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This paper deals with the segmentation and inversion of the Hangjinqi fault zone (HFZ), which is the dominant structure in the northern part of the Ordos basin in North China. HFZ was reactivated during the Late Triassic and obliquely inverted during the Middle Jurassic shortening. Subsurface geological mapping and structural analysis were carried out to determine the segmentation and kinematic history of the deformation. The HFZ was a left-stepping fault zone and was made up of three segments: the Porjianghaizi fault (PF), Wulanjilinmiao fault (WF) and Sanyanjing fault (SF), which are separated by two relay ramps. Two distinct phases can be identified in its structural evolution: (1) during the Late Triassic compressional deformation, the HFZ was characterized by shortening and thrusting to the north; and (2) During the Middle Jurassic phase the HFZ was oblique to the extensional fault trends, the reverse faults were reactivated as dextral strike-slip faults as a result of transtensional inversion. The inversion ratio of the HFZ indicates an increase in deformational degree from east to west over the whole region. The first deformation stage resulted from the N–S compression between the South China and North China plates during the Late Triassic. The second deformation stage of compression was related to the west-northwestward subduction of the paleo-Pacific plate during the Middle Jurassic. In the Jurassic deformation framework, the HFZ may be interpreted as an accommodation structure parallel to the Yanshan–Yinshan orogenic belt developed in the northern Ordos area.

This study examines how attachment and acculturation are associated with the general mental health of Chinese students in Japan. The participants were 194 Chinese students living in Japan, who were asked to complete a set of self-reported measures. The results showed that attachment anxiety predicted all subscales of general mental health, and attachment avoidance and acculturation predicted some aspects of general mental health. In addition, the number of years of residence in Japan was also found to be associated with the general mental health. The findings help improving intercultural communication between Asian countries as well as to facilitate clinical intervention and prevention.

Background Carbohydrate antigen 125 (CA-125) is one of the most common used tumor biomarkers in clinical practice. Previous studies showed an association of increased CA-125 levels with advanced characteristics and inferior outcome in non-Hodgkin lymphoma. Objective To identify the clinical significance of CA-125 in diffuse large B-cell lymphoma (DLBCL). Methods We retrospectively analyzed 181 patients with DLBCL with measured serum CA-125 concentration at diagnosis and follow-ups during the courses. Clinical significance of CA-125 was evaluated by assessing the association between CA-125 levels and clinical characteristics. Results CA-125 levels on admission were positively correlated with serum lactate dehydrogenase, β2-microglobulin (β2-MG), serum ferritin (SF) and cavity effusion, while negatively correlated with serum albumen (ALB). During the courses, CA-125 levels were positively correlated with β 2-MG, SF and effusion, and negatively correlated with ALB. A better correlation between effusion and CA-125 levels was observed. Using a cut-off value > 50.39 U/ml gave a sensitivity of 73.8% and a specificity of 92.1% for the indication of effusion at diagnosis, while during the courses the sensitivity was much lower. On the prognostic role of CA-125, we found prognostic relevance on progression-free survival (PFS) but not on overall survival (OS). Conclusions Our study revealed limited usefulness of CA-125 concentration at diagnosis and follow-ups in DLBCL.

The present study tested whether the LPS/TLR4 signal pathway in endometrial stromal cells is essential for the pathogenesis of adenomyosis. We tested the expression of TLR4, MD2 in the endometrium without adenomyosis (CE), the eutopic endometrium with adenomyosis (EuE) and the ectopic endometrium with adenomyosis (EE). We isolated the stromal cells from CE, EuE and EE (CESC, EuESC, EESC), treated with lipopolysaccharide (LPS) and TLR4 antagonist and detected the cell viability. And we also measured the key protein of the TLR4 signal pathway and inflammatory proliferation and invasive growth of experimental cells. We found that the viability of experimental cells treated with LPS was significantly greater than that of the non-treated cells, blocked by the TLR4 antagonist VIPER. TLR4 signal pathway and inflammatory proliferation and invasive growth of experimental cells stimulated by LPS and it was inhibited by VIPER. This study suggested that stromal cells were activated by the TLR4 signalling pathway, which processed the cellular inflammatory proliferation and invasive growth involved in the pathogenesis of adenomyosis.

Wenjun Yu,1,2,* Rui Guo,1,* Xiaoyan Qu,1 Hairong Qiu,1 Jianyong Li,1 Run Zhang,1 Lijuan Chen1 1Department of Hematology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 2Department of Cadre Health Care, Jiangsu Province Geriatric Institution, Jiangsu Province Official Hospital, Nanjing, People’s Republic of China *These authors contributed equally tothis work Abstract: The prognostic heterogeneity of multiple myeloma (MM) is largely due to different genetic abnormalities. Cytogenetic analysis has revealed that most of MM harbor chromosome aberrations. Amplification of 1q21 is one of the most common chromosomal aberrations. Interphase fluorescence in situ hybridization was applied to detect the 1q21 amplification in 86 Chinese patients with newly diagnosed MM. Amp(1q21) was found in totally 40 of 86 (46.5%) cases, among which 29 with three copies of 1q21 and eleven with at least four copies of 1q21. Further analysis revealed a significant difference of overall survival and progression-free survival among the three arms (P0.05). These findings suggest that 1q21 amplification with four copies or more is prognostic factor for adverse outcomes of MM patients. Furthermore, chromosome 1q21 gains predicted a poor overall survival even in those receiving bortezomib-based regimens. Keywords: multiple myeloma, 1q21 amplification, I-FISH, prognosis

