor for Efficacy of Dipeptidyl Peptidase-4 Inhibitors

Background@#It is not known which type 2 diabetes mellitus (T2DM) patients would most benefit from dipeptidyl peptidase-4 (DPP-4) inhibitor treatment. We aimed to investigate the predictors of response to DPP-4 inhibitors considering degree of DPP-4 inhibition. @*Methods@#This study is a post hoc analysis of a 24-week, randomized, double-blind, phase III trial that compared the efficacy and safety of a DPP-4 inhibitor (gemigliptin vs. sitagliptin) in patients with T2DM. Subjects were classified into tertiles of T1 <65.26%, T2=65.26%–76.35%, and T3 ≥76.35% by DPP-4 inhibition. We analyzed the change from baseline in glycosylated hemoglobin (HbA1c) according to DPP-4 inhibition with multiple linear regression adjusting for age, ethnicity, body mass index, baseline HbA1c, and DPP-4 activity at baseline. @*Results@#The mean age was greater in the high tertile group compared with the low tertile group (T1: 49.8±8.3 vs. T2: 53.1±10.5 vs. T3: 55.3±9.5, P<0.001) of DPP-4 inhibition. Although HbA1c at baseline was not different among tertiles of DPP-4 inhibition (P=0.398), HbA1c after 24-week treatment was lower in the higher tertile compares to the lower tertile (T1: 7.30%±0.88% vs. T2: 7.12%±0.78% vs. T3: 7.00%±0.78%, P=0.021). In multiple regression analysis, DPP-4 enzyme inhibition rate was not a significant determent for HbA1c reduction due to age. In subgroup analysis by tertile of DPP-4 inhibition, age was the only significant predictor and only in the highest tertile (R2=0.281, B=–0.014, P=0.024). @*Conclusion@#This study showed that HbA1c reduction by DPP-4 inhibitor was associated with increasing age, and this association was linked with higher DPP-4 inhibition.

Acute cerebral ischemia-induced down-regulation of Sirt3 protein expression contributes to neuronal injury via damaging mitochondrial function / 生理学报

This study was aimed to determine the effect of acute cerebral ischemia on the protein expression level of silent mating type information regulator 2 homolog 3 (Sirt3) in the neurons and clarify the pathological role of Sirt3 in acute cerebral ischemia. The mice with middle cerebral artery occlusion (MCAO) and primary cultured rat hippocampal neurons with oxygen glucose deprivation (OGD) were used as acute cerebral ischemia models in vivo and in vitro, respectively. Sirt3 overexpression was induced in rat hippocampal neurons by lentivirus transfection. Western blot was utilized to measure the changes in Sirt3 protein expression level. CCK8 assay was used to detect cell viability. Immunofluorescent staining was used to detect mitochondrial function. Transmission electron microscope was used to detect mitochondrial autophagy. The results showed that, compared with the normoxia group, hippocampal neurons from OGD1 h/reoxygenation 2 h (R2 h) and OGD1 h/R12 h groups exhibited down-regulated Sirt3 protein expression levels. Compared with contralateral normal brain tissue, the ipsilateral penumbra region from MCAO1 h/reperfusion 24 h (R24 h) and MCAO1 h/R72 h groups exhibited down-regulated Sirt3 protein expression levels, while there was no significant difference between the Sirt3 protein levels on both sides of sham group. OGD1 h/R12 h treatment damaged mitochondrial function, activated mitochondrial autophagy and reduced cell viability in hippocampal neurons, whereas Sirt3 over-expression attenuated the above damage effects of OGD1 h/R12 h treatment. These results suggest that acute cerebral ischemia results in a decrease in Sirt3 protein level. Sirt3 overexpression can alleviate acute cerebral ischemia-induced neural injuries by improving the mitochondrial function. The current study sheds light on a novel strategy against neural injuries caused by acute cerebral ischemia.

