2.Mechanism of MCP-1-JAK2/STAT3 signal transduction in spinal cord dorsal horn contributing to rats with type 2 diabetic neuropathic pain
Chao YUAN ; Jinchuan GUAN ; Hong CHAO ; Jun LI
Chinese Journal of Pathophysiology 2015;(8):1467-1471
AIM:ToexplorewhetherMCP-1-JAK2/STAT3signaltransductioninthespinaldorsalhornin-volves the formation and development of rat type 2 diabetic neuropathic pain (DNP).METHODS: The male Sprague-Dawley rats were fed with a high-fat and fructose diet for 8 weeks,and then received a single intraperitoneal streptozocin in-jection to prepare the type 2 DNP model.The type 2 DNP rats were randomly divided into 4 groups (n=16):DNP group, MCP-1 neutralizing (DM) group, DNP+AG490 (DA) group and solvent control (SC) group.A catheter of PE-10 was placed into the subarachnoid space of the rats in groups DM , DA and SC.After 3 d, the rats in DM,DA and SC groups were injected with MCP-1 inhibitor 10μL at 0.1 mg/L, AG490 10μL at 1 mmol/L and DMSO 10μL at 3.5%once a day for 14 days, respectively.Another 16 normal rats were selected as control (C) group and were fed with common forage. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured at 1, 3, 7 and 14 d after subarachnoid injection .The lumbar segments 4-6 of the spinal cord were removed at the same time for determination of the expressions of p-JAK2 and p-STAT3 by Western blot .RESULTS:Compared with C group , MWT was significantly de-creased, TWL was shortened and the expression of p-JAK2 and p-STAT3 in the spinal dorsal horn was up-regulated at 1, 3, 7 and 14 d in DNP and SC groups (P<0.05).Compared with DNP group, MWT was significantly increased, TWL was prolonged and the expression of p-JAK2 and p-STAT3 in spinal dorsal horn was down-regulated at 1, 3, 7 and 14 d in DM and DA groups (P<0.05).No significant difference in the MWT, TWL and expression of p-JAK2 and p-STAT3 between DNP group and SC group was observed (P>0.05).CONCLUSION:The MCP-1-JAK2/STAT3 signal transduction in the spinal dorsal horn involves the formation and development of DNP in rats .
3.Wnt/β-catenin signal pathway mediated Salidroside induced directional differentiation from mouse mesenchymal stem cells to nerve cells.
Chao GUO ; Run LIU ; Hong-Bin ZHAO ; Guan-Hua QIN
Chinese Journal of Integrated Traditional and Western Medicine 2015;35(3):349-354
OBJECTIVETo explore the molecule mechanism of Salidroside inducing directional differentiation of mouse mesenchymal stem cells (MSCs) into neuronal cells.
METHODSThe mouse multipotent mesenchymal precursor cell line (D1) was taken as the objective. Cultured MSCs were divided into the negative control group (complete culture solution), the positive control group (containing 1 mmol/L β-mercaptoethanol), the Salidroside induced group (20 mg/L Salidroside), and the blocked group (20 ng/ ml DKK1, a special inhibitor of Wnt/β-catenin signal pathway). All cells were inoculated in a 6-well plate (1 x 10(4) cells/cm2) and grouped for 24 h. The expression of p-catenin was detected by fluorescence Immunochemistry in the negative control group, the positive control group, and the Salidroside induced group. The expression of neuron-specific enolase (NSE), beta 3 class III tubulin (β-tubulin III), nuclear receptor related factor 1 (Nurr1), glial fibrillary acidic protein (GFAP) mRNA, Wnt3a, β-catenin, low-density lipoprotein receptor-related protein6 (LRP6), Axin mRNA were detected using reverse transcrip- tion PCR (RT-PCR). The expression of β-catenin and NSE protein were analyzed by Western blot in the negative control group, the positive control group, and the Salidroside induced group. Ca2+ chelating agents (EGTA), L-type Ca2+ channel blocker (Nifedpine), and IP3Ks special inhibitor (LY294002) were used to block Ca2+ signal pathway respectively. The expression of Wnt3a, LRP-6, Axin, glycogen syn- thase kinase (GSK-3), and β-catenin mRNA were detected by RT-PCR. The β-catenin protein expression was analyzed using Western blot.