Conventional cytogenetic analysis is often hampered owing to the low mitotic index of multiple myeloma (MM) cells in bone marrow samples of MM. Interphase fluorescence in situ hybridization (I-FISH) analysis combined with magnetic-activated cell sorting (MACS) has substantially enhanced the sensitivity of cytogenetic analysis. Here, we used I-FISH to explore the incidence of chromosomal abnormalities in 60 Chinese patients with newly diagnosed MM. Five different specific probes for the regions containing 13q14.3 (D13S319), 14q32 (IGHC/IGHV), 1q21, 1p12, and 17p13 were used to detect chromosomal aberrations, and LSI IGH/CCND1, LSI IGH/FGFR3, and LSI IGH/MAF probes were further applied to detect t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23) in patients with 14q32 rearrangement. Fifty of the patients (83.3%) had at least one type of abnormalities regarding the regions analyzed. Nine patients (15%) had one abnormality; 10 patients (16.7%) had two abnormalities; 31 patients (51.7%) had three or more abnormalities. The most frequent abnormality in the patients was illegitimate IgH rearrangement (70%), followed by 13q14 deletion (63.3%), 1q21 amplification (61.7%), 1p12 deletion (33.3%), and 17p13 deletion (13.3%). These aberrations are not randomly distributed, but strongly interconnected. Patients with 17p13 deletion or t(4;14)(p16;q32) had significant higher β2-microglobulin level (P < 0.05). However, all these abnormalities had no correlation with age, gender, disease stage, and Ig isotype; yet, it was showed that the frequencies of the individual chromosomal abnormalities were very high. Taken together, MACS in combination with I-FISH may be a promising tool to detect the molecular cytogenetic abnormalities of MM.

Multiple myeloma (MM) is characterized by complex genetic and chromosomal abnormalities involving both numerical and structural aberrations, which have clinical prognostic value. The plasma cell labeling index (PCLI) is one of the most important prognostic factors in newly diagnosed MM, and indicates plasma cell proliferative capacity. In this study, we determined the PCLI and the deletion of 13q14, retinoblastoma-1 gene (RB-1), 1p13, and 17p13, 1q21 amplification, and IgH rearrangements in 42 newly diagnosed patients with MM. A high PCLI was observed in 18 patients (42.9%), and the del(13q14) was present in 25 patients (59.5%), del(RB-1) in 23 patients (54.8%), del(17p13) in eight patients (19.1%), amp(1q21) in 23 patients (54.7%), del(1p13) in 17 patients (40.5%), and IgH rearrangements in 28 patients (66.7%). We further detected the IgH translocation partners: t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23) in 19, 15, and five patients, respectively. The PCLI had a significant correlation with del(13q14) (p = 0.006), but no correlation with other chromosome abnormalities or clinical and laboratory features (p 0.05). The PCLI was higher among patients with del(13q14), and patients with a high PCLI had a short time to disease progression. In conclusion, PCLI is a powerful and independent prognostic parameter in newly diagnosed MM, and correlates with del(13q14).

The hypothesis we tested was that administering corticotropin-releasing factor receptor agonists preserves muscle mass during cancer that is related to changes in tissue gene expression. cDNA microarrays were used to compare mRNAs from muscle and adipose tissues of non-treated and agonist-treated tumor-bearing rats. In muscle of non-tumor-bearing agonist-treated animals we observed decreased expression of genes associated with fatty acid uptake and esterification. In tumor-bearing animals, CRF2R agonist administration produced decreased mRNA content of the atrogene lipin-1. In white adipose tissue, agonist treatment of non-tumor-bearing animals induced genes typically related to muscle structure and function. The fact that this treatment decreased expression of atrogenes could have clinical application. In addition, agonist treatment changed the gene pattern of adipose tissue to render it similar to that of skeletal muscle; thus, treatment with this agonist alters the gene pattern to what could be called "muscularization of white adipose tissue."

Patients with intact immunoglobulin (Ig) multiple myeloma (MM) usually show parallel fluctuations of their intact Ig and light chain (LC) concentrations. Herein we report 11 patients with relapsed, intact Ig MM with a marked increase in urinary LCs in the absence of a parallel rise in serum intact Ig, known as light chain escape (LCE). A major feature accompanying the presentation of LCE was conversion of plasma cell morphology. An important feature preceding the onset of LCE was the use of biological therapies. These patients were not associated with a highly aggressive course. Median overall survival times after the diagnosis of MM and after LCE were 48 months and 24 months, respectively. These cases represent a documented series of a rare but clinically important mode. More attention should be directed toward patients with intact Ig MM when the clinical course deteriorates despite a reduction of intact monoclonal immunoglobins.