Changes in microglia number and Iba1 expression level in the prefrontal cortex of type 1 diabetic mice / 生理学报

The aim of the present study was to observe the activation of microglia in the prefrontal cortex of type 1 diabetes mellitus (T1DM) mice, and the expression of the marker genes of the disease-associated microglia (DAM) associated with neurodegenerative diseases. Sixty healthy adult male C57BL/6J mice were randomly divided into two groups, normal control (CON) group and T1DM group. Streptozocin (STZ) was injected intraperitoneally to induce T1DM mice. The spatial learning and memory function of mice was detected by Morris water maze at the 8th week after the successful model establishment. The number and activation of microglia in the prefrontal cortex of mice were detected by immunofluorescence staining and Western blot. Changes in the mRNA level of several DAM molecular markers were detected by RT-FQ-PCR. The results showed that, compared with CON mice, the fasting blood glucose of T1DM mice increased significantly, while the body weight of T1DM mice decreased remarkably (P < 0.05). The escape latency of water maze in T1DM mice was longer than that in CON mice (P < 0.05). Compared with CON group, the Iba1 protein expression and the number of microglia in prefrontal cortex of T1DM group increased significantly (P < 0.05). In addition, the mRNA levels of several DAM markers in prefrontal cortex of T1DM group were increased significantly (P < 0.05). These results suggest that the microglia are activated and transformed to DAM type in the prefrontal cortex of T1DM mice.

A 14-year multi-institutional collaborative study of Chinese pelvic floor surgical procedures related to pelvic organ prolapse / 中华医学杂志(英文版)

BACKGROUND@#It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011.@*METHODS@#A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided).@*RESULTS@#The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107).@*CONCLUSIONS@#The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly.@*TRIAL REGISTRATION NUMBER@#NCT03620565, https://register.clinicaltrials.gov.

Complement C3 Aggravates Post-epileptic Neuronal Injury Via Activation of TRPV1 / 神经科学通报·英文版

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3-TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.

Complement C3 Aggravates Post-epileptic Neuronal Injury Via Activation of TRPV1 / 神经科学通报·英文版

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron–glia interaction mediated by the C3–TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3–TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.

Sirt1-ROS-TRAF6 Signaling-Induced Pyroptosis Contributes to Early Injury in Ischemic Mice / 神经科学通报·英文版

Stroke is an acute cerebro-vascular disease with high incidence and poor prognosis, most commonly ischemic in nature. In recent years, increasing attention has been paid to inflammatory reactions as symptoms of a stroke. However, the role of inflammation in stroke and its underlying mechanisms require exploration. In this study, we evaluated the inflammatory reactions induced by acute ischemia and found that pyroptosis occurred after acute ischemia both in vivo and in vitro, as determined by interleukin-1β, apoptosis-associated speck-like protein, and caspase-1. The early inflammation resulted in irreversible ischemic injury, indicating that it deserves thorough investigation. Meanwhile, acute ischemia decreased the Sirtuin 1 (Sirt1) protein levels, and increased the TRAF6 (TNF receptor associated factor 6) protein and reactive oxygen species (ROS) levels. In further exploration, both Sirt1 suppression and TRAF6 activation were found to contribute to this pyroptosis. Reduced Sirt1 levels were responsible for the production of ROS and increased TRAF6 protein levels after ischemic exposure. Moreover, N-acetyl-L-cysteine, an ROS scavenger, suppressed the TRAF6 accumulation induced by oxygen-glucose deprivation via suppression of ROS bursts. These phenomena indicate that Sirt1 is upstream of ROS, and ROS bursts result in increased TRAF6 levels. Further, the activation of Sirt1 during the period of ischemia reduced ischemia-induced injury after 72 h of reperfusion in mice with middle cerebral artery occlusion. In sum, these results indicate that pyroptosis-dependent machinery contributes to the neural injury during acute ischemia via the Sirt1-ROS-TRAF6 signaling pathway. We propose that inflammatory reactions occur soon after oxidative stress and are detrimental to neuronal survival; this provides a promising therapeutic target against ischemic injuries such as a stroke.

