Objective Gastric cancer is the most common cancer in the world. In China, Patients with gastric cancer are mostly treated with platinum-based chemotherapy. Programmed cell death 4 (PDCD4) was found as an important proapoptosis recently, the aim of the present study was to investigate the role of PDCD4 reversed the apoptosis induced by cisplatin in gastric cancer cell. The study will provide the target marker for treatment and diagnosis of cisplatin resistance in gastric cancer.Methods Stable transfection with pCMV-PDCD4 vector into human cisplatin resistance gastric cancer cell line-SGC7901/DDP; the cells were divided into control group, over-expression group, control with cisplatin group, over-expression with cisplatin group for following experiments. Hoechst dying with immunofluorescence and flow cytometry were used to measure the cell apoptosis in vitro; Real-time PCR was used to detect the mRNA expression levels of PDCD4, and the protein levels of PDCD4, pAK, pGSK3β, BCL-2 and Bak were detected by Western blot. The cells were divided into vector group, PDCD4 group, PDCD4 with activator group for detect the level of PARP(C) by Western blot.Results Compared with control group, the Results of real-time PCR and western blot were showed the level of PDCD4 was augmented in over-expression group (also in the over-expression with cisplatin group), which was indicated stable transfection with PDCD4 was successful. Immunofluorescence (with hoechst dying) and flow cytometry demonstrated that PDCD4 facilitated cell apoptosis exposed to cisplatin. PDCD4 overexpression attenuated the protein levels of pAkt, pGSK3β and BCL-2, but increased the protein levels of BAK. Furthermore, incubation with SC-79 (the activator of Akt) reversed cell apoptosis induced by PDCD4.Conclusion Overexpression of PDCD4 promotes the apoptosis induced by cisplatin through pAKT/pGSK3β pathway, which is favorable to reverse cisplatin resistance in gastric cancer.

OBJECTIVE: Ideal cardiovascular health (CVH) could predict a lower risk of developing cardiovascular diseases. This study was conducted to investigate the association between ideal CVH and subclinical atherosclerosis in a population cohort of Chinese adults aged ⪖ 40 years. METHODS: This study was designed as a cross-sectional analysis of 8,395 participants who had complete data at baseline and a prospective analysis of 4,879 participants who had complete data at 4.3 years of follow-up. Ideal CVH metrics were defined according to the American Heart Association. Subclinical atherosclerosis was evaluated by plaques in carotid arteries, carotid intima-media thickness (CIMT), brachial-ankle pulse wave velocity (baPWV), and urinary albumin-to-creatinine ratio (UACR). RESULTS: Both the prevalence and incidence of atherosclerosis measures were found to be decreased with increasing numbers of ideal CVH metrics at baseline (all P values for trend < 0.01). The levels of CIMT and UACR at follow-up showed an inverse and significant association with the numbers of ideal CVH metrics at baseline (both P values for trend < 0.05) but a borderline significant association with baPWV (P for trend = 0.0505). Taking participants with 0-1 ideal metric as reference, we found that participants with 5-6 ideal metrics had significantly lower risks of developing carotid plaques (odds ratio, OR = 0.46; 95% confidence interval, CI 0.27-0.79), increased CIMT (OR = 0.60; 95% CI 0.42-0.84), and increased baPWV (OR = 0.57; 95% CI 0.34-0.97) after full adjustments. A significant interactive effect of age and CVH was detected on CIMT and baPWV progression (both P values for interaction < 0.05). CONCLUSION The numbers of ideal CVH metrics showed a significant and inverse association with the risk of developing subclinical atherosclerosis in middle-aged and elderly Chinese adults, whereas its dose-response effect was attenuated in individuals aged ≥ 60 years and partially weakened in male participants.
Aged ; Atherosclerosis ; epidemiology ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Health Status ; Humans ; Male ; Middle Aged ; Prospective Studies

Twenty target compounds were synthesized by the reduction reaction of HUANG Minglong and Friedel-Crafts acylation reaction in this study. The inhibitory effects of the new compounds were tested on NO production in LPS-induced mouse macrophage RAW264.7 cells, a cellular inflammation model. The structure-activity relationships were discussed. The structures of target compounds were confirmed by ESI-MS, ¹H NMR and ¹³C NMR. In vitro activity experiments showed that 18 compounds had certain anti-inflammatory effects at the concentration of 40 μmol·L^-1, of which 9a, 8b, 7c and 9c showed strong anti-inflammatory activities, and IC₅₀ of 7c and 9c were comparable to the positive control drug ibuprofen.