It is recognized that information on both quantity and composition of residential waste is important for the effective planning of household waste handling infrastructure. In this paper, we present the results of a survey on household waste generation and composition in Beijing, China. Sample communities were selected by the integration of five indices including family population, income, age, and education. Wastes were sampled on a daily basis from 113 households in six different districts of Beijing City for ten days. The results showed that the generation rate of household wastes was 0.23 kg/pers/day. The bulk density was approximately 221 kg/m(3), and the moisture content was approximately 50%. Household waste consisted of kitchen waste, paper/cardboard, plastics, textiles, metals, glass and other wastes, the proportion of each waste was approximately 69.3%, 10.3%, 9.8%, 1.3%, 0.8%, 0.6% and 2.7%, respectively. An evaluation of the relationship between daily per capita generation of household waste and socio-economic factors indicated that household size and income both showed a negative relationship with household waste generation (kg/pers/day). As for the effect of education, families with a secondary educational level produced fewer household wastes (kg/pers/day) than those with a primary or advanced educational level.

Interstitial pregnancy is a rare form of ectopic pregnancy, but it results in significant maternal morbidity and mortality. In this paper, describe a case of interstitial pregnancy that was successfully managed by laparoscopic occlusion of the ipsilateral ascending branch of uterine artery and the communication of the ovarian artery. It would help to minimize the active bleeding and allow removing the gestation sac, placental tissue, and repair the interstitial tube. In this case, the operative bleeding was 80 mL only, and the operative time was 70 minutes. The patient shared good postoperative recovery, and serum beta human chorionic gonadotropin decreased to below normal levels within 1 month after the operation. This procedure should be considered as a treatment option for unruptured interstitial pregnancy and may allow for conserving the patient’s uterus and fallopian tube and preserving the future fertility.

We sought to evaluate the clinical feasibility and mid- to long-term effects of laparoscopic uterine artery occlusion before myomectomy in the treatment of uterine myomas. A total of 566 patients with uterine myoma were treated by laparoscopic uterine artery occlusion before myomectomy from October 2001 through July 2007. Mean blood loss was 88.2 +/- 52.7 mL (95% CI 82.7-93.8). The highest postoperative temperature was 37.8 +/- 0.3 degrees C, and the postoperative morbidity was 5.7% (32/566). Number of days to the return of bowel movement was 1.9 +/- 0.5d and in hospital stay after surgery was 7.7 +/- 2.5d. Complications included 2 instances of subcutaneous emphysema, 1 of vaginal bleeding, and 3 of mild intestinal obstruction. At a median of 26.3 months (range 6-69 months) of follow-up, the rate of myoma recurrence was 3.0% (15/517), uterus volume reduction was 48.9%, and correction of menstruation abnormality was 97.1% (502/517). Laparoscopic uterine artery occlusion before myomectomy can expand myomectomy indications with better results.

A review of the literature published in 2014 on topics relating to public and environmental health risks associated with wastewater treatment, reuse, and disposal is presented. This review is divided into the following sections: wastewater management, microbial hazards, chemical hazards, wastewater reuse, wastewater treatment plants, wastewater disposal, and sludge and biosolids.

Background Transmembrane protein 158 (TMEM158) is a recently identified upregulated gene during Ras-induced senescence. Its association with various cancers has been recently reported. However, the expression and biological function of TMEM158 in ovarian cancer is still unclear. This study was aimed to elucidate the roles of TMEM158 in cell proliferation, adhesion and cell invasion of ovarian cancer cells. Methods We analyzed TMEM158 mRNA level in ovarian cancer tissues and adjacent no-tumorous tissues by real-time PCR. We then suppressed TMEM158 expression of ovarian cancer cells by RNA interference and examined the effects of TMEM158 knockdown on cancerous transformation of ovarian cancer cells. Results The RNA-sequencing data of the ovarian cancer cohort from The Cancer Genome Atlas project (TCGA) and our real-time PCR data showed that TMEM158 was overexpressed in ovarian cancer. Knockdown of TMEM158 by RNA interference in ovarian cancer cells significantly inhibited cell proliferation, which may be due to the increase of G1-phase arrest. Silencing of TMEM158 also inhibited cell adhesion, cell invasion as well as tumorigenicity in nude mice. Moreover, knockdown of TMEM158 notably repressed cell adhesion via down-regulating the expression intercellular adhesion molecule1 (ICAM1) and vascular cell adhesion molecule1 (VCAM1). Transforming Growth Factor-β (TGF-β) signaling pathway was also remarkably impaired by TMEM158 silencing. Conclusions Our data suggests that TMEM158 may work as an oncogene for ovarian cancer and that inhibition of TMEM158 may be a therapeutic strategy for ovarian cancer.

Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) of the elderly is defined as patients older than 50 years alone. However, recent studies showed young patients with sound immune status could also be affected. In this study, we investigated the clinical features and outcomes of patients with EBV positive DLBCL in the different age groups using different EBER cut-off values. The prevalence of EBV positive DLBCL was 14.0% (35/250) and 10.4% (26/250) for EBER cut-off of 20% and 50%, respectively. With both EBER cut-off values, patients with EBV DLBCL shared many unfavorable prognostic characteristics, regardless of age. EBV positive patients, both in the elderly and young groups, showed significantly worse overall survival and progression-free survival than negative cases. Moreover, no significant differences of outcomes were identified between different age groups with EBV positive DLBCL. In conclusion, EBV positive DLBCL patients, regardless of age, shared similar poor prognostic features and showed worse outcome than negative cases. We suggest that the age criterion of EBV positive DLBCL of the elderly and possibly the name itself, be modified in future.

