OBJECTIVETo assess the effects of LiCl on prostate cancer growth and to explore the underlying mechanisms.

METHODSEffects of LiCl on cell growth in vitro and in vivo were determined by cell counting and xenografts of prostate cancer cells. Alterations in cell proliferation and the expression of DNA replication-related protein were determined by MTT assay, BrdU incorporation and Western blot.

RESULTSCompared to PBS control group, the number of prostate cancer cells (PC-3) were lower treated with 10 mmol/L LiCl, the number was 1.9×10(5), 4.8×10(5) and the difference was significant (P < 0.05). The inhibition rate of cellular proliferation were 50%, 95% and 98%, respectively, in LiCl group, NaCl and KCl control group, the difference was significant (P < 0.05). The A-Value of BrdU incorporation was 1.5, 1.3 treated with 10 mmol/L, 30 mmol/L LiCl, while the A-value of BrdU incorporation was 4 in PBS control group, the difference was significant (P < 0.05). On the protein level, LiCl downregulates expression of cdc 6, cyclins A and cyclins E, and cdc 25C, and upregulates expression of the CDK inhibitor p21(CIP1). The mean volume and weight of xenograft tumor were 50 mm(3) and 296 mg after LiCl intraperitoneal injection, But PBS control group were 180 mm(3) and 957 mg, the difference was significant (P < 0.05).

CONCLUSIONLiCl disrupts DNA replication and suppresses tumor growth of prostate cancer cells in vitro and in vivo.

Animals ; Antineoplastic Agents ; pharmacology ; Cell Cycle Proteins ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin A ; metabolism ; Cyclin E ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; DNA Replication ; drug effects ; Humans ; Lithium Chloride ; pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Nuclear Proteins ; metabolism ; Prostatic Neoplasms ; metabolism ; pathology ; Tumor Burden ; drug effects ; cdc25 Phosphatases ; metabolism

Adult ; Aged ; Alcohol Drinking ; adverse effects ; epidemiology ; Alcoholism ; complications ; pathology ; China ; epidemiology ; Female ; Humans ; Liver Cirrhosis, Alcoholic ; epidemiology ; etiology ; Liver Diseases, Alcoholic ; complications ; epidemiology ; Male ; Middle Aged ; Risk Factors

Welder's siderosis was traditionally described as "benign pneumoconiosis" because of the absence of associated symptoms, functional impairment or pulmonary fibrosis. Although several authors have reported evidence of fibrosis in the lungs of welders, siderosis with local massive fibrosis has been rarely described. In this paper, we present a case of Welder's siderosis with local massive fibrosis mimicking lung cancer.
Fibrosis ; diagnosis ; diagnostic imaging ; Humans ; Male ; Middle Aged ; Radiography ; Siderosis ; diagnosis ; diagnostic imaging

OBJECTIVETo investigate the effect of tea polyphenols on the proliferation of human prostate cancer cells and its possible mechanism.

METHODSWe cultured androgen-independent prostate cancer DU145 cells in the medium with different concentrations (50, 100, 250 and 500 microg/ml) of tea polyphenols, and those in the normal medium as the control. After 48 hours of culture, we detected the survival rate of the cells by MTT assay and determined the expression of survivin by Western blot and quantitative RT-PCR.

RESULTSAt 48 hours, the survival rates of the prostate cancer DU145 cells were 0.97 +/- 0.12, 0.71 +/- 0.07, 0.20 +/- 0.03 and 0.08 +/- 0.01 in the 50, 100, 250 and 500 microg/ml tea polyphenols treatment groups, all significantly reduced as compared with the control group (P < 0.01) except that of the 50 microg/ml group (P = 0.42). Furthermore, the survival rate continued to decrease with the prolonging of time, dropping below 5% at 96 hours except in the 50 microg/ml group. The grey values of the survivin expression in the 100, 250 and 500 microg/ml tea polyphenols groups were 13 425 +/- 34, 2 017 +/- 24 and 1 274 +/- 22, respectively, at 48 hours, significantly lower than 15 075 +/- 48 in the control group (P < 0.01). Moreover, the content of survivin mRNA at 48 hours was markedly lower in the 50, 100, 250 and 500 microg/ml treatment groups (0.74 +/- 0.03, 0.64 +/- 0.02, 0.52 +/- 0.01 and 0.21 +/- 0.02) than in the control (P < 0.01).

CONCLUSIONTea polyphenols can inhibit the proliferation of human prostate cancer DU145 cells, which may be associated with the decreased expression of the survivin gene.

Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Male ; Polyphenols ; pharmacology ; Prostatic Neoplasms ; pathology ; Tea ; chemistry

OBJECTIVETo elucidate the pathogenic role of leukotriene B4 (LTB4) in increased pulmonary microvascular endothelial cell permeability induced by one lung ventilation (OLV) in rabbits.

