1.Expressions of p-Akt (Ser473) and p-Bad (Ser136) and apoptosis in peri-infarction tissue following permanent middle cerebral artery occlusion in rats
Min HE ; Jiangquan HAN ; Baiyun NI ; Xianping ZHANG
International Journal of Cerebrovascular Diseases 2013;21(8):624-629
Objective To investigate the relationship between the expression changes of p-Akt (Ser473),p-Bad (Ser136) and the cell apoptosis in peri-infarction tissue of permanent middle cerebral artery occlusion (MCAO) in rats.Methods Sixty male Sprague-Dawley rats were randomly allocated into sham operation,MCAO 3 h,MCAO 12 h,LY294002 intervention MCAO 3 h,and LY294002 intervention MCAO 12 h groups (n =12 in each group).A permanent MCAO model was induced by the modified suture method.At 15 minutes before modeling,the rats in the LY294002 intervention MCAO groups were administered via lateral ventricle.The neurological function score was scored by using Zea Longa method.2,3,5-triphenyltetrazolium chloride (TTC) staining was used to detect infarct volume.Immunohistochemical staining was use to detect pAkt (Ser473) and p-Bad (Ser136) expressions in peri-infaretion tissue.TUNEL assay was used to detect apoptotic cells in peri-infarction tissue.Results Three hours after modeling all the experimental rats awoke from anesthesia.The neurological deficit score in the sham operation group was 0,and the scores of the MCAO 3 h,MCAO 12 h,LY294002 intervention MCAO 3 h and LY294002 intervention MCAO 12 h groups were 2.25 ± 0.45,2.92 ± 0.99,3.00 ± 0.95,and 3.02 ± 0.36,respectively.There were significant differences among all groups (F =26.520,P =0.000).The score of the LY294002 intervention MCAO 3 h group was significantly higher than that of the MCAO 3 h group (P =0.009).There was no significant difference between the LY294002 intervention MCAO 12 h group and the MCAO 12 h group (P =0.354).TTC staining showed that no infarct was observed in the sham operation group.The infarct volumes of the MCAO 3 h,MCAO 12 h,LY294002 intervention MCAO 3 h and LY294002 intervention MCAO 12 h groups were 23.4 ± 1.4,40.3 ± 1.1,31.9 ±6.0 and 44.4 ±3.8 mm3,respectively.There were significant differences among the groups (F =30.440,P =0.000).The score of the LY294002 intervention MCAO 3 h group was significantly greater than that of the MCAO 3 h group (P =0.002).There was no significant difference between the LY294002 intervention MCAO 12 h group and the MCAO 12 h group (P=0.113).Compared with the sham operation group,the p-Akt (Ser473) expression in peri-infarction tissue in the MCAO 3 h group was significantly high,and it was significantly decreased in the MCAO 12 h group; the expression level of p-Bad (Ser136) showed a progressive decline with the passage of MCAO time,at the same time,the number of apoptotic cells increased progressively.After the LY294002 intervention,the expression levels of p-Akt (Ser473) and p-Bad (Ser136) in peri-infarction tissue decreased significantly at 3 h after MCAO,and the number of apoptotic cells increased significantly (P <0.05),but there was no significant effect on each index at 12 h after MCAO.Conclusions The activation of the PI3K/Akt signal transduction pathway in early cerebral infarction and the stress elevation of the key protein p-Akt (Ser473) of this pathway have brain protection,while the failure of this pathway activity and the drastical decrease of its key protein in the late cerebral infarction are associated with brain injury.
