The intracellular trafficking and subcellular distribution of exogenous gene is very important for gene delivery. A successful gene vehicle should overcome various barriers including endosomal membrane barriers to delivery gene to the target organelle. Traditional nonviral vehicle is unable to avoid endosomal pathway efficiently, so the efficiency of gene delivery is low and the application of gene drugs is limited. In order to achieve efficient nonviral gene delivery, a lot of researches based on endosomal escape have been carried out and some agents with the function of endsomal escape have been found. These agents facilitate the endsomal escape via various mechanisms, such as fusion into the lipid bilayer of endosomes, pore formation in the endosomal membrane, proton sponge effect and photochemical methods to rupture the endosomal membrane. In this review, various reported strategies for endsomal escape are described according to the escape mechanisms, and their applications in intracellular gene delivery are also discussed.
Cell Membrane ; metabolism ; Endosomes ; metabolism ; Gene Transfer Techniques ; Genetic Therapy ; Genetic Vectors ; Humans

BACKGROUND: The maximal problem of patient with serious hepatitis and surgical doctor is whether they can get donator and rational therapy timely. Looking for the suitable preoperative therapy method to enhance the success rate of operation and improve patient's prognosis is the focus of this domain.OBJECTIVE: To investigate the therapeutic effect of artificial liver support system (ALSS) combining with allotransplantation of the liver on patients with serious hepatitis.DESIGN: Retrospective case analysis. SETTING: Organ Transplantation Center, the Third Affiliated Hospital of Anhui Medical University.PARTICIPANTS: Five male patients with serious hepatitis who underwent allograft liver transplantation were selected from Organ Transplantation Center, the Third Affiliated Hospital of Anhui Medical University form June 2004 to May 2005. Their age ranged from 25 to 48 years. Inclusion criteria: The diagnosis was in accordance with phase standard established at the National Infectious Disease and Parasitology Academic Meeting in September 2000; all patients had signs of routine liver transplantation; their patients fiercely requested the operation.METHODS: Plasma exchange (PE) combined with continuous veno-venous hemofiltration (CVVH) technique was used in this study. Donor who supplied lives was from 20-38-year patients. All of them and their family agreed to donate their organ and signed the donate file before operation. All of 5 patients were used classical no-by-pass orthotopic liver transplantation (OLT). MAIN OUTCOME MEASURES: They were follow-up visited for 21-32 months for rechecking liver and kidney function,RESULTS: All of 5 patients' operation was succeeded. One continued coma postoperative and his serum creatinine and urea nitrogen raised up progressively and complicated by pulmonary infection 1 week after operation and died 2 weeks after operation although given medical treatment hemodialysis positively. The rest recovered well. All of them discharged one month after operation smoothly.CONCLUSION: Allotransplantation of the liver is an utilizable method to treat serious hepatitis. ALSS can be used as an effective method of supportive treatment preoperatively.

Objective To summarize the use of the CT-guided mandibular angle plastic osteotomy.Methods The clinical data of mandibular angle plastic osteotomy were analyzed under the CT navigation in recent 3 years in our department.Thin-slice CT scans of the mandibular angle were performed before the operation.The CT data were input to the system of neuronavigation.The surgical procedures were then taken under the CT navigation.Results All of patients who received this new technology obtained good plastic effects and safe operation.The anatomic location accurately achieched with short operation time and less bleeding during the operation and distinct curative effect and fast recovery after operation.The effects of the treatment were fine.No visible complications occurred.Conclusions The CT navigation could fix accurately on position of important blood vessels and nerves which could be injured accidentally during operation and,of course,the safety of the operation is improved.The CT navigation can also determine the position and quantities of osteotomy from three dimensional angles,reduce effectively the surgical complications and the risk of surgery,reduce the psychological burden of patients efficiently and increase their confidence and credibility to the operation and surgeons.

Angioplasty, Balloon ; methods ; Atherosclerosis ; pathology ; therapy ; Humans ; Hypertension ; complications ; drug therapy ; Renal Artery Obstruction ; etiology ; therapy ; Stents

OBJECTIVETo observe the efficacy and safety of modified Shengma Biejia Decoction (MSBD) combined with CAG program in treating elderly acute myeloid leukemia (AML) patients with yin deficiency toxin stasis syndrome (YDTSS).

METHODSTotally 46 elderly AML patients were assigned to the treatment group (24 cases; treated with MSBD + CAG) and the control group (22 cases; treated with CAG + placebos of Chinese medicine) according to random digit table. The therapeutic course of CM placebo or MSBD was 21 days. The clinical efficacy and adverse reactions were observed. Meanwhile, physical state (ECOG Score), transfusion dependency, and TCM syndrome score were compared before and after treatment.

