1.Challenges in Drug Discovery for Thiazolidinedione Substitute.
Acta Pharmaceutica Sinica 2011;1(3):137-142
Thiazolidinedione (TZD) is a powerful insulin sensitizer in the treatment of type 2 diabetes. It acts as a ligand to the nuclear receptor PPARγ (peroxisome proliferator-activated receptor-gamma) and induces transcription of PPARγ responsive genes. TZD controls lipid synthesis and storage in adipose tissue, liver and many other tissues through PPARγ. Derivatives of TZD, such as rosiglitazone (Avandia) and pioglitazone (Actos), are more powerful than metformin or berberine in insulin sensitization. Although they have common side effects such as weight gain and edema, these did not influence the side effects in general. However, recent findings of risk for congestive heart failure and bladder cancer have indeed significantly impaired their future in many countries. European countries have prohibited those drugs and in 2011, US will terminate application of rosiglitazone in clinics and hospitals. The multiple country actions may mark the end of TZD era. As a result, there is a strong demand for identification of TZD substitute in the treatment of type 2 diabetes. In this regard, literature about PPARγ ligands and potential TZD substitute are reviewed in this article. Histone deacetylase (HDAC) inhibitor is emphasized as a new class of insulin sensitizer here. Regulators of SIRT1, CREB, NO, p38, ERK and Cdk5 are discussed in the activation of PPARγ.
2.THE NON-AUDITORIAL AFFERENTS OF THE INFERIOR COLLICULUS IN THE RAT——WGA-HRP METHOD
Acta Anatomica Sinica 1954;0(02):-
WGA-HRP was injected into the inferior colliculus in the rat in order to study the non-auditorial afferents of the inferior colliculus. In the diencephalon and truncus encephali, retrograde labeling was observed in many non-auditorial regions: bilateral (with contralateral predominance) cuneate nucleus, gracile nucleus, nucleus of spinal tract of trigeminal nerve, nucleus medullae oblongatae centralis dorsalis; bilateral (with homolateral predominance) locus ceruleus, nucleus reticularis pontis oralis, laterodorsal tegmental nucleus, substantia nigra, sub-parafascicular nucleus, perifornical nucleus; bilateral medial parabrachial nucleus, deep tegmental nucleus of midbrain, lateral hypothalamic area; homolateral deep layer of superior colliculus, zona incerta; contralateral nucleus of solitary tract; and posteromedian septum, central tegmental nucleus, dorsal nucleus of the raphe. The afferent neurons from cuneate nucleus, gracile nucleus, nucleus of spinal tract of trigeminal nerve, nucleus of solitary tract mainly located below the level of obex. The results mentioned above suggested that the inferior colliculus is not only an auditorial relay nucleus, but also a complex body which is of different functions.
3.Clinical efficacy and safety of oxymatrine auxiliary treatment for hepatitis B viral hepatitis related primary liver cancer
Yanju YE ; Jianping YU ; Jun YE
Chinese Journal of Primary Medicine and Pharmacy 2016;23(5):653-656,657
Objective To study the clinical efficacy and safety of oxymatrine in auxiliary treatment of hepati-tis B virus(HBV) related primary hepatocellular carcinoma (PHC).Methods 345 patients were divided into treat-ment group (174 cases) and control group (171 cases).The control group was given hepatic artery chemoemboliza-tion therapy.The treatment group added with oxymatrine.The near future curative effect of solid tumor and patients'immune function,liver function,the improvement of the quality of life change,and adverse reaction were observed. Results KPS score of the treatment group was better(Z =-3.296,P <0.05),more significant in the near future curative effect of solid tumor (χ2 =4.676,P <0.01).The immune function of the treatment group was significantly improved [ Within group: t(treatment group:CD3) = 2.544, t(treatment