Acupuncture Therapy ; Adult ; Colitis, Ulcerative ; drug therapy ; therapy ; Combined Modality Therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Young Adult

Autophagy, a cellular process of "self-eating" by which intracellular components are degraded within the lysosome, is an evolutionarily conserved response to various stresses. Autophagy is associated with numerous patho-physiological conditions, and dysregulation of autophagy contributes to the pathogenesis of a variety of human diseases including cancer. Depending on context, activation of autophagy may promote either cell survival or death, two major events that determine pathological process of many illnesses. Importantly, the activity of autophagy is often associated with apoptosis, another critical cellular process determining cellular fate. A better understanding of biology of autophagy and its implication in human health and disorder, as well as the relationship between autophagy and apoptosis, has the potential of facilitating the development of autophagy-based therapeutic interventions for human diseases such as cancer.
Apoptosis ; Autophagy ; Cell Death ; Cell Survival ; Humans ; Neoplasms ; pathology

Objective Investigation and analysis of intelligence and psychomotor function in children born after implementingt universal salt iodization(USI). Methods Historical serious illness areas of water iodine below 10μg/L were selected as study sites, water iodine in 50 - 100 μg/L in the historical non-endemic areas were as control points in Henan, 2008. Cluster sampling was used to select children aged 6 - 15 years as observing subjects,IQ were measured with CRT- Man Test(CRT-C2). A "Tianjin Medical psychomotor test battery" (JPB) was carry out to test psychomotor function. Results In IDD regions 230 children were surveyed post-USI and 1284 children preUSI. The IQs post and pre USI were 99.3 and 99.9, respectively, and the proportion of IQ ≤69 were 2.17%(6/230) and 2.80%(36/1284), respectively. In non-IDD regions 650 children were surveyed post-USI and 2079children pre-USI. The IQs post and pre USI were 95.3 and 93.8, respectively, and the proportion of IQ ≤ 69 were 2.31%(15/650) and 3.37%(70/2079), respectively. In IDD regions, the abnormal rate of T scores and damage index post USI were 3.6%(2/56), 5.3%(3/56), respectively, significantly lower than pre USI [18.1%(29/160),18.1%(29/160), x2 = 7.54, 6.86, all P ＜ 0.01]. Conclusions USI could increase the IQs of children and decrease the positive rate of JPB, and significantly improve the quality of whole nation and persistently eliminating IDD.

For the purpose of expanding the analysis scope of medicines,a RPHPLC assay procedure has been established for quantitative analysis of indomethacin in human plasma.Analytical column was YWG C18(?4 6 mm?200mm).Mobile phase was methanol water acetic acid solution(67∶33∶0 1)(v/v) and wavelength of detector was 254nm.The linear relationship,precision,method of extraction and recovery were comparatively investigated by standard blank human plasma spiked with indomethacin.Indomethacin leved in the blood of the healthy volunteers was detected by using this method.The linear range of the method was 0 1～5 0?g?ml -1 .The calibration curve was linear (?=0 9995). The detection limit was 0 02?g?ml -1 (S/N≥3) and the recovery of indomethacin in human blood was between 97 5%～104 2%. Intra and inter day prccision of the mothod were(1 1?0 2)%(n=4) and(2 7?0 6)%(n=4)respectively.The CV% were no more than 3 0% (n=4).The method shows a high sensitivity,precision,fast and excellent selectivity.Thus it is suitable for investigation of the indomethacin in human blood and its toxicological analysis as well as the pharmacokinetic study.

