Objective: To study the possibility of liposomes to ta rget hepatocytes af ter being linked with asialofetuin(AF). Methods: The biodistribu tions in differen t cells in liver as well as in blood, in various organs such as heart, spleen, l ung and kidney of mice, of traditional sterically stabilized liposomes(SSL) , AF-linked normal liposomes(AF-NL) and AF-linked sterically stabilized lipos ome s(AF-SSL) were studied by radioisotopic labeling. Results: The half-live s of SSL, AF-NL and AF-SSL were 14.44, 4.73 and 11.49 h， respectively. The di strib ution of liposomes in liver was AF-NL>AF-SSL>SSL. There was significant differenc e among these three formulations. In hepatocytes and non-hepatocytes, the conce ntr ations of the liposomes were both in line with the sequence AF-NL>AF-SSL>SSL( P <0.05). However, the ra tios of the concentrations in hepatocytes to that of non-hepatocytes were AF-N L≈AF -SSLSSL( P <0.05). Conclusion: After being labeled with asi alofetuin, liposomes can target hepatocytes very we ll， whether in long-circulation or not.

OBJECTIVETo discuss whether asiaticosides could effectively reduce the endothelial cell damage as a biochemical modulator, so as to further inhibit the post-stenting intima-media membrane hyperplasia.

METHODHuman aortic smooth muscle cells and aortic fibroblasts were selected and divided into the blank group, the rapamycin group and the asiaticoside group and the rapamycin and asiaticoside group. The expressions of muscle cells and fibroblasts TGF-beta1, Smad7 and I-collagen gene were determined by RT-PCR. The expression quantity of I-collagen protein was assayed by ELISA. The coefficient of drug interaction (CDI) between rapamycin and asiaticoside was calculated. Additionally, 16 Chinese mini-swines were randomly divided into group A and group B. One sirolimus drug-eluting stent of the same type was implanted after the high-pressure pre-expansion of anterior descending artery balloon. After the operation, the group A was intravenously injected with normal saline 30 mL x d(-1). Whereas the group B was intravenously injected with asiaticoside 30 mg x kg(-1) x d(-1)(diluted to 30 mL). The expressions of plasma vWF of the two groups were measured at the 7th and 14th days after the operation. At the 28th day after the operation, tissues of the stented vessel segments were sliced and stained to calculate the vessel area, inner stent area, lumen area and neointima area

RESULTCompared with the control group, the combination group showed significant up-regulation in smooth muscle cells and fibroblast Smad7 gene, down-regulation in TGF-beta, and obvious inhibition of I-collagen gene expression (P < 0.01). As for smooth muscle cells, there was no difference in the expression of I-collagen between the combination group and the rapamycin group, with CDI at 0. 83. As for fibroblasts, there was a significant difference in the expression of I-collagen between the combination group and the rapamycin group (P < 0.05), with CDI at 0.77. Plasma vWF of the group B was significantly lower than that of the group A (P < 0.05) at the 7th and 14th days after the operation. At the 28th day after the operation, no difference was observed in vessel area and stent area between the two groups. However, the lumen area in the group B was significantly larger than that of the group A(P < 0.05), and the neointima area of the group B was significantly smaller than that of the group A (P < 0.05).

CONCLUSIONAs an effective biochemical modulator for rapamycin, asiaticosides could inhibit TGF-beta expression, significantly decrease the synthesis and secretion of extracellular matrix, further inhibit the post-stenting intima-media membrane hyperplasia and reduce the endothelial cell damage by effectively up-regulate the expression of Smad7 protein.

Animals ; Collagen ; genetics ; metabolism ; Coronary Restenosis ; drug therapy ; prevention & control ; surgery ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Hyperplasia ; drug therapy ; genetics ; metabolism ; prevention & control ; Smad7 Protein ; genetics ; metabolism ; Stents ; adverse effects ; Swine ; Transforming Growth Factor beta1 ; genetics ; metabolism ; Triterpenes ; administration & dosage

AIMTo investigate the formation mechanism, macromolecular drug loading capacity and release property of alginate-chitosan microcapsules (ACM).

