1.The characterisitics of temperature/pH sensitive block copolymer micelles in vitro.
Li JIA ; Mingxi QIAO ; Haiyang HU ; Xiuli ZHAO ; Dawei CHEN
Acta Pharmaceutica Sinica 2011;46(7):839-44
The dialysis method was employed to prepare blank and doxorubicin (DOX) loaded micelles formed by temperature- and pH- sensitive polyhistidine-co-polyDL-lactide-co-glycolide-co-polyethyleneglycol-co-polyDL-lactide-co-glycolide-co-polyhistidine (PHis-b-PLGA-b-PEG-b-PLGA-b-PHis). The critical micelle concentrations (CMC) of the copolymers were measured with Pyrene Fluorescent Probe Technique. The temperature- and pH- sensitive properties of the blank micelles solution were investigated by optical transmittance measurement. The morphology and diameter of DOX micelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The entrapment rate and drug-loading rate were determined with dialysis method. The in vitro release study was further performed to examine the temperature- and pH-responsive drug release behavior from DOX-loaded micelles. The results indicated that the CMC, entrapment efficiency and drug-loaded amount of the micelles were 7.5 x 10(-3) g x L(-1), 85.2 +/- 3.1% and 10.4 +/- 4.5%, respectively. The DOX micelle was globular-shaped with a mean diameter of 91.1 +/- 15.8 nm. The transmittance of micelle solution consistently increased with the increasing temperature or decreasing pH. In comparison to the drug release profile at physiological conditions (37 degrees C, pH 7.4), the DOX-loaded micelles showed faster drug release rate at higher temperature (41 degrees C), lower pH (pH 7.0, pH 6.5, pH 5.0) or higher temperature and lower pH (41 degrees C, pH 5.0). This indicated that the micelles showed a temperature and pH-triggered drug release pattern. Base on the above results, it can be concluded that PHis-b-PLGA-b-PEG-b-PLGA-b-PHis block copolymer micelles which respond to temperature and pH stimuli are promising smart carriers for anti-tumor drugs with the advantages of temperature- and pH- triggered drug release.
2.Impact of CYP2C19 polymorphisms on eradication of Helicobacter pylori using triple therapy with esomeprazole
Lei ZHANG ; Jianming XU ; Qiao MEI ; Qiusen LI ; Yongmei HU
Chinese Journal of Digestion 2009;29(9):545-548
Objective To prospectively compare the efficacy of omeprazole and esomeprazole on H. pylori eradication related to cytochrome P450 (CYP) 2C19 polymorphism in Chinese Han poputafion. Methods A total of 240 patients with peptic ulcer were randomly assigned to receive either EAC (amoxicillin, clarithromyein and esomeprazole) treatment or OAC (amoxicillin, clarithromycin and orneprazole) treatment for one week with 120 each. Then, the patients were sustained treated with esomeprazol or omeprazole for 3 weeks. The endoscopic evaluation was performed 2 weeks after treatment. At the end of the treatment, a carbon-13 (13C) urea breath test (13C-UBT) was performed to determine H. pylori status. Polymerase chain reaction and restriction fragment length polymorphism were used to detect CYP2C19 genotypes including extensive metabolizer (EM), poor metabolizer (PM), homozygous (homEM) and hetEM. Results Two hundred and twenty five of 240 patients completed the study. H. pylori eradication was 79.2% with OAC regimen and 88.3% with EAC regimen by intention to-treat (ITT) analyses without difference (P>0.05). Whereas H. pylori eradication was 87.20/00 with OAC regimen and 91.4% with EAC regimen by per-protocol (PP) analyses without difference (P>0. 05). However, both ITT and PP analysis showed that there was significant difference in H. pylori eradication between EAC regimen (91.9% and 97.1%) and OAC regimen (71.8% and 77.8%) in patients with homEM genotype (P= 0.037 and P=0.028). Two weeks after treatment, the percentage of ulcer healing was 79.2% or 81.9% in EAC group and 69.2% or 76.1% in OAC group by ITT or PP analysis, respectively (P> 0.05). Low side effects were noted in EAC or OAC groups (3.3% vs. 7.5%,P>0.05). Conclusion The high eradication will be achieved by esomeprazole-based triple regimen which is superior to omeprazole-based triple regimen in treatment of patients with homEM genotype.