group:CD4) =2.446, t(treatment group:CD8) = 2.745, t(treatment group:CD4 /CD8) =2.873,t(treatment group:NK) =2.542,t(control group:CD3) =2.614,t(control group:CD4) =2.337,t(control group:CD8) =2.545,t(control group:CD4 /CD8) =2.336, t(control group:NK) =2.672, P <0.05; Between groups: t(after treatment:CD3) =2.947, t(after treatment:CD4) =2.846,t(after treatment:CD8) =2.943,t(after treatment:CD4 /CD8) =2.879,t(after treatment:NK) =2.798,P <0.01].In the treatment group,the effect was more significant in the improvement of ALT,HBV -DNA,AFP[Within group:t(treatment group:ALT) =2.676,t(treatment group:HBV -DNA) =2.682,t(treatment group:AFP) =2.611,P <0.01,t(control group:ALT) =2.556, t(control group:AFP) =2.523,P <0.05,t(control group:HBV -DNA) =1.216,P >0.05;Between groups:t(after treatment:ALT) =2.417, t(after treatment:AFP) =2.432,P <0.05,t(after treatment:HBV -DNA) =2.674,P <0.01].Two groups appeared adverse reaction after chemotherapy,digestive system and hematopoietic system anomaly,the incidence rates of adverse events in the treatment group were lower than those in the control group (χ2 2 2 white blood cel s decreased =46.969,χthe pain =46.977,χheating =22.499,χ2nausea,vomiting =88.749,P <0.05).Conclusion The oxymatrine auxiliary treatment for HBV related PHC has curative effect,safe and reliable,and can significantly improve the patients quality of life,it is worth promoting.
4.Postoperative nursing of 41 patients with Arnold-Chiari malformation and syringomyelia
Ping SONG ; Yongli YE ; Jianping MIAO
Chinese Journal of Nursing 2010;45(4):300-301
This paper reports the post-operative care of 41 patients with Chiari malformation associated with syringomyelia. The nursing points included postoperative vital signs monitoring,management of the body posture and incision,observation of complications. Among these patients,21 of them had cerebrospinal fluid leakage,3 of them had cranial nerve palsy,a patient suffered from acute respiratory arrest caused by brainstem edema. Patients recovered and discharged after active appropriate treatment and care.
5.Langerhans cell histiocytosis: clinical analysis of 126 cases
Ye SHU ; Yinghong ZENG ; Bin ZHOU ; Weijian CHEN ; Jianping TANG
Chinese Journal of Dermatology 2013;(4):273-275
Objective To analyze lesional and clinical characteristics of Langerhans cell histiocytosis in children.Methods A clinical retrospective study was performed on 126 patients with Langerhans cell histiocytosis collected from 2006 to 2011 at the Hunan Children's Hospital.Results Of the 126 patients,the youngest was 2months old,and the oldest was 9 years old.The ratio of male to female was 2.5 ∶ 1.Clinical manifestations included eczematid,seborrheic lesions,hemorrhagic maculopapules,yellow nodules and white macules.Of the three clinical phenotypes of Langerhans cell histiocytosis,Letter-Siwe disease was the most prevalent,and most cases of LetterSiwe disease were associated with hepatosplenomegaly,abnormal chest X-ray,impaired hematopoietic function and multifocal bone injuries.The clinical grade was mainly Ⅲ and Ⅳ in patients with Letter-Siwe disease,Ⅰ in patients with eosinophilic granuloma,and varied from Ⅰ to Ⅳ in patients with Hand-Schuller-Christian disease with Ⅱ as the most common.Of these patients,those with eosinophilic granuloma had the oldest average age with bone as the only affected organ,while those with Letter-Siwe disease had the youngest average age with the greatest number of affected organs.The treatment of Langerhans cell histiocytosis included surgical operation and combined chemotherapy.Conclusions Langerhans cell histiocytosis has characteristic skin lesions and diverse clinical manifestations.Pathology has diagnostic significance to Langerhans cell histiocytosis.Therapy strategies and curative effects are dependent on the severity of,and the organs affected by Langerhans cell histiocytosis.
