1.Protective effect of telmisartan on rats with renal failure and its mechanism
Zhikui WANG ; Zhenying LIU ; Haibo YU
Asian Pacific Journal of Tropical Biomedicine 2015;(6):497-500
Objective:To study the protective effect of telmisartan on rats with renal failure and its mechanism. Methods:60 Wistar rats were chosen as study objective, and were divided into 4 groups randomly:15 in group A (sham operation group), 15 in group B (model group), 15 in group C (telmisartan group) and 15 in group D (telmisartan+GW9962 group). The difference of survival rate, blood-urine biochemical indexes, renal pathological change, and the expression level of PPARγ and nNOS were compared. Results:After 12 weeks, the survival rate of group A was 93.33%(14/15), that of group B was 46.67%(7/15), that of group C was 86.67%(13/15), that of group D was 60.00%(9/15), and the difference among 4 groups had statistical significance (P<0.05). After 1 week, the difference of Scr, that of BUN and that of 24h protein urine among 4 groups was not statistical significant (P>0.05);after 3 weeks, 6 weeks and 12 weeks, these difference was statistical significant (P<0.05). The difference of blood-urine biochemical indexes, that of renal pathological change, and that of the expression level of PPAR毭and nNOS was statistical significant (P<0.05). Conclusions:Telmisartan has protective effect on renal failure caused by 5/6 nephrectomy, which might be relative to the expression level of PPARγ and nNOS.
2.Injectable and biodegradable thermosensitive PLGA-PEG-PLGA copolymer-based hyd rogels for a controlled in vitro drug delivery
Zhikui CHEN ; Liwu LIN ; Yahfang LIN ; Ensheng XUE ; Liyun YU
Chinese Journal of Tissue Engineering Research 2008;12(49):9792-9796
BACKGROUND:Ricin possesses strong cytotoxicity but lacks of specificity.Severe adverse reactions can be caused if ricin is systemically administered.Interstitial chemotherapy with ricin coated by a sustained-release carrier can enhance local therapeutic effects of tumor,avoiding systemic-toxic occurrence.OBJECTIVE:To prepare injectable and biodegradable thermosensitive poly(D,L-lactide-co-glycolide)(PLGA)-polyethylene glycol(PEG)-PLGA copolymer-based hydrogels and to observe the in vitro drug delivery of the PLGA-PEO-PLGA copolymer hydrogel as a sustained-release carrier of ricin.DESIGN,TIME AND SETTING:A controlled observation was performed at the Center for Medical Bioengineering.Fujian Medical University between August and December 2007.MATERlALS:Ricin with a purity of 95%was purified by Fuiian Institute of Ultrasonic Medicine.DL-lactide and L-glycolide were provided by Glycolide Lactide Co.,Ltd..China.METHODS:PLGA-PEG-PLGA-copolymer was synthesized by ring-opening polymerization.MAIN OUTCOME MEASURES:Phase transition temperature was determined by test tube turnover.relativemolecular mass by high-performance gel permeation chromatography,the proportion of block copolymer by nuclear magnetic resonance spectrometry.the in vitro drug delivery of ricin coated by PLGA-PEG-PLGA copolymcr hydrogelby enzyme linked immunosorbent assay.the structural integrity of released ricin by high-performance liquid chromatography,the cytotoxicity of released ricin by methyl thiazolyl tetrazolium assay.RESULTS:The synthesized copolymer PLGA-PEG-PLGA exhibited reverse.thermosensitivity.The phase transition temperature of the copolymer was 26℃at 230 g/L.The weight-average molecular weight and number-average molecular weight of this copolymer was 8 027 and 6 643,respectively,and the multiple-dispersion toefficient was 1.17.The block ratio for PEG and PLGA was 3:2.Drug-loaded PLGA-PEG-PLGA hydrogel could release ricin in vitro for a total of 18 successive days and simultaneously well maintain cytotoxicity and the structural stability of ricin.CONCLUSION:PLGA-PEG-PLGA copolymer is an ideal carrier for sustained delivery of ricin
3.Ultrasound-guided percutaneous ethanol injection in the treatment of hepatocellular carcinoma combined with portal vein tumor thrombosis
Xiujuan ZHANG ; Liwu LIN ; Ensheng XUE ; Zhikui CHEN ; Liyun YU
Chinese Journal of Interventional Imaging and Therapy 2011;08(5):367-370
ObjectiveTo assess the clinical value of ultrasound-guided percutaneous ethanol injection (PEI) in the treatment of hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT).MethodsNinety HCC patients with different type PVTT underwent ultrasound-guided PEI once or twice a week.The follow-up lasted 12 to 60 months,and the 1-,2-,3-,4- and 5-year survival rates were calculated.ResultsThe median survival time of HCC combined with PVTT patients treated with PEI was 12 months,and the 1-,2-,3-,4- and 5-year survival rates was 52.22%,23.33%,15.56%,12.22% and 10.00%,respectively.The survival rate correlated significantly to the type of PVTT.The lower the type of PVTT was,the longer the patients lived.ConclusionUltrasound-guided PEI is a safe and effective method for the treatment of HCC combined with PVTT,and can prolong the survival time of HCC patients with low type PVTT.