3.Monocyte chemoattractant protein-1 and its correlation with lipoprotein inpolycystic ovary syndrome
Weihong HU ; Jie QIAO ; Shuyun ZHAO ; Xiaowei ZHANG ; Meizhi LI
Journal of Peking University(Health Sciences) 2003;0(05):-
Objective: To measure serum monocyte chemoattractant protein-1 (MCP-1) levels and study its associations with lipoproteins in patients with polycystic ovary syndrome (PCOS). Methods: Sixty-five PCOS women and 20 ovulating normal women with body mass index (BMI)
4.Effect of melatonin on colon immunological function during colitis in rats
Qiao MEI ; Li XIANG ; Zonghao ZHAO ; Yongmei HU ; Jianming XU
Chinese Journal of Pathophysiology 1986;0(03):-
AIM: To investigate the effects of melatonin (MT) on the immunological function in colon of rats immunological colitis. METHODS: The rats colitis was produced by enema with trinitrobenzene sulfonic acid and ethanol. The experiment groups included normal group, model group, 5-aminosalicylic acid (5-ASA) group (100 mg?kg~(-1)), MT groups (2.5,5.0,10.0 mg?kg~(-1)), and treated intracolon with saline, saline, 5-ASA and MT respectively (once per day, from the d7 after the establishment of colitis model to the end of the experiment). The content of interleukin (IL-1, IL-2) and tumour necrosis factor (TNF)-? in rats colon were detected; The inflammatory colon were homogenatized and incubated with lipopolysaccharides (LPS), and designed as control group, model group, 5-ASA group (100?mol/L), MT groups(0.01, 0.1, 1.0 mmol/L). The content of IL-1, IL-2, TNF-?, nitric oxide (NO), lactic dehydrogenase (LDH), myeloperoxidase (MPO) and malondiadehyde (MDA) in the supernant were detected. RESULTS: In model group, the contents of IL-1, IL-2 and TNF-? in colon elevated remarkably and MT depressed this effectively. In the inflammatory colon homogenates of rats colitis, the content of IL-1, IL-2, TNF-?, NO, LDH, MPO and MDA elevated remarkably, Pretreation with MT depressed the content of IL-1, TNF-?, LDH, MPO and MDA effectively. MT (1.0mmol/L) also reduced the production of NO obviously. CONCLUSION: The abnormal immunological function is shown obviously in rats colitis. MT normalizes this change in vivo and in vitro and attenuates the mucosal damage.
5.Diagnostic value of tri-phase dynamic enhancement scan with CT for acute renal infarction
Zhibo YU ; Yunquan ZHANG ; Lingheng SONG ; Qing QIAO ; Fusuo LI ; Min HUANG ; Wenyou HU ; Jinqing LI
Journal of Regional Anatomy and Operative Surgery 2015;(5):486-489
Objective To investigate the imaging characteristics and diagnostic value of tri-phase dynamic enhancement scan with CT for acute renal infarction. Methods The image features of CT plain scan and tri-phase dynamic enhancement scan of 10 patients (19 sides) with acute renal infarction were retrospectively analyzed, and the CTA expression of 6 patients were observed. Results Fourteen acute renal infarction lesions of 10 cases were diagnosed. The CT scan showed there were 4 cases with enlargement of kidney, and the other 6 cases were of no abnormality. The tri-phase enhancement CT scan showed there were 6 cases of unilateral renal infarction and 4 cases of bilateral renal infarction, which totally involving 14 sides. The acute renal infarction lesions lacked of high density region in the corticomedullary in cortical phase, and there were wedge-shaped hypodense area, even low density of full kidney in parenchymal phase and pyelographic phase. The a-cute renal infarction lesions were revealed better in parenchymal phase and pyelographic phase than in cortical phase. Six cases of CTA re-vealed the responsible vessels of renal infarction lesions and the other vascular diseases. Conclusion CT tri-phase dynamic enhancement scan has important value in the diagnosis of acute renal infarction, and CTA can identify the responsible vessels of renal infarction lesions.