RESULTSCompared with the positive control group, β-catenin protein was strong positively expressed; the expression of Wnt3a, β-catenin, LRP6, Axin, NSE, β-tubulin III, Nurr1 mRNA, and NSE protein were obviously up-regulated in the Salidroside induced group (P < 0.01). Compared with the positive control group and the Salidroside induced group, β-catenin, NSE, Nurr1, and β-tubulin III mRNA expression decreased; β-catenin and NSE protein expression were also down-regulated in the blocked group (P < 0.01). Compared with the Salidroside induced group, the expression of Wnt3a, LRP-6, β-catenin, and Axin mRNA were down-regulated in the Ca2+ signal blocked group and the salidroside induced group (P < 0.01, P < 0.05).
CONCLUSIONSalidroside affected directional differentia- tion of MSCs into neuronal cells through Wnt/β-catenin and Ca2+ signal pathway.
Animals ; Cell Differentiation ; drug effects ; Glucosides ; pharmacology ; Glycogen Synthase Kinase 3 ; Lipoproteins, LDL ; Low Density Lipoprotein Receptor-Related Protein-6 ; Mesenchymal Stromal Cells ; physiology ; Mice ; Neurons ; Phenols ; pharmacology ; Phosphopyruvate Hydratase ; RNA, Messenger ; Signal Transduction ; Wnt Signaling Pathway ; physiology ; beta Catenin ; metabolism
4.Harm of drug abuse ( drug driving ) on traffic safety in China
Guiyong CHEN ; Chao ZHANG ; Yiliang GUAN ; Wenjun LI ; Jihong ZHOU
Chinese Journal of Trauma 2012;28(1):8-11
Objective To investigate the harm of drug abuse of drivers on traffic safety and discuss the countermeasures.Methods Data were collected from sources including statistics of drug driving traffic accidents reported by mass media,inference analysis of the theoretical data,survey of outpatients in drug rehabilitation center,drug-related screening with drivers license during Shanghai World Expo 2010 Moat Security and integrated data from various areas.ResultsOf the over 10 million drug abusers including the registered and unregistered in China,more than 2 million drug abusers had drivers license,which greatly threatened the traffic safety.Conclusion Drug abuse (drug driving) has done great harm on traffic safety,which calls for appropriate preventive countermeasures.
5.Serum levels of growth differentiation factor-15 in patients with acute exacerbation of chronic heart failure and its prognostic significance
Jingshu GUAN ; Yun ZHOU ; Zhijing MIAO ; Chao ZHANG ; Shanlan SHI
Journal of Chinese Physician 2016;18(5):680-683,687
Objective To explore the serum levels of growth differentiation factor-15 (GDF-15) in patients with acute exacerbation of chronic heart failure (CHF) and its correlation with other common indexes,to provide reference for its clinical diagnosis,treatment and prognosis.Methods Two hundred patients with acute exacerbation of CHF were selected as CHF group,and 100 matched healthy volunteers were selected as control group.Serum levels of GDF-15 and N-terminal pronatriuretic peptide (NT-proBNP) were detected,and left ventricular end diastolic diameter (LVESD),left ventricular end diastolic diameter (LVEDD),and left ventricular ejection fraction (LVEF) were measured by echocardiography within 2 hours after admitted to hospital,and after the symptoms improved of CHF group,and on health examination day of control group.Patients in CHF group were followed up to record CHF related adverse events.Correlations between GDF-15 and other indicators were analyzed by Spearman correlation analysis,and the clinical value of serum GDF-15 on diagnosing CHF was analyzed by the receiver operating characteristic curve (ROC) and the area under the curve (AUC).Results The serum levels of GDF-15 and NT-proBNP in each time-point of CHF group were all higher than those of control group (t =4.70 ~ 7.11,P < 0.05 orP < 0.01).The serum levels of GDF-15 and NT-proBNP had negative correlation with LVEF (r =-0.539,-0.572,P < 0.01),and had positive correlation with LVESD,LVEDD,and NYHA cardiac functional grading (r =0.505 ~ 0.861,P < 0.01).Serum GDF-15 had positive correlation with serum NT-proBNP (r =0.528,P <0.01).With the increase of serum GDF-15 level,CHF group's readmission (rate) and death (rate) were both increased (x2 =36.86,26.59,P <0.01).AUC of predicting readmission risk by serum GDF-15 was 0.822 (95% CI:0.719 ~0.890,P <0.01),and the best predictive cutoff point was 2 876.30 ng/L (sensitivity was 91.86%,specificity was 73.27%).AUC of predicting mortality risk was 0.816 (95% CI:0.715 ~ 0.885,P < 0.01),and the best predictive cutoff point was 3 487.05 ng/L (sensitivity was 91.72%,specificity was 69.05%).Conclusions Serum GDF-15 level in patients with acute exacerbation of CHF is higher,decreases with symptoms improvement,has positive correlation with LVESD,LVEDD,and NYHA cardiac functional grading,and has negative correlation with LVEF,has higher sensitivity on predicting CHF-related adverse events,and the mechanism may be related to the activation of SMAD pathway.Therefore,it may be a promising biomarker for clinical diagnosis and prognosis of cardiovascular diseases.