4.Analysis of the experiment of mycobacterium tuberculosis sputum culture and heat-proof rifabutin antimicrobial susceptibility
Zhikui MI ; Shoujie YU ; Jiawu SU ; Kangxiao FANG
Chinese Journal of Primary Medicine and Pharmacy 2011;18(17):2315-2316
Objective To analyze influence mycobacterium tuberculosis sputum culture and heat-proof rifabutin antimicrobial susceptibility test results and related factors.Methods To the centers for disease control and prevention of Huainan tuberculosis clinic into the program to treat 227 sputum smear-positive patients in the sputum culture and heat-proof rifabutin of antimicrobial susceptibility test. Results Among 227 patients sputum culture positive 220 cases, accounting for 96. 9%, sputum culture-negative 2 cases, accounting for 0. 9%, pollution, 5 cases of 2. 2%. Resistance rifabutin antimicrobial susceptibility test,a new patient resistance ratio for 10. 4% ,early cure loser for 37.5%, concomitant person for 28.9%. Conclusion The mycobacterium tuberculosis in the process of cultivation should be strictly according to the requirements of collecting, processing, specimen vaccination, preservation and observation. Early cure failure patients and treat patients resistant rifabutin rate was far higher than new patients, the patients with irregular or unreasonable chemotherapy were concerned.
5.Experimental study on ultrasound-guided injection of paclitaxel-loaded thermosensitive hydrogel in treatment of breast cancer in rats
Jiajia YANG ; Zhikui CHEN ; Liwu LIN ; Ensheng XUE ; Yimi HE ; Liyun YU
Chinese Journal of Ultrasonography 2010;19(8):711-714
Objective To prepare a sustained-delivery of paclitaxel-loaded thermosensitive hydrogel for the treatment of breast cancer by ultrasound-guided intratumoral injection,and probe the antitumor effect and mechanism of the new method. Methods Paclitaxel-loaded thermosensitive hydrogel was prepared. A total of 40 rats bearing subcutaneous breast tumor were randomized into 4 groups. Each group of rats were administered ultrasound-guided intratumoral injection of different agents as follows: salin, thermosensitive hydrogel, paclitaxel injection and paclitaxel-loaded thermosensitive hydrogel. The tumor nodules were scanned by high frequence ultrasound. The rats were sacrificed on the 14th day,and then the tumors were stripped to calculate the growth inhibitory rate. Histological examinations were undergone and RT-PCR was performed for the detection of bcl-2 and bax expression. Results Greater decrease in average tumor weight was found in paclitaxel-gel group [(16. 04 ± 2. 82)g], compared with that in paclitaxel group [(27.45 ±5.13)g, P <0. 05],and tumor growth inhibitory rate in the group was 62.77 %. In this group, blood flow signals reduction was detected on ultrasound and extensive necrosis was found in histological examination. In addition,down-regulation in bcl-2 mRNA expression and up-regulation in bax were found. Conclusions Ultrasound-guided percutaneous intratumoral injection of paclitaxel-loaded thermosensitive hydrogel may provide an effective method for breast tumor ablation therapy. The mechanism may be related to the inhibition of proliferation and induction of apoptosis.
6.Effects of intratumoral injection of microspheres containing cobra venom cytotoxin on transplanted human hepatoma in nude mice.
