Construction of molecular subgroups of ulcerative colitis.

OBJECTIVE: Ulcerative colitis (UC), a chronic inflammatory disease of the colon with unknown etiology, is characterized by remission and recurrence. At present, a considerable number of UC cases are misdiagnosed or delayed in diagnosis and treatment. We aimed to identify UC-related genes to aid the development of drugs for this condition. PATIENTS AND METHODS: Transcriptome data of 362 patients with UC and 126 control subjects were obtained from the Gene Expression Omnibus. The 362 patients with UC were subgrouped using unsupervised machine learning. R software was used to analyze the clinical characteristics of the subgroups, screen subgroup-specific genes, assess the relationships between gene modules and clinical characteristics using weighted gene co-expression network analysis, and perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the subgroups. RESULTS: Patients with UC were classified into two subgroups. Genes specific to subgroup I included IL21R, ATP8B2, and PLEKHO1. Severe disease tended to be associated with immune cell infiltration; anti-tumor necrosis factor (TNF)-α antibodies and ustekinumab may have been effective in this subgroup. Subgroup II-specific genes included SLC4A4, EPB41L4B, and PLCE1. Patients in this subgroup had mild clinical conditions; however, their disease was more likely to progress to colorectal cancer. Thus, 5-aminosalicylic acid-based drugs may be effective for the treatment of UC in these patients. CONCLUSIONS: We divided UC into two molecular subgroups based on transcriptome data, providing molecular evidence for the development of diagnostic methods and individualized treatment strategies for UC.

LncRNA RPPH1 predicts poor prognosis and regulates cell proliferation and migration by repressing P21 expression in gastric cancer.

OBJECTIVE: The purpose of this study was to explore the expression and biological functions of long non-coding ribonucleic acid (lncRNA) ribonuclease P RNA component H1 (RPPH1) in gastric cancer (GC), and to analyze the correlations of lncRNA expression with the clinical features and prognosis of GC patients. PATIENTS AND METHODS: The relative expression of RPPH1 in tissue specimens from 60 GC patients was measured via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), and the correlations of RPPH1 expression with tumor-node-metastasis (TNM) stage, lymph node metastasis, etc. in GC patients were analyzed. Then, qRT-PCR was performed to detect the relative expression level of RPPH1 in GC cells. Moreover, colony formation assay, 5-Ethynyl-2'-deoxyuridine (EdU) staining, wound-healing assay, and transwell assay were employed to investigate the influence of RPPH1 on GC cell functions. After interfering in the expression of RPPH1, the changes in p21 (CDKN1A, cyclin dependent kinase inhibitor 1A) expression were determined through qRT-PCR and Western blotting. RESULTS: It was shown in qRT-PCR assay results that the expression of RPPH1 was upregulated in 60 cases of GC tissues. Statistical analysis revealed that RPPH1 expression was positively correlated with the TNM stage, lymph node metastasis, and infiltration depth in GC patients. Besides, highly expressed lncRNA RPPH1 suggested poor prognosis of GC patients. Based on the results of qRT-PCR assay, the expression of RPPH1 in GC cells was upregulated. After interfering in RPPH1 expression, both colony formation assay and EdU staining indicated that the proliferative capacity of GC cells was repressed. Furthermore, it was manifested in the results of wound-healing and transwell assays that the migratory and invasive abilities of GC cells were weakened. Finally, the qRT-PCR and Western blotting assay results demonstrated that p21 expression was upregulated after interfering in the expression of RPPH1 in GC cells. CONCLUSIONS: The expression of lncRNA RPPH1 is upregulated in GC, suggesting that the prognosis of the patients is poor. Highly expressed RPPH1 promotes the proliferation and metastasis of GC cells by regulating p21 expression.

Effect of anti-mullerian hormone on stem cell factor in serum, follicular fluid and ovarian granular cells of polycystic ovarian syndrome patients.