6.Relationship between infarct location and prognosis after emergency percutaneous coronary intervention in patients with acute myocardial infarction
Guohong YE ; Xiangjun YANG ; Jianping SONG ; Tingbo JIANG ; Xun LI
Chinese Journal of Postgraduates of Medicine 2008;31(10):37-40
Objective To investigate the relationship between infarct location and prognosis after emergency percutaneous coronary intervention (PCI) treatment in patients with acute myocardial infarction.Methods Consecutive 121 patients with ST elevation myocardial infarction (STEMI) who underwent primary PCI were divided into 3 groups according to the infarct location.Their clinical,ECG,echocardiography and coronary angiography features were analyzed,and the follow-up was made. Results Compared with inferior wall infarction group and inferior wall infarction combined with right ventricular infarction group,anterior wall myocardial infarction group had higher CPK-MB and cTnT,less frequent collateral,reduced ST-segment resolution,higher mortality rates in hospitalization and one year after discharge.On the other hand,inferior infarction combined with right ventricular infarction group had more occurrences of shock and atrial vetricular block or ventricular arrhythmia,more incidence of multivessel disease and thrombus,and higher readmission rate.Conclusion Patients with anterior wall myocardial infarction and inferior wall in
7.Cervical pedicle screw fixation for cervical spinal cord injury without fracture and dislocation
Jianping KANG ; Song WANG ; Jun LI ; Fei YE ; Daxiong FENG
Chinese Journal of Trauma 2012;28(7):620-623
Objective To summarize the efficacy of cervical pedicle screw fixation in the treatment of cervical spinal cord injury without fracture and dislocation.Methods From September 2007 to March 2010,21 patients with cervical spinal cord injury without fracture and dislocation combined with developmental cervical stenosis were managed by pedicle screw fixation in unstable segments,and then single open-door laminoplasty in stenosis segments.The clinical outcomes were reviewed and summarized.Results All the patients received follow-up of 1-3 years.Two patients had superficial wound infection,which was cured by dressing change.One presented intra-incisional hematoma one week post-operatively and was cured by hemostasis and drainage.One had door-reclosing without symptom aggravation.There was neither perforation of pedicle screws nor breakage,loosening or displacement of internal fixation.The curvature of cervical lordosis at follow-up had significant rectification in comparison with that at preoperation,but showed unobvious change as compared with that immediately after operation.According to the modified Japanese Orthopedic Association (JOA) score,the neurological score improved from preoperative 4-15 points to 9-17 points at the final follow-up,which revealed more than 80% of recovery in 13 patients,50% -80% of recovery in six and 5% -50% of recovery in two,with the average recovery rate of 75%.Conclusion For unstable segments in patients with cervical spinal cord injury without fracture and dislocation combined with developmental spinal stenosis,posterior pedicle screw fixation can avoid the risk of further spinal cord injury in single open-door laminoplasty and restore the physiological curvature of cervical vertebrae,which provides solid foundation for backward drift of spinal cord and creates favorable condition for recovery of spinal cord function.
8.Analysis of glucocorticoid receptor gene polymorphisms by denaturing high-performance liquid chromatography
Jianwei YE ; Jie DING ; Yan CHEN ; Jianping HUANG ; Jiyun YANG
Journal of Peking University(Health Sciences) 2003;0(04):-
G) was relatively rare. Conclusion: DHPLC is a rapid and reliable method for polymorphism screening. Eight polymorphisms in the NR3C1 gene are detected in Chinese population with the technique of DHPLC , of which two haplotypes have been identified for the first time.