6.Role of interelenkin-17, -6 and endothelin-1 in statins attenuated no-reflow phenomenon of rat acute myocardial infarction and reperfusion
Qiao-li, LIU ; Guang-you, WANG ; Hu-lun, LI ; Ke-cheng, ZHANG ; Jie, YUAN
Chinese Journal of Endemiology 2011;30(5):506-509
ObjectiveTo study the relevant effect of proinflammatory cytokines interelenkin-17(IL-17), -6 and endothelin-1 (ET-1) on statins attenuating no-reflow phenomenon after myocardial ischemia-reperfusion in rats.MethodsEighteen healthy male Wistar rats were randomly divided into 3 groups according to body weight: sham operation, injury, preconditioning groups. The preconditioning group was given atorvastatin 2 mg·kg-1 ·d-1 and the other two groups were given the same volume of saline once. After 7 days, the rats were anesthetized with an intraperitoneal injection of chloral hydrate, and then the thoracic cavity was opened. The coronary artery of injury group and preconditioning group were ligated for 60 minutes, and then opened for 15 minutes, to establish the rat acute myocardial ischemia-reperfusion model. The sham operation group was was treated with a seam through the coronary artery without ligation. Eleetrocardiogram was checked before ligation, and ligation was carried out for 15, 30, 45 minutes and then reperfusion for 15 minutes. After reperfusion for 15 minutes, the thioflavine S and Even's were injected from femoral venous, then the heart and blood were obtained(keeping left ventricular only). Hearts were flushed with saline and sliced transversely into five to seven sections. Finally, observed at 365 nm wave length the existence of non-fluorescent areas, which was no-reflow zone. The level of serum IL-17, IL-6 and ET-1 was detected by ELISA. Results The electrocardiogram confirmed that the sham operation group had no ischemic damage and the model of myocardial ischemia- reperfusion was established in preconditioning group and injury group. The noreflow phenomenon could be observed under 365 nm wave length in preconditioning group and injury group. The ligated area[LA%, (57.34 ± 11.49)%, (53.08 ± 8.66)%] of injury group and preconditioning group was higher than that of sham operation group(0, all P < 0.05); the area of no-reflow[ANF%, (48.96 ± 6.94)%, (21.37 ±3.35)%] of injury group and preconditioning group was higher than that of sham operation group(0, all P < 0.05),and the ANF% of preconditioning group was lower than that of injury group(P < 0.05) ; the level of serum IL-17,IL-6 and ET-1[(151.67 ± 11.19) × 10-9, (167.89 ± 5.13) × 10-9, (322.37 ± 19.08) × 10-9 g/L] of injury group was higher than those of sham group and preconditioning operation group[(49.75 ± 14.06) × 10-9, (59.32 ± 5.26) ×10-9, (109.9 ± 12.12) × 10-9, (90.45 ± 11.63) × 10-9, (112.47 ± 10.40) × 10-9 and(198.91 ± 27.88) × 10-9 g/L,P < 0.05], the level of serum IL-17, IL-6 and ET-1 of preconditioning group was higher than those of sham operation group(P< 0.05). Conclusionsno-reflow phenomenon is related with IL-17 and ET-1 which can promote the expression of IL-6, statins decreases the expression of IL-17 and ET-1, and then decreases the on-reflow phenomenon.
7.18F-FDG PET/CT for assessing therapeutic response to chemotherapy in patients with diffuse large B-cell lymphoma
Hong-sheng, LI ; Hu-bing, WU ; Quan-shi, WANG ; Qiao-yu, WANG ; Bao-yuan, LI
Chinese Journal of Nuclear Medicine 2011;31(3):145-150
Objective To explore the value of 18F-FDG PET/CT on the assessment of chemotherapy response in patients with diffuse large B-cell lymphoma (DLBCL). Methods 18F-FDG PET/CT was performed before and after 4 cycles of chemotherapy( R-CHOP or CHOP protocol) in 53 patients with DLBCL. The patients were divided into 3 groups: complete response group, partial response group and no response group. The therapeutic response was assessed by comparing post-treatment 18F-FDG PET/CT with pre-treatment PET/CT. Complete remission (CR) rate at the end of chemotherapy was calculated. χ2 test was performed with software SPSS 13.0. Results CR rates of complete response group, partially response group and no response group were 88.5% (23/26), 73.3% (11/15) and 8.3% (1/12), respectively (χ2=23.548, P=0.000). CR rates of the complete and partially response groups were significantly higher than those of no response group (χ2=22.656, P=0.000; χ2=11.407, P=0.001). Conclusion 18F-FDG PET/CT may be useful for the assessment of chemotherapy response in DLBCL.
8.Gastric fistulation with transcutaneous endoscopy in a child.
