1.Distribution of ulnar variance in healthy people
Orthopedic Journal of China 2006;0(21):-
[Objective] To investigate the correlation of ulnar variance with gender and age. [Method]Two hundreds healthy volunteers were randomly selected,right handedness,including 117 men,83 women,aged 18 to 84 years old,with an average age of 41.7~16.4.They had no previous history of acute or chronic disease of the wrist and no wrist or forearm fracture history.All the volunteers were randomly selected for unilateral or bilateral wrist X-ray.A total of 309 valid results were obtained.Numerical ulnar variance were divided into groups according to gender,age and left or right hand for statistical analysis.[Result]Among the volunteers,the incidence of ulnar variance were: 48.9% positive,39.8% neutral,and 11.3% negative.Among the male volunteers,the incidence of ulnar variance were: 50.0% positive,39.2% neutral,10.8% negative.Among the female volunteers,the incidence of ulnar variance were: 47.4% positive,40.6% neutral,and 12.0% negative.With the age increasing,the incidence of positive and negative ulnar variance on increased,but that of the neutral variance decreased.There was no significant difference between males and females.The incidence of ulnar variance of the left side were: 49.7% positive,39.3% neutral,and 11.0% negative.The incidence of the right side were 48.2% positive,40.6% neutral,and 11.5% negative.The incidence of ulnar variance showed no significant difference between the two sides.[Conclusion](1) In healthy people,the positive and neutral ulnar variance are more commonly seen than the negative variance.(2) With the growth of age,the ulnar variance tends to change dynamically.(3) In healthy people,the distribution of the ulnar variance at the same age shows no significant difference between men and women.(4) In healthy people,the distribution and change of the ulnar variance are not influenced by the daily activities of the wrist.
2.Diversity-oriented synthesis and its application in drug discovery.
Lei ZHANG ; Ming-yue ZHENG ; Hong LIU
Acta Pharmaceutica Sinica 2015;50(4):419-433
Diversity-oriented synthesis (DOS) aims to efficiently generate collections of small molecules with diverse appendages, functional groups, stereochemistry and skeletons, thus yielding diverse biological activities capable of modulating a wide variety of biological processes. In this review, we discussed the common strategies employed in DOS with specific examples from recent literature, including reagent-based approach, substrate-based approach, build-couple-pair strategy and privileged substructure-based DOS. The application of some DOS libraries in drug discovery is also presented.
Drug Design
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Drug Discovery
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Small Molecule Libraries
3.Correlative study of the relationship between hemorrhagic transformation and premorbid antithrombotic therapy after acute cerebral infarction
Yanchao CHEN ; Chunyan LEI ; Ming LIU
Chinese Journal of Cerebrovascular Diseases 2015;(4):174-179
Objective To investigate the impact of using antithrombotic drugs (anticoagulants or antiplatelet aggregation drugs)before the onset of cerebral infarction on hemorrhagic transformation after acute cerebral infarction. Methods The consecutive patients with acute cerebral infarction from Chengdu Stroke Registry Project admitted to the Department of Neurology,West China Hospital,Sichuan University from January 1,2004 to January 1,2014 were enrolled. The baseline data on admission,previous usage of anticoagulants and anti-platelet aggregation drugs,as well as CT/ MRI and other imaging data of all patients were collected. According to the results of CT/ MRI reexamined at 72 h after admission,the patients with hemorrhagic transformation were enrolled into a hemorrhagic transformation group;the patients with non-hemorrhagic transformation were enrolled into a non-hemorrhagic transformation group according to the ratio