METHODSForty-eight healthy Japanese white rabbits were randomly divided into control group (group C), saline pretreatment group (group S), bestatin (a leukotriene A4 hydrolase (LTA4H) inhibitor) plus saline pretreatment group (group B), OLV group (group O), saline pretreatment plus OLV group (group SO) and bestatin plus saline pretreatment with OLV group (group BO). ELISA was used to detect LTB4 content in the lung tissues, and LTA4H and phospholipase Cεl (PLCEl) expressions were examined by Western blotting and quantitative PCR. The wet/dry weight (W/D) ratio of the lung, lung permeability index and the expressions of myosin light chain kinase (MLCK) protein and mRNA in the lung tissues were determined to evaluate the permeability of the pulmonary microvascular endothelial cells (PMVECs). The severities of lung injury were evaluated by lung histomorphological scores.

RESULTSNo significant differences were found among groups C, S and B except that LTA4H expressions was significantly lower in group B than in groups C and S (P<0.05). OLV significantly increased the expressions of LTA4H (P<0.05) and resulted in LTB4 overproduction in the lungs (P<0.05) accompanied by significantly enhanced PLCE1 expression and PMVEC permeability (P<0.05). Pretreatment with bestatin, significantly reduced the expression of LTA4H and LTB4 production (P<0.05) and down-regulated the expression of PLCE1 in the lungs of the rabbits receiving OLV (P<0.05).

CONCLUSIONBestatin plays a protective role in OLV-induced rabbit lung injury by downregulating LTA4H to reduce the production of LTB4 in the lungs. LTB4 can increase PMVEC permeability by up-regulating PLCE1 expression in rabbits with OLV-induced lung injury.

OBJECTIVEHuman growth hormone (hGH) is an essential therapeutic drug for the treatment of growth hormone (GH) deficiency (GHD). However, the process of dissolving hGH of the powder form is complicated and potentially hazardous. In the present study, we evaluated the efficacy and safety of preparation in the replacement therapy for children with GH deficiency.

METHODSA 12-month randomized, open-label, multicenter trial was conducted in 31 previously untreated children with growth failure secondary to GH deficiency [20 boys and 11 girls, mean age (10.5 +/- 4.1) years]. An recombined human growth hormone (rhGH) solution (Iintropin AQ) was given via subcutaneous injection daily in every evening at a weekly dose of 0.25 mg/kg. The patients were followed up at 3, 6, 9, and 12 months of the treatment, and the course of treatment was 12 months. Body height was measured 3-monthly and height velocity (HV) and mean height standard deviation score (HT SDS) were calculated. Serum Insulin-like growth factor I (IGF-1), Insulin-like growth factor binding protein 3 (IGFBP-3), GH antibodies and safety parameters were assessed at the baseline and at 3-month intervals. Bone age (BA) was assessed at the baseline and the rate of skeletal maturation (DeltaBA/DeltaCA) was calculated after 6 and 12 months of rhGH treatment by a central bone age reader. Moreover, the safety of rhGH solution treatment was assessed.

RESULTSAfter 12 months of liquid rhGH therapy, growth parameters were significantly increased over baseline. (1) The mean (+/- SD) height increment DeltaHT (cm) was 4.0 +/- 1.3, 7.0 +/- 2.0, 10.3 +/- 2.6 and 12.9 +/- 3.3 after 3, 6, 9, and 12 months of treatment, respectively (P < 0.01), which indicated linear growth after treatment. The GV (cm/years) was 2.7 +/- 0.9 before treatment and increased to 16.0 +/- 5.1, 14.1 +/- 4.0, 13.7 +/- 3.5, and 12.9 +/- 3.3 after treatment, suggesting that catch-up growth was significant after treatment as compared to the pre-treatment status (P < 0.01). Accordingly, post-treatment catch-up growth was obvious, significant differences were observed in HT SDS, which was -4.62 +/- 1.46 at the onset of therapy and increased significantly after the treatment to -3.80 +/- 1.53, -3.28 +/- 1.60, -2.86 +/- 1.75 and -2.47 +/- 1.86, respectively (P < 0.01). The height difference between GH deficient children and unimpaired children of the same age and gender gradually decreased after treatment, which was significantly different from that seen before treatment (P < 0.01). (2) The levels of serum IGF-1 and IGFBP-3 were increased comparably for the treatment. IGF-1 level (microg/L) was 41 +/- 64 at baseline and increased to 179 +/- 155, 202 +/- 141, 156 +/- 155 and 159 +/- 167 after 3, 6, 9, 12 months of treatment. IGFBP-3 level (mg/L) was 1540 +/- 1325 at baseline, and increased to 3891 +/- 1815, 4051 +/- 1308, 3408 +/- 1435 and 3533 +/- 1413, respectively, suggesting that with the increases in height, IGF-1, and IGFBP-3 were significantly activated to relatively high levels by the medication and reached peak values between 3 and 6 months of treatment. The levels of IGF-1 and IGFBP-3 were significantly different before and after treatment (P < 0.01). The IGF-1/IGFBP-3 molar ratio significantly increased during GH therapy (0.143 +/- 0.013 pre-therapy up to 0.240 +/- 0.055 post-therapy, P < 0.01). The IGF-1/IGFBP-3 molar ratio tended to stabilize after 3-month GH therapy. (3) The bone age assessment carried out 6 and 12 months after treatment showed that the bone maturity (DeltaBA/DeltaCA) was 1.01 +/- 0.57 and 1.07 +/- 0.75, respectively, suggesting that there was no speed-up development in the bone age. No severe adverse events were observed during the trial and the most frequent accompanying event was mild hypothyroidism.

