Left atrial appendage ( LAA) arises from the left atrial free wall. It is the remnant of the original embryonic LA, distinct from the rest of the left atrium. It has a unique anatomical structure, physiological function, hemodynamic characteristics. LAA has complex surrounding structures, great variability, and close relation with thrombosis. This paper reviews the morphological and functional characteristics of LAA. Familiar with adjacent relationship of LAA and correlation between LAA and thrombus formation has important clinical significance that can reduce the risk of postoperative complications in interventional procedures, the incidence of car?dioembolic stroke, the clinical misdiagnosis on LAA thrombosis.

Objective:To prepare injectable interferon ?-2b(IFN-?-2b) loaded microsphere and develop a long-acting dosage form.Methods: IFN-?-2b loaded microspheres were prepared with poly(lactic-co-glycolic acid)(PLGA) as carrier material by double emulsion(w/o/w) method and solid in oil in oil(s/o/o) method separately.Physical and chemical characteristics of microspheres(mean diameter,morphology and drug entrapment efficiency) were evaluated;the in vitro release behavior and influencing factors of the microspheres were determined by micro-BCA(bicinchoninic acid) method;and IFN-?-2b stability during encapsulation and in vitro release was evaluated by sodium dodecyl sulfate polyacrylamide gel electropheresis.Results: The 2 types of microspheres produced had good shape and dispersive quality and a drug entrapment efficiency of more than 80%.IFN-?-2b bulk ultrafitration can significantly influence the mean diameter and in vitro release behavior of microspheres prepared by w/o/w method.The accumulated release(within 1 month) of the microspheres prepared by both methods was significantly improved when using PLGA with lower inherent viscosity.SDS-PAGE test showed aggregation of IFN-?-2b with s/o/o method,while there was no difference between the electrophoretic behavior of bulk IFN-?-2b and IFN-?-2b in microspheres prepared by w/o/w method.Conclusion: IFN-?-2b can be encapsulated into injectable microspheres to yield a one-month continuous release by both w/o/w method and s/o/o method.

A complex disease is rarely a consequence of abnormality in a single gene. It is known that many drugs exhibit a therapeutic effect by acting on multiple targets, produce synergies to intervene the occurrence and development of diseases. Unlike the traditional methods which act on single molecule or pathway, this disease-drug target network constructed with high throughput data vividly showed the complex relationship between drugs, their targets and diseases. However, the networks are usually extremely complex. In order to reduce the complexity, it is necessary to deconstruct the network and identify module structures. In this study, framework of module analysis was summarized from four aspects: module concept, structure and identification methods, importance of disease-drug module identification, and its application. Module-based analysis provides a new perspective for deciphering the drug intervention mechanisms for complex diseases, and provides new ideas and pathways to reveal the mechanisms of multi-target and multi-component drugs.
Drug Delivery Systems ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Gene Regulatory Networks ; drug effects ; Humans ; Molecular Targeted Therapy

OBJECTIVETo explore the effect of emodin on endoplasmic reticulum (ER) stress of pancreatic acinar AR42J cells.

METHODRat pancreatic acinar AR42J cells were cultured in 6-well plates, and divided into the normal control group, the model group (with the final concentration at 1 x 10(-7) mol · L(-1) for cerulean and lipopolysaccharide at 10 mg · L(-1)) and the emodin group (10, 20, 40 μmol · L(-1)). Cells in each group were cultured in three multiple pores for 24 h, and their supernate was removed after cell attachment. The normal control group was added with haploids, the model group was added with the modeling liquid for haploids, and the treatment groups were added with different concentrations of emodin at 15-20 min before the modeling liquid. The cells were continuously cultured for 3 h under 37 °C and 5% CO2. Their intracellular protease and lipase expressions were detected with kits. The cellular morphology was observed under optical microscope. The level of calcium in endoplasmic reticulum was measured under laser confocal microscopy. Western blot assay were used to determine the protein expression of ER-related signaling molecules.

RESULTEmodin could significantly inhibit levels of amylase, lipase and intracellular calcium and ER.

CONCLUSIONEmodin could reduce pancreatic acinar cell injury induced by the combination of cerulean and lipopolysaccharide. Its action mechanism is correlated with the inhibition of intracellular calcium overload and ER stress.