With the continuous development of DNA extraction and testing technology, the DNA left at a crime scene plays a decisive role in the determination of criminal suspects in criminal investigation. But in the meanwhile, the anti-reconnaissance awareness of suspect is growing, which leads to a decrease of evidence left at scene during and after a crime. Therefore, in the process of evidence collection at scene, the finding and extraction of touch biological evidence, and the DNA detection are more and more important. At present, the proportion of touch evidence at the crime scene increases, which plays an increasingly important role in the detection of cases. However, with the characteristics of minute quantities, small size and secrecy, these touch evidence is difficult to be observed. What's more, various forms of pollution at the scene greatly accelerate the degradation rate of trace material, thus, the test and analysis of such material has become the emphasis and difficulty of the forensic evidence identification. This article reviews different kinds, collection and extraction methods of touch DNA, the factors that affect the detection and the problems may meet in the detection for providing an application prospect to the forensic practice.
Crime ; Criminals ; DNA/isolation & purification* ; DNA Fingerprinting ; Forensic Genetics/methods* ; Humans ; Touch

BACKGROUNDRetinal edema is the major complication of retinal vein occlusion and diabetic retinopathy; it can damage visual function by influencing macular region. This study was to establish a rat retinal edema model and explore the related VEGF expression and observe the responses to anti-VEGF drugs in this model.

METHODSA rat retinal edema model was established by inducing photochemical reaction using a 532 nm laser after the intravenous injection of Erythrosin B. Immediately after the laser treatment, models were given intravitreal injections of Ranibizumab or Conbercept to inhibit VEGF expression, and the changes of retinal thickness were measured. Retinal edema was observed using fundus photography (FP), optical coherence tomography (OCT), and fluoresce in fundus angiography (FFA) at 0, 1, 2, 4, 7 and 14 days after intervention. The retinal VEGF expression was measured using enzyme-linked immunosorbent assay (ELISA) and western blotting at each time point. The rat retinal edema model was also used to verify the function of anti-VEGF polypeptide ZY1.

RESULTSBoth retinal edema and vascular leakage were clearly observed at 1, 2 and 4 days after photochemical induction and the retinal thickness increased notably over the same period. The retinal VEGF expression peaked at day 1 and retina became thickening simultaneously. After the interventions, the VEGF expression of the Ranibizumab and Conbercept groups decreased at each time point compared to the edema group (26.90 ± 3.57 vs. 40.29 ± 6.68, F = 31.269 on day 1 and 22.36 ± 1.12 vs. 29.92 ± 0.93 F = 163.789 on day 2, both P < 0.01); the mean RT (278 ± 4 vs. 288 ± 3, F = 134.190 on day 1 and 274 ± 7 vs. 284 ± 6, F = 64.367 on day 2, both P < 0.05) and vascular leakage in these groups also decreased. The same results were observed in the ZY1 group, particularly at day 2 (P < 0.05).

CONCLUSIONSThis retinal edema model induced by a photochemical reaction is reliable and repeatable. Induced edema increases expression of VEGF. This model can be used to test new drugs.

Angiogenesis Inhibitors ; therapeutic use ; Animals ; Enzyme-Linked Immunosorbent Assay ; Erythrosine ; toxicity ; Fluorescein Angiography ; Intravitreal Injections ; Macular Edema ; chemically induced ; drug therapy ; metabolism ; Ranibizumab ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins ; therapeutic use ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A ; metabolism