METHODSACM was prepared by emulsification-gelation method and its formation mechanism was studied by DSC analysis. Using bovine serum albumin (BSA) as model drug, the drug loading and release properties of the microcapsules on macromolecular drug were investigated.

RESULTSThe results of DSC analysis showed that there is electrostatic interaction between materials encapsulated in the microcapsule. With the increase of BSA microcapsule ratio, the BSA loading percentage rose from 9.20% to 35.08%; and with the ascent of chitosan (CTS) concentration, the BSA loading percentage increased from 30.29% to 38.12%. The BSA microcapsules whowed a two-phase release in both 0.1 mol.L-1 HCl and phosphate buffer saline (pH 7.4). With the increase of CTS concentration, the BSA release more and more slowly in 0.1 mol.L-1 HCl.

CONCLUSIONSpheric and well-dispersed alginate-chitosan microcapsules were prepared. The microcapsule showed good loading capacity to BSA as well as sustained release to a certain degree.

Alginates ; chemistry ; Biopolymers ; Calorimetry, Differential Scanning ; Capsules ; Chitin ; analogs & derivatives ; chemistry ; Chitosan ; Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Serum Albumin, Bovine ; administration & dosage ; Technology, Pharmaceutical ; methods

Purpose To investigate the location and distribution of EV71 receptors scavenger receptor class B member 2 ( SCARB2 ) and human P-selectin glycoprotein ligand-1 (PSGL-1) in lung tissues of fatal hand, foot and mouth disease (HFMD), healthy children and adults. Methods The expression of EV71 receptors SCARB2 and PSGL-1 was detected by using immunohistochemistry in lung tissues of 15 autopsies of HFMD, 3 of healthy children, 8 of healthy adults. Results SCARB2 distributed in bronchial, bronchioli ep-ithelia, alveolar epithelial cells and inflammatory cells among HFMD, healthy children and adults. No significant difference was noted of the positive rates of SCARB2 expression among these three groups (P>0. 05). PSGL-1 distributed in bronchial and bronchioli epi-thelium of adults, but no PSGL-1 expression was found in HFMD and healthy children. The positive rates of PSGL-1 were 100%, 0, 0 in bronchial and bronchioli epithelium among the three groups, respectively (P<0. 05). The positive rates of PSGL-1 were 100%, 66. 7%, 100% in inflammatory cells among HFMD, healthy children and adults, respectively. No significant difference was noted of PSGL-1 expression among the three groups (P>0. 05). Further, no PSGL-1 expression was observed in alveolar epithelia cells of all groups tested. Conclusions EV71 receptor SCARB2 distributes in bronchial, bronchioli, alveolar epithelial and inflammatory cells of HFMD. Meanwhile, PSGL-1 only distributes in inflammatory cells of HFMD, suggesting that SCARB2 possibly plays a role on HFMD infection.

Objective To analyze the clinical manifestations,diagnosis and treatment of cerebral amyloid angiopathy (CAA) associated intracerebral hemorrhage.Methods The clinical manifestations,treatment and prognosis of CAA associated intracerebral hemorrhage were analyzed in 4 patients who were identified as CAA-related hemorrhage (CAAH) by pathology.Results All of the 4 patients showed massive lobar intracranial hemorrhage,and underwent craniotomy evacuation of hematoma.One patient had postoperative hemorrhage,and 2 patients were treated with recombinant activated factor Ⅶ after operation.In the next 6 months,re-hemorrhage was found in 3 patients in whom one patient died due to massive hemorrhage.Conclusions CAAH has varied clinical manifestations with high risk of cerebral hemorrhage,and pathological diagnosis is necessary for a definite diagnosis.The very elderly patients with CAAH can benefit from the craniotomy evacuation of hematoma.Although surgery for massive hemorrhage has risks in very elderly patients,it is a better treatment to save their lives.