Effects of tetramethylypyrazine nitrone on proliferation and differentiation of neural stem cells / 中国应用生理学杂志

OBJECTIVES@#To investigate the role of tetramethylpyrazine(TMP) nitrone in proliferation and differentiation of neural stem cells (NSCs).@*METHODS@#We separated and cultivated the original generation of NSCs from cerebral cortex of 14 days rat embryo, and the phenotype characteristics of the third-generation NSCs was tested by immunofluorescence. The experiment was divided into control group, β-mercaptoethanol positive control group, tetramethylpyrazine nitrone group and tetramethylpyrazine nitrone + ethylene glycol tetraacetic acid(EGTA) group (=4). The third-generation cultivation of NSCs was used in the experiment. The effect of tetramethylpyrazine nitrone on the number of NSCs proliferation was determined by BrdU and MTT, and the differentiation of NSCs was determined by Western blot.@*RESULTS@#The primary NSCs was isolated successfully, neurospheres with typical NSCs morphology and expressing nestin was formed at 3-5 days. As BrdU and MTT assay results shown, compared with the control group andβ-mercaptoethanol positive control group, the NSCs proliferation numbers of tetramethylpyrazine nitrone group increased significantly(<0.05). The results of Western blot showed that the neuronal differentiation rate of NSCs was increased significantly in both the tetramethylpyrazine nitrone group and tetramethylpyrazine nitrone + EGTA group, and the differentiation rate of NSCs in tetramethylpyrazine nitrone + EGTA group increased more significantly(<0.05).@*CONCLUSIONS@#Tetramethylpyrazine nitrone can significantly enhance the proliferation and neuronal differentiation rate of NSCs. Decrease in extracellular Ca can promote the differentiation of NSCs into neurons induced by tetramethylpyrazine nitrone. Ca signaling plays an important role in the differentiation of NSCs into neurons.

The effect of short-term particular matter(2.5) exposure on asthma attacks in asthma children in Fukuoka, Japan / 고신대학교의과대학학술지

OBJECTIVES: We investigated whether asthma attacks in asthmatic children were caused by short-term exposure to particulate matter(PM)2.5. METHODS: Subjects were 411 patients who received inhalation therapy in National Fukuoka Hospital, from March to May 2013. All subjects were outpatients. We surveyed the air quality measurement results in the stations closest to the address of the patients. Data were used from the City of Fukuoka website data on air pollution. We carried out a case-crossover study and compared PM2.5 concentration between 7 days after asthma attack occurred and the day asthma attack occurred and 1, 2 and 3 days before asthma attack occurred. RESULTS: Highest hourly concentration of the day (OR 1.013, 95%CI 1.000–1.025) showed a significant association with 1 day before PM2.5 concentration statistically. And 0–1 year-old infants were more vulnerable to the highest concentration of 1 day before PM2.5 concentration(P < 0.05). Average concentration of NO2 and O3 and asthma attack also showed a significant association. CONCLUSIONS: Maximal daily PM2.5 concentrations within 24 hours prior to the attack affect asthma exacerbation. 0–1 year-old infants are particularly vulnerable to PM2.5 concentration. Asthma exacerbation is aggravated by NO2 and O3 concentration on the day of the asthma attack.

Morphine promotes glioblastoma cell proliferation through activating ERK1/2 signaling pathway / 基础医学与临床

Objective To observe the effect of morphine on the proliferation of glioblastoma T98G and U118MG cells and to explore the possible mechanism. Methods Glioblastoma T98G and U118MG cells were cultured in plates for 24 h and randomly divided into five groups: control (con), morphine 0.1 μmol/L(M1),1.0 μmol/L (M2),10.0 μmol/L (M3) and 100.0 μmol/L (M4). MTS and BrdU methods were used to detect the prolifera-tion of glioblastoma T98G and U118MG cells-treated with morphine for 24 h and 48 h. Western blot analysis was applied for determing the level of p-ERK1/2 and cyclin D1 protein expression.Results Compared with the control group,morphine in M3 and M4 groups significantly promoted the proliferation of T98G and U118MG cells (P<0.05) in a concentration-and time-dependent manner. In addition,the level of ERK1/2 phosphorylation and cyclin D1 protein expression significantly increased in both M3 and M4 groups as compared with those of control group (P<0.05). Conclusions Morphine may promote the proliferation of glioblastoma T98G and U118MG cells through activating the ERK1/2 signaling pathway.