Yan WANG ; Liwu LIN ; Zhikui CHEN ; Ensheng XUE ; Xiaodong LIN ; Liyun YU ; Zhenhu LIN
Journal of Integrative Medicine 2009;7(9):831-5
Objective: To evaluate the safety and efficacy of intratumoral injection of polylactic-co-glycolic acid (PLGA) microspheres containing cobra venom cytotoxin in nude mice with transplanted human hepatoma. Methods: Cytotoxic activity of cytotoxin from cobra venom was determined by using methyl thiazolyl tetrazolium method in vitro. Microspheres containing cobra venom cytotoxin were prepared with a double emulsion-solvent evaporation method. Forty BALB/c nude mice were inoculated subcutaneously in right flank with hepatoma BEL-7404 cells. Thirty-two mice whose tumor size reached about 1.0 cm in diameter, were randomly assigned into normal saline group, blank microsphers group, cytotoxin group and cytotoxin-PLGA group. Nude mice were intratumorally injected with normal saline, blank microspheres, cytotoxin or cytotoxin-PLGA microspheres respectively. Internal echo characteristics and blood flow of tumors were observed by high-frequency ultrasound every week after treatment. Twenty-six days after treatment, the tumors were removed to calculate the inhibition rate of tumor growth. The tumor, heart, liver and kidney tissues were obtained for histopathological examination. Results: The cytotoxin separated and purified from crude cobra venom caused intense cytotoxic effects to the BEL-7404 cells in vitro. The diameter of PLGA microspheres containing cobra venom cytotoxin was about (34.45+/-9.85)mum. Encapsulation rate was up to (78.13+/-8.92)%, and cumulative amount of cobra venom cytotoxin released from the PLGA microspheres in vitro during 30 days was up to 84.3%. After intratumoral injection, tumor volumes and weights in the cytotoxin-PLGA group were lower than those in the normal saline group, with a tumor growth inhibition rate of 52.36%. Observed under a light microscope, most tumor tissues were necrotic. No obvious morphological change could be seen on the liver, kidney and heart tissues. Conclusion: The above findings indicate that intratumoral injection of cytotoxin-PLGA microspheres has strong antitumor effect and can obviously lessen systemic toxicity, which may provide an effective and feasible method for hepatocellular carcinoma treatment.
7.Superficial property and drug release in vitro of poly lacticoglycolic acid-loaded cytotoxin nanoparticles
Zhikui CHEN ; Liwu LIN ; Zhiqiang ZHANG ; Ensheng XUE ; Yan WANG ; Liyun YU
Chinese Journal of Tissue Engineering Research 2009;13(3):575-578
BACKGROUND: Cytotoxin (CTX) is characterized by strong cytotoxic activity and absent specificity, of which systemic administration can cause severe toxicity and side effects; however, interstitial chemotherapy may improve therapeutic effect of local tumor and relieve general toxicity using sustained release vector. OBJECTIVE: To prepare cytotoxin/poly lacticoglycolic acid (CTX-PLGA) nanoparticles, and to study the general property and drug release in vitro. DESIGN, TIME AND SETTING: Observational study was performed at Medical Bicangineedng Center of Fujian Medical University between December 2007 and May 2008. MATERIALS: Poly lacticoglycolic acid (PLGA) and polyvinyl alcohol were purchased from Chengdu, and CTX was purchased from Guangdong. METHODS: CTX was purified by molecular sieve, ion exchange separation, and reversed-phase high performance liquid chromatography; cytotoxic activity was measured by MTT method; nanoparticles were prepared by multiple emulsion-solvent evaporation technique. MAIN OUTCOME MEASURES: Superficial morphological characteristics were observed using scanning electron microscope, while diameter was measured using laser particle sizing analyzer in order to calculate encapsulation efficiency, drug loading, and release cycle in vitro. RESULTS: Purified CTX had apparent cytotoxic activity, and the IC<,50> values of HepG2 cells were respectively 1.43 and 1.12 mg/L at 12 and 24 hours. By using multiple emulsion-solvent evaporation technique, the nanoparticles were smooth and intact, diameter 2-8 μ m. The encapsulation efficiency was (74.10±9.92)%, and the drug loading was (0.72±0.09)%. In addition, drug accumulated release was 63.3% at day 21. The released CTX still had a great biologic activity. CONCLUSION: Multiple emulsion-solvent evaporation technique is surely prepared the CTX-PLGA nanoparticles, characterizing by high encapsulation efficiency, great drug release, and entire biologic activity.
