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Objective: To retrospectively evaluate possible impact factors of HIFU treatment outcome for unresectable pancreatic cancer patients., Patients and Methods: A total of 689 patients with unresectable pancreatic cancer were recruited in our center from December 30, 2007 to January 30, 2015. 436 patients with unresectable pancreatic cancers received HIFU treatment; the other 253 patients received non-HIFU treatment. Among these 436 patients, 345 patients received a one-time HIFU treatment, 91 patients received HIFU treatment from 2 to 5 times in the same pancreatic mass; 89 patients received HIFU treatment alone; 347 patients received HIFU-based combined therapies. Complications and overall survivals (OS) data in each group were collected., Results: The median overall survivals (mOS) in HIFU group and non-HIFU group were 7.1 vs. 5 months (P=0.005): 9.3 vs. 7.3 months (P=0.202) for patients with stage II disease, 8.3 vs. 7.3 months (P=0.783) for patients with stage III disease, and 6.4 vs. 4.2 months (P<0.0001) for patients with stage IV disease, respectively. Furthermore, there was a significant difference between repeated HIFU and one-time HIFU (mOS: 8.6 vs. 6.8 months, P=0.011). Time of HIFU treatment (P=0.0027), chemotherapy (P<0.0001), radiotherapy (P=0.0006), regional intra-arterial chemotherapy (RIAC) (P<0.0001), and stage (P<0.0001) were independent prognostic factors for the patients who received HIFU treatment. Cox analysis on the relative risk of prognostic factors showed that repeated HIFU vs. one-time HIFU (HR=0.729: 95% CI=0.576-0.924), chemotherapy vs. non-chemotherapy (HR=0.664: 95% CI=0.576-0.766), radiotherapy vs. non-radiotherapy (HR=0.580: 95% CI=0.427-0.789), RIAC vs. non-RIAC (HR=0.737: 95% CI=0.648-0.837), and stage (HR=1.386, 95% CI=1.187-1.619) were associated with significantly inferior survival. Overall, adverse events occurred in 23.2% (101/436) in the HIFU group, which included increase of serum or urinary amylase levels, incomplete intestinal obstruction, mild fever, etc. There were no severe adverse events such as skin burns or GI perforation related to HIFU therapy in any of the patients treated., Conclusion: This retrospective analysis revealed that the use of a multimodal treatment approach (the combined therapy of HIFU, RIAC, and chemotherapy, with or without radiotherapy) could improve survival of patients with unresectable pancreatic cancer, and repeated HIFU presented a survival benefit and did not increase risk.

Human breast cancers include cancer stem cell populations as well as non-tumorigenic cancer cells. Breast cancer stem cells possess self-renewal capability and thus are the root cause of recurrence and metastasis of malignant tumors. Hypoxia is a fundamental pathological feature of solid tumor tissues and exerts a wide range of effects on the biological behavior of cancer cells. However, there is little information on the role of hypoxia in modulating the stemness of breast cancer cells. In the present study, we cultured MDA-MB-231 cells in a hypoxic gas mixture to simulate the hypoxic environment in tissues and to determine how hypoxia conditions could affect the cell proliferation, apoptosis, cytotoxicity, and colony-forming ability. Expression of the stem cell phenotype CD24(-)CD44(+)ESA(+) was analyzed to assess the effects of hypoxia on stemness transformation in MDA-MB-231 cells. Our results found that the cell toxicity of MDA-MB-231 cells was not affected by hypoxia. Hypoxia could slightly inhibit the growth of MDA-MB-231 cells, but the inhibitory effect is not significant when compared with normoxic control. Moreover, hypoxia significantly blocked the apoptosis in MDA-MB-231 cells (P < 0.05). The proportion of CD24(-)CD44(+)ESA(+) cells in MDA-MB-231 cells was increased greatly after they were treated with hypoxia, and cell colony-formation rate of MDA-MB-231 cells also increased significantly in hypoxia-treated cells. These results encourage the exploration of hypoxia as a mechanism which might not be underestimated in chemo-resistant breast cancer treatment.