Assessing facial fat volume at 6 months after structural fat grafting / 中国组织工程研究

BACKGROUND: With the increasing pursuit of beauty, facial cosmetics have become popular, and thereupon various cosmetic methods and surgical methods have emerged. However, high costs, large trauma, slow recovery, permanent scars and even scar hypertrophy can result from these cosmetic surgeries. Transplantation is a relatively new method for facial cosmetics, and the choice of graft is crucial for cosmetic effects. OBJECTIVE: To evaluate the curative effect of facial rejuvenation surgery with structural fat grafting. METHODS: From May 2016 to May 2017, 21 cases of facial rejuvenation were selected. All subjects were assessed for donor sites and affected areas by combining various factors. Fat tissues were isolated from the donor site, and implanted into the affected area after sediment and grease removal. Patient satisfaction and the severity of facial wrinkles were scored through a survey questionnaire. At 6 months after transplantation, the number of request to replenish injections and number of complication cases were statistically recorded. The volume of facial fat tissues in the affected area was calculated before and after transplantation. RESULTS AND CONCLUSION: Two subjects required re-transplantation during the 6-month postoperative follow-up. Facial capacity, depression, and static patterns of all subjects were well improved after one or two autologous fat transplantations. The average satisfaction score on fat transplantation for all the subjects was 8.47±0.43. The volume of facial fat tissues at 6 months after transplantation was significantly increased compared with that before operation (P < 0.05). The postoperative severity of facial wrinkles was significantly lower than before operation (P < 0.05). Only three subjects had complications within 6 months after transplantation, including one case of infection, one of liquefaction and one of fat embolism. V-Line liquid lift with structural fat grafting can effectively improve facial relaxation, sagging and other issues, with a good upgrade of facial rejuvenation effect.

Expression Profile of CircularRNA in Tongue Squamous Cell Carcinoma / 中山大学学报(医学科学版)

[Objective]To analyze the expression profile variation of circle RNA(circRNA)in tongue squamous cell carcinoma(TSCC)tissue and para-carcinoma tissue.[Methods]CircRNA microarray technology was performed to in-spect the difference of circRNA expression in 4 cases of TSCC tissues and 4 cases of para-carcinoma tissues,and then make analysis after the quality control and homogenization of raw data,to identify which have more than 2 times variation and significant difference(P<0.05)by statistical analysis as circRNA with differential expression. To perform functional analysis on circRNA with differential expression.[Results]Compared with para-carcinoma tissue,there were 17171 circRNA differentially expressed in TSCC tissue,while 9982 increase more than 2 times and 7189 reduce more than 2 times.[Conclusion]circRNA expression profile in TSCC changes significantly comparing with the para-carcinoma tis-sue,some differentially expressed circRNA may regulate the occurrence and progression of TSCC through a competitive combination of miRNA.

The Bone Defect Repairment in Vivo with Co-cultured EPCs and BMSCs / 昆明医科大学学报

Objective To reconstruct the deformity of appearance and function of patients with bone defect, co-cultured system with two stem cells were combined with partial deproteinized biological bone to reconstruct the defect of tibia which is one of the main weight-bearing bone. Methods The bone marrow and peripheral blood were harvested form 18 New Zealand rabbits to isolated bone marrow stem cells and epithelial progenitor cells, and engineering bone was constructed with co-cultured system with these two stem cells and partial deproteinized biological bones; about 1 CM of bone defect of each rabbit was made with bone rongeur, then engineering bones were transplanted into the defect area, the osteogenesis and bone defect recovery were observed on day 14, 28 and month 2.Results The difference of absorbance values of BMSCs group, co-cultured cell group and blank group at each time point and between groups were all statistically significant (P＜0.001), and the collagen content of bone tissue increased gradually after implantation of tissue engineered bone, and the difference between each group was statistically significant (P ＜0.001). The repairment of bone defect with the PDPBB combined with BMSCs and EPCs system has the strongest ability to repair the structure andfunction of the tibial defect area. Conclusion The engineering bone constructed with two stem cells and partial deproteinized bone is a good material for bone defect reconstruction.

