2.Model rats with membranous nephropathy induced by cationic bovine serum albumin:expressions of related proteins in podocytes
Jing LIANG ; Yuan ZHANG ; Yurong ZHAO ; Xianglong MENG ; Li WANG
Chinese Journal of Tissue Engineering Research 2016;20(40):6028-6033
BACKGROUND:Establishing the animal model of membranous nephropathy is of importance to figure out the pathogenesis of membranous nephropathy.
OBJECTIVE:To investigate the expression of nephrin and podocin in the model of membrane nephropathy in rats, and to investigate their relationships with the pathogenesis of membranous nephropathy.
METHODS:A total of 40 Sprague-Dawley rats were equivalently randomized into model and control groups. Rats in the model group were in premunity by given subcutaneous and multi-point injection of 1 mg cationic bovine serum albumin firstly dissolved in 0.5 mL normal saline and then ful y emulsified with the equal incomplete Freund’s adjuvant for 1 week, and 16 mg/kg cationic bovine serum albumin was injected via vein tails, once every other day for 4 weeks. The same volume of normal saline was injected into the controls. The mRNA expressions of nephrin and podocin in renal tissues were detected using real-time PCR, and biochemical indicators and morphological observation were measured at 2 and 4 weeks after modeling.
RESULTS AND CONCLUSION:(1) In the model group, the total amount of urine and serum albumin levels were significantly decreased accompanying with overt proteinuria, and the serum creatinine, urea nitrogen, cholesterol and triglyceride levels were significantly increased al in a time-independent manner compared with the control group (P<0.01), and the difference was significant (P<0.05). (2) The pathological examination showed that rats in the model group had different degrees of renal tubular dilatation, glomerular basement membrane thickening, mesangial cel s and stromal hyperplasia, which was typical of membranous nephritis. (3) Moreover, the mRNA expressions of podocin and nephrin in the model group were lower than those in the control group. (4) In conclusion, the decreased expressions of podocin and nephfin may disturb the integrity of the slit membrane of podocytes giving rise to the damage of glomerular filtration barrier, and proteinuria appears in final.
3.Effect of fibrinolytic system on the podocyte injury in rats with membranous nephropathy
Jing LIANG ; Yuan ZHANG ; Ling CAO ; Xianglong MENG ; Li WANG
Acta Laboratorium Animalis Scientia Sinica 2016;24(3):283-287
Objective To observe the expression of uPA, tPA and PAI-1 in whole blood of rat membranous ne-phropathy ( MN) models induced by cationic bovine serum albumin ( C-BSA) , and to explore the effect of fibrinolytic sys-tem on podocyte apoptosis and pathological changes. To explore the possible preventive and therapeutic effects and the pos-sible mechanisms of early prevention of fibrinolysis. Methods We developed a MN model with the modified Border meth-od. At the end of the 1st, 2nd, 3th, and 4th week of immunization, respectively, the levels of whole blood uPA, tPA and PAI-1 were determined by ELISA. The rat kidney tissues were examined by light microscopy and electron microscopy to i-dentify the pathological changes. The expression levels of nephrin and WTl were detected with immumofluorescence staining and their correlation was analyzed. Results Compared the treatment group with control group, the levels of whole blood uPA, tPA and PAI-1 of the model group were decreased, while PAI-1 was elevated, showing a significant difference ( P<0. 05). The degree of renal interstitial fibrosis was more serious. Correlation analysis showed that the whole blood tPA and uPA levels were positively correlated with the changes of nephrin protein expression in the kidney tissue, while the whole blood PAI-1 level was negatively correlated with the nephrin protein expression in the kidney tissue. Conclusions In the process of MN development, the fibrinolytic system may have important significance for podocyte apoptosis. Determination of early phase of MN podocyte injury may be another therapy target for prevention of the disease development, and then pro-vide new ideas for clinical research and drug development for MN.
