Targeting drug delivery system (TDDS) is one of the most concerned research fields in cancer treatment because it can bind selectively and react with the target diseased sites at the cellular or sub-cellular level, making distribution and release of drugs in a controlled manner, thus enhance therapeutic effects and reduce toxic and side-effects on normal cells. Polyamidoamine dendrimer (PAMAMD) is a kind of newly developed polymer in nanometer degree. Hyper-branched, monodispersity, three-dimensional structure and host-guest entrapment ability make it used as drug carrier, gene delivery system and imaging agent. Various targeting ligands, which have high affinity to specific organs, tissues or cells in human body, can be linked to surface functional groups of PAMAMD. And drugs and theoretical gene are carried by encapsulation or chemical conjugation. Finally, PAMAMD targeting drug delivery system can carry drugs and theoretical gene to diseased sites and then release them for targeted therapy. The PAMAMD-based conjugates have small size, ligh permeability and retention effect (EPR), low toxicity and so on. The research progress of PAMAMD modified by different ligands in targeting drug delivery system is reviewed, and research direction of the PAMAMD targeting delivery system in the future is also suggested.
Amino Acids ; administration & dosage ; chemistry ; Animals ; Antibodies, Monoclonal ; administration & dosage ; chemistry ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Biotin ; administration & dosage ; chemistry ; Dendrimers ; administration & dosage ; chemistry ; Drug Carriers ; administration & dosage ; chemistry ; Drug Delivery Systems ; Folic Acid ; administration & dosage ; chemistry ; Gene Transfer Techniques ; Humans ; Ligands ; Neoplasms ; drug therapy ; Polyamines ; administration & dosage ; chemistry ; pharmacokinetics ; Polyethylene Glycols ; administration & dosage ; chemistry ; Transferrin ; administration & dosage ; chemistry

0.05),but expression of VEGF,GLUT1 and MDR1 were all enhanced and overall proliferation was promoted,apoptosis inhibited [(11.46?0.28)% vs (29.27?0.18)%,(15.77? 0.49)% vs (31.13?0.08)%],and transmembrane behavior enhanced [(37?12)% vs (26?7)%, (40?9)% vs (28?5)%],and the variations were significant (P

Objective To reversing methicillin-resistant Staphylococcus(MRS) to methicillin-susceptible Staphylococcus(MSS) by changing nutritional conditions and continuous transfer of culture .Methods MRS trains separating from clinical specimens were cultured in different conditions ,continuous cultural transfer ,and drug sensitive test were proceeded periodically to observe the phe-notypic and chemical reaction change of MRS .The mecA gene were detected of the original and mutant strains by polymerase chain reaction(PCR) ,then the gene sequenced and compared .Results 53 MRS strains were studied .6 strains were phenotype successful-ly converted to MSS in different cultural conditions ,among them mecA gene was undetected in 2 strains ,and down expressed in 4 strains .Conclusion The MRS strains separated from clinical specimens may revert to MSS by culture under different nutritional conditions .The mecA gene of MRS may be lost or lower expressed and the MRS and mutant strains may be different in genomics .

OBJECTIVETo assess the association of single nucleotide polymorphisms (SNPs) of ubiquitin-specific protease 8 gene (USP8) with male infertility among ethnic Han Chinese from Sichuan.

METHODSA total of 316 infertile males were recruited (case group), which included 72 severe oligozoospermic (SO) cases and 244 non-obstructive azoospermic (NOA) cases. The control group consisted of 149 fertile males. The genotypes of 4 SNPs (rs2241769, rs11857513, rs7174015 and rs3743044) were determined with a Sequenom MassArray technique. The frequencies of genotype, allele and haploptye were analyzed.

RESULTSNo significant difference was detected in the allelic or genotypic frequencies of the 4 SNPs between the two groups (P>0.05). Based on linkage disequilibrium analysis and haplotype construction, the frequency distribution of haplotype CAAG showed a significant difference between non-obstructive azoospermic patients and the controls (P=0.021).

CONCLUSIONThe 4 SNPs (rs2241769, rs11857513, rs7174015 and rs3743044) of USP8 gene may not be associated with male infertility in ethnic Hans from Sichuan. While the haplotype CAAG may be a down-regulating factor for the risk of NOA.

