Objective To prepare the cleavable PEG and RGD co-modified liposome for tumor targeting.Methods Liposomes were prepared by film-ultrasonic method.The particle size,Zeta potential and stability in FBS were evaluated.Cellular uptake by HepG2 cell was explored.MTT assay was used to evaluate the cytotoxicity of blank liposomes. Results The particle diameter of C/RGD-LP was (104.8 ±5.5 )nm with the Zeta potential of (-4.45 ±1.75 )mV.The cellular uptake of C/RGD-LP increased 2.8 times after Cys was added.The C/RGD-LP showed little cytotoxicity to HepG2 cell.Conclusion Cleavable PEG and RGD co-modified liposomes were easy to prepare and has a special application value for targeting tumor.

Polycystic ovary syndrome (PCOS) is one of the most popular diseases in obstetrics and gynecology research at internal and abroad at present, traditional Chinese medicine(TCM)in the clinical treatment of the disease have the advantage. Clinical epidemiological study of descriptive research method this research adopts investigation, observation of TCM syndromes and improper diet through 401 cases in Jiangsu Province confirmed PCOS patients, to explore the relationship between TCM syndrome type distribution and improper diet factors, and to provide the clinical basis for further etiology of this disease research. TCM syndrome type distribution of the disease is kidney deficiency, phlegm stagnation syndrome, qi stagnation and blood stasis syndrome, syndrome of dampness heat of liver channel and is composed of 4 basic syndromes and formed complex syndrome, and the composite and syndrome type (60.85%); combined with the analysis of traditional Chinese medicine dialectical, Pure empirical syndrome this disease (46.88%), followed by the actual card (45.39%), pure deficiency is rare. Improper diet factors associated with the disease, in which improper diet with different TCM syndrome type distribution significantly related. Stagnation of phlegm dampness syndrome is the main syndrome of the disease type, improper diet factors and every syndrome PCOS type distribution is as follows: the partial eclipse fatness greasy with basic syndromes of phlegm dampness stagnation of kidney deficiency syndrome, the nephrasthenia syndrome is less; eating spicy stimulation by basic syndromes of stagnation of Qi and blood stasis; eating cold people the basic certificate type of qi stagnation and blood stasis; The diet of patients are more prone to stagnation of phlegm dampness syndrome.
Adolescent ; Adult ; China ; Diagnosis, Differential ; Diet ; Eating ; Female ; Humans ; Medicine, Chinese Traditional ; Polycystic Ovary Syndrome ; diagnosis ; metabolism ; physiopathology ; Young Adult

Objective To synthesize 628F-Py-AMD3465,to investigate its biodistribution in mice and to perform the microPET/CT imaging on mice bearing human lung cancer cell (A549).Methods AMD3465 quaternary ammonium salt precursor was directly labeled with 18F,then 628F-Py-AMD3465 was synthesized through nucleophilic reaction,hydrolysis,neutralization and the product was purified using HPLC.The labeling yield and radiochemical purity were analyzed by HPLC.Fifteen Kunming mice were injected with 5.55 MBq of 628F-Py-AMD3465 and sacrificed at 5,20,40,60 and 120 min postinjection.The selected tissues were harvested and weighed,and the radioactivity in the tissues was measured by an automated γ-spectrometer.The ％ID/g was calculated.MicroPET/CT studies were performed on A549-bearing mice after injecting 6-18F-Py-AMD3465 through vena caudal.Paired t test was used.Results 6-18F-Py-AMD3465 was successfully synthesized with the labeling yield of (9.0±2.0)％,the total synthesis time was about 60 min,and the radiochemical purity was more than 98％.Biodistribution studies showed that the radiouptake was higher in the kidneys and bladder of normal mice,which demonstrated that 6-18 F-Py-AMD3465 was mainly excreted through the kidneys.Biodistribution in A549-bearing mice was similar to that in normal mice.The tumor/muscle ratio at 40 min was 5.0,but the radiouptake of the tumor was still lower than that of the normal lung:(8.05±0.35) ％ID/g vs (9.33±0.66) ％ID/g;t=5.26,P＜0.05.MicroPET/CT imaging showed that the high-uptake location of 6-18F-Py-AMD3465 in tumor-bearing mice was similar to the normal mice,and the tumor uptake reached the maximum level at 45 min post-injection (SUV 0.67).Conclusions 6-18F-Py-AMD3465 can be synthesized by a simple method.A lower uptake could be shown in the tumor compared to that in the lung and the tracer has limited diagnostic value for lung cancer.