Drug therapy is one of the efficient methods for prostate cancer treatment. However, drug resistance greatly hindered the treatment of prostate cancer patients. Herein, the mechanisms of drug resistance in prostate cancer have been exhaustively reviewed, and that can provide an alternative strategy and new targets for anti-prostate cancer therapy.
Drug Resistance, Neoplasm ; Humans ; Male ; Prostatic Neoplasms ; drug therapy

The aim of this paper is to report the synthesis of the mPEG-PCL-g-PEI copolymers as small interfering RNA (siRNA) delivery vector, and exploration of the siRNA delivery potential of mPEG-PCL-g-PEI in vitro. The diblock copolymers mPEG-PCL-OH was prepared through the ring-opening polymerization. Then, the hydroxyl terminal (-OH) of mPEG-PCL-OH was chemically converted into the carboxy (-COOH) and N-hydroxysuccinimide (NHS) in turn to prepare mPEG-PCL-NHS. The branched PEI was reacted with mPEG-PCL-NHS to synthesize the ternary copolymers mPEG-PCL-g-PEI. The structure of mPEG-PCL-g-PEI copolymers was characterized with Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The mPEG-PCL-g-PEI/siRNA nanoparticles were prepared by complex coacervation, and the nanoparticles size and zeta potential were determined, separately. The cytotoxicities of mPEG-PCL-g-PEI/siRNA nanoparticles and PEI/siRNA nanoparticles were compared through cells MTT assays in vitro. The inhibition efficiencies of firefly luciferase gene expression by mPEG-PCL-g-PEI/ siRNA nanoparticle at various N/P ratios were investigated through cell transfection in vitro. The experimental results suggested that the ternary (mPEG5k-PCL(1.2k))1.4-g-PEI(10k) copolymers were successfully synthesized. (mPEG(5k)-PCL(1.2k))1.4-g-PEI(10k) could condense siRNA into nanoparticles (50-200 nm) with positive zeta potential. MTT assay results showed that the cytotoxicity of (mPEG(5k)-PCL(1.2k))1.4-g-PEI(10k)/siRNA nanoparticles was significantly lower than that of PEI(10k)/siRNA nanoparticles (P < 0.05). The expression of firefly luciferase gene could be significantly down-regulated at a range of N/P ratio from 50 to 150 (P < 0.01), and maximally inhibited at the N/P ratio of 125. The mPEG-PCL-g-PEI polymers could delivery siRNA into cells to inhibit the expression of target gene with very low cytotoxicity, which suggested that mPEG-PCL-g-PEI could serve as a new type of siRNA delivery vector.

ObjectiveTo observe clinical features and identify causative genes of reticulate pigmented anomaly of the flexures in a pedigree.Methods A survey was conducted in a pedigree with reticulate pigmented anomaly of the flexures.Clinical manifestations were recorded in details for each patient in this pedigree.Tissue specimen was obtained from the proband for histopathological examination and ultrastructural observation.Mutation scanning was carried out by PCR and direct sequencing in 3 patients in the family.ResultsAll the patients in this pedigree presented with reticular pigmentation of the flexures and idiopathic guttate hypomelanosis on the abdomen and back.Histopathological and ultrastructural study revealed epidermal hyperpigmentation with an increase in melanin content in epidermal keratinocytes but no changes in the number of melanocytes.No mutation was found in the KRT5 gene in this family.ConclusionsThis is the first case report of reticulate pigmented anomaly of the flexures associated with idiopathic guttate hypomelanosis.No mutation is identified in the KRT5 gene of patients with reticulate pigmented anomaly of the flexures in this family,indicating the existence of other causative genes.

Objective To explore the change of serum osteopontin levels in preoperative and postoperative patients with non-small cell lung cancer (NSCLC) and its clinic significance.Methods The levels of serum osteopontin were detected by ELISA.Results In 88 NSCLC patients,serum osteopontin levels were significantly higher than in benign pulmonary disease and healthy control group(P＜0.05.P＜0.01.respectively) There was no difference between benign pulmonary disease and healthy control group(P＞0.05).Serum osteopontin levels were related to clinical stage and lymph node metastasis,and the levels of serum osteopontin were lower in postoperative patients than in preoperative cases(P＜0.05).For NSCLC.the detection of osteopontin had a sensitivity of 84.1%,a specificity of 92.5%,and an accuracy of 88.1%. Conclusion Increased serum levels of osteopontin may be useful as a helpful clinical biomarker to diagnose earlier,predict prognosis and differentiate from benign pulmonary disease.