Objective To investigate immunophenotypic characteristics of uterine natural killer (uNK)cells and helper T cell 1/helper T cell 2(Th1/Th2)immunity in third trimester decidua in preeclampsia.Methods The proportions of uNK cell subsets,expression of CD_(69)and CD_(94)on uNK cells and Th1/Th2 immunity in decidua were determined in 20 cases of preeclampsia patients and 11 cases of normal term pregnancies by flow cytometric analysis.Results The percentage of CD_(56)~(bright)CD_(16)~-uNK cell subset in preeclampsia patients and the controls was(17.3?11.1)% vs(17.9?16.8)%,that of CD_(56)~(dim) CD_(16)~+uNK cell subset was(16.3?8.7)% vs(16.2?8.8)%;that of CD_(56)~+CD_(69)~+uNK cells was(37.9 ?18.9)% vs(36.8?19.7)%,that of CD_(56)~+CD_(94)~+uNK cells was(34.9?15.2)% vs(32.7?16.2)% and the ratio of CD_(56)~+CD_(69)~+/CD_(56)~+CD_(94)~+was 1.1?0.2,1.2?0.6.No statistical difference was shown in the above values between the preeclampsia patients and controls.The percentage of cytoto xic T cell(Tc)2 cells was significantly lower in the decidua of preeclampsia patients [(3.0?1.0)% vs(4.3?0.9)%,P= 0.001 ],and the ratio of Tc1/Tc2 in preeclampsia patients was significantly higher than that of normal term pregnancies(17.8?3.4 vs 11.8?4.6;P=0.001);the ratio of Th1/Th2 was increased(15.1?2.4 vs 13.2?3.1;P=0.06).Conclusions The immunophenotypie characteristics of uNK cells do not present any significant change in preeclampsia patients.Owing to Tc2 cell decrease,the Th1/Th2 immunity shifts to Th1 type immunity in the decidua,which might contribute to the pathogenesis of preeclampsia.

The prognostic value of phosphatidylinositol-4,5-bisphosphate 3-kinase,catalytic subunit alpha (PIK3CA) in patients with esophageal squamous cell carcinoma (ESCC) is controversial.We aimed to investigate the prognostic significance of PIK3CA mutation in patients with ESCC.EMBASE,PubMed,and Web of Science databases were systematically searched from inception through Oct.3,2016.The hazard ratios (HRs) and 95％ confidence intervals (CI) were calculated using a random effects model for overall survival (OS) and disease-free survival (DFS).Seven studies enrolling 1505 patients were eligible for inclusion of the current meta-analysis.Results revealed that PIK3CA mutation was not significantly associated with OS (HR:0.90,95％ CI:0.63-1.30,P=0.591),with a significant heterogeneity (I2=65.7％,P=0.012).Additionally,subgroup analyses were further conducted according to various variables,such as types of specimen,the sample size,technique and statistical methodology.All results suggested that no significant relationship was found between PIK3CA mutation and OS in patients with ESCC.For DFS,there was no significant association between PIK3CA mutation and DFS in patients with ESCC (HR:1.00,95％ CI=0.47-2.11,P=0.993,I2=73.7％).Publication bias was not present and the results of sensitivity analysis were very stable in the current meta-analysis.Our findings suggest that PIK3CA mutation has no significant effects on OS and DFS in ESCC patients.More well-designed prospective studies with better methodology for PIK3CA assessment are required to clarify the prognostic significance of PIK3CA mutation in ESCC patients.

AIMTo prepare thrombus-targeted urokinase liposomes and observe its improved thrombolytic efficacy on thrombus model rats.

