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

To elucidate the effect of established primary bone marrow stromal layers on the gene transduction of human hematopoietic stem/progenitor cells (HSC/HPC), mononuclear cells (MNC) from adult bone marrow were isolated by centrifugation on Ficoll-Hypaque gradients and plated in stromal culture medium. The cells were incubated until passage 4 to establish primary stromal layers. The HSC/HPC prestimulated by cytokines were transduced by retroviral supernatant containing mdr1 gene in presence of irradiated stroma-contact support. Transduced cells were plated in a colony-forming unit assay with and without vincristine (VCR) to assess the efficiency of transduction. Individual colonies were also analyzed by polymerase chain reaction (PCR) for the presence of provirus. The results showed that the mixed adherent cell layers were formed when adult bone marrow stromal cells were incubated for four to six weeks, mainly being composed of fibroblasts. In the presence of stroma-contact support, the average of gene transduction efficiency in marrow-derived progenitors increased 2.1 to 3.3 folds measured by colony-forming assay and/or PCR, significantly higher than those without support of stroma. It is concluded that the presence of bone marrow stroma support in combination with cytokine facilitates augmenting the extent of retroviral-mediated gene transduction.
Bone Marrow Cells ; physiology ; Genes, MDR ; Hematopoietic Stem Cells ; metabolism ; Humans ; Retroviridae ; genetics ; Stromal Cells ; physiology ; Transduction, Genetic

α-HgS is the main component of traditional Chinese medicine cinnabar, while β-HgS is the main component of Tibetan medicine Zuotai. However, there was no comparative study on the dissolution and absorption in gastrointestinal tract and bioaccumulation in organs of mercury in Cinnabar, Zuotai, α-HgS and β-HgS. In this study, the dissolution process of the four compounds in the human gastrointestinal tract was simulated to determine the mercury dissolutions and compare the mercury dissolution of different medicines and the dissolution-promoting capacity of different solutions. To explore the absorption and bioaccumulation of cinnabar and Zuotai in organisms, mice were orally administered with clinical equivalent doses cinnabar and Zuotai. Meanwhile, a group of mice was given α-HgS and β-HgS with the equivalent mercury with cinnabar, while another group was given β-HgS and HgCl2 with the equivalent mercury with Zuotai. The mercury absorption and bioaccumulation capacities of different medicines in mice and their mercury bioaccumulation in different tissues and organs were compared. The experimental results showed a high mercury dissolutions of Zuotai in artificial gastrointestinal fluid, which was followed by β-HgS, cinnabar and α-HgS. As for the mercury absorption and bioaccumulation in mice, HgCl2 was the highest, β-HgS was the next, and a-HgS was slightly higher than cinnabar. The organs with the mercury bioaccumulation from high to low were kidney, liver and brain. This study is close to clinical practices and can provide reference for the clinical safe medication as well as a study model for the safety evaluation on heavy metal-containing medicines by observing the mercury dissolution, absorption, distribution and accumulation of mercury-containing medicines cinnabar and zuotai.
Animals ; Brain ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Gastrointestinal Tract ; metabolism ; Kidney ; metabolism ; Liver ; metabolism ; Male ; Mercury ; chemistry ; pharmacokinetics ; Mercury Compounds ; chemistry ; pharmacokinetics ; Mice ; Solubility

Zuotai (gTso thal) is a typical representative of Tibetan medicines containing heavy metals, but there is still lack of modem safety evaluation data so far. In this study, acute toxicity test, sub-acute toxicity test, one-time administration mercury distribution experiment, long-term mercury accumulative toxicity experiment and preliminary study on clinical safety of Compound Dangzuo were conducted in the hope of obtain the medicinal safety data of Zuotai. In the acute toxicity test, half of KM mice given the lethal dose of Zuotai were not died or poisoned, and LD50 was not found. The maximum tolerated dose of Zuotai was 80 g x kg(-1). In the subacute toxicity test, Zuotai could reduce ALT, AST, Crea levels in serums under low dose (13.34 mg x kg(-1) x d(-1)) and medium dose (53.36 mg x kg(-1) x d(-1)), with significant difference under low dose, and increase the levels of ALT, AST, MDA, Crea in serums under high dose (2 000 mg x kg(-1) x d(-1)); besides, the levels of BUN and GSH in serums reduced with the increase in dose of Zuotai, indicating a significant dose-effect relationship. In the one-time administration distribution experiment, the content of mercury in rat kidney, liver and lung increased after the one-time administration with Zuotai, with a significant dose-dependent relationship in kidney. In the long-term mercury accumulative toxicity experiment, KM mice were administered with equivalent doses of Zuotai for 4.5 months and then stopped drug administration for 1.5 months. Since the 2.5th month, they showed significant mercury accumulation in kidney, which gradually reduced after drug withdrawal, without significant change in mercury content in liver, spleen and brain and ALT, AST, TBIL, BUN and Crea in serum. At the 4.5th month after drug administration, KM mice showed slight structural changes in kidney, liver and spleen tissues, and gradually recovered to normal after drug withdrawal. Besides, no significant difference in weight gain was found between the Zuotai group and the control group. According to the findings of the clinical safety study of Dangzuo, after subjects administered Dangzuo under clinical dose for one month, their serum biochemical indicators, blood routine indicators and urine routine indicators showed no significant adverse change. This study proved that traditional Tibetan medicine Zuotai was slightly toxic, with a better safety in clinical combined administration and no adverse effects on bodies under the clinical dose and clinical medication cycle. However, long-term high-dose administration of Zuotai may have a certain effect on kidney.
Adult ; Animals ; Clinical Trials as Topic ; Drugs, Chinese Herbal ; analysis ; pharmacokinetics ; toxicity ; Female ; Humans ; Kidney ; drug effects ; Liver ; drug effects ; Male ; Medicine, Tibetan Traditional ; Mice ; Middle Aged ; Rats ; Rats, Wistar ; Young Adult