Objective To investigate the correlation between ultrasound-guided diffuse optical tomography (US-DOT) and hypoxia-inducible factor-1Α (HIF-1Α) of breast cancer. Methods Totally 69 patients with pathologically confirmed breast cancer underwent preoperative conventional breast ultrasonography examinations and US-DOT at Peking Union Medical College Hospital From October 2007 to February 2010 were enrolled in this study.After surgery,immunohistochemical staining of HIF-1Α and CD34 were performed,and the differences of total hemoglobin concentration (THC) and microvessel density (MVD) between HIF-1Α positive and negative groups were analyzed. Results HIF-1Α was positive in 12 cases (17.4%) and negative in 57 cases (82.6%). The average THC and MVD of HIF-1Α-positive cases were (274.763±77.661) Μmol/L and (33.8±10.8)/0.2 mm(2) respectively. The average THC and MVD of HIF-1Α-negative cases were (228.059±65.760)Μmol/L and (28.4±7.4)/0.2 mm(2). MVD(t=2.049,P=0.04) and THC(t=2.167,P=0.034) of HIF-1Α-positive group were significantly higher than those of HIF-1Α-negative group. Conclusions HIF-1Α can promote tumor angiogenesis and thus increase the blood supply and THC. As an indicator of tumor blood supply,THC can indirectly reflect the angiogenic activity of breast cancer.
Breast Neoplasms ; diagnostic imaging ; metabolism ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Neovascularization, Pathologic ; Tomography, Optical ; Ultrasonography, Mammary

Recent studies indicated that interleukin (IL)-17, growth-related oncogene (GRO)-α and IL-8 play an important role in the pathogenesis of nasal polyps. However, the effects of the increased amount of IL-17 and the production of GRO-α and IL-8 in human nasal polyp fibroblasts are not completely understood. This study aimed to determine the effects of the increased IL-17 on the changes of GRO-α and IL-8 expression in human nasal polyp fibroblasts and further investigate the mechanism of neutrophil infiltration in nasal polyps. Nasal polyp fibroblasts were isolated from six cases of human nasal polyps, and the cells were stimulated with five different concentrations of IL-17. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of GRO-α and IL-8. The mRNA of GRO-α and IL-8 was expressed in unstimulated controls and remarkably increased by stimulation with IL-17. Moreover, the levels of GRO-α and IL-8 produced by fibroblasts were increased gradually with the increases in IL-17 concentrations. The present study showed that nasal fibroblasts can produce GRO-α and IL-8, and their production is remarkably enhanced by IL-17 stimulation, thereby clarifying the mechanism of the IL-17 mediated neutrophil infiltration in nasal polyps. These findings might provide a rationale for using IL-17 inhibitors as a treatment for nasal inflammatory diseases such as nasal polyps.
Adult ; Cells, Cultured ; Chemokine CXCL1 ; biosynthesis ; Female ; Fibroblasts ; metabolism ; pathology ; Humans ; Interleukin-17 ; pharmacology ; Interleukin-8 ; biosynthesis ; Male ; Middle Aged ; Nasal Polyps ; metabolism ; pathology ; Neutrophil Infiltration ; drug effects ; RNA, Messenger ; biosynthesis

To investigate the cell-killing effect and its possible mechanism of rClone30-hDR5 in combination with TRAIL on human hepatic carcinoma (HCC) cell line, first of all, recombinant plasmid pee12.4-hDR5 was introduced into HepG2 cells by liposome transfection. After five rounds of screening by flow cytometry, HepG2 cells expressing high levels of DR5 on cell surface were isolated. The cytotoxicity of TRAIL to selected cells was higher than that of TRAIL to HepG2 cells by MTT method (P < 0.01). The result suggested that the cloned hDR5 gene had biological activity. MTT assay showed that, rClone30- hDR5 in combination with TRAIL more efficiently inhibited the tumor growth of HepG2 cells compared to rClone30-hDR5 or TRAIL in vitro. The results of Annexin V-FITC/PI staining and Quantitative Real-time PCR indicated that rClone30-hDR5 in combination with TRAIL significantly increased the mRNA levels of caspase 3 and caspase 8, and induced the apoptosis of tumor cells. HepG2 cells were infected with rClone30-hDR5 or rClone30 at MOI of 1. The expression of hDR5 on tumor surface increased significantly by rClone30-hDR5 compared to that by rClone30, which contributed to the sensitivity to TRAIL. In conclusion, rClone30-hDR5 in combination with TRAIL has potential application value in cancer treatment.
Apoptosis ; Carcinoma, Hepatocellular ; pathology ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Drug Synergism ; Hep G2 Cells ; Humans ; Liver Neoplasms ; pathology ; Real-Time Polymerase Chain Reaction ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; pharmacology ; TNF-Related Apoptosis-Inducing Ligand ; pharmacology ; Transfection