OBJECTIVE: Polycystic ovarian syndrome (PCOS) is a common disorder in gynecological practice. Anti-mullerian hormone (AMH) and ovarian granular stem cell factor (SCF) participate in the occurrence and progression of PCOS. This study aimed to investigate the expression of AMH and SCF in PCOS patients and attempt to analyze the effect of AMH on SCF. PATIENTS AND METHODS: Both PCOS and non-PCOS patients who received in vitro fertilization (IVF) in our hospital were recruited for measuring AMH and SCF levels in serum, ovarian follicular fluid and granular cells by using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry (IHC) and Real-time PCR were employed to quantify mRNA and protein levels of SCF in ovarian granular cells after treatment using different dosages of AMH. RESULTS: AMH levels in serum, follicular fluid and granular cells in PCOS patients were significantly elevated, whilst SCF level was significantly decreased (p<0.05 in both cases). Therefore, there was a negative correlation between AMH and SCF level (p<0.05). In 5 ng/ml, 10 ng/ml and 15 ng/ml group, SCF protein positive rate was gradually decreased and was significantly lower compared to that of blank control (p<0.05). After treatment using AMH for 12, 24 and 48 h, SCF mRNA expression in the granular cell was significantly decreased (p<0.05). With higher dosage, SCF mRNA was gradually down-regulated in granular cells (p<0.05). CONCLUSIONS: High level of AMH and low level of SCF existed in serum, follicular fluid, and granular cells in PCOS patients. AMH exhibited negative regulatory effects on SCF.

Correlation of genetic results with testicular histology, hormones and sperm retrieval in nonobstructive azoospermia patients with testis biopsy.

To investigate the frequency and types of genetic results in different testicular histology of patients with nonobstructive azoospermia (NOA), and correlated with hormones and sperm retrieval (SR), a retrospective study was conducted in 286 Chinese NOA patients who underwent testis biopsy and 100 age-matched fertile men as the control group. Chromosome karyotype analyses were performed by the peripheral blood chromosome G-band detection method. Screening of Y chromosome microdeletions of azoospermia factor (AZF) region was performed by polymerase chain reaction (PCR) amplification of 11 sequence-tagged sites (STS). The serum levels of follicle-stimulating hormone, luteinising hormone and testosterone (T) and the appearance of scrotal ultrasound were also obtained. In 286 cases of NOA, 14.3% were found to have chromosomal alterations. The incidence of chromosomal abnormality was 2.8%. Sex chromosomal abnormalities were seen in six cases (four cases of Klinefelter's syndrome (47, XXY) and two cases of mosaics). The incidence of polymorphic chromosomal variants was 3% in the normal group and 11.5% in the NOA group. In total, 15.7% of NOA patients were found to have AZF microdeletions and AZF (c + d) was the most frequent one. The results of hormone and SR were found to be significantly different among all testicular histological types, whereas no significant differences were found when it comes to genetic alterations. It is concluded that the rate of cytogenetic alterations was high in NOA patients. So screening for chromosomal alterations and AZF microdeletions would add useful information for genetic counselling in NOA patients with testis biopsy and avoid vertical transmission of genetic defects by assisted reproductive technology.

Early evaluation of targeted therapy effectiveness in non-small cell lung cancer by dynamic contrast-enhanced CT

Purpose. To study the feasibility and clinical value of dynamic contrast-enhanced (DCE) computed tomography (CT) for early evaluation of targeted therapy efficacy in non-small cell lung cancer (NSCLC). Methods. We measured tumor diameter, peak height (PH), time to peak (TP), tumor mass-aortic peak height ratio (M/A), and blood perfusion (BP) in 20 patients with advanced NSCLC using DCE-CT before and 7 days after treatment. Therapy efficacy was assessed with conventional CT 4-6 weeks post-treatment. Results. Patients were grouped into those with partial response (PR), stable disease (SD), and progressive disease (PD) according to the therapy efficacy assessment at 4-6 weeks post-treatment. The PR group primary tumor diameter (P = 0.0007) and BP (P = 0.0225) were reduced at 7 days post-treatment; the SD group DCE-CT value changes were not significant. The PD group M/A (P = 0.0443) and BP (P = 0.0268) were increased 7 days post-treatment. The BP decrease group had significantly longer progression-free survival than the BP increase group (median, 54 vs. 6 weeks). Conclusion. DCE-CT can evaluate targeted therapy efficacy at 7 days post-treatment. Decreased primary tumor diameter and BP indicate tumor sensitivity to therapy; increased BP with unchanged tumor diameter suggests the tumor is not sensitive to therapy. Reduced BP suggests treatment effectiveness (AU)

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Early evaluation of targeted therapy effectiveness in non-small cell lung cancer by dynamic contrast-enhanced CT.