OBJECTIVETo understand the situation of institutional delivery of rural pregnant women in Guangxi Autonomous Region in the period of 1998 - 2003 and to identify the determinants on institutional delivery utilization.

METHODSUsing Andersen's behavioral model as analytical framework and Guangxi databank of the 3rd National Health Service Survey as data source, we described the status of institutional delivery with the rural women having had live birth history in the period of 1998 - 2003 as subjects, while and the univariate analysis and multivariate logistic analysis were done to identify determinants of institutional delivery utilization.

RESULTSAmong a total number of 407 women with live birth history, 39.80 percent of them delivered at the health-care facilities. The rate of institutional delivery increased annually in 1998 - 2003 (P< 0.0001). The proportion of delivery in township health centers increased and the proportion of home delivery decreased by year (P< 0.0001). Results from both univariate and multivariate analysis showed that parity, education background of women, type of drinking water, time needed to get to the nearest healthcare facilities by the most convenient traffic,frequency of prenatal checkup, together with whether or not being advocated on institutional delivery etc. were determinants of delivery utilization. The OR value were 1.749 for multipara, 1.995 for those going to the nearest healthcare facilities by the most convenient traffic in less than 10 minutes, 3.011 for those drinking tap water, 5.435 for those with the education of high school, 29.149 for those with over 5 times in terms of frequency of prenatal checkup and 37.822 for those being advocated on institutional delivery.

CONCLUSIONSocio-economic situation, status of maternal health care and parity made main contribution to institutional delivery and skilled birth attendance for women in rural Guangxi.

China ; Choice Behavior ; Delivery, Obstetric ; methods ; utilization ; Female ; Hospitalization ; statistics & numerical data ; Humans ; Models, Statistical ; Pregnancy ; Rural Population

OBJECTIVETo investigate the composition and morphology of the stones in the enlarged prostatic utricle (EPU).

METHODSWe took out 36 EPU stones from 11 patients by transurethral fenestration between 1992 and 2011, and analyzed the stones by scanning electron microscopy, x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIS).

RESULTSUnder the scanning electron microscope, all the EPU stones were constituted of many intensive minicrystals and amorphous matrix. XRD and FTIS revealed that all were hydroxyapatite crystal.

CONCLUSIONEPU stones belong to the category of prostatic pseudo-calculi, whose formation is ascribed not to the abnormal change of urine composition, but to the continuous secretion, absorption and concentration of EPU liquid and ablated epithelial cells from the EPU.

Calculi ; chemistry ; Durapatite ; chemistry ; Humans ; Male ; Prostate ; chemistry ; pathology ; Prostatic Diseases ; pathology ; physiopathology

The identification of genes inducing resistance to anticancer chemotherapeutic agents and their introduction into hematopoietic cells represents a promising approach to overcome bone marrow toxicity, the limiting factor for most high-dose chemotherapy regimens. Because resistance to cyclophosphamide has been correlated with increased levels of expression of the aldehyde-dehydrogenase (ALDH1) gene in tumor cells lines in vitro, this study tested whether ALDH1 overexpression could directly induce cyclophosphamide resistance. Results showed that a retroviral vector was used to transduce full-length human ALDH1 cDNA into human hematopoietic cell line K562 that was then tested for resistance to 4-hydroxycyclophosphamide (4-HC), an active analogue of cyclophosphamide. Overexpression of the ALDH1 gene resulted in a significant increases in cyclophosphamide resistance in transduced K562 cells (50% inhibition concentration, IC50 = 10 micro mol/L). These findings indicate that ALDH1 overexpression is sufficient to induce cyclophosphamide resistance in vitro and provide a basis for testing the efficacy of ALDH1 gene transduction to protect bone marrow cells from high-dose cyclophosphamide in vivo.
Aldehyde Dehydrogenase ; genetics ; Antineoplastic Agents, Alkylating ; pharmacology ; Cell Division ; drug effects ; Cell Survival ; drug effects ; Cyclophosphamide ; analogs & derivatives ; pharmacology ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Enzymologic ; Genetic Vectors ; genetics ; Humans ; Inhibitory Concentration 50 ; K562 Cells ; drug effects ; enzymology ; metabolism ; Retroviridae ; genetics ; Transfection

BACKGROUNDProteasome subunits (PSMB) and transporter associated with antigen processing (TAP) loci are located in the human leukocyte antigen (HLA) Class II region play important roles in immune response and protein degradation in neurodegenerative diseases. This study aimed to explore the association between single nucleotide polymorphisms (SNPs) of PSMB and TAP and Parkinson's disease (PD).