Adult ; Asian Continental Ancestry Group ; ethnology ; genetics ; Azoospermia ; genetics ; Base Sequence ; Case-Control Studies ; China ; ethnology ; Endopeptidases ; genetics ; Endosomal Sorting Complexes Required for Transport ; genetics ; Genetic Predisposition to Disease ; ethnology ; Genotype ; Humans ; Infertility, Male ; ethnology ; genetics ; Male ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; Ubiquitin Thiolesterase ; genetics

Objective To observe the state of endemic flurosis, construction and running status of water improvement projects in order to provide a scientific basis for prevention and treatment fluorosis. Methods Water samples of the diseased and nondiseased villeges were collected from east, west, south, north and centre of each villege in 2005, and fluoride concentration was determined for each surveyed village with unimproved-water. At the same time, all the tap water and source water samples were collected to determine fluoride concentration in each water-improved village surveyed. In 2008, all the endemic fluorosis villages in Guied county were divided into slight, medium and heavy types according to the water fluoride content before water improved, and 1,1,3 survey villages were chosen from each type. In all of the village children aged 8 to 12 years were tested for dental fluorosis by Dean method. Six copies of the urinary fluoride were sampled in different age groups. The fluorine content in water and urine was determined by F-ion selective electrode. The situation of clinical skeletal fluorosis of adults over 16 years of age was investigated, 20 adults (evenly divided between men and women) in the villages of medium and heavy types were examined by X-ray for skeletal fluorosis. Results In 3 village fluoride content of drinking water exceeded the national drinking water standards ( <1.0 mg/L) of 85 surveyed villages with improved-water. Among the 16 projects, 8 were intermittently running and 3 were retired, leaving only 31.25% of the projects active. Theprevalence of enamel fluorosis was 41.13%( 116/282), that of skeletal flurosis was 47.95%(969/2021) and that of X-ray checked was 20.73% (17/82). The median of urine fluoride was 1.06 mg/L and the scope was 0.20 - 9.44 mg/L.Conclusions Most of the improved-water projects do not normally supply water in the disease ward of Guide county. Therefore, there is an increasing trend of the disease, so further control measures are needed.

OBJECTIVETo study the effect of pGCsi-H1-APRIL on the growth of human colorectal cancer cells in transplated tumor in nude mice and to improve the effect of APRIL on proliferation and apoptosis of colorectal cancer (CRC).

METHODSHuman CRC model was established in nude mice, and the nude mice were treated with APRIL siRNA twice per week for 2 weeks. APRIL mRNA expression was surveyed by PCR and APRIL protein expression was detected by immunohistochemistry. The expression of PCNA protein was detected by ELISA. The expression of bcl-2 and bcl-xl was assessed by immunohistochemical staining, and TUNEL staining was used to detect apoptosis.

RESULTSThe expression of APRIL mRNA in the APRIL siRNA group was (0.13 ± 0.05) × 10(-3), significantly lower than that in the vector group (0.95 ± 0.04) × 10(-3) and the PBS group (0.96 ± 0.05) × 10(-3). The expression of APRIL protein in the APRIL siRNA group was (87.5 ± 5.0)% lower than that in the vector and PBS groups (P < 0.05). APRIL siRNA significantly suppressed the growth of SW480 tumor: the IR (inhibitory rate) of APRIL siRNA group was (60.7 ± 1.5)% (P < 0.05). The expression of PCNA in APRIL siRNA group was (176.8 ± 18.1) ng/ml, was (56.5 ± 2.0)% lower than that of PBS group (328.4 ± 22.8) ng/ml. Furthermore, the expressions of anti-apoptosis proteins bcl-2 and bcl-xl of APRIL siRNA group were (82.6 ± 4.5)% and (79.2 ± 3.5)% lower than those of the PBS group. The apoptotic rate of the APRIL siRNA group was 40.1% ± 2.5%, significantly higher than that in the vector group (2.5 ± 0.1)% and PBS group (2.5 ± 0.2)% (P < 0.05).

CONCLUSIONAPRIL siRNA may significantly suppress the growth and promote apoptosis in transplanted tumor of human colorectal cancer in nude mice. APRIL may become a candidate gene of gene therapy of human colorectal cancer.

Animals ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; Female ; Humans ; Ligands ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Proliferating Cell Nuclear Antigen ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Random Allocation ; Tumor Necrosis Factor Ligand Superfamily Member 13 ; biosynthesis ; genetics ; bcl-X Protein ; metabolism

OBJECTIVETo investigate the biological characteristics of xenogenic acellular dermal matrix( Xeno-ADM) incorporated with silver, and to observe its effect in grafting.