7.Anatomic study of single-nostril transsphenoidal approach for pituitary adenoma
Guan-Min HUANG ; Chao-Shi NIU ; Xian-Ming FU ;
Chinese Journal of Microsurgery 2006;0(06):-
Objective To provide the anatomical data for single-nostril transsphenoidal microsurgery for pituitary adenoma.Methods Microanatomic structures were observed and measured in 20 cadaveric a- dults heads.Results(1)The diaphragmal opering was 5 mm or greater broad in 90%.The mean thick- ness of the diaphragma sellae was (0.18?0.08)mm.(2) A sphenoid sinus with complete pneumatization was named as all-sellae type,its percentage in all specimens was 85%,85% sphenoid sinus had middle sep- tum of which only 18.8% located in the medial sagital section.(3)The meant thickness of the sellar floor was (0.81?0.34) mm,70% of which were not more than 1 mm.Of the sellar floors,that the shape was flatness reach 15%.(4) The relationship between ICA and sphenoid sinus had two aspects,one was to be mutually apart (55%),the other was to communicate (45%),which formers carinae on the lateral wall of the sphe- noid sinus,espeially in the superior surface of posterior part.The relationship between optic nerve and sphe- noid sinus,one was to be mutually apart (27.5%),the other was to communicate (72.5% ),which formers carinae on the lateral wall of the sphenoid sinus,especially in the superior surface of anterior part.(5) Three main types of the intercavernous sinus were the anterior intercavernous sinus,present in 80%,the inferior in- tercavenous sinus (25%),and the posterior intercavenous sinus (15%).Conclusion The knowledge of the anatomy of the sellar region and sphenoid sinus is helpful to safe operation in the single-nostril transsphe- noidal approach for pituitary,adenoma microsurgery.
8.Clinical observation of the patients with malignant coelom effusion treated with pseudomonas aeruginosa injection combined with ulinastatin by body cavity injection
Guangzhi WAN ; Jingzhi GUAN ; Penghui LIU ; Wenhua ZHU ; Chao PAN
Cancer Research and Clinic 2014;26(1):17-19
Objective To evaluate the effect and safety of pseudomonas aeruginosa injection (PA-MSHA) combined with ulinastatin (UTI) injection in the treatment of patients with malignant pleural effusion and/or ascites.Methods 52 patients were randomly divided into PA-MSHA group and PA-MSHA combined with UTI group,each group including 26 patients.All patients were given ultrasonic testing before treatment.The single drug group was given PA-MSHA 10 ml intrapleural and/or intraperitoneal injection.The two-drug combination group was given PA-MSHA 10ml and UTI 300 000 U,twice per week.Evaluation of the efficacy and adverse reaction was performed after 4 times.Results The effective rate of single PA-MSHA group was 34.6 % (CR 1 case,PR 8 cases),while the effective rate of PA-MSHA combined with UTI group was 61.5 % (CR 2 cases,PR 14 cases).The effective rate of PA-MSHA combined with UTI group was statistically higher than that of single PA-MSHA group (P < 0.05).8 cases got fever in single PA-MSHA group,3 cases in PA-MSHA combined with UTI group got fever,side effect had no statistical significance (P > 0.05).Conclusion PA-MSHA combined with UTI has better effect in the treatment of patients with malignant pleural effusion and/or ascites compared with single PA-MSHA,and both treatments have low side effects.