Ovarian cancer is the most lethal gynecologic malignancy worldwide. ETS homologous factor (EHF), a member of E26 transformation specific (ETS) transcription factors, has been reported overexpressed in ovarian cancer. However, the molecular mechanism underlying the biological function of EHF in ovarian cancer is still unclear. Here, we found that EHF was elevated in ovarian cancer tissues compared with non-tumorous tissues. Moreover, high EHF expression level was correlated with short survival time of patients with ovarian cancer. Knockdown of EHF in ovarian cancer cells, SKOV3 and OVCAR3, significantly inhibited cell proliferation and increased cells population in G1 phase. The proteins promoting cell cycles (Cyclin B1, Cyclin D1, and PCNA) were down-regulated and the protein negatively regulating cell cycle progression (P21) was up-regulated after EHF knockdown. Moreover, inhibition of EHF in ovarian cancer cells dramatically induced cell apoptosis, but impaired cell adhesion and cell invasion. Furthermore, phosphorylation levels of ERK and AKT were notably reduced in EHF knockdown cells. Finally, in vivo data showed that knockdown of EHF inhibited tumor growth in nude mice. Our data indicates that EHF could be a potential prognosis marker for ovarian cancer and work as an oncogene by targeting ERK and AKT signaling, which can serve as a new target for ovarian cancer treatment. © 2015 Wiley Periodicals, Inc.

The association of TMEM45A with various cancers has been recently reported. However, the biological function of TMEM45A in ovarian cancer remains unclear. The present study aimed to elucidate the role of TMEM45A in regulating the biological behavior of ovarian cancer cells. We compared the expression of TMEM45A between ovarian cancer tissues and normal tissues based on RNA-sequencing data of the ovarian cancer cohort from The Cancer Genome Atlas (TCGA) project and our real-time PCR data from 25 pairs of ovarian cancer and their matched non-cancerous tissue samples. The expression of TMEM45A was then suppressed in two ovarian cancer cell lines, HO-8910 and A2780, by RNA interference. Cell proliferation, cell cycle distribution, adhesion and invasive ability were then detected using the Cell Counting Kit-8 assay (CCK-8), propidium iodide (PI) staining, and cell adhesion and Transwell assays, respectively. In addition, the mRNA and protein levels of transforming growth factor-β (TGF-β1 and TGF-β2), Ras homolog family member A (RhoA) and Rho-associated kinase 2 (ROCK2) were detected with real-time PCR and western blotting, respectively. TCGA data and our real-time PCR results demonstrated the overexpression of TMEM45A in ovarian cancer. Silencing of TMEM45A significantly inhibited cell proliferation and significantly increased the cell population in the G1 phase. Moreover, knockdown of TMEM45A also inhibited cell adhesion as well as cell invasion. More importantly, suppression of TMEM45A notably downregulated the expression of TGF-β1, TGF-β2, RhoA and ROCK2. In conclusion, TMEM45A may function as an oncogene for ovarian cancer, and inhibition of TMEM45A may be a therapeutic strategy for ovarian cancer.

In order to solve the longtime problem of fault location and low efficiency of fault clearing for a certain ordnance launch circuit, a fault diagnosis expert system based on hybrid case-based reasoning (CBR) and rule-based reasoning (RBR) is designed. According to the structure of systematic fault tree and historical fault cases, fault repository is established. The inference mechanism based on hybrid CBR and RBR is adopted to the fault diagnosis. Practical application shows that the expert system can improve the efficiency of ordnance launch circuit fault diagnosis and reduce the fault-clearing strength of maintenance crew.

Extramedullary disease (EMD) in multiple myeloma (MM) patients is an uncommon event and more attention was directed toward the feature of these patients. Cytogenetic aberration is an important characteristic of MM and is associated with patients’ outcome. In this study, we aimed to compare the cytogenetic abnormality of patients with and without extramedullary manifestation, and to analyze the clinical outcomes of novel agents in EMD patients. We retrospectively investigated data from 41 MM patients. Our analyses showed del(17p13) in 31% of EMD versus 13% of medullary disease (P=0.03) and amp(1q21) in 55% versus 32% (P=0.019). No differences were shown in del(13q14) and t(4;14). 24/27 patients with EMD at diagnosis responded to the novel agents-containing regimens. However, when relapsed, 70% of patients did not benefit from the sequential use of novel agents as salvage therapy. In 14 patients who developed EMD at relapse phase, only 2 patients responded to novel agents therapy. Median overall survival of patients with extramedullary manifestations was 30 months, in comparison to 104 months for patients without EMD (P=0.002). Patients with extramedullary manifestation bore high incidence of poor cytogenetic aberration and novel agents resistance.

In order to achieve adaptive control and single parameter identification of one order system, an ordinary adaptive control method is used in this paper. By introducing integral control and considering multiple variables, an adaptive control law is designed, and the result of parameter identification is analyzed. In the end, a conclusion can be made that theoretical analysis is correct and parameter identification method is effective by numerical simulation.

