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.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.
6.Over-expression of signal transducer and activator of transcription 2 gene in the peripheral blood cells is correlated with active disease in patients with systemic lupus erythematosus
Jianping TANG ; Shuang YE ; Nan SHEN ; Yueying GU
Chinese Journal of Rheumatology 2010;14(1):30-32
Objective To investigate the expression of Signal transducer and activator of transcription 2 (STAT2) gene in the peripheral blood mononuclear cells of patients with systemic lupus erythematosus, and to evaluate the possible connections between STAT2 gene expression levels and clinical features. Methods One hundred and forty-four SLE patients, 27 non-SLE patients with other rheumatisms and 58 normal controls were recruited for this research, and the subjects were surveyed for clinical data collection. SYBR Green Dye based real-time quantitative PCR method was used to compare the expression levels of STAT2 in patients with SLE and those in the controls. The correlation of the gene expression levels and disease activity and specificity was studied. Results STAT2 expression levels (5.2±1.7) in SLE patients were remarkably higher than those in non-SLE patients and normal controls (4.3±1.1, 4.5±1.2, P<0.01 in both). The expression levels of STAT1 were increased in active SLE patients(5.2±1.5), comparing with those observed in inactive SLE patients (4.8±2.9, P<0.01), and expression levels of STAT1 in SLE patients were negatively correlated with C3 levels in sera (r=-0.449, P<0.01) whereas were positively correlated with SLEDAI-2K score and 24 hour urine protein (r=0.317, 0.309, P<0.01 in both). Conclusion Over-expression of STAT2 gene in the peripheral blood cells is linked with the pathogenesis of systemic lupus erythematosus, and the elevated expression level of STAT2 is correlated with SEE disease activity.
7.Clinical analysis of 272 patients with Kawasald disease
Yinghong ZENG ; Jianping TANG ; Lei SUN ; Ye SHU ; Zhu WEI
Chinese Journal of Dermatology 2009;42(4):234-236
Objective To investigate the clinical features of Kawasaki disease.Methods A retrospective analysis was performed in 272 children diagnosed as Kawasaki disease from 2002 to 2006.Clinical data,laboratory findings and auxiliary examination results were collected for these patients.Results The male-to-female ratio Was 2.58:1.Onset ages between 1 to 3 years accounted for 59.2%of patients.Of these patients,100%had a fever for more than 5 days,76.1%transient polymorphous exanthema,74.6% bilateral conjunctival hyperemia,47.8%flare and fissure on the oral lip,58.5%strawberry tongue,22.8% firm swelling of hands and feet as well as flushing of palms and soles,3 1.2%subacute desquamation at the junctional site between nail bed and skin,36%cervical lymphadenopathy.Laboratory findings showed a significant increase in the count of peripheral blood leukocytes and pefipheral blood platelets as well as erythrocyte sedimentation rate in 80.5%,87.5%and 96.2% of Patients,respectively.Additionally,81.6%of these patients were positive for C reactive protein and the frequency of coronary aaery involvement was 54.3%.All patients were treated with aspirin,and high-dose intravenous immunoglobulin was given to 258 patients.Fever relieved and the condition was controlled in all patients with an average hospitalization period of 8.9 days.Conclusions Kawasaki disease should be suspected in Patients with exanthematous lesions,fever lasting for more than 5 days and poor response to antibiotic therapy.Peripheral blood platelet count and cardiac ultrasound are of great value in the diagnosis of Kawasaki disease.Aspirin iS the first choice in treating Kawasaki disease,and adjunctive high-dose intravennous immunoglobulin treatment may facilitate the quick control offever.
8.Analysis of risk factors for perioperative acute cerebral vascular accident in the elderly
Jinglan ZHANG ; Qing YE ; Jianping SUN ; Zhuo ZHANG ; Jiakai LU
Chinese Journal of Geriatrics 2009;28(3):213-216
Objective To analyze the risk factors for perioperative acute cerebral vascular accident (PACVA) and put forward the corresponding preventive measures.Methods The clinical data of elderly patients in our hospital who suffered from PACVA in recent 5 years were retrospectively studied.The correlation between risk factors and the occurrence of PACVA was analyzed.Results One hundred and fifty cases were enrolled in the study.Seventy eight cases of them suffered from PACVA with the average age of 70 years ranging from 60 to 98 years.Fifty six cases(71.8%)were found PACVA in one week after operation.Multiple regression analysis showed that hypertension, history of cerebrovascular disease, unstable blood pressure and obesity were independent risk factors for PACVA.The newly diagnosed perioperative atrial fibrillation and carotid atheroselerosis were the high risk factors for PACVA.Conclusions PACVA is one of the common perioperative complications.Necessary check, monitor and treat measures should be taken in the perioperative period, especially for patients with risk factors.
9.Protective effects of Glutamine on intestinal mucosa barrier dysfunction following traumatic brain injury in rats
Ming LI ; Chuahua HANG ; Jixing SHI ; Huaiyi ZHANG ; Jianping YE
Chinese Journal of Trauma 2008;24(8):624-627
Objective To observe the effect of Glutsmine on intestinal barrier function after traumatic brain injury in rats. Methods A total of 54 adult male Wistar rats were divided randomly into 3 groups, ie, normal group (Group N, 6 rats), TBI group (Group T, 24 rats) and Giutamine intervention group (Group G, 24 rats). Group T and Group G were subdivided into 4 groups according to detection time at days 1,3, 5 and 7 respectively. Meanwhile, 6 rats were enlisted in each group. The intestinal mucosa structure was detected by histopathological examination and electron microscopy. Apoptosis was detected by in situ immunohistochemical staining (TUNEL). Results Glutamine could relieve the pathological lesion of gut mucosa and decrease intestinal mucosa cell apoptosis after traumatic brain injury. Conclusion Glutamine can protect intestinal mucosa barrier function following traumatic brain injury.
10.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