Objective: Previous studies indicated that the relationship between lysyl oxidase-like 1 (LOXL1) gene polymorphisms and primary open-angle glaucoma (POAG) remains inconsistent. In the present study, we aimed to perform a meta-analysis to investigate the association of LOXL1 polymorphisms with POAG risk., Methods: Literatures were electronically searched in the PubMed, EMBASE, CNKI, Wanfang, and VIP databases. The published literatures, which are case-control or cohort studies on the relationship between the polymorphisms (rs1048661, rs3825942, rs2165241) of the LOXL1 gene and POAG, were documented., Results: We included 13 literatures including 5,293 subjects for the present study. A meta-analysis showed that the risk of POAG in individuals carrying the C allele of rs2165241 was 1.26 times higher compared with those carrying the T allele (odds ratio (OR)=1.26, 95% confidence interval (CI): 1.09~1.46) in the total population. In the Caucasian population, we also found that individuals carrying the C allele of rs2165241 have an increased risk for POAG compared to those subjects carrying the T allele (OR=1.42, 95% CI: 1.19~1.69, p=0.0001). In addition, we found that the rs1048661 polymorphism was associated with POAG in the Asian population (OR=1.17, 95% CI: 1.02~1.35, p=0.03), and rs3825942 was associated with POAG in the Caucasian population (OR=2.69, 95% CI: 1.61~4.47, p<0.001)., Conclusions: The polymorphisms of the LOXL1 gene were associated with the susceptibility of POAG.

In the present study, an in situ control experiment was carried out to explore the response of testate amoebae to exogenous nitrogen addition in peatland of Sanjiang Plain. The results showed that nitrogen addition increased the biomass of testate amoebae at lower levels (6 g N · m(-2)), while decreased it at higher levels (> 12 g N · m(-2)). At genus level, nitrogen addition significantly increased the biomass of Arcella and Phryganella, decreased the biomass of Euglypha. Only lower nitrogen addition significantly increased the biomass of Centropyxis. At species level, nitrogen addition significantly decreased the biomass of Euglypha rotunda, while the biomass of either Centropyxis cassis or Phryganella acropodia was increased by a lower nitrogen addition treatment. This study suggested that the response of peatland testate amoebae to nitrogen addition was species specific, which could potentially be used as an indicator for the environment of peatlands.

Objectives: To perform a meta-analysis of clinical trials and investigate the effect of stem cell therapy on dilated cardiomyopathy., Methods: A systematic literature search was carried out between May 2012 and July 2013 in PubMed, Medline, Cochrane Library, and Excerpta Medica Database (EMBASE). The study took place in the Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China. The weighted mean difference (WMD) was calculated for left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), mortality and heart transplantation, and the 6-minute walk test (6-MWT) distance using the RevMan 5.0 software., Results: Seven trials with 599 participants evaluated the association between the stem cell therapy and control groups. Compared with the control group, stem cell therapy group improved the LVEF (WMD: 3.98%, 95% confidence interval [CI]: 0.55 - 7.41%, p=0.02) and the 6-MWT distance (WMD: 132.12 m, 95% CI: 88.15-176.09 m, p&lt;0.00001), and reduced mortality and heart transplantation (odds ratio [OR]: 0.48, 95% CI: 0.29-0.80, p=0.005). However, the LVEDD showed no significant difference between the 2 groups (WMD: -1.53 mm, 95% CI: -1.15-0.10 mm, p=0.10)., Conclusion: This meta-analysis demonstrated that stem cell therapy improves cardiac function and reduces mortality in dilated cardiomyopathy patients, which suggested that stem cell therapy may represent a new therapy option for dilated cardiomyopathy.

Background/aims: Programmed death-1 (PD-1) expression was investigated in CD4(+) and CD8(+) T cells from hepatitis B virus (HBV)-infected patients at the chronic hepatitis B (CHB) infection, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) stages., Methods: PD-1 expression in circulating CD4(+) and CD8(+) T cells was detected by flow cytometry. The correlations between PD-1 expression and HBV viral load, alanine aminotransaminase (ALT) levels and aspartate aminotransferase (AST) levels were analyzed using GraphPad Prism 5.0., Results: PD-1 expression in CD4(+) and CD8(+) T cells was significantly increased in both the CHB group and advanced-stage group (LC plus HCC). In the CHB group, PD-1 expression in both CD4(+) and CD8(+) T cells was positively correlated with the HBV viral load, ALT, and AST levels. However, in the LC plus HCC group, significant correlations between PD-1 expression and the clinical parameters were nearly absent., Conclusions: PD-1 expression in peripheral CD4(+) and CD8(+) T cells is dynamic, changes with HBV infection progression, and is related to HBV viral load and liver function, especially in CHB. PD-1 expression could be utilized as a potential clinical indicator to determine the extent of virus replication and liver injury.