CONCLUSIONSrhGH solution (Iintropin AQ) is a safe and effective preparation in the replacement therapy for children with GH deficiency.

Child ; China ; Dwarfism, Pituitary ; blood ; drug therapy ; Female ; Growth Disorders ; blood ; drug therapy ; Human Growth Hormone ; deficiency ; therapeutic use ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; metabolism ; Male ; Prospective Studies ; Recombinant Proteins ; therapeutic use

In this study, the texture analyzer acupuncture pressure sensor was used to objectively characterize the "herb soaking with exact amount of water" for moistening process of ginseng. The single factor rotation experiment was used to investigate the effects of puncture speed, puncture depth and puncture site on puncture force and work. According to ginseng processing method in Chinese Pharmacopoeia, ginseng medicinal materials with diameters of about 1 cm and 2 cm were selected, and puncture experiments were carried out at the set measurement time to determine the hardness, work and water absorption of the ginseng moistening process. The endpoint threshold for the ginseng softening process was determined and verified. To reflect the actual internal conditions of the ginseng softening process, the puncture depth was preferably 70%, and the puncture speed was 30 mm·min~(-1). In the ginseng moistening process, the softening hardness and the puncture work were in accordance with the first-order kinetic equation y=a×exp(-k×x). The 0 h initial hardness a of 1 cm and 2 cm ginseng herbs were 289.8 N and 1 227 N, and the rate constants K were 0.149 4 N·h~(-1) and 0.100 7 N·h~(-1), respectively. After the ginseng was completely softened, the force required for puncture was 10 N, which can be used as the standard for "drug penetration". At this time, the water absorption rate of ginseng was 70%-100%. The softening time of ginseng with a diameter of 1 cm was about 20-22 h, and the softening time of ginseng with a diameter of 2 cm was about 40-46 h. A needle-type pressure sensor was used to accurately determine the end point of the softening process of ginseng and reduce the loss of active ingredients. The study results provide reference for the softening process kinetics and the process intelligent monitoring of other dried roots and rhizomes.
Drugs, Chinese Herbal ; Panax ; Plant Roots ; Rhizome ; Technology, Pharmaceutical ; Water

ObjectiveTo examine the changes in the immune functions of CD8⁺ T cells in the spleen of mice following Echinococcus multilocularis infections at various doses and at different time points. MethodsThe E. multilocularis protoscoleces were collected, and E. multilocularis infection was modeled in mice via the hepatic portal vein at doses of 50 (low-dose), 500 (medium-dose) and 2 000 protoscoleces (high-dose), while physiological saline served as controls. Mouse spleen was isolated 2 (earlystage), 12 (middle-stage) and 24 weeks post-infection (late-stage), and spleen lymphocytes were harvested. The phenotype of memory CD8⁺ T cells and 2B4 expression were quantified in the mouse spleen, and the secretion of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-17A and IL-10 was measured. Results A central-memory phenotype was predominant in the CD8⁺ T cells in the spleen of mice at the early stage of high-dose protoscolece infections, and the proportion of central-memory CD8⁺ T cells was significantly greater in the high-dose group than in the control group (35.50% ± 2.00% vs. 25.90% ± 2.46%, P < 0.01), while a effector- memory phenotype was predominant in the CD8⁺ T cells in the spleen of mice at the late stage of medium- and high-dose protoscolece infections, and the proportions of effector-memory CD8⁺ T cells were significantly greater in the medium- (25.70% ± 4.12%) and high-dose group (28.40% ± 4.12%) than in the control group (10.50% ± 6.45%) (P < 0.05). The proportions of the central-memory CD8⁺ T cells were significantly higher in the high-dose group than at middle and late stages than at the early stage (P < 0.01), and the proportion of effector-memory CD8⁺ T cells was significantly greater in the high-dose group at the late stage than at early and middle stages (P < 0.05). The secretion of IFN-γ and IL-17A by spleen CD8⁺ T cells was elevated in the low- and medium-dose groups at the early stage of infection, and high-dose protoscolece infection promoted the secretion of IFN-γ and TNF-α by spleen CD8⁺ T cells; however, the levels of IFN-γ and TNF-α were significantly lower at the late stage than at the early and middle stages (P < 0.05). In addition, high 2B4 expression was detected in spleen CD8⁺ T cells in the middle- and high-dose groups at the late stage of infection, and the 2B4 expression was significantly higher in the medium(4.73% ± 1.56%) and high-dose groups (4.94% ± 1.90%) than in the low-dose group (2.49% ± 0.58%) and the control group (2.92% ± 0.60%) (P < 0.05). Conclusions E. multilocularis may be killed and eliminated through the host immune responses at the middle and late stages of low- and medium-dose protoscolece infections, while high-dose protoscolece infections may trigger the upregulation of 2B4 expression in mouse spleen CD8⁺ T cells at the late stage, which leads to immune exhaustion and the resultant chronic infections.