of 1 ∶ 1. Their gender and age were matched with the hemorrhagic transformation group. The baseline data and drug used of the patients in both groups were compared. The differences of risk factors between the two groups were analyzed with multivariate Logistic regression analysis. The relationship between hemorrhagic transformation and premorbid use of antithrombotic drugs were observed. Results A total of 6 916 patients with acute cerebral infarction were enrolled,including 433 (6. 3%)hemorrhagic transformation (hemorrhagic transformation group)and 433 non-hemorrhagic transformation. (1)There were significant differences between the patients of the two groups on admission in the National Institutes of Health Stroke Scale (NIHSS)score,atrial fibrillation,previous cerebral infarction,and blood glucose levels on admission (all P < 0. 05). (2)The proportions of using anticoagulants and antiplatelet aggregation agents in the hemorrhagic transformation group were higher than those of the non-hemorrhagic transformation group (anticoagulants:14. 1% [n = 61]vs. 3. 9% [n = 17];P < 0. 01,OR,4. 01,95% CI 2. 303 -6. 993;anti-platelet aggregation drugs:14. 3% [n =62]vs. 8. 3% [n = 36];P = 0. 005,OR,1. 84,95% CI 1. 194 -2. 846). (3)The results of multivariate Logistic regression analysis showed that the use of anticoagu-lants,anti-platelet aggregation drugs,NIHSS score on admission,and random blood glucose on admission were the independent risk factors for hemorrhagic transformation (OR [95% CI]3. 302 [1. 860 -5. 862], 2. 081 [1. 281 -3. 382],1. 047 [1. 026 -1. 069],and 1. 055 [1. 011 -1. 100],respectively (all P <0. 05). Conclusion The NIHSS score and blood glucose levels on admission are the independent risk factors of hemorrhagic transformation. Using anticoagulants or anti-platelet aggregation drugs before symptom onset is independently associated with hemorrhagic transformation,however,its relationship with the long-term prognosis of acute cerebral infarction need to be further studied.
4.The main fields and trends of anti-inflammation and immunopharmacology study in china
Ming XIANG ; Lei WU ; Ping LIU
Chinese Pharmacological Bulletin 1987;0(02):-
The main fields and trends of research on anti-inflammation and immunopharmacology were reviewed as: signal transduction pathways as target for therapy, cytokine regulating network, new types of immunotherapy, new mechanisms of anti-inflammation drugs, the mechanisms and inductive methods of immune tolerance and the development of natural immune system.
5.One-stage anterior radical debridement,titanium mesh bone fusion and internal fixation for the treatment of thoracolumbar spinal tuberculosis
Lei ZHOU ; Ming LI ; Peilai LIU
Orthopedic Journal of China 2006;0(07):-
[Objective]To evaluate the curative effect of the one-stage anterior radical debridement,titanium mesh cage bone fusion and inernal fixation for the treatment of thoracolumbar spinal tuberculosis.[Method]Twenty-two thoracolumbar spinal tuberculosis cases from January 2003 to February 2006 were analyzed retrospectively,among whom 12 were male and 10 were female,age ranging from 19 to 76 years with a mean of 36 years.T_9~L_5 vertebrae were involved in,in detail 1 was involved in single vertebra,17 were involved in 2 vertebrae,3 were involved in 3 vertebrae,1 was involved in the type of jumping style,M=2,Q=0.All cases received one-stage anerior radical debridement,titanium mesh cage bone fusion and internal fixation along with strict anti-tuberculosis chemical therapies.The improvement of symptoms and neurological function,angles reduced by the surgeries and bone fusion,angles lost as well as the subsidence of the titanium mesh during the long-term follow-up were observed and compared statistically.[Result]No recurrence was found in the follow-up period extending from 6 months to 24 months with an averaging of 12.5 months.All the incisions acquired primary healing.The systematic and local symptoms were released postoperatively.Neurological function recovered in different degrees(P
6.Changes of ultrastructure and level of nitric oxide in the myocardium of rats with experimental non-insulin-dependent diabetes mellitus
Ming LEI ; Xinqiu LIU ; Fengyo XING
Chinese Journal of Pathophysiology 1986;0(04):-
AIM:The ultrastructure,the levels of NO - 2/NO - 3 were investigated in the myocardium of rats with non-insulin dependent diabetes mellitus. METHODS: In order to establish a model of non-insulin dependent diabetes mellitus (NIDDM), we injected rats with small dose streptozocoi (iv). Two weeks after the injection, the rats developed impaired glucose tolerance. Then, they were fed with high energy diet for eight weeks to form NIDDM. RESULTS: (1) The ultrastructures of cardiac myocytes of NIDDM rats were changed evidently, with swelled mitochondrion and widened intercalated-disk gap; (2) The levels of NO - 2/NO - 3 in the heart tissue of NIDDM rats were significantly lower than those of normal rats( P