Zhi-hong HU ; Ming SHEN ; Li SUN ; Rong QIAO ; Fu-mei JIA ; Si-yuan YANG
Chinese Journal of Pediatrics 2004;42(3):222-223
9.Application of gene capture technology combined with next generation sequencing technology on methylmalonic acidemia
Jun WANG ; Erzhen LI ; Liwen WANG ; Shenghai YANG ; Tao HU ; Zhilong WANG ; Qiao ZHOU
Chinese Journal of Applied Clinical Pediatrics 2014;29(20):1548-1551
Objective To assess the efficiency and reliability of clinical genetic diagnosis of methylmalonic acidemia(MMA) using new generation sequencing platform (HiSeq2000).Methods 1.Nine patients diagnosed with clinical signs of MMA were recruited.DNA library from the patients were mixed with designed gene capture probe.The whole exons region of 48 genes related to organic acid metabolism were screened using the gene capture combined with high-throughput sequencing.2.The joints were removed and the low quality data were filtered,the data were analyzed by means of SNP and InDel.To avoid the false positive,the abnormal sites were verified using the Sanger sequencing method.3.The detection of the organic acid in the urine was performed through gas chromatography-mass spectrometry and other auxiliary examinations.Results 1.Gene mutation:7 gene mutations of MMACHC were identified in 7 patients.Seven mutations:c.482G > A,c.567_568insT,c.609G > A,c.440_441del,c.80A > G,c.315C > G,c.90G > Awere screened.The mutation c.440_441del had not been reported before,and others were all related to the disease.Two gene mutations of mutase apoenzyme(MUT) were identified in 1 case,all of which were introns:.c.754-1G > C,c.1677-1G > A.The novel mutation was c.754-1G > C.No gene mutation was identified in 1 patient.2.Clinical manifestation:all of the patients were development delay,but the degrees were different;3 patients with convulsion; 1 patient with headache and central facial paralysis;1 patient with repeated intractable metabolic acidosis;1 patient with repeated hemolysis.Electroencephalogram of the all patients were abnormal;the result of cranial MRI of the 8 patients were abnormal;In all patients,urine level of methylmalonic acid significantly increased (273.4-146 022.8 times).Blood homo cysteine of 8 patients were significantly increased(27.13-396.84 μmol/L,normal < 20 μmol/L).3.Sanger sequencing:there were no false positive exists.Conclusions 1.There were not a correlation between the clinical manifestation and gene mutation of the patients with MMA.The c.609G > A was the hotspot mutation of MMACHC gene in Chinese patients with MMA and homocysteinemia.2.The mutations c.440_441del and c.754-1G > C were presumed to be novel mutations.3.Gene capture technology combined with next-generation sequencing technology could be used to interrogate the wealth of data available in the human genome and lay the foundations for counseling of gene.This platform can be readily and timely adopted by clinical molecular diagnosis of MMA and represents a high throughput,high sensitivity,high efficiency and other characteristics approach for screening common genetic diseases.
10.Alteration of transient outward potassium current in ventricular myocytes from 1-week and 2-month infarcted rabbit hearts
Chao DING ; Zhenshan HE ; Junyu CUI ; Li YANG ; Qiao SHI ; Liye HU ; Shuying QI ; Xiaoyun LIU
Chinese Journal of Pathophysiology 2000;0(08):-
AIM: To study the current density of transient outward potassium current (I_(to)) in cells from the epicardial zone of the 1-week and 2-month infarcted rabbit heart. METHODS: Rabbits were infarcted by ligation of the left anterior descending coronary artery, 1 week as well as 2 months later, the single ventricular myocytes were isolated enzymatically from the infracted area of 1-week infracted rabbit heart (PMI-1 week) and 2-month infracted heart (PMI-2 months), region remote from the infracted zone of 2-month infracted heart (REM-2 months) and free wall of left ventricule from noninfarcted heart (CON). I_(to) was recorded using whole cell patch-clamp techniques. (RESULTS:) Membrane capacitance of myocytes in REM-2 months group was signifitantly larger than that in CON. I_(to)current density (at +60 mV) was significantly reduced in PMI-1 week [(7.5?2.4) pA/pF, n=12] and PMI-2 months [(10.6?4.1) pA/pF, n=18] compared with CON [(17.4?5.2) pA/pF, n=16], P