Cost-effectiveness analysis of five drugs for treating postmenopausal women in the United States with osteoporosis and a very high fracture risk.

PURPOSE: Five strategies were recommended by the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) guidelines for the treatment of postmenopausal osteoporosis (PMO) patients with a very high fracture risk. We aimed to assess their cost-effectiveness in the United States (US). METHODS: A microsimulation Markov model was created to compare the cost-effectiveness of five treatment strategies, including zoledronate, denosumab, abaloparatide, teriparatide, and romosozumab in PMO patients with a recent fracture from the healthcare perspective of the US. The data used in the model were obtained from published studies or online resources. Base-case analysis, one-way deterministic sensitivity analysis (DSA) and probability sensitivity analysis (PSA) were conducted for 65-, 70-, 75-, and 80-year-old patients. RESULTS: In base case, at 65 years, zoledronate was the cheapest strategy. The incremental cost-effectiveness ratios (ICER, which represent incremental costs per QALY gained) of denosumab, teriparatide, abaloparatide, and romosozumab against zoledronate were $13,020/QALY (quality-adjusted years), $477,331 /QALY, $176,287/QALY, and $98,953/QALY, respectively. Under a willing-to-pay (WTP, which means the highest price a consumer will pay for one unit of a good of service) threshold of $150,000/QALY, denosumab and romosozumab were cost-effective against zoledronate. The PSA results showed that denosumab was the most cost-effective option with WTP thresholds of $50,000/QALY, $100,000/QALY and $150,000/QALY. The results were similar in other age groups. The DSA results indicated that the most common parameters that have important influence on the outcome were drug persistence, incidence of adverse events, the efficacy of drugs on hip fractures and the cost of the drug. CONCLUSION AND RELEVANCE: Among PMO patients with a very high fracture risk in the US, zoledronate is the cheapest strategy and denosumab is the most cost-effective choice among these five strategies.

LncRNA HULC alleviates HUVEC inflammation and improves angiogenesis after myocardial infarction through down-regulating miR-29b.

OBJECTIVE: The aim of this study was to investigate the long non-coding RNA (lncRNA) HULC in promoting angiogenesis after myocardial infarction (MI) and to further investigate its possible mechanism. MATERIALS AND METHODS: Twenty-four male Sprague Dawley (SD) rats were randomly divided into two groups, namely, operation group and control group. The rats in the operation group were induced by ligation of the left anterior descending coronary artery, while those in control group received the same surgery without ligating the blood vessels. Seven days after the operation, the myocardial tissues of rats were collected to detect HULC expression by quantitative real-time polymerase chain reaction (RT-PCR). At the same time, the expression of HULC in primary myocardial cells and cardiac microvascular endothelial cells were induced by hypoxia. A hypoxia model was constructed in HUVEC cells, and the effects of HULC were explored by RT-PCR, Western blot Technology (WB), Cell Counting Kit-8 (CCK8) assay, EdU staining, Tube-like structure formation experiments. Thereafter, HULC downstream miRNAs were verified by Luciferase, pull-down, and RNA IP experiments. Similarly, the effects of miR-29b on HUVEC were verified by RT-PCR, WB, CCK8 assay, EdU staining, and tube-like structure formation experiments, respectively. RESULTS: RT-PCR detection results showed that the expression of HULC in myocardial tissues was down-regulated after MI, and the expression of HULC in cardiac microvascular endothelial cells was decreased under hypoxia-induced inflammation. In addition, the overexpression of HULC in HUVEC cells could inhibit the expressions of inflammatory factors (IL-1, IL-6 and IL-8) and promote angiogenesis (increased cell viability, increased tube-like structure formation, and increased cell proliferation). Through Dual-Luciferase reporter gene experiments, it was found that HULC could directly target miR-29b. At the same time, miR-29 overexpression significantly reversed the effects of HULC on cell viability, pro-inflammatory cytokines, and angiogenesis. CONCLUSIONS: LncRNA HULC protects HUVEC cells from hypoxia-induced inflammation damage by interacting with miR-29b and inhibiting its expression, and it can also promote angiogenesis.

MiR-1290 targets CCNG2 to promote the metastasis of oral squamous cell carcinoma.