7.Hyaluronic acid protects tissue engineering cartilage from the inhibitory effect of nitroprusside sodium
Ming LEI ; Shiqing LIU ; Yulan LIU ; Zhe WANG ; Hao PENG
Chinese Journal of Rheumatology 2008;12(10):684-687,插2
Objective To investigate the protective mechanism of hyaluronic acid (HA) antagonistic to nitmprusside sodium (SNP) on the tissue engineering cartilage. Methods Alginate culture for two weeks was used to recover phenotype of dedifferentiated chondrocytes. Differentiation state of chondrecytes was analyzed by immunostaining. The growth of alginate-recovered chondrocytes on the chitosan-based scaffold was observed by scanning electron microscope. After cultured for 3 weeks, this tissue engineering cartilage was treated with SNP in the absence or presence of HA combined with specific β1 integrin blocking antibody collagen type Ⅱ and aggreean were detected by RT-PCR and Western blot. Results Collagen type Ⅱ expression in dedifferentiated chondrocytes was significantly enhanced by alginate bead culture. The chitosan-based scaffold supported cell adhesion, proliferation and migration. A dose-dependent inhibitory effect on the expression of collagen type Ⅱ and aggrecan was observed when tissue engineering cartilage was treated with SNP alone. HA significantly promoted collagen type Ⅱ, and aggrecan expression antagonistic to low concentrations of SNP (p<0.05). However, the specific β1,integrin blocking antibody abrogated the effects of HA. Conclusion Alginate culture recovers the phenotype of dedifferentiated chondrocytes. HA abrogats the inhibitory effect of SNP via β1 integrin signal pathway to protect tissue engineering cartilage.
8.Clinical Observation of Recombinant Human Brain Natriuretic Peptide on Acute Decompensated Heart Failure
Shaoguang SUI ; Lei SUN ; Yufei LIU ; Ming CUI ; Xiangdong LI
China Pharmacy 2016;27(29):4136-4138
OBJECTIVE:To observe therapeutic efficacy and safety of recombinant human brain natriuretic peptide (rhBNP) in the treatment of acute decompensated heart failure (ADHF). METHODS:129 ADHF patients admitted in our hospital during Jul. 2013-Jul. 2015 were randomly divided into observation group(69 cases)and control group(60 cases). Control group was giv-en routine treatment. Observation group was additionally given rhBNP 1.5 μg/(kg·d)vein shock(d1),and then rhBNP 1 mg+5%Glucose injection 100 ml by 0.007 5 μg/(kg·min),ivgtt(d2-4). Treatment courses of 2 groups lasted for 7 d. Therapeutic efficacy and heart function indexes [left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVDd)] were observed in 2 groups as well as NT-proBNP level,medication fluid intake and urine volume 24 h after medication. The occurrence of ADR was observed. RESULTS:3 cases dropped out and 66 cases were included finally in doservation group. Total effective rate of AD-HF therapy in observation group (96.97%) was significantly higher than in control group (86.67%),with statistical significance (P<0.05). There was no statistical significance in LVEF,LVDd and NT-proBNP between 2 groups before treatment(P>0.05). Af-ter treatment,LVEF of 2 groups were increased significantly while LVDd were decreased significantly;LVEF of observation group [(42.3±3.6)%] was significantly higher than in control group[(37.9±3.3)%],while LVDd of observation group [(55.5± 3.6)%] was significantly lower than in control group[(61.3 ± 3.4)%]. NT-proBNP levels of 2 groups were decreased significant-ly,and the observation group [(1 389.5±29.6)pg/ml] was significantly lower than the control group [(2 778.0±26.8)pg/ml]. 24 h after medication,urine volume of 2 groups were significantly higher than medication fluid intake,and urine volume of observation group [(1 781.4 ± 89.7)ml] was significantly higher than that of control group [(1 372.6 ± 78.3)ml],with statistical significance (P<0.05). There was no statistical significance in the incidence of ADR between observation group (3.03%) and control group (5.00%),without statistical significance(P>0.05). CONCLUSIONS:rhBNP is significantly effective for ADHF,promotes heart function recovery and reduces renal function injury with good safety.