4.Clinical Observation of the Application of Alprostadil Combined with Papaverine in Uremic Hemodialysis Patients after Initial Arteriovenous Fistula
Jing LIANG ; Yuan ZHANG ; Xianglong MENG ; Li WANG
China Pharmacy 2017;28(8):1069-1071
OBJECTIVE:To observe the effects of alprostadil combined with papaverine on blood coagulation indexes and complications in uremic hemodialysis patients after initial arteriovenous fistula.METHODS:One hundred and eighteen uremic hemodialysis patients undergoing initial arteriovenous fistula in our hospital during Feb.-Jun.2015 were divided into control group and observation group according to random number table,with 59 cases in each group.Both groups received local irradiation with hemodialysis internal fistula repair instrument 30 min,tid,from 3 days before surgery to 10 days after surgery.Control group was treated with Alprostadil injection 10 μg,iv,qd,immediately after surgery.Observation group was additionally treated with Papaverine in jection 30 mg,iv,qd,on the basis of control group.Both groups received treatment for 10 d.The orificium fistulae blood flow,hemodialysis blood flow and the time of initial hemodialysis were compared between 2 group.The plasma prothrombin time (PT),activated partial thromboplastin time (APTT),fibrinogen (Fib),platelet count (PLT) and C-reactive protein (CRP) levels were observed in 2 groups before and after surgery.The occarrence of postoperative complications was observed.RESULTS:The orificium fistulae blood flow and hemodialysis blood flow of observation group were significantly higher than those of control group,and ini tial hemodialysis time was significantly shorter than control group,with statistical significance (P<0.05).Before surgery,there was no statistical significance in PT,APTT,Fib,PLT and CRP between 2 groups (P>0.05).After surgery,APTT and CRP of 2 groups were increased significantly,Fib was decreased significantly;the above indexes of observation group was significantly better than that of control group,with statistical significance (P<0.05).There was no statistical significance in PT,PLT between 2 groups (P>0.05).There was no statistical significance in the incidence of internal fistula infection and postoperative wound bleeding volume> 10 mL between 2 groups (P>0.05).The incidence of internal fistula occlusion and orificium fistulae thrombus in observation group were significantly lower than control group,with statistical significance (P<0.05).CONCLUSIONS:The application of alprostadil combined papaverine on uremic hemodialysis patients after initial arteriovenous fistula can effectively prevent inflammation reaction,fistula thrombus formation and fistula occlusion,and improve the maturation of fistula.
5.Clinical significance of drug sensitive test for the eradication of Helicobacter pylori infection and peptic ulcer
Shuyun WANG ; Xia ZHANG ; Wenjun YUAN ; Yanping MENG
Chinese Journal of Biochemical Pharmaceutics 2015;(11):107-109
Objective To explore the value of Helicobacter pylori( Hp) drug sensitivity test for clinical treatment of Hp infection and peptic ulcer. Methods Selected from February 2013 to October 2014 gastroenterology clinic in the hospital inpatient treatment and 120 patients( Steering Group) , of which 69 cases of gastric ulcer, duodenal ulcer 51 patients, mucosal lesions in patients took tissue culture Hp, Hp strain cultured to antibiotic susceptibility testing by disk diffusion method and based on susceptibility testing to guide treatment , alternative 120 cases of peptic ulcer patients as a routine group, ulcer treatment effect was observed between two groups and Hp eradication therapy.Results Steering group of 120 patients, 75 patients were successfully cultured Hp, susceptibility test results: the most sensitive to gentamicin(94.67%), followed furazolidone(88.00%), the lowest sensitivity to metronidazole(8.00 %);reviewed 4 weeks after treatment, ulcer healing rate of steering group of patients 93.33% was significantly higher than the end of treatment 4 weeks after the ulcer healing rate of regular group of 81.67%, steering group of patients with abdominal pain short time (3.5 ±1.5)d was significantly shorter than conventional group of patients(4.3 ±1.7) d; Hp eradication of steering group patients was 89.17%significantly higher than conventional group were 78.33% and the difference was statistically significant ( P<0.05 ) .Conclusion According Hp susceptibility testing, can choose Hp sensitive proton pump inhibitor combination of antibiotics amoxicillin treatment, can achieve more significant clinical effect.