RESULTS(1) The complete remission rate was 54% (13/24) and the objective response rate (ORR) was 71% (17/24) in the treatment group, obviously higher than those of the control group [36% (8/22); 54% (13/24)], with statistical difference (P = 0.036, 0.042). When comparing the efficacy based on risk level, the moderate and poor ORR was 71% (10/14) and 67% (6/9) in the treatment group, and 57% (8/14) and 33% (2/6) in the control group, with statistical difference between the two groups (P = 0.048; P = 0.010). (2) Compared with before treatment in the same group, the ECOG score significantly decreased, the average infusion time of red cells and platelets were markedly prolonged in the treatment group after treatment (P < 0.05). ECOG score, the average infusion time of red cells and platelets were significantly better in the treatment group than in the control group after treatment (P < 0.05). (3) Compared with before treatment in the same group, scores of fever, hemorrhage, and bone pain were markedly reduced in the control group (P < 0.05); scores of fever, fatigue, hemorrhage, dry mouth, and bone pain were markedly reduced in the treatment group (P < 0.05). Better effect in relief of fever, fatigue, hemorrhage, dry mouth, and so on was obtained in the treatment group than in the control group (P < 0.05). (4) In aspect of hematotoxicity, the incidence of neutropenia, anemia, thrombocytopenia was obviously lower in the treatment group than in the control group [29.2% (7/24) vs 54.5% (12/22); 16.7% (4/ 24) vs 45.5% (10/22); 33.3% (8/24) vs 63.6% (14/22); P < 0.05]. The incidence of fatigue and anorexia was obviously lower in the treatment group than in the control group [37.5% (9/24) vs 63.6% (14/22), 37.5% (9/24) vs 81.8% (18/22); P < 0.05].

CONCLUSIONMSBD combined with CAG program in treating elderly AML patients with YDTSS, with efficacy enhancing toxicity reducing effect, had distinct advantages in improving physical condition and clinical symptoms, and reducing transfusion dependency.

Aclarubicin ; therapeutic use ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Medicine, Chinese Traditional ; Phytotherapy ; Yin Deficiency ; drug therapy

Chondroblastoma ; pathology ; Chondrosarcoma ; diagnostic imaging ; pathology ; Chondrosarcoma, Mesenchymal ; pathology ; Diagnosis, Differential ; Female ; Hamartoma ; pathology ; Humans ; Lung Neoplasms ; diagnostic imaging ; pathology ; Middle Aged ; Radiography

OBJECTIVETo observe the effect of panaxadiol saponin (PDS) and panaxtrol saponin (PTS) on proliferation of human bone marrow hemopoietic progenitor cells (HPC).

METHODSPDS and PTS were separated and purified from ginsenosides, and the effects on HPC were studied using in vitro hemopoietic progenitor cell colony-forming technique, by observing the proliferation of human burst forming unit-erythroid progenitor (BFU-E), colony-forming unit-erythroid (CFU-E), colony-forming unit-granulocyte/macrophage (CFU-GM) and colony-forming unit-pluripotent hemopoietic progenitor (CFU-Mix) in mice after PDS and PTS stimulation.

RESULTSDifferent concentration of PDS (2.5-200 micrograms/ml) could stimulate the proliferation of HPC obviously, showing increase of CFU-E, BFU-E, CFU-GM and CFU-Mix by 54.9 +/- 6.3%, 48.8 +/- 5.1%, 27.6 +/- 4.2% and 48.9 +/- 3.9% respectively, which was higher than that of the control group. While stimulated by PTS of the same concentration, the CFU-E and BFU-E was lower than that of control significantly (P < 0.05); when the terminal concentration of PTS was 200 micrograms/ml, CFU-E and BFU-E was zero respectively. In the CFU-GM culture, PTS in concentration of 12.5 micrograms/ml could cause the proliferation increased by 29.7 +/- 2.2% (P < 0.05), but in concentration of 100 micrograms/ml and 200 micrograms/ml, it showed inhibitory effect on CFU-GM, the inhibition rate being 48.6 +/- 3.9% and 100% respectively.

CONCLUSIONPDS is the effective component of ginsenosides in stimulating proliferation of human bone marrow HPC. PTS is an component with inhibitory action on proliferation of CFU-E and BFU-E and its effect on CFU-GM was depending on its concentration.

Bone Marrow Cells ; cytology ; Cell Differentiation ; drug effects ; Cell Division ; drug effects ; Cells, Cultured ; Colony-Forming Units Assay ; Erythroid Precursor Cells ; Ginsenosides ; pharmacology ; Granulocyte Colony-Stimulating Factor ; Hematopoiesis ; drug effects ; Hematopoietic Stem Cells ; cytology ; Humans ; Panax ; chemistry ; Saponins ; pharmacology ; Triterpenes ; pharmacology

OBJECTIVETo explore the correlation between pathological characteristics of target organs and excess evil syndrome in IgA nephropathy.