Adult ; Female ; Hemoperfusion ; Humans ; Male ; Neurotoxicity Syndromes ; etiology ; therapy ; Organophosphate Poisoning ; Pesticides ; poisoning ; Retrospective Studies ; Treatment Outcome

Seven sinapine analogs (6a-6g) were synthesized using cinnamon acid or benzoic acid and their derivatives as starting materials, which obtained from substituted benzaldehyde and malonate. The structures of target compounds were characterized by IR, 1H NMR and elemental analysis. The effects of compounds 6a-6g on the smooth muscle of intestine isolated from rabbit were studied, and the experimental results showed that compounds 6a, 6d and 6g had diastolic action, while 6f had contractile action.

Objective To investigate the antitumor effects on ovarian cancer using recombinant adenoviruses expressing autocatalytic caspase-3 driven by amplified human telomerase reverse transcriptase promoter (AdHTVP2G5-rev-casp3) combined with flavopiridol. Methods Following the treatment with AdHTVP2G5-rev-casp3 combined with flavopiridol, cell survival rate was measured by cell counting kit 8;cell apoptotic rate and cell cycle distribution were detected by flow cytometry. Western blot was performed to observe the expression of p17, the active subunit of caspase-3, and p85, the cleavage segment of substrate of caspase-3, in AO cells. The mice survival rates were measured for abdominally metastatic tumor models and the volume of tumor nodules were determined for subcutaneous tumor models following the treatments of AdHTVP2G5-rev-casp3 combined with flavopiridol. HE staining was used to detect the histopathological changes of various organs, and the serum level of alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured to monitor liver damages following the intraperitoneal administration of AdHTVP2G5-rev-casp3 and flavopiridol. Results There was no significant cell-killing effects or apoptosis in AO cells following treatments with AdHTVP2G5-rev-casp3 or flavopiridol at low dosage alone (apoptotic rate all ＜ 11% ), whereas significant synergism of their sequential combination was observed in AO cells. This sequential treatment of AdHTVP2G5-rev-casp3 [multiplicity of infection (MOI) was 20]infection for 72 hours, followed by flavopiridol ( 300 nmol/L) for 48 hours, could result in the most substantial cell death, and AO cells survival rate and apoptotic rate were 73. 5% and 11.6%, respectively.Following treatments with AdHTVP2G5-rev-casp3 at low doses ( MOI = 10), there was a significant increase in cell number with S-phase content ( 62. 5% ), which resulted in the most marked apoptosis induced by sequential treatments with flavopiridol. The sequential combination could induce significantly higher levels of p17 and p85 expression than that when their applications alone. Combined AdHTVP2G5-rev-casp3 and flavopiridol treatment prolonged mouse survival [ mean survival time of ( 286 ± 6) days ] and suppressed tumor growth significantly (tumor growth suppression rate of 81% ), when compared with treatment using either alone. The levels of serum ALT and AST were not significantly elevated and no obvious lesions were found in any organs in treatments with AdHTVP2G5-rev-casp3 of low doses combined with flavopiridol.Conclusions AdHTVP2G5-rev-casp3 at low doses results in a significant increase in cell number with Sphase content, which significantly enhanced the sensitivity of cells to flavopiridol. Treatments of autocatalytic caspase-3 combined at low doses with flavopiridol result in significant synergistic antitumor effects,significant tumor growth suppression and prolonged survival of mice. When compared with normal dose flavopiridol alone, the combination could resulted in minimal liver toxicity.

AIM: To clarify whether advanced glycation end products (AGEs) can influence the expression of mitochondrial fusion proteins Mfn1 and Mfn2 in cultured human aortic endothelial cells (HAECs) in vitro.METHODS:AGE-BSA was used as AGEs.Purchased primary human aortic endothelial cell line was multiplied, and transferred to dif-ferent passages for subsequent grouping.For dose-dependent experiment, HAECs were divided into 4 groups, and the con-centrations of AGE-BSA in each group were 0 mg/L (control group), 50 mg/L, 100 mg/L and 200 mg/L, respectively. For time-dependent experiment, HAECs were divided into 5 groups with the same concentration (100 mg/L) of AGE-BSA, but the intervention time was 0 h (control group), 6 h, 12 h, 24 h and 48 h, respectively.The mRNA and protein expres-sion levels of Mfn1 and Mfn2 in the HAECs were detected by real-time PCR and Western blot, respectively.RESULTS:Exposure of the HAECs to AGEs at different concentrations for 24 h all down-regulated the mRNA and protein expression levels of Mfn1 and Mfn2.Except for 6 h intervention group, 100 mg/L AGEs intervention for 12 h, 24 h and 48 h all down-regulated the mRNA and protein expression levels of Mfn1 and Mfn2 in cultured HAECs.CONCLUSION: AGEs down-regulates the expression of mitochondrial fusion proteins Mfn1 and Mfn2 in cultured HAECs, indicating that AGEs may influence mitochondrial dynamics of human aortic endothelial cells.