METHODSThe ligand H-Arg-Gly-Asp-Ser-OH (RGDS) which has specific affinity to thrombus was synthesized by liquid phase method and anchored on the surface of liposomes by incorporating its conjugate with DSPE-PEG3,500-COOH into liposomal lipid bilayers, thus thrombus-targeted liposomes were produced. Urokinase (UK) liposomes were prepared at room temperature through method modification using hydrogenated soy phosphatidylcholine (HSPC); the in vivo thrombolysis of the obtained thrombus-targeted UK liposomes and its comparison with TBS (Tris-HCl buffered solution) control, free UK and UK liposomes were assessed on common carotid artery model rats.

RESULTSThe obtained liposomes were characteristic of high UK entrapment efficiency, small mean diameter and good storage stability. At the same dose (60,000 U.kg-1), compared to the wet thrombi weights of TBS control group, those of free UK group and UK liposome group showed no statistical difference, while those of targeted UK liposomes group were significantly decreased (P < 0.001); when evaluated in term of dry thrombi weights the result was slightly different. Compared to UK liposomes of the same dose, the targeted UK liposomes showed significantly improved thrombolytic efficacy (P < 0.01 in wet weights decrease and P < 0.05 in dry weights decrease respectively).

CONCLUSIONThe targeted UK liposomes displayed good targeted thrombolytic effect.

Animals ; Disease Models, Animal ; Drug Carriers ; Drug Delivery Systems ; Fibrinolytic Agents ; administration & dosage ; therapeutic use ; Liposomes ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Technology, Pharmaceutical ; Thrombosis ; drug therapy ; Treatment Outcome ; Urokinase-Type Plasminogen Activator ; administration & dosage ; therapeutic use

Objective To investigate clinical features and antifungal therapeutic effect of chronic severe hepatitis (CSH) patients with invasive fungal infection (IFI), and to improve the diagnosis and treatment.Methods Clinical manifestation, blood routine, imageology and mycetology characteristic, antifungal treatment perscription and therapeutic effect of 79 CSH patients with IFI were retrospectively analyzed. Antifungal therapeutic effect was compared between fluconazole and voriconazole. Results Thirteen (16.5%) patients received glucocorticoid or other immunodepressants for a relatively long time, 40 (50.6%) patients had invasive operation, and 61 (77.2 %) patients were administered 1-6 kinds of broad-spectrum antibiotics. Seventy-three patients had fever. Leucocytes and neutrophilic granulocyte increased in 96.2% of the patients. Lung (31.6%), intestinal tract (26.2%) and oral cavity (14%) infections were common. Fungus was found in 70.9% of the patients. Candida albicans (40.9%) and aspergillus (21.1%) were often seen. Halo signs and crescent signs on lung CT were relatively specific in 40% of the patients with fungal pneumonia. Voriconazole was more effective than fluconazole(71.4% vs. 39.0%, P<0.05). Twelve patients with lung aspergillus infection were administered voriconazole, 8 (66.7%) patients of whom was effective, and the other 4 (33.3%) patients died. Conclusion There are high risk factors in major CSH patients with IFI. The most common clinical manifestations of CSH patients with IFI are fever, leukocytosis, lung and intestinal tract infection. Candida albicans and aspergillus infection are common. Voriconazole is more effective than fluconazole, and can increase the survival rate of CSH patients with IFI.

Objective To determine the value of acute phase protein in the early diagnosis of recurrence after curative gastric cancer surgery. Methods Acute phase serum protein level was measured before and after the gastric cancer surgery in 120 patients,and was compared with that of the control group. At 1, 3, 6, 9, 12 months after the operation in 87 patients undergoing curative gastric cancer surgery, the levels of acute phase proteins were measured. They were followed up for at least 12 months or until death. Results The levels of serum C reactive protein(CRP), ?1 antitrypsin (?1 AT) and ? acid glycoprotein (? AG) in gastric cancer group were significantly higher than those in the control group (P0.05). In patients who underwent curative gastric cancer surgery in a certain period after the operation, the serum levels of CRP, ?1 AT and ? AG were significantly lower than those before the surgery(P0.05).There were significant difference in CRP,?1 AT and ? AG between the recurrence groups and nonrecurrence group before and after the operation (P