9.Aggrecanases and osteoarthritis
Chao LI ; Yongping CAO ; Zhenpeng GUAN ; Deyong HUANG ; Zigang GE
Journal of Peking University(Health Sciences) 2003;0(05):-
Osteoarthritis is mainly caused by the degenerative changes of cartilage and cartilage extracellular matrix,while Aggrecanases degradate Proteoglycans which are the major components of cartilage.This review includes three aspects:(1) We have concluded the major enzymes(ADAMTS-4 and ADAMTS-5) which regulate the metabolism of cartilage extracellular matrix.Meanwhile,we have summarized the structure of aggrecanases(ADAMTS-4 and ADAMTS-5) and introduced the function of each regional structure;(2) We have concluded the way cytokines and glycosaminoglycans regulate the metabolism of aggrecanases,and discussed the regulation and control principle of cytokines and glycosaminoglycan;(3) We have summarized the majority of inhibitors to the aggrecanases,introduced the endogenic inhibitors,and put our emphasis on the extrinsic inhibitors(chelating agents,polypeptides and so on).Through deeper research on the enzymes,it will help us further understand the pathogenesis of osteoarthritis,and open up new avenues to clinical treatment.Abstract:SUMM ARY Osteoarthritis is mainly caused by the degenerative changes of cartilage and cartilage extra-cellular matrix,while Aggrecanases degradate Proteoglycanswhich are the major components of cartilage.This review includes three aspects:(1) W e have concluded the major enzymes(ADAMTS-4 and ADAMTS-5) which regulate the metabolism of cartilage extracellular matrix.Meanwhile,we have sum-marized the structure of aggrecanases(ADAMTS-4 and ADAMTS-5) and introduced the function of each regional structure;(2) W e have concluded the way cytokines and glycosam inoglycans regulate the metab-olism of aggrecanases,and d iscussed the regulation and control principle of cytokines and glycosam inogly-can;(3) W e have summarized the majority of inhibitors to the aggrecanases,introduced the endogenic inhibitors,and put our emphasis on the extrinsic inhibitors(chelating agents,polypeptides and so on).Through deeper research on the enzymes,it will help us further understand the pathogenesis of osteoar-thritis,and open up new avenues to clinical treatment.
10.Frequency and prognosis of extracapsular spread in neck metastasis in supraglottic carcinomas
Bin LIU ; Wenyue JI ; Chao GUAN ; Zimin PAN
Chinese Archives of Otolaryngology-Head and Neck Surgery 2006;0(11):-
OBJECTIVE To study the frequencyof extracapsular spread (ECS) in neck metastasis and its impact on prognosis in supraglottic carcinoma. METHODS A total of 177 patients with radical or modified neck dissection between Jan. 1994 and Dec. 1997 for supraglottic carcinoma were summarized. Transparent lymph node detection and a series of sectioning method were applied on all neck dissection specimens. The SPSS software package (version 11.5) was used to make statistical analysis. Survival curves were calculated with the Kaplan-Meier model. Impact of extracapsular spread on prognosis was assessed for significance with the Log-Rank test. RESULTS Eighty one patients were pathologically positive in neck specimens and the neck metastatic rate was 45.8 %. ECS was found in 32 cases and the ECS frequency was 39.5 % (32/81). The ECS was related with pathological N stage and the number of positive nodes. Patients with ECS had a higher possibility of regional recurrence and contralateral metastasis. The 5-year survival rates of patients with neck metastasis ECS- and patients with ECS+ were 61.9 % and 22.2 % respectively. The differences had statistically significance. CONCLUSION ECS in neck metastasis affects the prognosis in patients with supraglottic carcinoma. If bilateral neck dissection was not selected simultaneously, close follow-up on contralateral neck should be selected in patients with ECS because of a higher incidence of contralateral neck metastasis.