Drug co-prescription (or drug combination) is a therapeutic strategy widely used as it may improve efficacy and reduce side-effect (SE). Since it is impractical to screen all possible drug combinations for every indication, computational methods have been developed to predict new combinations. In this study, we describe a novel approach that utilizes clinical SEs from post-marketing surveillance and the drug label to predict 1,508 novel drug-drug combinations. It outperforms other prediction methods, achieving an AUC of 0.92 compared to an AUC of 0.69 in a previous method, on a much larger drug combination set (245 drug combinations in our dataset compared to 75 in previous work.). We further found from the feature selection that three FDA black-box warned serious SEs, namely pneumonia, haemorrhage rectum, and retinal bleeding, contributed mostly to the predictions and a model only using these three SEs can achieve an average area under curve (AUC) at 0.80 and accuracy at 0.91, potentially with its simplicity being recognized as a practical rule-of-three in drug co-prescription or making fixed-dose drug combination. We also demonstrate this performance is less likely to be influenced by confounding factors such as biased disease indications or chemical structures.

To explore the value of serum levels of CA125, platelet count (PLT), neutrophil–lymphocyte ratio (NLR), and modified CA125 markers CA125a and CA125b in predicting pelvic dense adhesion (PDA) associated with adenomyosis, CA125a = lg(CA125 × PLT × 109), CA125b = lg(CA125 × NLR). This retrospective study included 304 patients who underwent surgery for adenomyosis. Correlations of serum levels of CA125, PLT, NLR, and modified CA125 markers with adenomyosis-derived PDA were analyzed by Logistic regression. Receiver operating characteristic curve was applied to assess the utility of these parameters for predicting PDA. All the parameters including CA125, PLT, NLR, and modified CA125 markers were positively correlated with PDA (P

The objective of the present study was to investigate differences in the expression of apoptosis-related factors in the eutopic and ectopic endometrium (EuE/EE) in women with adenomyosis before and after laparoscopic bilateral uterine artery occlusion (LUAO). Ten patients with uterine adenomyosis who received LUAO were selected as the research subjects, from whom EuE and EE tissues were obtained before and after LUAO and detected for the expression of apoptosis-related molecules in EuE and EE by PT-PCR and Western blot, and changes in the mitochondrial structure by electron microscopy. Normal endometrial stromal cells (NESC), and EuE/EE stromal cells in women with adenomyosis were cultured in a 1% O2, 5% CO2 incubator to establish a physical anoxia state in an in vitro stromal cell model. The expression of apoptosis-related molecules was observed at 0, 6, 12, 24 and 48h of hypoxic. The results showed that the expression of apoptosis-related factors in EuE and EE were increased significantly after LUAO and under hypoxic conditions in vitro, suggesting that transient ischemia and hypoxia were involved in the apoptosis of adenomysis lesions, and that uterine artery occlusion could remove adenomyosis lesions on tissue/cell level by cytoreduction, thus reaching the goal of treating adenomyosis effectively.

Dysregulation of miRNA expression plays an important role in cancer development, and circulating miRNAs are biomarkers of several cancers. We explored whether the miRNAs in plasma could be useful clinical biomarkers for multiple myeloma. miRNA microarray was conducted to identify elevation of four miRNAs and reduced levels of eight miRNAs in the plasma of nine multiple myeloma patients and seven healthy controls. Increased miR-483-5p levels and decreased miR-20a were further validated in the plasma of 40 myeloma patients and 20 healthy controls using TaqMan quantitative real-time PCR. Receiver operating characteristic (ROC) analysis revealed that miR-483-5p and miR-20a had considerable diagnostic accuracy, yielding the areas under the ROC curve of 0.745 (sensitivity 58%, specificity 90%) and 0.74 (sensitivity 63%, specificity 85%), respectively. Plasma levels of miR-483-5p were associated with ISS staging. Within 14 months of diagnosis, the median progression-free survival of patients with high levels of plasma miR-483-5p was 15 months, in comparison with 21 months for patients with low levels of plasma miR-483-5p (p=0.025). However, miR-20a levels were not correlated with progression-free survival (p>0.05). miR-483-5p has the potential to be a predictor of myeloma survival.

The orphan nuclear receptor, retinoic acid receptor-related orphan nuclear receptor γt (RORγt), is required for the development and pathogenic function of interleukin-17A-secreting CD4(+) T helper type 17 (Th17) cells. Whereas small molecule RORγt antagonists impair Th17 cell development and attenuate autoimmune inflammation in vivo, the broader effects of these inhibitors on RORγt-dependent gene expression in vivo has yet to be characterized. We show that the RORγt inverse agonist TMP778 acts potently and selectively to block mouse Th17 cell differentiation in vitro and to impair Th17 cell development in vivo upon immunization with the myelin antigen MOG35-55 plus complete Freund's adjuvant. Importantly, we show that TMP778 acts in vivo to repress the expression of more than 150 genes, most of which fall outside the canonical Th17 transcriptional signature and are linked to a variety of inflammatory pathologies in humans. Interestingly, more than 30 genes are related with SMAD3, a transcription factor involved in the Th17 cell differentiation. These results reveal novel disease-associated genes regulated by RORγt during inflammation in vivo, and provide an early read on potential disease indications and safety concerns associated with pharmacological targeting of RORγt.