PURPOSE: To study the feasibility and clinical value of dynamic contrast-enhanced (DCE) computed tomography (CT) for early evaluation of targeted therapy efficacy in non-small cell lung cancer (NSCLC). METHODS: We measured tumor diameter, peak height (PH), time to peak (TP), tumor mass-aortic peak height ratio (M/A), and blood perfusion (BP) in 20 patients with advanced NSCLC using DCE-CT before and 7 days after treatment. Therapy efficacy was assessed with conventional CT 4-6 weeks post-treatment. RESULTS: Patients were grouped into those with partial response (PR), stable disease (SD), and progressive disease (PD) according to the therapy efficacy assessment at 4-6 weeks post-treatment. The PR group primary tumor diameter (P = 0.0007) and BP (P = 0.0225) were reduced at 7 days post-treatment; the SD group DCE-CT value changes were not significant. The PD group M/A (P = 0.0443) and BP (P = 0.0268) were increased 7 days post-treatment. The BP decrease group had significantly longer progression-free survival than the BP increase group (median, 54 vs. 6 weeks). CONCLUSION: DCE-CT can evaluate targeted therapy efficacy at 7 days post-treatment. Decreased primary tumor diameter and BP indicate tumor sensitivity to therapy; increased BP with unchanged tumor diameter suggests the tumor is not sensitive to therapy. Reduced BP suggests treatment effectiveness.

A population-based study of associations between functional gastrointestinal disorders and psychosocial characteristics in Xi'an, China.

BACKGROUND: Functional gastrointestinal disorders (FGIDs) are disorders with chronic and recurring gastrointestinal symptoms. This study investigated the prevalence of FGIDs, assessed the association between FGIDs and psychosocial factors, and identified potential risk factors for FGIDs in a population in Xi'an, China. METHODS: Of 752 recruited residents in Xi'an, 720 were selected for an epidemiological survey using a cluster sampling method. All subjects were interviewed face-to-face to complete the Chinese version of ROME III FGIDs questionnaire, the Symptom Check-List-90, the Eysenck Personality Questionnaire, a Life Event Scale, and a questionnaire regarding personal childhood adversity. The prevalence of FGIDs and associations between FGIDs and psychosocial factors were determined using EpiData Software. Logistic regression analysis was performed to identify the potential risk factors for FGIDs. KEY RESULTS: The prevalence of FGIDs in this sample population was 14.3% (103/720). There were 13 (1.8%) cases of overlap of different FGIDs. No significant difference in the prevalence of FGIDs was observed between men and women. Alcohol intake and smoking habits were significantly associated with the presence of FGIDs. The presence of FGIDs was significantly associated with psychological factors and influences such as personality type, life events, childhood adversity, and psychopathology. The potential risk factors for contracting FGIDs were certain life events, childhood adversity, somatization, and a hostile affect (P < 0.001). CONCLUSIONS & INFERENCES: The prevalence of FGIDs and overlap syndrome in Xi'an, China was lower than that reported in other countries. There was a strong correlation between specific lifestyle habits and psychosocial characteristics and the presence of FGIDs.

Prompt gamma neutron activation analysis of toxic elements in radioactive waste packages.

The French Alternative Energies and Atomic Energy Commission (CEA) and National Radioactive Waste Management Agency (ANDRA) are conducting an R&D program to improve the characterization of long-lived and medium activity (LL-MA) radioactive waste packages. In particular, the amount of toxic elements present in radioactive waste packages must be assessed before they can be accepted in repository facilities in order to avoid pollution of underground water reserves. To this aim, the Nuclear Measurement Laboratory of CEA-Cadarache has started to study the performances of Prompt Gamma Neutron Activation Analysis (PGNAA) for elements showing large capture cross sections such as mercury, cadmium, boron, and chromium. This paper reports a comparison between Monte Carlo calculations performed with the MCNPX computer code using the ENDF/B-VII.0 library and experimental gamma rays measured in the REGAIN PGNAA cell with small samples of nickel, lead, cadmium, arsenic, antimony, chromium, magnesium, zinc, boron, and lithium to verify the validity of a numerical model and gamma-ray production data. The measurement of a ∼20kg test sample of concrete containing toxic elements has also been performed, in collaboration with Forschungszentrum Jülich, to validate the model in view of future performance studies for dense and large LL-MA waste packages.

The plasma level of soluble receptor for advanced glycation end products is decreased in patients with systemic lupus erythematosus.