2.Correlation betw een common carotid artery mechanical stress and cerebral small vessel disease
Houqin CHEN ; Baiyun NI ; Xianping ZHANG ; Wenbing WANG
International Journal of Cerebrovascular Diseases 2015;(5):335-338
Objective To investigate the correlation between the indicators of common carotid artery mechanical dynamics, a circumferential wal tension (CWT) and a shear stress (SS), and cerebral smal vessel disease (SVD). Methods The neurological outpatients without obvious cardiovascular disease were enrol ed consecutively. The inner diameters of carotid arteries and blood flow velocity of the patients w ere measured by ultrasound examination, and their CWT and SS w ere calculated. Lacunar infarction and/or leukoaraiosis w ere determined according to the findings of MRI. Results A total of 296 patients w ere enrol ed, 163 of them had lacunar infarction and 132 had leukoaraiosis. Univariate analysis show ed that there w ere significant differences in the distributions of age, hypertension, diabetes, systolic blood pressure, diastolic blood pressure, CWT, and SS betw een the lacunar infarction group and the non-lacunar infarction group, as wel as between the leukoaraiosis group and the non-leukoaraiosis group (al P<0.05). After adjusting for relevant risk factors, multivariate logistic regression analysis show ed that the peak systolic CWT (odds ratio [OR] 3.60, 95% confidence interval [CI] 1.48-8.30) and end diastolic CWT (OR 1.22, 95%CI 1.21-1.25) w ere the independent risk factors for lacunar infarction, w hile the peak systolic SS (OR 0.90, 95%CI 0.75-0.95 ) and end diastolic SS ( OR 0.87, 95%CI 0.84-0.98 ) w ere the independent protective factors for lacunar infarction; the peak systolic CWT (OR 4.67, 95%CI 2.05-10.52) and end diastolic CWT (OR 1.25, 95%CI 1.22-1.47) were the independent risk factors for leukoariosis, w hile the peak systolic SS (OR 0.93, 95%CI 0.75-0.94) and end diastolic SS (OR 0.91, 95%CI 0.85-0.98) w ere the independent protective factors for leukoaraiosis. Conclusions The common carotid artery mechanical stress w as associated w ith the occurrence of SVD.
3.PI3K/Akt signal transduction pathway and apoptosis after cerebral ischemia
Min HE ; Jiangquan HAN ; Baiyun NI ; Xianping ZHANG ; Zhen LI ; Houqin CHEN ; Qiang ZHANG
International Journal of Cerebrovascular Diseases 2010;18(7):553-558
Apoptosis is one of the important forms during cerebral ischemia.Phosphoinositide-3 kinase (PI3K)/serine/threonine kinase (Akt) is the important cell survival signaling pathway,while c-jun N-terminal kinase (JNK) is the important pro-apoptotic signaling pathway.The dynamic equilibrium of the two signal transduction pathways maintains cell survival and apoptosis under the physiological state.Stimulation during cerebral ischemia breaks this physiological balance and results in the apoptosis of massive neurons.A variety of proved neuroprotective factors are associated with the amplification of enhancement of cell survival signal or inhibition of apoptosis signal,and thrus maintain the balance between the two signal pathways.
4.The application of ultrasonography in breast cancer′s screening of chinese women with dense breast
Lili TANG ; Ni LIAO ; Ying XIAO ; Jintang LIAO ; Baiyun WU ; Jie MAO ; Zhentang SHEN ; Huiying OU ; Yuhui WU ; Jian HAI ; Yan LI
Chinese Journal of General Surgery 2001;0(10):-
Objective To explore the contribution of ultrasonic examination and localization in early breast cancer screening of chinese women with dense breast.Methods From February,2002 to April,2006,the breasts of 5 000 women were examined using ultrasonic examination,and in about 4 000 women a mass was detected,which included 142 cases of breast cancer proved by pathology with diameter ≤2cm occurred in patients with dense breast.In these parients,ultrasonic visualization and molybdenum target mammographic were performed.Results In these with breast cancer and dense breast,there were 47 cases(33.10%) with microcalcification detected by ultrasonography,the sensitivity rate was 74.60% and the accuracy rate was 88.73%.Only 38(26.76%) cases were detected by mammography,the sensitivity rate was(60.32)% and the accuracy was 82.39%.About 44.37% breast cancer with dense brast display as the(microcalcification).There were 110 cases(77.46%) of the small breast cancer detected by ultrasonography,the sensitivity was 88.71% and the accuracy rate was 90.14%.There were 100 cases(70.42%)(detected) by mammography,the sensitivity rate was 80.65% and the accuracy rate was 83.10%.Also,in 12 patients an unpalpation breast lesion was correctly excised by the use of ultrasonic localization.(Conclusions)(1)For the small breast cancer in dense breast the sensitivity and the accuracy of ultrasonography(surpassed) those of mammography.(2)The ultrasonic examination is an effective way for early breast cancer screening in young women with dense breast and flat breast.Ultrasonography can improve the rate of dignosis in early breast cancer,and also improve the breast-conserving surgical rate.Ultrasonography is worth of widespread use spreading.