Animals ; Calcium ; metabolism ; Cell Line, Tumor ; Emodin ; pharmacology ; Endoplasmic Reticulum Stress ; drug effects ; Pancreatic Neoplasms ; metabolism ; pathology ; Rats ; Unfolded Protein Response ; drug effects

Objective To explore the clinicopathological features of IgA nephrolpathy associated with malignant hypertension (IgAN-MHT) and to analyze their correlation with renal vascular lesions. Methods Twenty-nine patients of IgAN-MHT were screened from 2000 biopsy-proven eases with primary IgA nephropathy (IgAN) in our department from April 1997 to May 2007. Data of clinicopathology and follow-up of these 29 patients were collected. Semi- quantitative analysis was performed to evaluate the pathological changes. Inner lumen, outer lumen, intimal thickness, tunica media-to-internal lumen ratio of 436 arterioles, 124 interlobular arteries and 5 arcuate arteries were measured. The primary endpeint was the composite of a doubling of serum creatinine level and ESRD. Correlations of renal vascular lesions with clinical manifestation, pathological change and prognosis were examined by Spearman and Cox methods. Results 1.5% of all the IgAN patients presented malignant hypertension. The common clinical features were renal failure (100%), hyperurieacidemia (62.7%) and hypertriglyceridemia (51.7%). The average amount of urine protein excretion was 2.8 g/d. The common pathological changes were moderate mesangial proliferation, severe global sclerosis, severe interstitial inflammation and severe interstitial- tubular fibrosis. The small arteries (arcuate arteries and interlobular arteries) and arterioles (afferent arterioles) were both involved in IgAN-MHT. The characteristic lesions of intrarenal arteries included vascular occlusion, media thickening, proliferative endarteritis (onionskin lesion, musculomucoid intimal hyperplasia), hyaline arteriosclerosis, but mainly vascular occlusion (86.2%). The arteriole lesion was negatively correlated with age and total protein level; vascular occlusion was positively correlated with uric acid level. The average foUow-up period was 21.1 months. Forteen patients reached the endpoint. The arteriole lesion was the main independent risk factor for the progression of IgAN-MHT (RR=10.21, 95%CI=1.16～89.67). Conclusions The main clinical feature of IgAN-MHT is renal failure. The main histological feature of intrarenal vascular lesions is occludes arterioles. Arteriole lesion is the main independent risk factor for the progression of IgAN-MHT.

Objective Allograft vasculopathy (AV), feature of chronic rejection, is a major serious long-term post-operation complication in organ transplantation. The accurate mechanisms for AV have not been definitively established, but extensive basic and clinical studies demonstrate AV is triggered by immune reaction and nonimmunologic factors, and also possibly attributed to the metabolism of branched-chain amino acids (BCAA). Methods The transplanted hearts from Lewis to Sprague-Dawely rats served as allografts and those from Lewis to Lewis rats as isografts based on Ono 's model. The differential proteins in transplanted hearts were separated by comparative proteomic technique, and some enzymes which regulated the metabolism of BCAA were identified and validated.Results All transplanted hearts at second week postoperation were characterized by lumen loss (total area-luminal area/total area) in coronary artery, but more predominant at 8th week. All samples from the left ventricles were analyzed by proteomic techniques and the subunits E1 a, E1β and E3 of branched-chain α-ketoacid dehydrogenase (BCKDH) complex were decreased in the heart allografts.Immunohistological detection also showed the expression of BCKDH was reduced not only in the cardiac muscle but also more significantly in blool vessels with cardiac allograft vasculopathy (CAV).BCAA concentrations were increased in the cardiac allografts, but there was no difference in the serum. Conclusion These findings suggest that the catabolic pathways of the BCAA may be inhibited owing to the reduced expression of BCKDH complex, and elevated intracellular concentrations of leucine. The vascular smooth muscle cell and cardiac muscle cell proliferation is stimulated via mTOR-dependent and mTOR-independent pathways, which is associated with the formation of myocardial hypertrophy and AV in the heart allografts.

Purpose To prepare 68Ga-NOTA-SPIO as PET/MRI dual mode imaging probe with high sensitivity and resolution,and further evaluate its in vitro and partly in vivo biological properties.Materials and Methods The precursor SPIO-PEG2000-NOTA was prepared and characterized.The precursor was radiolabeled by using one step method to prepare 68Ga-NOTA-SPIO as dual mode imaging probe.The labeling rate of the probe was determined by rapid thin-layer chromatography.Besides,the in vitro stability and lipid water partition coefficient of the probe were evaluated,and its biodistribution in normal mice was also observed.Results The precursor SPIO-PEG2000-NOTA with uniform dispersion and uniform particle size was prepared,and the dual mode probe 68Ga-NOTA-SPIO was synthesized.The labeling rate reached 99％,and the lipid water partition coefficient (Log P) was (-2.60±0.13).The radiochemical purity of the probe was higher than 95％,as it was incubated in the phosphate buffer and fetal bovine serum within 2 hours.The probe was mainly distributed in the liver and spleen of mice,and its clearance velocity in blood was fast.Conclusion The double mode probe 68Ga-NOTA-SPIO synthesized by one step method has high labeling rate with no need of purification,which has good physic-chemical properties and biocompatibility.The probe can be used in the further research of PET/MRI dual modality imaging.