OBJECTIVE: MicroRNAs (miRNAs) have been demonstrated to be involved in the pathogenesis of various human cancers, including oral squamous cell carcinoma (OSCC). Here, we designed this study to explore the potential effect of miR-1290 on tumorigenesis of OSCC. PATIENTS AND METHODS: The expressions of miR-1290 and cyclin G2 (CCNG2) in OSCC were observed by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Dual-Luciferase Reporter Assay was performed to confirm the relationship between miR-1290 and CCNG2. The functions of miR-1290 and CCNG2 were analyzed using transwell assay. The Western blot analysis was used to detect epithelial-mesenchymal transition (EMT). RESULTS: Upregulation of miR-1290 and downregulation of CCNG2 were identified in OSCC. And upregulation of miR-1290 was associated with clinicopathological characteristics and poor prognosis in OSCC patients. Moreover, the downregulation of miR-1290 inhibited cell metastasis and EMT in OSCC cells. Furthermore, CCNG2 was a direct target of miR-1290. Its expression was inversely regulated by miR-1290 in OSCC cells. At the same time, the suppressive effect of CCNG2 was observed in OSCC. Furthermore, overexpression of CCNG2 weakened the promoted effect of miR-1290 on cell metastasis in OSCC. CONCLUSIONS: MiR-1290 promoted cell metastasis and EMT, inhibiting CCNG2 expression in OSCC.

LINC01116 promotes proliferation, invasion and migration of osteosarcoma cells by silencing p53 and EZH2.

OBJECTIVE: The aim of this study was to elucidate the expression pattern and potential function of LINC01116 in regulating the progression of osteosarcoma. PATIENTS AND METHODS: Expression levels of LINC01116 in osteosarcoma tissues (n=52) and adjacent normal tissues (n=52) were detected by quantitative Real-time polymerase chain reaction (qRT-PCR). Survival analysis and univariate analysis were performed in osteosarcoma patients based on the relative expression levels of LINC01116 and clinical data. Overexpression or silence of LINC01116 in osteosarcoma cells was achieved by transfection of plasmid complementary deoxyribonucleic acid (pcDNA)-LINC01116 or si-LINC01116, respectively. Subsequently, the regulatory effects of LINC01116 on cellular behaviors of osteosarcoma cells were examined by cell counting kit-8 (CCK-8), transwell and flow cytometry. Meanwhile, the potential mechanism of LINC01116 in regulating the progression of osteosarcoma was explored by RNA binding protein immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and Western blot. Potential target genes in osteosarcoma were searched, and their functions were clarified through a series of rescue experiments. RESULTS: LINC01116 expression in osteosarcoma tissues was significantly higher than adjacent normal tissues. The expression of LINC01116 was negatively correlated with overall survival, whereas positively correlated with tumor size and clinical grade of osteosarcoma patients. Transfection of pcDNA-LINC01116 significantly enhanced proliferative, migratory and invasive abilities of U2OS cells, shortened G0/G1 phase period, and inhibited cell apoptosis. However, transfection of si-LINC01116 in MG63 cells obtained the opposite trends in the above-mentioned cellular behaviors. Furthermore, RIP assay confirmed the binding of enhancer of zeste homolog 2 (EZH2) to LINC01116. Knockdown of LINC01116 significantly up-regulated the expressions of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and p53. Moreover, EZH2 knockdown could reverse the inhibitory effect of LINC01116 on carcinogenesis of osteosarcoma. CONCLUSIONS: LINC01116 is highly expressed in osteosarcoma. Up-regulated LINC01116 can promote cell proliferation, invasion and cell cycle progression, while inhibiting the apoptosis of osteosarcoma cells. Furthermore, LINC01116 is involved in the development of osteosarcoma by binding to EZH2 to regulate expressions of PTEN and p53.

PLZF regulates apoptosis of leukemia cells by regulating AKT/Foxo3a pathway.

OBJECTIVE: To explore the regulatory role of PLZF in the malignant phenotype of non-APL acute myeloid leukemia (AML) and its underlying mechanism. MATERIALS AND METHODS: The expression level of PLZF in AML cell lines KG-1a, HL-60, OCI-AML3, THP-1 and K562 was detected by quantitative Polymerase Chain Reaction (qPCR) and Western blot, respectively. Subsequently, THP-1 cells were divided into mock group (no treatment), scramble group (transfection with scramble shRNA) and shPLZF group (transfection with shPLZF). THP-1 cell line stably expressing shPLZF was constructed, followed by determination of its transfection efficiency by qPCR and Western blot, respectively. The proliferation and colony formation of THP-1 cells were accessed using CCK-8 (cell counting kit-8) assay and colony formation assay, respectively. The apoptotic rate in THP-1 cells was determined using flow cytometry. Protein levels of apoptosis-related genes in THP-1 cells were detected by Western blot. Finally, protein levels of AKT, Foxo3a, pAKT and pFoxo3a were detected by Western blot as well. RESULTS: Both mRNA and protein levels of PLZF were relatively high in THP-1 cells, and were selected for the following experiments. After construction of THP-1 cell line stably expressing shPLZF, proliferative rate and colony formation abilities increased in the shPLZF group compared with the mock group and the scramble group. We found a decreased apoptotic rate, downregulated Bax and upregulated Bcl-2 in the shPLZF group than those of the mock group and scramble group. Phosphorylation levels of AKT and Foxo3a increased after interference with PLZF, whereas no significant changes in total levels of AKT and Foxo3a were observed. CONCLUSIONS: PLZF inhibits the malignant phenotype of AML by regulating the AKT/Foxo3a pathway.