METHODSA case-control study was conducted by genotyping SNPs in PSMB8, PSMB9, TAP1, and TAP2 genes in the Chinese population. Subjects included 542 sporadic patients with PD and 674 healthy controls. Nine identified SNPs in PSMB8, PSMB9, TAP1, and TAP2 were genotyped through SNaPshot testing.

RESULTSThe stratified analysis of rs17587 was specially performed on gender. Data revealed that female patients carry a higher frequency of rs17587-G/G versus (A/A + G/A) compared with controls. But there was no significant difference with respect to the genotypic frequencies of the SNPs in PSMB8, TAP1, and TAP2 loci in PD patients.

CONCLUSIONChinese females carrying the rs17587-G/G genotype in PSMB9 may increase a higher risk for PD, but no linkage was found between other SNPs in HLA Class II region and PD.

ATP-Binding Cassette Sub-Family B Member 2 ; genetics ; ATP-Binding Cassette, Sub-Family B, Member 3 ; genetics ; Adult ; Aged ; Antigen Presentation ; Case-Control Studies ; Cysteine Endopeptidases ; genetics ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease ; genetics ; immunology ; Polymorphism, Single Nucleotide ; Proteasome Endopeptidase Complex ; genetics

Abstract：Objective To improve the replication level of varicella⁃zoster virus（VZV）in human diploid cell line MRC⁃5 and increase the yield of VZV vaccine by reducing the expression of interferon（IFN）related genes via optimizing the cell line MRC⁃5. Methods Interferon receptor 1（IFNAR1）silenced MRC⁃5 cell line（MRC⁃5IFNAR1⁃）was constructed by CRISPR／Cas9 gene editing technology，which was determined for the relative expression of IFNAR1 mRNA，and for those of mRNA of IFN related genes IFNβ and OAS1 after VZV infection by qRT⁃PCR to evaluate the effect of gene silencing. Gene mutation sequences were further identified by sequencing of the silenced sites. The replication of VZV in MRC⁃5 and MRC⁃5IFNAR1⁃ cell lines was compared 168 h after VZV infection by using qRT⁃PCR and plaque formation unit（PFU）assay， to evaluate the effect of MRC⁃5IFNAR1⁃cell line on VZV replication. Results The growth status of MRC⁃5IFNAR1⁃ cell line wasconsistent with that of MRC ⁃ 5 cells，and the relative expression of IFNAR1 mRNA decreased by 73%；The relative expressions of IFNβ and OAS1 mRNA in MRC⁃5IFNAR1⁃ cell line were 61% and 90% lower than those in MRC⁃ 5 cells respectively after VZV infection；In addition，168 h after VZV infection，the level of DNA replication and the titer of VZV increased by 5. 7 folds and 4 folds respectively. Conclusion The successful establishment of MRC⁃5IFNAR1⁃ cell line may be a potential scheme to increase the yield of vaccines based on human diploid cells，and provided a reference for expanding production of VZV vaccine.

OBJECTIVETo evaluate the patients with bone injury in Wenchuan earthquake.

METHODSFrom May 12th to June 15th 2008 the data of 1410 patients with bone injury in Wenchuan earthquake were analyzed to evaluate clinical intervention and remedy-managing experience.

RESULTSThe 1410 patients average age was from 4 to 103 years old. And 744 cases (52.7%) suffered from blunt injuries, 379 cases (26.9%) from buried injuries, 287 cases (20.4%) from falling injuries; And 1317 cases were with fracture, 93 with limbs soft tissue injuries; 261 patients combined with other parts of injuries including 45 cases with paralysis; 66 cases were with crush syndrome, 25 with gas gangrene, 76 with acute kidney failure, 26 with multiple organ failure. And 912 operations were performed including 402 fracture fixation, 224 debridement, 152 debridement and suture, 85 amputation, 29 implant skin, 8 fixation of joint dislocation, 5 surgical flaps transplantation, 4 nerve and tendon suture, 2 arthroscopes, 1 joint replacement. Among the 66 crush syndrome patients, 49 accepted continuous renal replacement therapy, in which 9 cases were bleeding from named arteries and 20 blood vessels were getting embolism. Among the 1410 cases, 1 died from multiple organ failure.

CONCLUSIONSAmong the patients with bone injury in Wenchuan earthquake, the elderly patients are more than the youth; The injuries are always combined with other complications; Opened injuries are polluted severely; It is difficult to deal with the crush syndrome; Paraplegia cases are less, but the amputees are more.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Earthquakes ; Female ; First Aid ; Humans ; Male ; Retrospective Studies ; Wounds and Injuries ; surgery