6.Combined Pharmacokinetics-pharmacodynamics Study of Rabeprazole in Inhibition of Gastric Acid Secretion
Hongyu YUAN ; Yongqin WANG ; Hongwen ZHANG ; Ling MENG ; Kun HAO
Herald of Medicine 2014;(6):699-702
Objective To investigate the pharmacokinetics ( PK ) and pharmacodynamics ( PD ) processes of rabeprazole in inhibiting gastric acid secretion with the combined PK-PD model. Methods A total of 10 healthy volunteers were given a intravenous infusion of 20 mg rabeprazole over a 30-min period. The concentration of rabeprazole in the plasma at different time points was detected by HPLC,and the PK parameters were calculated by DAS 2. 0 software. At the same time the intragastric pH was monitored over 24 hours to fit the PD parameters with indirect inhibition model. Results The main PK parameters,t1/2,Cmax,and AUC were(60. 5±17. 3)min,(1 299. 1±201. 0)ng·mL-1,and(106. 4±26. 0)mg·min·L-1, respectively.The corresponding PD parameters,Kin,Ke,IC50 and Imax were(8.200±3.362)h-1,(1.080±0.378)h-1,(0.286± 0. 129)mg·L-1 and(6. 93± 2. 15)pH,respectively. Conclusion The PK of rabeprazole in healthy volunteers conforms to one compartment model,and the PD fits the indirect response inhibition model. The equation can effectively establish the relationship between the blood drug concentration and the effect.
7.Clinical and muscular pathological features with chronic graft-versus-host disease-related polymyositis: one case report
Lingchao MENG ; Wei ZHANG ; Zhaoxia WANG ; Feng GAO ; Yun YUAN
Chinese Journal of Neurology 2012;45(2):116-119
Objective To report the clinical and pathological features of chronic graft-versus-host disease-related polymyositis by summarizing the clinical data of the patient with chronic graft-versus-host disease-related polymyositis. Methods One patient with chronic graft-versus-host disease-related polymyositis was hospitalized in our hospital on December 29,2010.The patient,40 years old,female,underwent allogeneic haematopoietic stem cell transplantation because of acute granulocytic-monocytic leukemia.Fourteen months later she manifested as slowly progressive muscle weakness and myalgia in all limbs.Serum creatine kinase level was between 426-1948 U/L. Myositis antibody EJ was strongly positive.Electromyogram showed a neurogenic impairment and slow peripheral nerve conduction speed.Muscle biopsies were carried out in the left biceps brechii.In addition of standard histological and enzyme histochemical staining for the muscle sections,immunohistochemical workup was performed with mouse antiCDs,anti-CD20,anti-CD68 and anti major histocompatibility complex- Ⅰ ( MHC- Ⅰ ) monoclonal antibodies as first antibodies.Results The muscle biopsy showed large variation of fiber size,with muscle fiber necrosis,regeneration.Some angular fibers distributed in small cluster.The inflammatory cells infiltrated around the small vessel or in the endomysium,mainly CD8+ T-lymphocytes and CD6+8 macrophages.The most muscle fibers were MHC-Ⅰ positive. Conclusion The graft-versus-host disease-related polymyositis manifests as chronic myositis process with neurogenic lesions.
8.ROI-CTM cervical fusion or titanium plate for treatment of Hangman fractures:a comparison of cervical stability and fusion rate
Weihong ZHANG ; Chunyang MENG ; Feng GAO ; Wen YUAN
Chinese Journal of Tissue Engineering Research 2015;(38):6074-6080
BACKGROUND:The self-locking ROI-CTM interbody fusion has zero profile design which can significantly reduce the impact on the esophagus and pharynx, and also simplify the operation procedure. However, there is no report whether it has satisfactory outcomes in the treatment of Hangman fractures.
OBJECTIVE: To compare the clinical effects of ROI-CTM or titanium plate internal fixation on postoperative cervical stability and fusion rate in the treatment of Hangman fractures.
METHODS:Twenty-one cases of Hangman fractures were included, including 13 males and 8 females, aged 25-62 years old. Fifteen cases were treated with titanium plate internal fixation, and the other five cases were treated with ROI-CTM fusion device. Cervical anteroposterior and lateral radiographs, lateral flexion extension radiographs and CT scanning were carried out before, 3 days and 3 months after repair to assess angular displacement, horizontal displacement and fusion rate; visual analog scale score and Bazaz dysphagia score were determined.