METHODSXeno-ADM was prepared with 0. 25% trypsin and 0. 5% triton X-100 , and then it was immersed in 2 g/L silver nitrate solution to prepare xeno-ADM incorporated with silver. The bacterial inhibitory effect of two kinds of xeno-ADM on burn wound was determined, and the histological characteristic of the wounds was observed with optical microscope, transmission electron microscope and scanning electron microscope. The Ag+ content in the xeno-ADM incorporated with silver was measured with atomic absorption spectrometer. Twenty-seven rabbits with full-thickness skin defects on the back were randomly divided into three groups, i. e. split-thickness skin autograft only( group A, n = 9) , xeno-ADM with overlying split-thickness skin autograft( group B, n = 9) , xeno-ADM incorporated with silver with overlying split-thickness skin autograft ( group C, n = 9). The skin specimens from grafted area in each group were harvested at 2,4 and 6 post-operation weeks( POW) and examined under light microscope and transmission electron microscope. The condition of the graft, the contraction degree of the grafts and the historical changes in grafting area were observed at 2,4,6 POW. The survival rate of the grafts was calculated and the proliferative activity of the lymphocyte in each group was determined at 2 POW.

RESULTS1. Compared with xeno-ADM, the anti-bacterial effect of xeno-ADM incorporated with silver was much better ( P < 0. 05). No epidermis was seen in both types of xenografts ,and the collagen fibers were even in size and arranged regularly, with no obvious degeneration, and the dermis was also devoid of cells and cellular components. The Ag + content in xeno-ADM incorporated with silver measured (2. 7+/-0. 7) mg/g. 2. The grafts in B and C groups presented similar color to that of normal skin at 6 POW, and it was smooth, with fine texture and no scarring. The collagen fibers was arranged regularly, and conjunction between epidermis and dermis, the structure of basal cell desmosome and semi-desmosome were well reconstructed. The grafts in A group was in dark red color, with obvious contraction, and easily broken. The contraction rate in A group at 2,4 and 6 POW were obviously higher than those in B and C groups( P < 0. 05), while no obvious difference was observed between B and C groups. ( P >0. 05). The overall survival rate of the grafts in C group at 2 POW was 91.7% , which was evidently higher than that in A (77.8%) and B (80. 6% ) groups. The lymphocyte proliferative activity exhibited no difference among A, B and C groups( P >0.05).

CONCLUSIONThe xeno-ADM incorporated with silver has good anti-bacterial effect. In addition, it preserves the basic tissue structure and integral collagen fiber scaffold, without cells to induce rejection, so that it can be used as an ideal dermal substitute.

Animals ; Dermis ; transplantation ; ultrastructure ; Rabbits ; Silver ; therapeutic use ; Skin Transplantation ; Skin, Artificial ; Swine ; Transplantation, Heterologous ; Wound Healing

Objective To explore the effect of folic acid and DNA methyltransferase 1 (DNMT1) on cervical cancer and cervix precancerous lesion. Methods 100 patients with cervix squamouscell carcinoma (SCC), 101 patients with cervical intraepithelial neoplasm (CIN) and 109 patients with cervix inflammation (CI) diagnosed by histology were included in this study. Radioimmunoassay (RIA), polymerase chain reaction (PCR) and Western blot were used to detect the levels of serum folate, HPV16 infection and the expression of DNMT1 protein,respectively. Results The average levels of serum folate were (2.60 ± 1.61) ng/ml, (3.14 + 2.08) ng/ml and (3.32+1.74) ng/ml,and the expression of DNMT1 protein were 2.40 + 0.99,1.88 + 0.33 and 0.89 ± 0.29 in the group of SCC, CIN and CI, respectively.The relationship of folate levels and DNMT1 protein expression showed inverse correlation (r=-0.186, P=0.00l). The results in our study indicated that there was an additive interaction between low-level of serum folate and high-expressionof DNMT1 protein related to the risk of CIN and SCC, with OR value as 2.50(95%C/: 1.21-9.22) and 6.03 (95%C/: 2.79-21.72) respectively. The relative excessrisk of interaction (RERI) , attributableproportion of interaction (API) and synergy index (S) were 0.92, 0.36 and 2.59 in the CIN group while 2.47, 0.41 and 1.96 in the SCC group. Conclusion The low level of serum folate and high expression of DNMT1 protein seemed to be associated with high risk of cervical cancer and its precancerous lesion. It suggested that there might be a synergistic action between serum folate and DNMT1 in the progression of cervix carcinogenesis.