Recent studies indicated that interleukin (IL)-17, growth-related oncogene (GRO)-α and IL-8 play an important role in the pathogenesis of nasal polyps. However, the effects of the increased amount of IL-17 and the production of GRO-α and IL-8 in human nasal polyp fibroblasts are not completely understood. This study aimed to determine the effects of the increased IL-17 on the changes of GRO-α and IL-8 expression in human nasal polyp fibroblasts and further investigate the mechanism of neutrophil infiltration in nasal polyps. Nasal polyp fibroblasts were isolated from six cases of human nasal polyps, and the cells were stimulated with five different concentrations of IL-17. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of GRO-α and IL-8. The mRNA of GRO-α and IL-8 was expressed in unstimulated controls and remarkably increased by stimulation with IL-17. Moreover, the levels of GRO-α and IL-8 produced by fibroblasts were increased gradually with the increases in IL-17 concentrations. The present study showed that nasal fibroblasts can produce GRO-α and IL-8, and their production is remarkably enhanced by IL-17 stimulation, thereby clarifying the mechanism of the IL-17 mediated neutrophil infiltration in nasal polyps. These findings might provide a rationale for using IL-17 inhibitors as a treatment for nasal inflammatory diseases such as nasal polyps.

OBJECTIVETo explore the association between polycyclic aromatic hydrocarbons (PAHs) exposure and telomere length (TL), so as to investigate the effective biomarkers to evaluate the genetic damage in peripheral blood of workers exposed to PAHs.

METHODSThe exposure group consisted of 145 coke-oven workers (including 30 top-oven workers, 76 side-oven workers and 39 bottom-oven workers), and the non-exposure control group comprised 68 medical staffs. At 6 hours after the weekend duty shift, the samples of urine and 1 ml venous blood were collected from each subject. Airborne benzene-soluble matter (BSM) and particulate-phase B(a)P in the working environment of coke-oven and controls were sampled and analyzed. The concentration of urinary 1-hydroxypyrene (1-OHPyr) was determined. A real-time PCR method was used to determine the relative telomere length (RTL) of genomic DNA in peripheral blood. The relationship between the RTL and external exposure of PAHs, the potential factors which might have influence on TL were analyzed.

RESULTSThe medians of air BSM and particulate-phase B(a)P were higher in coke-oven (BSM: 328.6 µg/m(3); B(a)P: 926.9 ng/m(3)) than those in control working environment (BSM:97.8 µg/m(3); B(a)P: 49.1 ng/m(3)). The level of 1-OHPyr among coke-oven workers was significantly higher than that of non-exposed group (12.2 µmol/mol Cr vs 0.7 µmol/mol Cr; t = 26.971, P < 0.01). RTL in coke-oven workers were significantly shorter than those of controls (1.10 ± 0.75 vs 1.43 ± 1.06; t = 2.263, P = 0.026), and after adjusting for cigarettes per day and urinary 1-OHPyr, the significant difference was still observed (F(adju) = 5.496, P(adju) = 0.020). Stratification analysis found that RTL among the male and non-drinking groups in coke-oven workers were shorter than those the same sex and alcohol using status in controls (1.08 ± 0.73 vs 1.51 ± 1.10, F = 9.212, P = 0.003; 0.96 ± 0.38 vs 1.26 ± 0.46, F = 6.484, P = 0.012). Significant correlation between RTL and age was found (r = -0.284, P = 0.019) in non-exposure group.

CONCLUSIONPAH-exposure has effect on TL of genomic DNA in peripheral blood, which is mainly observed in the male and non-drinking groups between PAH-exposed workers and controls. It indicates that TL of genomic DNA in peripheral blood might be an effective biomarker as PAH-induced genetic damage.

Adult ; Benzene ; Case-Control Studies ; Coke ; DNA Damage ; Female ; Humans ; Male ; Occupational Exposure ; adverse effects ; analysis ; Polycyclic Aromatic Hydrocarbons ; adverse effects ; analysis ; Pyrenes ; analysis ; Telomere ; drug effects ; genetics