RESULTS AND CONCLUSION:At 3 days after operation, the ROI-CTM group was significantly better than the titanium plate group in visual analog scale scores and Bazaz dysphagia grade (P < 0.05), and there were no significant differences in angular displacement and horizontal displacement (P > 0.05). However, at 3 months after operation, there was no significant difference between the two groups in visual analog scale score, Bazaz dysphagia grade, angular displacement and horizontal displacement and fusion rate (P > 0.05). Postoperative complete reduction rate of spondylolisthesis was higher in the ROI-CTM group than the titanium plate group (P < 0.05). In each group, the angular displacement and horizontal displacement were significantly reduced at 3 day and 3 months after operation (P < 0.05), but there was no significant difference at 3 days and 3 months after operation (P > 0.05). No rejection reaction, internal fixation fracture and loosening occurred in the two groups. These findings indicate that the self-locking ROI-CTM fusion for treatment of Hangman fractures are characterized as higher reduction rate of spondylolisthesis, less dysphagia, and less neck pain.
9.Optimization of alkaline hydrolysis based on the side chain of diethyl ester 4-amino-N5-formyl-N8,N10-dideazatetrahydrofolic acid
Mengmeng YUAN ; Meng WANG ; Junyi LIU ; Zhili ZHANG
Journal of Peking University(Health Sciences) 2017;49(4):714-718
Objective: To optimize and establish the best hydrolysis method of diethyl ester 4-amino-N5-formyl-N8,N10-dideazatetrahydrofolate through the optimization of simple compound of diethyl N-(4-aminobenzoyl)-L-glutamate.Methods: To increase the low yield of hydrolysis reaction of diethyl ester 4-amino-N5-formyl-N8,N10-dideazatetrahydrofolate due to the by-products and difficult purification, we studied the effect of NaOH and KOH, two kinds of alkalis, three concentrations between 0.175-1 mol/L and five types of reaction time involved in 20, 30, 60, 120 and 180 min on the common side chain diethyl N-(4-aminobenzoyl)-L-glutamate.A high performance liquid chromatography was established for measuring the target product and the by-products in reaction liquid in different reaction conditions.Finally, on the basis of the best hydrolysis method of diethyl ester 4-amino-N5-formyl-N8,N10-dideazatetrahydrofolate, we completed the optimization of the hydrolysis reaction conditions of diethyl ester 4-amino-N5-formyl-N8,N10-dideazatetrahydrofolate.Results: We developed the best reaction condition for the hydrolysis of diethyl ester 4-amino-N5-formyl-N8,N10-dideazatetrahydrofolate, which could be carried out easily and efficiently.The results indicated that treated with the optimized condition of 0.3 mol/L KOH in 60 min at the room temperature, diethyl ester 4-amino-N5-formyl-N8,N10-dideazatetrahydrofolate was converted into its diacid derivative in 95.6 % yield, which turned to be a better reaction condition compared with the previous reaction condition.The structures of those compounds were identified to be correct by 1H nuclear magnetic resonance(1H NMR), 13C nuclear magnetic resonance(13C NMR) and electrospray ionization time of flight mass spectrometry (ESI-MS).The purity of the diacid derivative of the compound was determined to be 96% by high performance liquid chromatography(HPLC).The new hydrolysis reaction condition could not only avoid the formation of single ester hydrolysis product and amide bond hydrolysis product, but also improve the yield of the hydrolysis reaction.Conclusion: We have developed an efficient reaction for the hydrolysis of diethyl ester 4-amino-N5-formyl-N8,N10-dideazatetrahydro.Since the final step of the synthesis of classical folic acid antagonists is always the catalyzed hydrolysis of the side chain glutamate, the reaction also has great significance for anti-folic acid anti-tumor inhibitors synthesis.
10.Study on cost-effectiveness of primary cerebral infarction patients
Yuan YANG ; Meng WANG ; Liang ZHANG ; Fuchun CHENG ; Ling YIN
Chinese Journal of Disease Control & Prevention 2009;0(02):-
Objective To study cost-effectiveness of primary cerebral infarction patients. Methods The neural function of primary cerebral infarction patients was studied by the National Institutes of Health Stroke Scale (NIHSS) with rank test and multiple regression analysis. Results After treatment in hospitals of different grades, no obvious difference was detected in the NIHSS score, but difference was found in therapy cost and therapy time; the NIHSS score and therapy time of primary cerebral infarction patients in different attack positions were obviously different, but therapy cost had no significant statistical difference. The NIHSS score of primary cerebral infarction patients with different treatments was obviously different, but therapy cost and therapy time was not. Conclusions Patients are advised to choose grade hospitals in nearby cities for treatment. Clinician are expected to choose low-cost treatment plan to relieve patients' economic burden.