Many Chinese patients with hematologic diseases, who need allogeneic hematopoietic stem cell transplantation (HSCT), lack a human leukocyte antigen-matched donor. To save these patients and to avoid collecting donor bone marrow graft, we adopted haploidentical peripheral blood HSCT with granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood stem cells as the grafts without ex vivo T cell depletion. Thirty-eight patients were enrolled, and they received myeloablative preconditioning. Thirty-five patients attained a successful neutrophil and platelet recovery. The median time for the neutrophil recovery was 16 days (range of 10-23 days), and the median time for the platelet recovery was 19 days (range of 10-66 days). During the follow-up at a median time of 33.1 weeks (range of 1.1-412.6 weeks), eleven (28.9 %) patients developed aGVHD grade I-II and seven (18.4 %) patients developed aGVHD grade III-IV. The incidence of cGVHD was 27.6 %, and nine (23.7 %) patients died within the first 100 days after transplantation. The cumulative survival proportions at 1 and 2 years were 52.51 ± 8.57 % and 43.76 ± 9.11 %, respectively. These results suggested that the G-CSF-primed peripheral blood stem cell grafts, without in vitro T cell depletion, could be an appropriate stem cell source for Haplo-HSCT.

This chapter aims at obtaining the complete sequence of the Philadelphia 1 strain of Legionella pneumophila, derived from the original 1976 outbreak that established the clinical entity known as Legionnaires' disease. The GC content of L. pneumophila is ~38% over most of its length. From the genomic sequence so far (more than 85% of the sequence is currently contained in contigs greater than 1 kb), 3,000 open reading frames (ORF) were covered, about 2,000 of which are complete, and on the basis of homology to genes from other prokaryotes, more than 1,100 putative genes in L. pneumophila were identified. Genes in L. pneumophila Philadelphia 1 can be compared with genes in other pathogenic organisms. The amino acid sequence can guide structural and functional analyses of enzymes and other proteins of the organism. The authors used knockout strategies in the past to assess the function of genes discovered in the course of the sequencing project; and this continues to be their preferred method for functional analysis.

Determining the specific construction time forms the important content of construction in multitask flow network plan. A general calculating approach of time parameters is proposed in the process of dealing with such problems by flow network planning, and their features are collected preparedly. Main critical impact parameters are picked up, and procedure waiting float and global critical activity are defined as well. Determination approaches of activity construction time with various project duration desires are proposed when work intensity is considered, and application of flow network planning is extended. Finally, an example is given to analyze and demonstrate that the approach is available.

Systematically evaluating the exponentially growing body of scientific literature has become a critical task that every drug discovery organization must engage in in order to understand emerging trends for scientific investment and strategy development. Developing trends analysis uses the number of publications within a 3-year window to determine concepts derived from well-established disease and gene ontologies to aid in recognizing and predicting emerging areas of scientific discoveries relevant to that space. In this chapter, we describe such a method and use obesity and psoriasis as use-case examples by analyzing the frequency of disease-related MeSH terms in PubMed abstracts over time. We share how our system can be used to predict emerging trends at a relatively early stage and we analyze the literature-identified genes for genetic associations, druggability, and biological pathways to explore any potential biological connections between the two diseases that could be utilized for drug discovery.

Deletions of the 13q14 chromosome region are associated with B-cell chronic lymphocytic leukemia (B-CLL) and several other types of cancer, suggesting the presence of a tumor suppressor gene. In previous studies the minimal region of deletion (MDR) was mapped to a less than 300-kilobase (kb) interval bordered by the markers 173a12-82 and 138G4/1.3R. For the identification of the putative tumor suppressor gene, the entire MDR (approximately 347 kb) has been sequenced, and transcribed regions have been identified by exon trapping, EST-based full-length complementary DNA cloning, database homology searches, and computer-assisted gene prediction analyses. The MDR contains 2 pseudogenes and 3 transcribed genes: CAR, encoding a putative RING-finger containing protein; 1B4/Leu2, generating noncoding transcripts; and EST70/Leu1, probably representing another noncoding gene (longest open reading frame of 78 codons). These genes have been sequenced in 20 B-CLL cases with 13q14 hemizygous deletion, and no mutations were found. Moreover, no somatic variants were found in the entire MDR analyzed for nucleotide substitutions by a combination of direct sequencing and fluorescence-assisted mismatch analysis in 5 B-CLL cases displaying 13q14-monoallelic deletion. The nondeleted allele of theCAR and EST70/Leu1 genes was expressed in B-CLL specimens, including those with monoallelic loss, whereas no expression of 1B4/Leu2 was detectable in B-CLL, regardless of the 13q14 status. These results indicate that allelic loss and mutation of a gene within the MDR is an unlikely pathogenetic mechanism for B-CLL. However, haplo-insufficiency of one of the identified genes may contribute to tumorigenesis.

【Abstract】 Objective Multiple myeloma (MM) is a kind of plasma cell malignancy tumor with larger heterogeneity. Patient's survival varies greatly. This study retrospectively analyzed serum lactate dehydrogenase (LDH) in 107 cases of elderly MM patients, to discuss its correlation with other clinical indicators of MM and the prognostic significance. Methods 107 cases of elderly MM patients were selected from our hospital from July 2008 to January 2016 as the research objects, all of whom were above 60 years and were newly diagnosed. OLIPAS AU5400 fully automatic biochemical analyzer was used to assay serum LDH concentration, and prognosis analysis was carried out combined with patients' clinical data. On this basis, 73 cases of MM patients were given R-ISS staging. Results At primary diagnosis, about 9.4% patients had increased LDH (10/107), with the median follow-up time of 15 (1-88.5) months. Median overall survival (OS) was 52.5±6.9 months in normal LDH group, while 15.5±5.2 (months) in elevated LDH group, and there were statistically significant differences (p Disclosures No relevant conflicts of interest to declare.