In recent years, the role of high mobility group box-1 (HMGB1) protein and its receptors in autoimmune diseases has received increasing attention. It has been documented that HMGB1 is associated with disease activity in patients with systemic lupus erythematosus (SLE). This study was undertaken to determine the potential role of receptor for advanced glycation end products (RAGE), one receptor for HMGB1, in the pathogenesis of SLE. Plasma levels of soluble RAGE (sRAGE) from 105 patients with clinical diagnosis of SLE and 43 healthy controls were determined by ELISA. Associations between sRAGE levels and clinical, laboratory characteristics were assessed. The data showed that plasma levels of sRAGE in patients with SLE were significantly lower than those in healthy controls (HC) (P = 0.003). Plasma sRAGE in patients receiving short-period treatment showed an immediate decrease compared with the untreated patients (P = 0.023). In contrast, plasma sRAGE in patients receiving long-period treatment were significantly increased compared to those with short-period treatment (P = 0.000) and comparable with those in HC (P = 0.305). The significant decreased levels of sRAGE in patients with SLE suggest the potential association of RAGE signalling and SLE clinical pathology, whereas, long-period antilupus treatment may counteract the decreased sRAGE levels in patients with SLE.

Combined inhibitory effects of celecoxib and fluvastatin on the growth of human hepatocellular carcinoma xenografts in nude mice.

This study was designed to investigate the in vivo growth inhibitory effects of celecoxib, a cyclo-oxygenase-2 inhibitor, and fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on the hepatocellular carcinoma (HCC) cell line, BEL-7402. Athymic nude mice implanted with BEL-7402 cells were given celecoxib and fluvastatin, either alone or in combination, and the effect of treatment on tumour growth was evaluated after 6 weeks. The combination of celecoxib and fluvastatin enhanced inhibition of tumour growth, induction of apoptosis, inhibition of tumour cell proliferation, and inhibition of tumour angiogenesis compared with either treatment alone. The combination of celecoxib and fluvastatin also increased levels of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1), decreased levels of p-Akt, myeloid cell leukaemia-1 (Mcl-1) and survivin protein, but had no effect on Akt protein levels in tumours. These results suggest that celecoxib combined with fluvastatin would be more efficacious for the treatment of HCC than either treatment alone and this combination of therapy warrants further research.

Expression and correlation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor and microvessel density in experimental rat hepatocarcinogenesis.

An experimental rat hepatocellular carcinoma (HCC) model was established using diethylnitrosamine and N-nitrosomorpholine to induce carcinogenesis in Sprague-Dawley rats. During hepatocarcinogenesis, seven rats were sacrificed at 0, 4, 8, 12 and 16 weeks and 10 rats were sacrificed at 20 weeks. The levels of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) protein and mRNA were examined by immunohistochemistry, Western blot and semi-quantitative reverse transcriptase-polymerase chain reaction at different stages in the rat HCC model. Twenty weeks after induction of hepatocarcinogenesis, the expression of HIF-1alpha and VEGF protein and mRNA significantly increased compared with week 0. Microvessel density (MVD) increased considerably once liver cancer developed. There was a significant positive correlation between MVD and both HIF-1alpha and VEGF, and between HIF-1alpha and VEGF levels. These results suggest that HIF-1alpha and VEGF play important roles in tumour occurrence and development during rat hepatocarcinogenesis, possibly through promoting tumour angiogenesis.

Laser ion acceleration via control of the near-critical density target.

Duration-controlled amplified spontaneous emission with an intensity of 10(13) W/cm(2) is used to convert a 7.5-microm -thick polyimide foil into a near-critical plasma, in which the p -polarized, 45-fs , 10(19) -Wcm (2) laser pulse generates 3.8-MeV protons, emitted at some angle between the target normal and the laser propagation direction of 45 degrees . Particle-in-cell simulations reveal that the efficient proton acceleration is due to the generation of a quasistatic magnetic field on the target rear side with magnetic pressure inducing and sustaining a charge separation electrostatic field.

4-(N-Hydroxyethyl-N-methylamino)benzaldehyde thiosemicarbazone

In the crystal structure of the title compound, C(11)H(16)N(4)OS, the phenyl ring and the thiosemicarbazone moiety from a dihedral angle of 7.7 (1) degrees. The crystal structure is governed by N-H.O and O-H.S hydrogen bonds leading to the formation of a two-dimensional network.