8.Value of ultrasonography in diagnosis and differential diagnosis of breast sclerosing adenosis
Ying HOU ; Liwu LIN ; Ensheng XUE ; Zhikui CHEN ; Liyan HUANG ; Liyun YU ; Yimi HE
Chinese Journal of Ultrasonography 2014;23(10):889-892
Objective To investigate the value of color Doppler ultrasonography in diagnosis and differential diagnosis of breast sclerosing adenosis (SA).Methods Preoperative sonography in 32 SA,99 invasive ductal carcinoma(IDC),51 ductal carcinoma in situ(DCIS) and 64 fibroadenoma(FA) confirmed by pathology were retrospectively analyzed.Results The average age of SA group was younger than IDC and DCIS groups',but older than FA group's (P <0.05).The focal maximum diameter of SA group was the smallest among all(P <0.05).All the SA sonograms showed solid hypoechoic lesions,with spiculate margin was less than IDC group and larger than DCIS and FA groups (P <0.05).Similar ultrasonic characteristics,such as irregular shape,unclear border,acoustic halos were seen in SA and DCIS groups (P >0.05),while IDC group showed the highest rate and FA group had the least(P <0.05).SA masses' uneven internal echo,calcification,posterior acoustic attenuation was higher than FA group(P <0.05),but less than IDC and DCIS groups(P >0.05).Meanwhile,A/T ratios(≥0.7) were higher than DCIS and FA groups,but less than IDC group(P >0.05).In addition,SA group had a similar detection rate of the internal blood flow with FA group(P >0.05),but less than the IDC and DCIS groups(P <0.05).Conelusions Ultrasonography has a significant clinical value in diagnosis and differential breast sclerosing adenosis.
9.Application of ultrasonography in diagnosing and preoperative TNM staging for invasive micropapillary carcinoma of breast
Wanping CHEN ; Yimi HE ; Liwu LIN ; Ensheng XUE ; Zhikui CHEN ; Min LIN ; Liyun YU
Chinese Journal of Ultrasonography 2013;22(12):1049-1052
Objective To investigate the ultrasonic characteristics of invasive micropapillary carcinoma(IMPC) of breast and the metastatic lymph nodes,and to evaluate the value of ultrasonography for preoperative TNM staging.Methods The ultrasonic characteristics of 16 IMPC and 81 invasive ductal carcinoma (IDC) confirmed by pathology,as well as the metastatic lymph nodes were analyzed retrospectively.The TNM-staging for IMPC by preoperative ultrasonography was evaluated according to pathology.Results Compared with IDC group,the masses showed higher A/T ratio (< 0.7),larger maximum diameter,more calcification,unclear border and lymph node metastasis rate,while less acoustic halo in IMPC group.Meanwhile,similar ultrasonic characteristics,such as irregular shape,uneven internal echo,spiculate margin,posterior acoustic attenuation and internal blood flow were seen in IMPC and IDC groups (P >0.05).According to pathology,the ultrasonic coincidence rate for T staging was 56.3 %,and T2-staging was 85.7%.The sensitivity,specificity,positive predictive value and negative predictive value of ultrasonic diagnosis on lymph node metastases was 70.0%,83.3%,87.5% and 62.5%,respectively.Conclusions Ultrasonography displayed more typical malignant signs,higher lymph node metastasis rate and diagnosis accuracy for IMPC,which possessed certain value for preoperative TNM staging.
10.Comparative analysis on ultrasonic and mammographic characteristics of breast chronic inlfammation
Min, LIN ; Weili, WEI ; Zhikui, CHEN ; Liwu, LIN ; Ensheng, XUE ; Yimi, HE ; Liyun, YU
Chinese Journal of Medical Ultrasound (Electronic Edition) 2014;(3):50-53
Objective To compare the ultrasonic and mammographic appearances of breast chronic inflammation (BCI). Methods The ultrasonic and mammographic features of 20 pathologically conifrmed BCI cases were analyzed retrospectively. All cases were of single lesion. Fisher deifnite probability method was used to compare the differences between ultrasonic and mammographic appearances as well as the diagnostic coincidence rate. Results Under ultrasonography, the mean longitudinal diameter/transverse diameter (L/T) ratio of 20 lessions was calcultated as 0.47±0.15, 17 lesions were of irregular shape, unclear boundary and inhomogeneous hypoecho, 13 lesions were of posterior echo enhancement, the blood lfow of 10 lesions belonged to 0-Ⅰ, and the other 10 belonged toⅡ-Ⅲ. The lesion shape, boundary and homogeneity detected by mammography were coincident to those by ultrasonography (P=1.00, 1.00, 0.61, respectively). In 5 lesions, dotted high-echoes were detected by ultrasonography, however no calciifcation was found by mammography. Meanwhile, 1 lesion with sporadic calciifcation detected by mammography was missed by ultrasonography. Ultrasonography detected 5 cases with axillary lymphadenopathy, in which only 1 case was found by mammography. The diagnostic coincidence rate of ultrasonography was 40%(8/20), which was obviously higher than 6% (1/16) by mammography (P=0.03). Conclusion BCI possesses certain ultrasonographic characteristics, and ultrasonography combined with mammography will be helpful for the differential diagnosis of malignant and benign diseases.