Myosin is involved in cell contraction and motility, but it is unclear whether it is involved in cell proliferation in uterine myoma. In this study therefore we aimed to explore the role of myosin in uterine myoma.Immunohistochemistry and real-time polymerase chain reaction were used to determine the expression of myosin light chain (MLC), myosin heavy chain (MHC) and myosin light chain kinase (MLCK) in patient uterine myoma and adjacent smooth muscle tissue. Human uterine fibroid cells were isolated and cultured in vitro, myosin heavy chain 11 (MHC subtype expressed in uterine fibroid cells) was knocked down by RNA interference to reduce the expression of myosin, then cell proliferation was determined by the methyl thiazol tetrazolium bromide method. To explore the possible mechanism of reduced cell proliferation after myosin heavy chain 11 knockdown, the downstream proteins collagen I, insulin-like growth factor-1, fibronectin and proteoglycans were analyzed.Expression of MLC, MHC, MLCK and p-MLCK in uterine myoma cells was significantly higher than in adjacent smooth muscle cells. After knockdown of MHC, smooth muscle cell proliferation decreased, and the production of collagen I, insulin-like growth factor-1 and fibronectin was also reduced, but proteoglycans did not show any significant change.Myosin is overexpressed in uterine myoma, and the overexpression of myosin is associated with both uterine contraction and tumor development of uterine myoma.

Multiple neoplasias including B-cell non-Hodgkin's lymphoma, breast carcinoma, and ovarian carcinoma, have been associated with frequent deletions of the distal region on the long arm of human chromosome 6, suggesting the presence of one or more tumor suppressor gene(s) at this locus. Loss of heterozygosity analysis of breast and ovarian tumors has further restricted the minimal region of loss within 6q27. To further characterize this genomic region for gene content including putative tumor suppressor genes as well as other elements that may contribute to tumorigenesis, a 68940-bp contiguous sequence, encompassing markers D6S193 and D6S297, was generated by random shotgun sequencing of a cosmid, P1, and PAC contig. In addition, exon trapping was performed utilizing a subset of these clones. Sixteen trapped exons, ranging in size from 44 to 399 bp, span this approximately 69-kb region. Many other putative exons have been identified computationally. Further analysis has identified 13 potential promoters and 13 putative polyadenylation sites in the region. Northern analysis identified a transcript mapping within this interval that is expressed in ovarian, breast, and lymphoid-derived tumor cell lines. Consideration of these data, together with the demonstration of several regions of high CpG content, suggests the possibility of several genes at this locus.

Interferon regulatory factor 4 (IRF4) is a member of the interferon regulatory family, which plays an important role in many lymphoid and myeloid malignancies. In the current study, using immunohistochemical staining, we found that IRF4 only expressed in plasma cells in bone marrow biopsy samples of multiple myeloma. IRF4-positive patients displayed increased disease stage (Durie-Salmon stage, p = 0.026; and International Staging System, p = 0.005). Silencing IRF4 in myeloma cell lines could inhibit myeloma cells proliferation and induce myeloma cell apoptosis, partly by JNK/Jun pathway. These results demonstrate that IRF4 plays important roles in myelomagenesis and disease progression.

The fungal endophyte Chaetomium globosum No.04 was isolated from the medicinal plant Ginkgo biloba. The crude extract of the fungus fermentation were active in the agar-diffusion tests against the phytopathogenic fungi Rhizopus stolonifer and Coniothyrium diplodiella. Further bioassay-guided chemical investigation led to the isolation and purification of six alkaloids and three non-targeted compounds from 50 L fermentation of this endophytic fungus and their structures were elucidated as chaetoglobosin A, C, D, E, G, R (1-6), ergosterol, allantoin and uracil, by means of spectroscopic analysis. Compounds 1-6 showed significant growth inhibitory activity against R. stolonifer and C. diplodiella at a concentration of 20 μg/disc. We present here, for the first time, the potent antifungal activity of chaetoglobosins from endophytic fungi against two important phytopathogenic fungi R. stolonifer and C. diplodiella.

Ligand-gated ion channels are multi-subunit complexes where each subunit-type is encoded by several related genes. Heterologous expression of any one of the neuronal nicotinic acetylcholine receptors (nAChR) alpha-type subunits, either alone or with any beta-type subunit, typically yields functional nAChR channels. A striking exception is the nAChR alpha5 subunit: although apparently complexed with beta2 and beta4 nAChR subunits in neurons, and expressed in a subset of neurons within the central and peripheral nervous systems, heterologous expression of alpha5, either alone or with any beta-type subunit has failed to yield functional channels. We demonstrate here that alpha5 does participate in nAChRs expressed in hetrologous systems and in primary neurons, and further that alpha5 contributes to the lining of functionally unique nAChR channels, but only if coexpressed with both another alpha- and beta-type subunit. Furthermore, channels containing the alpha5 subunit are potently activated and desensitized by nanomolar concentrations of nicotine.