5.Association between mechanical stresses and brain burden of small vessel diseases
Houqin CHEN ; Baiyun NI ; Wenbing WANG ; Fei GUO
Chinese Journal of Neuromedicine 2015;14(7):661-664
Objective To investigate the relationship between total burden of cerebral small vessel disease (cSVD) on brain MR imaging and circumferential wall tension (WT) in patients with acute lacunar stroke.Methods A total of 227 patients with first-ever acute lacunar stroke,admitted to our hospital from September 2010 to December 2012,were recruited in the study.All patients underwent conventional imaging sequences and susceptibility-weighted imaging sequences of 1.5T MRI system.The presences of each marker of cSVD,including asymptomatic lacunar infarct,white matter lesion,cerebral microbleed,and enlarged perivascular space,were scored on brain MRI.Internal diameters of the common carotid artery,and circumferential WT were measured.Logistic regression analysis was performed to determine the associations between WT levels and an increasing total burden of cSVD.Results According to cSVD scores,five groups of patients were concluded:6 with 0 point,37 with one point,103 with 2 points,61 with 3 points and 20 with 4 points;systolic WT in them were (5.79±0.24)×104 dyne/cm2,(5.70±0.49)×104 dyne/cm2,(5.89±0.71)×104 dyne/cm2,(7.12±i.19)×104 dyne/cm2 and (6.63± 0.76)×104 dyne/cm2,and diastolic WT in them were (3.37±0.31)×104 dyne/cm2,(3.29±0.26)×104 dyne/cm2,(3.50±0.43)×104 dyne/cm2,(3.99±0.49)×104 dyne/cm2 and (4.30±0.85)×104 dyne/cm2.Univariate analysis suggested that age,hypertension,diabetes,intemal diameters of the common carotid artery,diastolic WT and systolic WT had significant differences among the five groups (P<0.05).After adjustment for confounding parameters,higher systolic WT (OR:1.555,95%CI:1.203~2.479) and higher diastolic WT (OR:5.287,95%CI:2.713~10.302) were associated with an increasing total burden of cSVD.Conclusions WT is associated with total burden of cSVD.
6.Consideration about chemistry, manufacture and control (CMC) key problems in simplified registration of classical traditional Chinese medicine excellent prescriptions.
Zhi-Min WANG ; Ju-Yan LIU ; Xiao-Qian LIU ; De-Qin WANG ; Li-Hua YAN ; Jin-Jin ZHU ; Hui-Min GAO ; Chun LI ; Jin-Yu WANG ; Chu-Yuan LI ; Qing-Chun NI ; Ji-Sheng HUANG ; Juan LIN
China Journal of Chinese Materia Medica 2017;42(10):1819-1824
As an outstanding representative of traditional Chinese medicine(TCM) prescriptions accumulated from famous TCM doctors' clinical experiences in past dynasties, classical TCM excellent prescriptions (cTCMeP) are the most valuable part of TCM system. To support the research and development of cTCMeP, a series of regulations and measures were issued to encourage its simplified registration. There is still a long-way to go because many key problems and puzzles about technology, registration and administration in cTCMeP R&D process are not resolved. Based on the analysis of registration and management regulations of botanical drug products in FDA of USA and Japan, and EMA of Europe, the possible key problems and countermeasures in chemistry, manufacture and control (CMC) of simplified registration of cTCMeP were analyzed on the consideration of its actual situation. The method of "reference decoction extract by traditional prescription" (RDETP) was firstly proposed as standard to evaluate the quality and preparation uniformity between the new developing product under simplified registration and traditional original usages of cTCMeP, instead of Standard Decoction method in Japan. "Totality of the evidence" approach, mass balance and bioassay/biological assay of cTCMeP were emphatically suggested to introduce to the quality uniformity evaluation system in the raw drug material, drug substance and final product between the modern product and traditional decoction.