9.Promotion of axonal regeneration of DRG neurons with combined use of Y27632 and TDZD-8
Daxiong FENG ; Yize HUANG ; Jun LI ; Fei YE ; Jianping KANG
Chinese Journal of Trauma 2011;27(6):522-529
Objective To explore the effect on effect of combined use of Y27632 (ROCK II inhibitor)and TDZD-8(GSK-3β inhibitor)on axonal regeneration of dorsal root ganglion (DRG) neurons in neogenetic rats. Methods All the thoracolumbar DRGs of two neogenetic Sprague-Dawley (SD)rats(<5 days)were harvested under the stereopsis raicrostat,and then the DRG neurons were cultured,purified and indentified.Fifteen adult female SD rats were randomly divided into three groups,ie,complete paraplegia group(5 rats),sham operation control group(5 rats)and normal group(5 rats)respectively.The T8-10 spinal cord extracts (SCEs) were harvested in the complete paraplegia group,sham operation control group and normal group respectively at day 7 after spinal cord injury.The experiment was divided into group A(DRG neurons + PBS),group B(DRG neurons + complete paralysis SCE),group C(DRG neurons + complete paralysis SCE + different concentration Y27632),group D(DRG neurons + complete paralysis SCE + different concentration TDZD-8)and group E(DRG neurons + complete paralysis SCE + proper concentration Y27632 and TDZD-8).The average axonal length and expression intensity of Tubulin βⅢ at distal end of neuronal axons were observed after two days of co-culture respectively in intro. Results (1)The average axonal length and expression intensity of Tubulin βⅢ at axon shaft and growth cone in the group B were significantly shorter and weaker than that in the group A,with statistical difference.(2)In the group C,the average axonal length and expression intensity of Tubulln βⅢ at axon shaft and growth cone in 5-10 μmol/L Y27632 treatment groups were more than that in the group B but lower than that in the group A.The average axonal length and expression intensity of Tubuhn βⅢ at axon shaft and growth cone in 20-50 μmol/L Y27632 treatment group were longer and stronger than that in the group A and the group B,especially the group B.Among different concentration Y27632 treatment groups,there was a longest average axonal length and strongest expression intensity of Tubulin βⅢ in 30 μmol/L treatment group.(3) In the group D,there was a longer average axonal length in 0.5-3 μmol/L TDZD-8 treatment group than that in the group A and the group B,with the longeat average axonal length in l μmool/L TDZD-8 treatment group.In 5-25 μmol/L TDZD-8 treatment groups,the average axonal length showed no difference compared with the group B but wns shorter than that in the group A.In all different concentration TDZD-8 treatment groups,the expression intensity of Tubulin βⅢ at axon shaft and growth cone was significantly stronger than that in the groups A and B.(4) In the group E,although the average axonal length was increased in the group E,there was no statisilcal difference compared with the group A,30 μmol/L Y27632 treatment group and l μmol/L TDZD-8treatment group.There was a significantly longer average axonal length in the group E than it in the group B and the expression intensity of Tubulin βⅢ at axon shaft and growth cone was stronger in the group E compared to the group A,30 μmol/L Y27632 treatment group and l μmol/L TDZD-8 treatment group.Conclusion The complete paralysis SCEs obviously inhibits DRG axonal growth,induces axonal retraction and growth cone collapse.High concentration of Y27632 can more obviously promote the axon growth compared with the low concentration,while the low concentration of TDZD-8 can obviously promote the axon growth.Combined use of appropriate concentration of TDZD-8 and Y27632 can promote the axon growth and induce the axons branching,as facilitates the formation of the axon circuit.
10.Treatment of 15 patients with open spinal cord injury
Jianping KANG ; Jun LI ; Fei YE ; Daxiong FENG
Chinese Journal of Trauma 2010;26(6):528-530
Objective To study the clinical feature, diagnossis and therapy of open spinal cord injury. Methods A retrospective study was performed in 15 patients with open spinal cord injury including 14 males and one female, at age range of 15-46 years (mean 23 years). There were two patients with open cervical spinal cord injury, 11 with open thoracic spinal cord injury and two with open lumbar spinal cord injury. Injury causes included sharp knife injury in 12 patients, firearm injury in two and stick stabbing in one. According to ASIA scale, there was one patient at Grade A, two at Grade B, seven at Grade C, four at Grade D and one at Grade E preoperatively. Foreign bodies were found in the wound in four patients. There were three patients combined with spinous process fracture, eight with vertebral plate fracture and five with vertebral body fractures. All 15 patients were treated by emergency management including vertical canal exploration, hematoma debridement or foreign body removal. Results Postoperative complications included cerebrospinal fluid leakage in two patients and wound infection ( without spinal cord infection) in one. There were different degrees of neural functional recovery in five patients. The post-operation ASIA scale: one patient at Grade A, three at Grade C, 10 at Grade D and one at Grade E,with no patient at Grade B. Conclusions For open spinal cord injury, emergency operation is necessary under adequate preoperative preparation. Preoperative identification of foreign bodies, exploration and decompression are beneficial to spinal cord function recovery and reduction of the incidence rate of postoperative complications like infection or hemorrhage.