9.A new tale of p21 activated protein kinase in the heart:pathophysiology to drug discovery
Shoubao WANG ; Hoyee TSUI ; Wei LIU ; Ming LEI ; Xin WANG
Chinese Journal of Pharmacology and Toxicology 2014;(4):475-483
CardiovascuIar disease is the number one cause for morbidity and mortaIity worIdwide. Possi-biIities for new therapies in the emerging fieId of cardiac signaIIing prompted extensive research on myocardiaI re-modeIIing over the past decades. In this review,we as-sembIe an overview of the recent findings on the muIti-functionaI enzyme,p21-activated kinase 1( Pak1),a member of a serine/ threonine protein kinase famiIy in the heart,particuIarIy its cardiac protective effects. We pres-ent a modeI for Pak1 signaIing that provides a mecha-nism for specificaIIy affecting cardiac ceIIuIar processes. We discuss its cardiac protective effects such as anti-hy-pertrophy,anti-ischaemic injury and roIe in maintaining ventricuIar Ca2+ homeostasis and eIectrophysioIogicaI stabiIity under physioIogicaI, β-adrenergic and hyper-trophic stress conditions.We aIso discuss the potentiaIs of Pak1 activation by naturaIIy occurring sphingosine and its anaIogues FTY720,and bioactive peptides designed to diminish Pak1 auto-inhibition as noveI thera-peutics for major cardiovascuIar diseases.
10.Influencing factors analysis of hemorrhagic transformation in non-thrombolysis patients after acute cerebral infarction
Ge TAN ; Ming LIU ; Chunyan LEI ; Yanchao CHEN ; Zilong HAO
Chinese Journal of Cerebrovascular Diseases 2015;(8):409-414
Objective To investigate the influencing factors of hemorrhagic transformation in non-thrombolysis patients after acute cerebral infarction. Methods According to Chengdu Stroke Registry Project,2598 consecutive patients with acute cerebral infarction admitted to the Department of Neurology,West China Hospital within 1 week of attack from January 2010 to December 2013 were enrolled prospectively. The patients were divided into a hemorrhagic transformation group and a non-hemorrhagic transformation group according to whether they had hemorrhagic transformation or not. As for patients with hemorrhagic transformation,they were divided into a symptomatic hemorrhagic transformation (SHT)group and an asymptomatic hemorrhagic transformation (ASHT)group according to whether they had aggravation of symptom and sign. The baseline data of all patients were collected and compared between the groups. The P<0. 1 variables of the univariate analysis result were enrolled in multivariate logistic regression analysis in order to identify the independent influencing factor of hemorrhagic transformation. Results In 2598 patients,249 (9. 6%)had hemorrhagic transformation,28 of them (1. 1%)were SHT and 221 (8. 5%)were ASHT. There were significant differences in male,hypertension,dyslipidemia,atrial fibrillation,drinking and smoking ratio,blood glucose,cholesterol,low density lipoprotein cholesterol, National Institutes of Health Stroke Scale (NHISS)scores,and the trial of Org 1072 in acute stroke treatment (TOAST)classification between the HT group and the non-HT group (all P<0. 05). There were no significant difference in the related influencing factors between the SHT group and the ASHT group (all P>0. 05). The results of multivariate logistic regression analysis showed that dyslipidemia (OR,0. 588, 95%CI 0. 374-0. 924,P=0. 021)was negatively correlated with hemorrhagic transformation. Atrial fibrillation (OR,3. 188,95%CI 2. 159-4. 707,P<0. 001),blood glucose (OR,1. 081,95%CI 1. 044-1. 119,P<0.001),and NHISS score (OR,1. 305,95%CI 1. 170-1. 455,P<0. 001)were positively correlated with hemorrhagic transformation. In TOAST classification,relative to the large atherosclerotic stroke,the small artery occlusive cerebral infarction was negatively correlated with hemorrhagic transformation (OR,0. 315, 95%CI 0. 167-0. 596,P<0. 001). After removing the influencing factor of atrial fibrillation,compared with the large artery atherosclerotic stroke,cardioembolism stroke was positively correlated with hemorrhagic transformation (OR,2. 823,95%CI 1. 946-4. 095,P<0. 001). Conclusion Dyslipidemia,atrial fibrillation,blood glucose,NHISS score and TOAST classification were independently associated with hemorrhagic transformation in non-thrombolysis patients after acute cerebral infarction.