Effect of umbilical cord mesenchymal stem cells on VEGF and MCP-1 of acute myocardial ischemia-reperfusion injury in rats / 国际生物医学工程杂志

Objective To investigate the effects of human umbilical cord mesenchymal stem cells (UC-MSCs ) on vascular endothelial growth factor ( VEGF ) and monocyte chemoattractant protein-1 ( MCP-1 ) of acute myocardial ischemia-reperfusion (AMI-R) injury in rats. Methods 24 Sprague-Dawley rats were randomly divided into sham group, AMI-R group and UCMSCs treatment groups on average. The rats were sacrificed on the 10th day after UCMSCs transplantation, and the myocardial tissues below the ligature were taken. The mRNA and protein expressions of MCP-1 of the tissue were detected by RT-PCR and Western Blot respectively, and the expression of VEGF protein was detected by immunohistochemistry. Results The relative expression levels of MCP-1 mRNA and the protein in UCMSCs group were significantly lower than those in sham group and AMI-R group (all P<0.05). The expression of VEGF protein in UCMSCs group was significantly higher than that in sham group and AMI-R group, the differences were statistically significant(all P<0.05). Conclusion UCMSCs transplantation can promote the angiogenesis and decrease the inflammation reaction in the treatment of acute myocardial ischemia-reperfusion injury.

Synovial chondromatosis in the temporomandibular joint: analysis of 5 cases / 南方医科大学学报

Five patients with synovial chondromatosis in the temporomandibular joint were treated in our hospital between August, 2011 and August, 2014. All the patients underwent preoperative imaging examinations for clinical diagnosis and determining the involvement of the lesions. Surgeries were performed and the lesions were confirmed as synovial chondromatosis by pathological diagnosis. The clinical manifestations, imaging features, diagnosis and treatment results were analyzed. All the 5 patients had pain in the joint region, 3 had limited mouth opening, and 3 had swelling in the joint region. X-ray film showed widening of the joint space in all the 5 cases and radiographic findings showed space-occupying lesions in the intra-articular space. Open joint surgeries was performed and completed successfully in all the cases. The postoperative imaging showed no residual lesions in the surgical area. As a rare clinical entity, synovial chondromatosis in the temporomandibular joint was poorly documented without specific clinical manifestations. The diagnosis of synovial chondromatosis relies on imaging, arthroscopic and pathological findings. Corpus liberum is an important feature of the disease occurring frequently in the joint cavity. Surgical intervention is the primary choice for treatment of synovial chondromatosis in the temporomandibular joint, in which the corpus liberum and the affected synovial membrane shall be removed after joint incision.

VCAM-1 improves migration and invasion of human glioma cell lines / 基础医学与临床

Objective To investigate the effects of VCAM-1 on migration and invasion of glioma cell lines . Methods The techniques of lentivirus pSGU6/GFP/Neo-based VCAM-1 shRNA and EF1 a-GFP/puro-based VCAM-1 expression vector, the scratch wound healing migration and transwell invasion assays , and the Western blot and cell staining were applied to observe the effects of VCAM-1 expression levels on migration and invasion of glioma cell line cells.There are four groups in T98G cells including control, vector, scramble and shRNA-VCAM-1 groups and three groups in U251 cells covering control, vector and VCAM-1 overexpressed groups ( n=6 per group) .Results The stabled glioma cell lines of T98 G cells with down-regulated VCAM-1 and U251 cells with VCAM-1 overexpression were established by using lentivirus-based VCAM-1 shRNA and expression vector.The ability of scratch wound healing (migration activity) decreased significantly (P<0.01) in T98G cells with lower VCAM-1 expression levels, while the migration activity was obviously improved in U251 cells with overexpressed VCAM-1 ( P <0.05 ) .Similarly, the invasion ability was significantly inhibited ( P <0.05) in T98G cells with silenced VCAM-1, as well as VCAM-1 overexpression could enhance the invasion ability of U251 cells ( P<0.01 ) .Conclusions VCAM-1 improves the migration activity and invasion ability of human glioma cell line cells.