Background/aims: To investigate the effects of edaravone, a potent free radical scavenger, on dibutyltin dichloride (DBTC)-induced chronic pancreatitis (CP) and pancreatic fibrosis., Methods: Male Sprague-Dawley rats were randomly divided into four groups (n = 16 each): control, DBTC, DBTC + edaravone, and control + edaravone. Edaravone or normal saline at a daily dose of 6 mg/kg body weight was given intraperitoneally from day 5 to day 28 after DBTC administration. On days 14 and 28, the rats were evaluated morphologically and biochemically. The expression of cytokines in pancreas TGF-β, IL-6 and TNF was detected using RT-PCR. The activation of nuclear factor (NF)-κB in pancreatic tissue was evaluated by immunostaining and western-blot for NF-κB p65. α-smooth muscle actin (α-SMA) expression was also evaluated by immunostaining and western-blot to investigate the activation of pancreatic stellate cells (PSCs)., Result: Edaravone treatment improved the rats' body weight (p < 0.01) and feed intake levels (p < 0.05), improved the histological scores and alleviated the fibrosis of pancreas samples (p < 0.05), as well as markedly increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) concentrations in pancreatic tissue (p < 0.01 for both). The expression of cytokines TGF-β, IL-6 and TNF in pancreas of DBTC group was also down-regulated by edaravone after treatment. Edaravone inhibited the activation of NF-κB and PSCs and exhibited protective effects on pancreatic tissue damage in CP., Conclusions: This antioxidant may be a promising therapeutic intervention for human CP., (Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objective: To explore the protective effects and possible mechanism of lipoxin A(4)-methyl ester (LXA(4)-ME) in rats with acute pancreatitis (AP)., Methods: A total of 120 male SD rats were randomly divided into 3 groups: Sham operation (n = 40), AP (n = 40) and LXA(4)-ME (n = 40). Sham operation group received normal saline after sham operation. AP was induced by a retrograde infusion of 5% sodium taurocholate into pancreatobiliary duct. AP group received normal saline after modeling. In the LXA(4)-ME group, LXA(4)-ME was administered (87.5 µg/kg) intravenously after the onset of AP. The rats were sacrificed at 12 h and 24 h post-induction. Their serum levels of amylase were detected. The amount of ascites was calculated and histological changes of pancreas were observed. The activities of myeloperoxidase (MPO) and levels of malonaldehyde (MDA) in pancreas were determined. The mRNA levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-10, intercellular adhesion molecule (ICAM-1), E-selectin and nuclear factor (NF)-κB p65 in pancreas were measured by reverse transcription-polymerase chain reaction (RT-PCR). The expression of NF-κB p65 protein was also measured by immunohistochemistry., Results: Compared with the AP group, the pathological scores of the LXA(4)-ME group improved (12 h: 8.7 ± 1.3 vs 11.3 ± 1.5, 24 h: 7.8 ± 1.1 vs 11.7 ± 0.8) and the amount of ascites was lower(12 h: (6.88 ± 1.23) ml vs (12.32 ± 1.94) ml, 24 h: (6.53 ± 0.91) ml vs (14.15 ± 1.68) ml, all P < 0.01). The serum levels of amylase in the LXA(4)-ME group were significantly lower than those in the AP group respectively at 12 h and 24 h post-operation (all P < 0.01). The activity of MPO and the level of MDA in pancreas in the LXA(4)-ME group were significantly lower than those in the AP group (all P < 0.01). The pancreatic expressions of TNF-α mRNA, IL-1β mRNA, ICAM-1 mRNA, E-selectin mRNA and NF-κB p65 mRNA at 12 h and 24 h decreased in the LXA(4)-ME group versus the AP group at the corresponding time points (all P < 0.01)while the expression of IL-10 mRNA increased versus the AP group at the corresponding time points (all P < 0.01). Compared with that in the AP group, the pancreatic expression of NF-κB p65 protein decreased in the LXA(4)-ME group (12 h: 24.8% ± 3.0% vs 45.3% ± 3.4%, 24 h: 31.6% ± 3.0% vs 48.1% ± 4.6%, both P < 0.01)., Conclusion: LXA(4)-ME exerts protective effects in AP rats. And its mechanism may be due to the suppression of NF-κB activation.