OBJECTIVETo investigate the changes of levels and clinic significance of serum soluble Fas (sFas) and soluble FasL (sFasL) in coal workers' pneumonoconiosis.

METHODSSerum levels of sFas and sFasL were determined in 52 patients with silicosis, 57 coal workers' pneumonoconiosis, 46 healthy underground coal workers' (the underground control group) and 40 healthy volunteers working on the ground (the ground control group) with a sandwich ELISA.

RESULTSCompared to the underground control and the ground control group, the serum levels of sFas and sFasL in the patients with silicosis and the coal workers' pneumonoconiosis were significantly higher (P < 0.01). Serum levels of sFas and sFasL in the underground control group were significantly higher than those in the ground control group (P < 0.01); Serum sFas levels in coal workers' pneumonoconiosis was significantly higher than those in the patients with silicosis (P < 0.01). Although the serum sFasL levels was also increased, there was no significant difference (P > 0.05). In the patients with silicosis and the coal workers' pneumonoconiosis patients, the serum sFas levels in Phase I patients combined with emphysema and simple Phase II + III patients were significantly higher than those in simple Phase I patients (P < 0.01). There was no significant difference in the serum sFasL levels among various groups with different parameters of pneumonoconiosis. In the patients with silicosis and the coal workers' pneumonoconiosis, serum levels of sFas and sFasL were not significantly altered among different duration of exposure to dusts. There was no correlation between serum levels of sFas and sFasL in the patients with silicosis while there was a slightly positive correlation between sFas and sFasL levels in the coal workers' pneumonoconiosis (r = 0.479, P < 0.05).

CONCLUSIONIn the patients with silicosis and the coal workers' pneumonoconiosis, the serum levels of sFas and sFasL are abnormal and associated with the development of the pneumonoconiosis. The changes of serum sFas levels may indicate the development and progression of the pneumonoconiosis. The detection of the serum sFas level may be used in the differential diagnosis for the silicosis and the coal worker's pneumonoconiosis.

Adult ; Aged ; Coal Mining ; Enzyme-Linked Immunosorbent Assay ; Fas Ligand Protein ; blood ; Female ; Humans ; Male ; Middle Aged ; Pneumoconiosis ; blood ; Silicosis ; blood ; fas Receptor ; blood

Objective To identify the prevalence and etiology of kidney disease and the related risk factors in type 2 diabetic patients in rural Shanghai.Methods A cross-sectional study in type 2 diabetic patients was conducted in a community of Shanghai.Questionnaire,clinical examination and laboratory tests were completed to collect the information about sociodemographic and healthcare characteristics.Results A total of 1421 eligible patients with complete information were screened from 1487 type 2 diabetic patients between November 2008 and March 2009.Of them,40.75％ were men,59.25％ were women,aged 37-86 (61.33 ± 9.65 ) years old,with diabetic duration of 0.25-43.92 (7.85 ± 6.34) years.Among them,43.42％ had diabetic retinopathy,21.18％ had neuropathy; 69.95％ met the screening definition for hypertension,76.07％ for hyperlipidemia,15.55％ for hyperuricemia and 23.65％ for cardiovascular disease.The control rates of fasting blood glucose,glycosylated hemoglobin,blood pressure and serum cholesterol were 57.71％,33.99％,14.22％ and 2.46％,respectively.The prevalence of kidney disease,diabetic nephropathy and non-diabetic renal disease was 41.31％,18.51％ and 13.44％,respectively; and 9.36％ were diagnosed as renal insufficiency of unknown reasons.Age,diabetic duration,hyperuricemia,diabetic retinopathy and poor control of blood pressure were independently associated with kidney disease;age and poor control of blood pressure were independently associated with diabetic nephropathy; age and hyperuricemia were independent risk factors of renal insufficiency in patients with diabetic nephropathy.Conclusions Although the diabetic duration of these subjects is relatively short,the prevalence of complications including diabetic nephropathy is high.The high prevalence of non-diabetic renal disease shows the importance of further screening and diagnoses for prevention.Strict control of blood glucose,blood pressure,serum cholesterol and serum uric acid are key points of cutting down the prevalence of diabetic nephropathy and chronic kidney disease.