Notch signal pathway is closely related to the organism's development and a variety of cancers. Current models available for screening modulators of Notch signal pathway all use mouse Notch protein as substrates and those models which use human Notch protein have not been reported. To make the screen results much more reliable, the authors cloned a truncated form of human Notch1 called N100, and built the screening models for the use of it instead of mouse Notch protein. The models included an in vitro screening model based on the purified gamma-secretase enzyme and a cell model using luciferase reporter system. The screening models then have been verified by the known modulators of Notch signal pathway and the IC50 values have been obtained. The verified models can be used to screen modulators of human Notch signaling pathway effectively and it can lay the foundation for finding new modulators of this kind effectively.
Amyloid Precursor Protein Secretases ; Animals ; Drug Evaluation, Preclinical ; methods ; Humans ; Luciferases ; Mice ; Receptors, Notch ; antagonists & inhibitors ; Signal Transduction

Notch signal pathway is closely related to the organism's development and a variety of cancers. Current models available for screening modulators of Notch signal pathway all use mouse Notch protein as substrates and those models which use human Notch protein have not been reported. To make the screen results much more reliable, the authors cloned a truncated form of human Notch1 called N100, and built the screening models for the use of it instead of mouse Notch protein. The models included an in vitro screening model based on the purified gamma-secretase enzyme and a cell model using luciferase reporter system. The screening models then have been verified by the known modulators of Notch signal pathway and the IC50 values have been obtained. The verified models can be used to screen modulators of human Notch signaling pathway effectively and it can lay the foundation for finding new modulators of this kind effectively.

BACKGROUND: Most cases of early-onset familial Alzheimer disease (AD) are associated with presenilin-1 mutation, which mainly occurs in the 5th and 8th exons. Except for the onset age and family history, sporadic AD is basically the same as early-onset familial AD regarding clinical manifestations and pathological characteristics. Is its pathogenesis also related to the mutation of presenilin-1 gene?OBJECTIVE: To probe into the relationship between sporadic AD and presenilin-1 mutation.DESIGN: Case control analysis based on clinical diagnosis.SETTING: Neurology Department of the First Hospital Affiliated to Sun Yat-sen University.PARTICIPANTS: Outpatients who came to the Memory Obstacle Clinic of the First Hospital Affiliated to Sun Yat-sen University between April 1998 and June 2000 but without familial history of AD were selected and divided into 3 groups: [1] AD group: There were 68 cases confirmed as probable having AD according to the clinical diagnostic standard of NINCDS-ADRDA. [2] Vascular dimentia (VaD) group: There were 25 cases confirmed as probable having vascular dimentia according to the clinical diagnostic standard of NINCDS-ADRDA. [3] Normal control group: There were 20 healthy elders (spouses of some patients in the above two groups)without dimentia.METHODS: The conventional phenol extraction method was used to withdraw DNA from peripheral blood, and polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SCCP) was applied to detect the mutation of the 5th and 8th exons in presenilin-1 gene.RESULTS: All the 5th and 8th exons in presenilin-1 gene were proved to be composed of two single strands and a double strand by PCR-SCCP analysis.No abnormal electrophoresis was found, suggesting no that mutation occurred.CONCLUSION: Sporadic AD differs from familial AD in pathogenicity;mutation does not occur or seldom occurs in the 5th and 8th exons in presenilin-1 gene, thereby cannot be considered as an important causive factor for sporadic AD.

Objective To investigate the positive detective rate of interlobar node in the operation of non-small cell lung cancer (NSCLC), and to compare the effect of interlobar node dissection by video-assisted thoracoscopic surgery (VATS) with thoracotomy in treatment of lung cancer. Methods 108 patients with NSCLC who received the surgery by the same group of thoracic surgeons were collected from Aug 2012 to Mar 2016 in Guangdong Medical University Affiliated Kaiping Central Hospital. The positive transfer and detective rates of interlobar node in patients with different clinical and pathological stage were analyzed. Then the patients were divided into traditional open thoracotomy group and VATS group according to the operation mode, meanwhile, the number of interlobar nodes dissection in the two groups were compared. Results The positive transfer rates of the interlober nodes in patients with different clinical stage were ⅠA 5.7 % (2/35),ⅠB 5.0 % (1/20), ⅡA 14.3 % (3/21), ⅡB 13.3 % (2/15), ⅢA 29.4 % (5/17); For patients with different pathological T stage were T1A 8.3 % (2/24), T1B 9.1 % (2/22), T2A 12.9 % (4/31), T2B 14.3 % (2/14), T3 21.4 %(3/14), T4 33.3 % (1/3), and over-all transfer rate was 13.0 % (14/108). In pathology stage and pathology T stage, the number of interlober nodes had no statistical difference in traditional open thoracotomy group and VATS group (all P>0.05). Conclusions Even in the early clinical stage, the transfer of interlobar node may be positive. The transfer rate of interlobar node is correlated positively with pathology T stage. VATS can achieve the same effect in interlobar node dissection compared with the traditional approach.