Objective: This study was to investigate the condom use and its factors on sex workers in Shandong province, and to provide effective suggestions for AIDS prevention strategies and interventions., Methods: From April to July in 2009, 4732 female sex workers were investigated through anonymous questionnaires from 11 cities which were selected based on the AIDS epidemic, geographic location, economic conditions in Shandong province. Serum samples were collected and antibodies were tested by ELISA and TPPA from 4641 people., Results: 4732 female sex workers who were 15 - 58 years old were investigated and the majority belonged to the low age group (≤ 24 years old) which accounted for 61.5% (2912/4732). Among the 4732 female sex workers, the unmarried, the divorced, or the widowed females accounted for 72.8% (3441/4725) and 72.0% (3403/4726) of them were poorly educated.42.3% (1994/4719) of them were found from other provinces. The right answers for knowledge of AIDS accounted for 45.7% (2164/4732). 80.6% (3416/4236) of these females were found to used condoms in the most recent commercial sex activity. The rate of consistently using condoms in sex activity during the last month was 58.4% (2467/4221). In this survey, 7.3% (337/4637) of investigated females had been diagnosed with sexually transmitted diseases, 30.7% (1449/4726) of them had received HIV antibody test, 70.4% (3323/4732) of these people had received the AIDS intervention services, and 3.6% (167/4668) of them had ever used drug. Multivariate logistic regression analysis showed that high education level (junior high school or lower vs senior high school or higher, adjusted OR = 0.77, 95%CI: 0.67 - 0.90), having received the HIV intervention (received vs unreceived, adjusted OR = 1.36, 95%CI: 1.17 - 1.58), antibody detection (done vs not done, adjusted OR = 1.33, 95%CI: 1.15 - 1.55), and good knowledge about AIDS (low score group vs high score group, adjusted OR = 0.37, 95%CI: 0.32 - 0.44) were independent factors that increased safe sex behavior; while using drug (drug vs not drug, adjusted OR = 0.22, 95%CI: 0.15 - 0.31) was a negative factor., Conclusion: The prevalence rate of HIV infection among female sex workers was low in Shandong province. However, the low rate of condom use and the high prevalence of self-reported STD-related symptoms suggested that more attentions should be paid to the factors of risk behaviors, and more targeted interventions are critically needed.

Hydrogen sulfide (H(2)S) is now considered a member of a group of signaling molecules termed 'gasotransmitters'. H(2)S has been shown to be generated in the endocrine and reproductive organs and elicits various actions. H(2)S modulates insulin secretion in pancreatic islets. Adipose tissues have the ability to produce H(2)S, which regulates the local insulin sensitivity and vascular responsiveness. H(2)S also acts on the hypothalamic-pituitary-adrenal axis and is involved in stress responses. The effects of H(2)S on male and female reproductive function have also attracted great interest for their potential therapeutic implications in reproductive disorders. Alterations of H(2)S biosynthesis are associated with various endocrine disorders, and hormones can be important factors in the regulation of H(2)S production. Understanding the regulatory mechanisms for H(2)S synthesis pathways may help develop new therapeutic strategies.

Unlabelled: Founded upon the database of 570 public signatures, ICPS is a web-based application to obtain biomarker profiles among 11 common cancers by integrating genomic alterations with transcription signatures on the basis of a previously developed integrative pipeline. ICPS supports both public data and user's in-house data, and performs meta-analysis at a cancer subtype level by combining heterogeneous datasets. Finally, ICPS returns the robust gene signature containing potential cancer biomarkers that may be useful to carcinogenesis study and clinical cancer diagnosis., Availability: http://server.bioicps.org, Contact: zhxy@mail.tsinghua.edu.cn; zxy-dcs@mail.tsinghua.edu.cn

Objective: To investigate the relationship between C923T (Ala308Val) polymorphism in exon 10 of protein 47000 phagocyte oxidase(p47(phox)) gene and stroke and to evaluate the effect of C923T (Ala308Val) polymorphism on plasma lipid levels in Hunan Hans population., Methods: Hunan Han population C923T (Ala308Val) polymorphism in p47phox gene was determined by PCR-single strand conformation polymorphism analysis and DNA sequencing in 100 healthy controls, 220 patients with stroke, and 10 stroke pedigrees. Plasma lipid levels were measured by routine methods., Results: No statistically significant differences were found in frequencies of genotypes and alleles of C923T (Ala308Val) polymorphism between the controls and stroke patients (P > 0.05). The serum levels of triglyceride in cerebral infarction patients and controls with CT genotype were markedly higher than those with CC genotype (P < 0.05)., Conclusion: There is no association between C923T (Ala308Val) polymorphism and stroke in Hunan Hans; C923T (Ala308Val) polymorphism is associated with plasma lipid metabolism in Hunan Han population with cerebral infarction.