METHODSData were collected in multicenter cooperation. Totally 266 IgA nephropathy patients were typed into exogenous wind-heat affection syndrome (49 cases), lower energizer damp-heat syndrome (100 cases), damp-phlegm syndrome (43 cases), and blood stasis syndrome (74 cases). Meanwhile, percutaneous renal biopsy was performed in all patients for Hass classification, Oxford classification, Katafuchi integral, and Jiang's classification methods. The correlation between excess evil syndrome and pathological index was analyzed.

RESULTSFour syndrome types were correlated with their Hass levels (r = 0. 341, P <0. 01). Affection of exogenous wind-heat syndrome was correlated with segmental proliferation of endothelial cells and damaged active lesions of segmental capillary loops. Lower-energizer damp-heat syndrome was associated with Hass III level, destroying active lesions of capillary loops, segmental proliferation of endothelial cells, glomerular segmental lesions, focal interstitial infiltration of inflammatory cells, focal interstitial fibrosis and tubular atrophy. Blood stasis syndrome was associated with Hass IV level, glomerular sclerosis, segmental glomerulosclerosis (S)/adhesion, mesangial hypercellularity (M), angiohyalinosis, multi-foci interstitial infiltration of inflammatory cells, multi-foci interstitial fibrosis and tubular atrophy. Phlegm-damp syndrome had higher proportions of Hass I and III levels, but with no association with other pathological parameters.

CONCLUSIONSExcess evil syndrome was associated with partial pathological characteristics of IgA nephropathy. It could reflect pathological damage degree of target organs, activities, chronic lesions, and prognosis of IgA nephropathy to certain extent. Correlated pathological characteristics and its evolution could indicate excess evil syndrome types and their evolution rules.

Capillaries ; Fibrosis ; Glomerulonephritis, IGA ; pathology ; Glomerulosclerosis, Focal Segmental ; Humans ; Kidney Glomerulus ; Medicine, Chinese Traditional ; Prognosis ; Syndrome

OBJECTIVETo evaluate the effect of Yufeining, a traditional Chinese medicine, on induced sputum interleukin-8 (IL-8) in patients with chronic obstructive pulmonary disease (COPD) at the stable phase.

METHODSThirty-six patients with COPD were divided into trial group (18 cases) and control group (18 cases) randomly. The trial group was treated with Yufeining pills taken orally for half a year; the control group was not given any medicine. Routine lung function was recorded before and after treatment. Total cell count (TCC), differential cell counts (DCCs) and IL-8 in induced sputum were determined at the baseline and 6 months later.

RESULTSThe indices of lung function improved significantly after 6 months' treatment in trial group (P < 0.05); TCC and absolute neutrophil count decreased significantly compared with baseline in the trial group (P < 0.05); Sputum IL-8 concentration dropped significantly after 6 months' treatment, from a mean of 5.216 +/- 2.914 microg/L to 4.222 +/- 2.140 microg/L (P < 0.05). There were insignificant changes in the parameters in the control group between baseline and 6 months later.

CONCLUSIONYufeining could improve lung function, decrease sputum TCC, absolute neutrophil count and IL-8 concentration, and relieve airway inflammation in patients with COPD in the stable phase.

Aged ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Interleukin-8 ; analysis ; immunology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; immunology ; Respiratory Function Tests ; Sputum ; chemistry

Abstract?AlM: To observe the effects of Shuangdanmingmu capsule on VEGF expression and retinal vascular morphology in rats with diabetic retinopathy ( DR) .?METHODS: DR rats were fed with Shuangdanmingmu capsule. By comparing with the normal group, the model control group, and positive control group, the effect of Shuangdanmingmu capsule on retinal tissue of DR rats was observed under electron microscopy. After HE staining, retinal structure was observed under the light microscope. lmmunohitochemical staining was used to detect the VEGF expression in retina.?RESULTS:Two months after treatment, the layers tissue of retina presented mild edema, capillary pericytes performed edema, mitochondria showed mild swelling and less clear structure, some endothelial cells showed slight proliferation in Shuangdanmingmu group. Compared with the normal group, the expression level of VEGF in retina increased in the other groups, especially in model control group. A significant differential in expression of VEGF was found between Shuangdanmingmu group, positive control group and model control group (P<0. 01).? CONCLUSlON: Shuangdanmingmu capsule can effectively improve the retinal microvascular, reduce edema and necrosis of each layer of retina, improve the ultrastructure of retina's tissue and inhibit VEGF expression in DR rats.