Objective To investigate the distribution of ligustrazine hydrochloride in guinea pig blood, cerebrospinal fluid and perilymph fluid afte intramuscular injection. Methods The HPLC was used for determination of ligustrazine hydrochloride in guinea pig blood, cerebrospinal fluid and perilymph fluid afte intramuscular injection by internal and external standard method.Results Ligustrazine hydrochloride could be absorbed into blood rapidly after intramuscular administration in guinea pig. The concentration reach its high level in 20 min.It was 357.76 ?g/ml. It decreased to low level 2 h after injection.It could be found in cerebrospinal fluid 10 min after injection. The concentration reached its high level in 20 min.It was 120.50 ?g/ml.It decreased to low level 70 min after injection. The ligustrazine hydrochloride could be found in perilymph fluid 5 min later.Its high level in 20 min was 215.79 ug/ml.It decreased to low level 70 min after injection.The results indicated that ligustrazine hydrochloride was rapidly absorbed and eliminated after intramuscular administration in guinea pig.Conclusion Ligustrazine hydrochloride can be absorbed into blood, enter cerebrospinal fluid and perilymph fluid. It can pass through blood-brain barrier and blood-labyrinth barrier. The results indicates that ligustrazine hydrochloride is rapidly absorbed and eliminated after intramuscular administration in guinea pig.

Objective To investigate the analgesic effect of adenosine A1 receptor agonist R( - )-N6-(2-phenylisopropyl)-adenosine (R-PIA) administered into the brainstem medial pontine reticular formation (mPRF) and the underlying mechanism. Methods Sixty male SD rats aged 8-10 weeks weighing 250-300 g were used in this study. The animals were anesthetized with intraperitoneal 10% chloral hydrate 300 mg?kg-1 .A 24-gauge stainless steel cannula was inserted into mPRF on one side using a stereotaxic apparatus. One week after operation the animals were randomly divided into 12 groups ( n=5 each) : groupⅠcontrol; groupⅡR-PIA 0.5?g; groupⅢR-PIA 1.0?g; groupⅣR-PIA 2.0?g; groupⅤtheophylline (an adenosine receptor antagonist) 5.0?g; groupⅥ8-cyclopentyl-1 ,3-dipropylxanthine (DPCPX, an adenosine A, receptor antagonist) 1.0?g; groupⅦglibenclamide (an ATP-sensitive K+ channel blocker) 5.0?g; groupⅧ4-aminopyridine (4-AP, a voltage dependent K+-channel blocker) 5.0?g; groupⅨtheophylline 5.0?g + R-PIA 2.0?g; groupⅩDPCPX 1.0?g + R-PIA 2.0?g; groupⅪglibenclamide 5.0?g + R-PIA 2.0?g and groupⅫ4-AP 5.0?g + R-PIA 2.0?g. All the drugs were injected into mPRF in 0.3?l of normal saline. In groupⅨ-ⅫR-PIA 2.0?g was administered 15 min after pretreatment with theophylline, DPCPX, glibenclamide or 4-AP. Analgesia was determined using the tailflick latency (TFL) (the time between the onset of the radiant heat stimulus and voluntary tail withdrawal) at 5, 15, 30, 45, 60 and 90 min after R-PIA injection into mPRF. The pain threshold was expressed as percentage of the maximal possible effect ( MPE) : MPE = (TFL after drug - baseline TFL)/( 10.0 -baseline TFL)?100% .Results R-PIA 0.5-2.0?g injected into mPRF produced significant analgesia in a dose-dependent manner. Pretreatment with theophylline or DPCPX completely reversed the analgesic effect of R-PIA while pretreatment with glibenclamide or 4-AP only partially reversed the analgesic effect of R-PIA.Conclusion R-PIA administered into mPRF produces analgesia through activation of both ATP-sensitive and voltage-dependent K+ -channel in mPRF.

Purpose: To confirm the therapeutic effects of thyrotropin-releasing hormone(TRH) on the experimental spinal cord injury. Method: Wistar rats were subjected to incomplete spinal cord injury using the modified Allen method. The effects were observed by means of neurologic scoring, quantitative enzyme histocytoehemistry、quantitative immunohistocytochemistry and electron microscopy. Results: 1) The treated group exhibited significantly higher scores than the control group. 2) Acetylcholinesterase (AchE) activity of anterior horn cells in the treated group was higher than that of the control group invarious time, and its activity restored to normal level two weeks after injury; Acid phosphatase(AePase) activity was lower than that of the control group in various time. and its activity restored to normal level four weeks after injury. The content of Nissl's bodies in anterior horn cells in the treated group was higher than that of the control goup one week after injury. 3)The number of axon in a certain area of spinal white matter in the treated group was more than that of the control group. 4)Ultrastructural observation showed that both the nerve tissue injury and the extent of hemorrhage were milder in the treated group than that of the control group. Conclusion: The therapeutic effects of TRH on the spinal cord injury" are shown not only in the improving recovery of motor function, but also in the morphology.