OBJECTIVETo explore the feasibility of preparing novel gypenosides long-circulating liposomes with PEG grafted on beta-sitosterol (PEG-Sito).

METHODSuccinicanhydride was adopted to connect beta-sitosterol and PEG 2000. Sphingomyelin and PEG-Sito was used as material to prepare gypenosides long-circulating liposomes by using ethanol injection method. Encapsulation efficiency was determined by using protamine precipitation method. H-NMR was used to verify the synthesis of PEG-Sito, the novel gypenosides long-circulating liposomes were characterized by particle size, zeta potential and atomic force microscope.

RESULTThe synthesis of PEG-Sito was verified by 1H-NMR. Encapsulation efficiency of long-circulating liposomes prepared by ethanol injection method was 74.3%, particle size was 288.1 nm, zeta potential was -20.25 mV, the morphology were round observed by AFM.

CONCLUSIONThe novel gypenosides long-circulating liposomes prepared with PEG-Sito was feasible, it had a high encapsulation efficiency and good morphology.

Drug Compounding ; methods ; Feasibility Studies ; Gynostemma ; chemistry ; Liposomes ; blood ; chemistry ; Plant Extracts ; chemistry ; Polyethylene Glycols ; chemistry ; Reproducibility of Results ; Sitosterols ; chemistry ; Sphingomyelins ; chemistry

OBJECTIVE Topreparealipidderivativeofgemcitabine(Gem)anditspolymericmi-celles to overcome the disadvantages of Gem.METHODS N-benzyl-3′-acetyl-gemcitabine(BAG)was synthesized.A BAG-loaded poloxamer polymeric micelle (BAG∶poloxamer 188 =10∶1 ,mol/mol)was prepared using an injection method.The micelles were characterized with a laser particle size and elec-tric charge instru ment and negatively-stained trans mission electron microscopy.Hu man breast cancer cells MCF-7 were cultured with Gem or BAG polymeric micelles of 5,10,20,30,50,70,90 μmol·L-1 for 24,48 and 72 h,respectively.The inhibitory rate of cells was measured with an MTT method.The MCF-7 cytotoxicity of BAG polymeric micelles was investigated.A pharmacodynamic study was per-formed on the mice bearing mouse hepatocellular cancer cells H22.Intravenous (iv)and oral (ig)ad-ministration was used at the dose of Ge m 40 mg·kg -1 or BAG polymeric micelles 62 mg·kg -1 .The mice were administered on the 1 st,4th and 7th day and sacrificed on the 8th day.Tumor inhibitory rates were measured.RESULTS TheBAGstructurewasidentifiedbythinlayerchromatograph,1Hand13C NMR,infrared ray chromatograph and mass spectrum.The appearance of BAG micelles was a slightly blue suspension.The micelles were spheres according to the electron microscopic observation.Their size was 62.82 nm and the zeta potential was -18.8 mV.The half inhibition concentration (IC50)of Gem and BAG polymeric micelles was 40.6 and 90.0 μmol·L-1 ,5.0 and 14.9 μmol·L-1 ,5.0 and 1 3.6 μmol·L-1 at 24,48 and 72 h,respectively according to the MTT results.According to the in vivo results,compared with the tumor model group,Gem (ig),Gem (iv)and BAG polymeric micelles (iv and ig)had significant effect on the tumor weight of H22 cell xenograft mice (P<0.01 ).As for anti-tumor efficiency,BAG polymeric micelles (ig)were better than Gem (ig)(P<0.05);BAG polymeric micelles (iv)were better than BAG polymeric micelles (ig)(P<0.05),and BAG polymeric micelles (iv)were almostequaltoGem(iv).CONCLUSION ThelipidderivativeofGemcanbeloadedinthepoloxamer 1 88 polymeric micelles.BAG polymeric micelles show in vitro MCF-7 cell inhibition and in vivo inhibition of mouse H22 xerografts;iv or ig.BAG polymeric micelles (ig)show better anti-tumor effect than Gem (ig),indicating that BAG polymeric micelles are a promising novel anti-tumor oral preparation.