Objective: To compare the effects of droperidol, midazolam sedation on implicit memory in patients under epidural anesthesia. Methods: Thirty- two patients with ASA I 一 II un-dergoing general surgery operations with epidural anesthesia were divided into 2 groups,group D received droperidol 2.5mg and fentanyl 0.05mg as sedative, group M received midazolam 3mg and fentanyl 0.05 mg as sedative. The explicit memory and implicit memory scores were gained by methods of process dissociation procedure, and the patients' assessment of alertness/sedation scales were graded simultaneouly. Results: The median of patient' assessment of alertness/ seda-tion scale in group D and group M were 4 and 3 respectively. Patients in group D had higher explicit memory scores and lower implicit memory scores than those in group M. But the implicit memory had not disappeared completely in group D. Respiratory depression emerged when increasing the dosage of droperidol. Conclustion: Droperidol can specifically depress the implicit memory, but it results in respiratory depression when the dosage of droperidol increased. It limits the usage of droperidol to eliminate the implicit memory completely.

AIM:To establish a rat hyperlipidemia model for studying the aortic expression of heat shock protein 22 (HSP22), tumor necrosis factor alpha (TNF-α) and endothelial nitric oxide synthase (eNOS) and the effect of atorvasta-tin intervention.METHODS:Hyperlipidemia model was established in SD rats.Afterwards, the rats were divided into nor-mal control group, high fat group and high fat+atorvastatin intervention group.The expression of HSP22 and TNF-αin the rat aortas was detected by immunohistochemical assay and the expression of eNOS was assessed by Western blotting.RE-SULTS:No detectable expression of HSP22 and TNF-αin the normal control group was observed.However, the expression of HSP22 and TNF-αwas positive in the high fat group and the atorvastatin intervention group.The mean densities of HSP22 and TNF-αpositive particles were significant lower in the atorvastatin intervention group as compared with high fat group ( both P<0.05) .The expression of eNOS protein in the high fat group and atorvastatin intervention group was significantly lower than that in normal control group (P<0.01).However, no marked difference of eNOS protein expression between high fat group and atorvastatins intervention group was observed.CONCLUSION:The expression of HSP22 and TNF-αin the rat aortas is increased in the hyperlipidemia rat model.This effect can be restored by atorvastatin treatment.The expression of eNOS in the rat aortas is decreased in the hyperlipidemia rat model, but this tendency could not be attenuated by atorvastatin.

Objective To understand the endemic characteristics and regularity of cystic echinococcosis by evaluating and classifying its endemic situation in Non Tibetan Plateau regions,so as to provide the evidence for formulating effective preventive and control measures. Methods The prevalence data of cystic echinococcosis in 174 counties(cities,districts,banners)in Non Tibetan Plateau regions from a national survey were collected and analyzed by the sample cluster method in 2012. Results The 174 counties(cities,districts,banners)could be classified into 4 clusters by spatial distribution. The first cluster with human high prevalence rate,low infection rate of livestock,and positive rate of dog stool antigen included 3 counties. The second cluster with high infection rate of livestock,low prevalence rate of human,and positive rate of dog stool antigen included 20 counties(cit-ies). The third cluster with high positive rate of dog stool antigen,low prevalence rate of human,and low infection rate of livestock included 39 counties(cities,districts,banners). The fourth cluster with low rates of the above 3 indices included the rest 112 counties. Conclusions The results of the cluster analysis conform to the current epidemiological status of cystic echinococcosis in the Non Tibetan Plateau regions. The epidemiological characteristics and geographical distributions of the four area types will pro-vide a basis for the classified management and guidance of cystic echinococcosis control in these areas.

Adolescent ; Adult ; Aged ; China ; epidemiology ; Dust ; Female ; Humans ; Lung Diseases ; epidemiology ; prevention & control ; Male ; Middle Aged ; Occupational Diseases ; epidemiology ; prevention & control ; Pneumoconiosis ; prevention & control ; Young Adult

Adolescent ; Adult ; Aged ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Occupational Diseases ; epidemiology ; Young Adult

OBJECTIVETo investigate the effect of Ningxintong Granule (NXTG) on left ventricular diastolic dysfunction (LVDD) in patients with coronary heart disease (CHD) of qi-deficiency and blood-stasis syndrome in Chinese medicine.

METHODSSeventy-six CHD patients with LVDD of qi-deficiency blood-stasis syndrome were randomized into two groups. The 36 patients in the control group were treated by Western medical conventional treatment alone, and 40 patients in the treated group were treated by NXTG (Consisting of milk vetch root, pueraria root, ligustici, ilex-puhesceus, manchurian wildginger, 10 g in each package) and Western medical conventional treatment in combination, one package each time, thrice daily, 4 weeks as one therapeutic course. The left ventricular function (LVF) of all patients (including Emas, Amas, E/A, DT and IVRT) was evaluated by Doppler echocardiography before and after treatment, and the changes of clinical effectiveness and TCM syndrome effectiveness were observed.

RESULTSCompared with the control group after treatment, Emas, E/A increased, while Amas, DT, IVRT decreased showing statistical difference (P < 0.05). The therapeutic effects in the treated group were significantly better (P < 0.05).

CONCLUSIONNXTG with qi-enriching and blood-activating actions shows favorable effect in treating CHD patients with LVDD.

Aged ; Coronary Disease ; diagnosis ; drug therapy ; physiopathology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; Qi ; Ventricular Dysfunction, Left ; drug therapy ; Ventricular Function, Left