Objective: To investigate the relationship between the polymorphism of apolipoprotein A5 gene (APOA5) -12238 T>C and atherosclerotic cerebral infarction (ACI)., Methods: Three hundred and forty-one subjects (170 ACI patients and 171 healthy controls) were collected to determine the genotypes by using polymerase chain reaction-restriction fragment length polymorphisms., Results: APOA5 allele frequencies of T/C were 0.588/0.412 and 0.424/0.576 in ACI group and control group respectively. There was significant difference in allele and genotype frequencies between ACI group and control group (P < 0.05). The levels of plasma triglyceride in ACI patients with TT genotype were higher than those in patients with CC genotypes (P < 0.05)., Conclusion: The relationship is found between the site of APOA5 gene -12238 T>C and ACI. There is a significant correlation between TT genotype of APOA5 and the levels of plasma triglyceride in patients with ACI.

Objective: To observe the transcriptional regulation of the two isoflavones genistein and daidzein on target genes., Methods: In this study, we used ERalpha or ERbeta over-expressing Hela cells to observe the transcriptional regulation of genistein and daidzein on ERE reporter gene with calcium-phosphate method, and furthermore observing the effects of phytoestrogen antagonist ICI 182780 on their activation., Results: Our results showed that both genistein and daidzein could activate ERE receptor gene through ERalpha and ERbeta, and these effects could be blocked by ICI 182780., Conclusion: Both genistein and daidzein can mimic estrogen's effect to activate the transcription of target genes through binding to the ERs.

The aim of this paper is to develop and validate a rapid and sensitive LC-APCI/MS method for the determination of triptolide (TP) in plasma and to study the pharmacokinetic properties of TP in Beagle dogs. Sample preparation consisted of liquid-liquid extraction of interests. with ethyl acetate from dog plasma. The analytes and internal standard prednisolone were well separated on a Zorbax Extend-C18 analytical column. Plasma TP was detected by selected-ion monitoring (SIM) of LC-APCI/MS as its deprotonated molecular ions [M - H] - at m/z 358.9. Pharmacokinetic studies were undertaken in dogs following an iv dose of 0.05 mg x kg(-1) of TP or an ig dose of 0.05, 0.08, 0.1 mg x kg(-1), separately. The pharmacokinetic parameters were calculated by DAS software. Calibration curves were linear over the concentration range of 1 - 200 ng x mL(-1) of TP with the within- and between-batch precisions less than 10%. The within and between-batch accuracy was 95.0% to 105.0%. Recovery of LC-MS method for TP in plasma was over 75%. The T1/2beta was (2.5 +/- 0.8) h after intravenous administration of TP at the dose of 0.05 mg x kg(-1). There were no significant differences in T(max), T1/2 alpha and T1/2 beta among the three ig dosage groups. AUC and C(max) increased proportionally with doses. The absolute bioavailability of TP after ig administration of 0.05 mg x kg(-1) was (75 +/- 17)%. The LC-MS method for determination of triptolide in dog plasma was sensitive and rapid. It was showed that the elimination of triptolide was rapid. The absolute bioavailability of triptolide given orally was high.

Objective: To explore the distribution of lecithin-cholesterol acyltransferase gene (LCAT) 608C/T polymorphism in Chinese Han population and the relationship of the polymorphism association with the occurrence of atherosclerotic cerebral infarction., Methods: The lecithin:cholesterol acyltransferase gene 608C/T polymorphism is identified by polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP)and restriction fragment length polymorphism (RFLP) in 150 patients with ACI and 122 healthy controls matching age and sex., Results: The distribution of LCAT 608C/T gene polymorphism was in accordance with Hardy-Weinberg equilibrium. The CT genotype frequency (14.0%) and T allele frequency (7.0%) in ACI group were significantly higher than those in control group (P<0.05). The concentration of high density lipoprotein cholesterol (HDL-C) in 608CC subgroups were significantly higher than those in 608CT subgroups both in ACI group and in control group (P<0.05)., Conclusion: The LCAT 608C/T polymorphism is possibly a predisposing factor in ACI happening of Chinese Han population. T allele frequency is possibly concerned with the metabolism of HDL-C.