The interferons(IFNs) are a family of the multifunctional cytokines, which are a kind of highly active and multifunctional glycoproteins.Studies in recent years have shown that IFNs exert a powerful antitumor effect by regulating the proliferation of tumor cells, suppressing tumor metastasis and angiogenesis, and activating antitumor immune response.Combined with other tumor treatment methods, it can inhibit the development of a variety of blood system tumors and solid tumors.In addition, the use of IFNs inducers or IFNs combined with emerging immunotherapy can significantly increase the effectiveness of tumor therapy.This review focuses on our understanding of antitumor mechanism and clinical application of IFNs, and provides some guidance for future research and clinical treatment.

Objective To explore the preparation and quality control of As2 O3 nanoparticle .Methods PEG‐PLA was used as the vector material to prepare As2 O3 nanoparticle with ultrasonic emulsification method ,and the VEGFR‐2 was coupled to obtain VEGFR‐2/As2 O3‐PEG‐PLA nanoparticle .The particle size distribution ,Zata potential ,loading efficiency (LE) ,encapsulation effi‐ciency(EE) ,drug release in vitro and stability was determined ,and morphological characteristics was observed by transmission elec‐tron microscope(TEM) .Tweety‐four hepatocellular carcinoma nude mices were randomly divided into VEGFR‐2/As2O3‐PEG‐PLA nanoparticles group and As2 O3‐PEG‐PLA nanoparticles group ,by tail vein injection of nanoparticles .High performance liquid chro‐matography was used to determine content of As2 O3 .After 21 d ,six nude mices in each group were killed ,and the immunohisto‐chemistry and western blot method was used to detect the expression of VEGFR‐2 .Results The particle size of VEGFR‐2/As2 O3‐PEG‐PLA was determined to be (141 .9 ± 13 .2)nm ,Zata potential was (10 .2 ± 1 .1)mV .It was found to spherical or oval shape , with uniform size and dispersibility under TEM .LE and EE was (5 .51 ± 1 .83)% and (62 .12 ± 5 .98)% ,respectively .Drug release in vitro showed that VEGFR‐2/As2 O3‐PEG‐PLA exhibited controlled release effect ,with half of the release time as 10 h .Besides , VEGFR‐2/As2 O3‐PEG‐PLA showed a good stability in 3 days .Compared with As2 O3‐PEG‐PLA nanoparticles group ,the concen‐tration of As2 O3 in tumor and liver tissue was high ,the concentration of As2 O3 in blood ,heart ,kidney tissue was low ,the expression of VEGFR‐2 in tumor tissue was low in VEGFR‐2/As2O3‐PEG‐PLA nanoparticles group(P< 0 .05) .Conclusion The prepared As2 O3 nanoparticle using PEG‐PLA as vector and VEGFR‐2 as target showed uniform size ,high EE and LE ,good stability .And it preliminarily proved that VEGFR‐2 could be targeted in nude mice .

Objective To discuss the efficacy of Compound Anisodine Injection combined with Iodized Lecithin Tablets in treatment of central serous chorioretinopathy.Methods Totally 60 patients with CSC were selected,and divided into two groups randomly.The patients in control group (29 cases) were given Iodized Lecithin Tablets.The patients in observation group (31 cases) were given Iodized Lecithin Tablets and Compound Anisodine Injection.The efficacy of Compound Anisodine Injection combined with Iodized Lecithin Tablets in treatment of central serous chorioretinopathy was evaluated by efficacy,visual acuity,light sensitivity,and adverse reaction during treatment.Results After treatment,the effective rates of observation and control groups were 93.5％ and 79.3％,and the observation group was significantly higher than control group (P ＜ 0.05).There were no statistical significance on visual acuity between two groups.After treatment,rhe visual acuity of two groups was increased and the visual acuity in the observation group was better (P ＜ 0.05).Before treatment,there were no statistical significance on light sensitivity between two groups.After 2 and 4 weeks treatment,the light sensitivity of two groups were increased and the light sensitivity in the observation group was higher (P ＜ 0.05).During treatment,there was no statistical significance on adverse reaction between two groups.Conclusion Compound Anisodine Injection combined with Iodized Lecithin Tablets has a curative effect on central serous chorioretinopathy.It could increase the visual acuity and improve the light sensitivity of eyes with good security.It is worthy of clinical use.