A modified three-vessel occlusion mouse model with ischemic stroke / 基础医学与临床

Objective To develop a reliable and reproducible model of ischemic stroke .Methods Male C57BL/6J mice were randomly divided into three groups:three-vessel occlusion (3VO, 15-min temporary occlusion of the bi-lateral common carotid arteries superimposed on a permanent occlusion of the right distal middle cerebral artery , n=20 ) , suture MCAO control ( n=20 ) , and sham-operated group ( n=10 ) .At 24 h functional outcome was as-sessed using corner test , cerebral ischemic lesion was determined by TTC staining ( n=10 ) , and then the surviral rate was measured till day 7 (n=10).Results The 3VO group got significantly lower neurological deficit score as compared to sham-operated group ( -0.7 vs -0.04 , P<0.01 ) .Infarct volume of mice in 3 VO group was 17.6%±1.6%, while 42.6%±15.0%in MCAO group ( n=10 ) .The 3 VO group got a significantly increased 7-day survival rate compared to suture MCAO group (90%vs 60%, n=10).Conclusions The present three-ves-sel occlusion model is stable and reliable for research on ischemic stroke .

Discussion on Cultivation of Clinical Profession Ability of Integrated Traditional Chinese and Western Medicine Graduates / 中国中医药信息杂志

Cultivation of clinical profession ability of integrated traditional Chinese and Western medicine graduates involves the policy, management, evaluation, training, and many other aspects of colleges and universities. This article put forward the organic convergence of cultivation education and clinical profession post competence. According to the real situation of graduates, sectional, individualized, and true practice of clinical cultivation education was conducted, which could make graduates get into the cultivation education mode of "early clinical practice, more clinical practice, true clinical practice". This could effectively enhance the cultivation effects and clinical profession post competence of integrated traditional Chinese and Western medicine graduates.

Clinical Features, Surgical Treatment and Prognosis in Acute Myocardial Infarction Patients With Ventricular Septal Rupture Complicating Cardiogenic Shock / 中国循环杂志

Objective:To explore the clinical features,surgical treatment and prognosis in acute myocardial infarction (AMI) patients with ventricular septal rupture (VSR) complicating cardiogenic shock (CS).Methods:A total of 77 AMI-VSR patients received surgical repair in our hospital from 2005-01 to 2015-05 were retrospectively studied.The patients were divided into 2 groups:CS group n=52 and Without CS group,n=25.Clinical features were compared between 2 groups and the outcomes in CS group were analyzed.Results:Both groups showed multiple aneurysm (73.0％ vs 68.0％);CS was more occurred in patients with posterior VSR (48.0％ vs 24.0％),P=0.044.Compared to Without CS group,CS group had the larger diameter of VSR (16.16±6.73) mm vs (11.86±4.62) mm,P=0.003;lower LVEF (45.0±8.8) ％ vs (47.9±12.3) ％,higher pre-operative application rates of IABP (34.6％ vs 0％) and vasoactive drugs (96.2％ vs 28.0％),more patients received emergent surgery (42.3％ vs 8.0％) and less patients received elective surgery (57.7％ vs 92.0％),all P＜0.05.In CS group,there were 3 in-hospital death,49 patients survived with the mean follow-up time at (4.5±3.1) years and 2 patients died during that period.Conclusion:Larger or posterior VSR were more likely to develop CS,the patients survived after surgical treatment may have good mid-term outcomes.