We present the genomic sequence of Legionella pneumophila , the bacterial agent of Legionnaires' disease, a potentially fatal pneumonia acquired from aerosolized contaminated fresh water. The genome includes a 45–kilobase pair element that can exist in chromosomal and episomal forms, selective expansions of important gene families, genes for unexpected metabolic pathways, and previously unknown candidate virulence determinants. We highlight the genes that may account for Legionella 's ability to survive in protozoa, mammalian macrophages, and inhospitable environmental niches and that may define new therapeutic targets.

Cachexia is a wasting condition that manifests in several types of cancer. The main characteristic of this condition is a profound loss of muscle mass.By using a microarray system, expression of several hundred genes was screened in skeletal muscle of rats bearing a cachexia-inducing tumor, the AH-130 Yoshida ascites hepatoma. This model induced a strong decrease in muscle mass in the tumor-bearing animals, as compared with their healthy counterparts.The results show important differences in gene expression in EDL skeletal muscle between tumor-bearing animals with cachexia and control animals.The differences observed pertain to genes related to intracellular calcium homeostasis and genes involved in the control of mitochondrial oxidative phosphorylation and protein turnover, both at the level of protein synthesis and proteolysis. Assessment of these differences may be a useful tool for the design of novel therapeutic strategies to fight this devastating syndrome.

To investigate the expression of cyclooxygenase-2 (COX-2) in uterine fibroids and healthy uterine smooth muscle as well as its role in the pathogenesis of uterine fibroids.We collected uterine fibroid tissues and their paired adjacent healthy uterine smooth muscle tissues from 30 cases of uterine fibroids. We used immunohistochemistry and quantitative real-time PCR, as well as western blot to detect COX-2 expression. Using the COX-2 inhibitors NS-398 and celecoxib, we observed the response to the inhibitors in the healthy and fibroid smooth muscle cell pairs.COX-2 was detected by immunohistochemistry in both uterine fibroids and uterine smooth muscle, with higher immunoreactivity in uterine fibroids; the positive index of the smooth muscle cells was 11.90 and the positive index of uterine fibroids cells was 46.50 (P0.05). The expression of COX-2 mRNA in uterine fibroids was higher (0.122±0.062) than in normal smooth muscle tissue (0.025±0.009; P0.05). Also, the western blot results showed that COX-2 expression was significantly higher in uterine fibroid cases, as compared to the expression in uterine smooth muscle. Immunofluorescence showed that the occurrence of COX-2 was obviously higher in smooth muscle cells of uterine fibroids than in the healthy smooth muscle cells. NS-398 or celecoxib significantly inhibited the proliferation of smooth muscle cells of uterine fibroids, but did not inhibit the proliferation of healthy smooth muscle cells. Accordingly, NS-398 or celecoxib significantly reduced the expression of the downstream metabolite of COX-2, PGE2, in the smooth muscle cells of uterine fibroids, but not in healthy smooth muscle cells.COX-2 expression in uterine fibroids was significantly higher than in healthy uterine smooth muscles. The inhibition of COX-2 activity significantly reduced the proliferation of smooth muscle cells of the uterine fibroids, suggesting that COX-2 plays an important role in the pathogenesis of uterine fibroids.

This paper describes the characteristics of anti-radiation missile/radar target end game, and points out the disadvantages of ARM only with contact burst model. An adaptive burst strategy is put forward to estimate proximity fuze detonation delay-time, so as to improve the destruction probability. A Monte-Carlo simulation study is discussed.

Service fault management in distributed computer systems and networks is a difficult task that requires high efficient inferences from mass data. In this paper, we propose a corresponding solution. Firstly, challenges of distributed systems service fault management are analyzed, and a multilayer model is recommended. Then, a dependency matrix to represent the causal relationship between faults and probes is defined and the framework of fault management is built. After these, a service fault management scheme using active probing is proposed. This scheme is composed of two phases: fault detection and fault localization. In first phase, we propose a probe selection algorithm, which selects a minimal set of probes while remaining a high probability of fault detection. In second phase, we propose a fault localization probe selection algorithm, which selects probes to obtain more system information based on the symptoms observed in previous phase. Finally, the instance proves the validity and efficiency of our scheme.

An appropriate selection of kernel function and its parameters is very important for the relevance vector machine (RVM) to achieve a good performance. To overcome the limitation of RVM with single kernel, a multi-scale RVM classification method based on intelligent optimization is proposed. Multiple Gaussian kernels are combined by linear weighting and the kernel parameters are tuned by quantum-behaved particle swarm optimization (QPSO) algorithm. The experimental results show that the proposed method has higher classification accuracy than typical RVM classifiers with single kernel.

Genome-wide expression profiling of gene transcripts has been successfully applied in biomedical discovery for over a decade. Based on the premises of this technology, Connectivity Map provides a data-driven and systematic approach for discovering associations among genes, chemicals and biological conditions such as diseases. Since its first introduction in 2006, the approach has shown emerging promises in uncovering avenues for drug discovery and development such as in identifying and suggesting new indications for existing drugs and elucidating mode of actions for novel chemicals in addition to potentially predicting side effects.