Abatacept alleviates rheumatoid arthritis development by inhibiting migration of fibroblast-like synoviocytes via MAPK pathway.

OBJECTIVE: To investigate whether Abatacept could regulate the occurrence and progression of rheumatoid arthritis (RA) by mediating cell migration of fibroblast-like synoviocytes (FLS) via mitogen-activated protein kinase (MAPK) pathway. PATIENTS AND METHODS: Levels of MMP1, MMP3 and MMP13 in RA-FLS treated with Abatacept or MAPK pathway inhibitor were detected by quantitative Real-time-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The regulatory effect of Abatacept on MAPK pathway was detected by Western blot. Transwell assay was performed to access the role of Abatacept in regulating cell migration of RA-FLS. RESULTS: Abatacept treatment remarkably downregulated levels of MMP1, MMP3 and MMP13 in FLS, which were confirmed by qRT-PCR and ELISA. Migratory ability of FLS was inhibited by Abatacept treatment. Western blot results suggested that Abatacept treatment downregulated MAPK pathway-related genes in FLS. The effects of Abatacept on MMPs expressions and cell migration were partially reversed by SB203580 treatment, the MAPK pathway inhibitor. CONCLUSIONS: Abatacept inhibits FLS migration and MMPs expressions via inhibiting MAPK pathway, thereby inhibiting RA development.

MicroRNA-9-5p promotes osteoporosis development through inhibiting osteogenesis and promoting adipogenesis via targeting Wnt3a.

OBJECTIVE: To explore the role of microRNA-9-5p in regulating osteoporosis (OS) development and its underlying mechanism. PATIENTS AND METHODS: MicroRNA-9-5p expression in peripheral blood of 30 OS patients and 30 healthy subjects was examined by quantitative Real-Time-Polymerase Chain Reaction (qRT-PCR). During the processes of osteogenesis and adipogenesis, mRNA levels of microRNA-9-5p, osteogenesis-related genes, and adipogenesis-related genes in marrow stromal stem cells (MSCs) were detected by qRT-PCR as well. After overexpression or knockdown of microRNA-9-5p, the regulatory effects of microRNA-9-5p on osteogenesis-related genes and adipogenesis-related genes in MSCs were accessed by detecting their mRNA and protein levels. Alizarin red staining and oil red staining were performed to determine the osteogenic and adipogenic capacities of MSCs after microRNA-9-5p overexpression, respectively. The dual-luciferase reporter gene assay was conducted to verify the binding condition of microRNA-9-5p and Wnt3a. Finally, rescue experiments were performed to confirm whether microRNA-9-5p could regulate OS development via targeting Wnt3a. RESULTS: Higher expression of microRNA-9-5p was found in OS patients than that of healthy controls. MicroRNA-9-5p expression was downregulated with the prolongation of osteogenic induction, whereas it was upregulated during the process of adipogenic differentiation. Overexpression of microRNA-9-5p downregulated mRNA levels of osteogenesis-related genes (ALP, RUNX2, and OPN), whereas upregulated adipogenesis-related genes (PPARγ, Adipsin, and C/EBPα) in MSCs. The number of calcified nodules became fewer after microRNA-9-5p overexpression in MSCs. MSCs that overexpressed microRNA-9-5p showed more lipid droplets than that of controls. Subsequently, the dual-luciferase reporter gene assay verified that Wnt3a is the target gene of microRNA-9-5p. Both mRNA and protein levels of Wnt3a were negatively regulated by microRNA-9-5p. Rescue experiments indicated that the regulatory effects of microRNA-9-5p on osteogenesis and adipogenesis of MSCs were reversed by Wnt3a overexpression. CONCLUSIONS: MicroRNA-9-5p is lowly expressed in the peripheral blood of OS patients. MicroRNA-9-5p promotes the occurrence and progression of OS through inhibiting osteogenesis and promoting adipogenesis via targeting Wnt3a.

MicroRNA-424 inhibits cell migration, invasion and epithelial-mesenchymal transition in human glioma by targeting KIF23 and functions as a novel prognostic predictor.

OBJECTIVE: To investigate the expressions, biological effects and potential mechanism of miR-424 in glioma. METHODS AND METHODS: A total of 54 glioma tissues and 12 normal brain tissues were collected. Human glioma cells (A172, SHG-44, T98, LN18, and LN229) and normal human astrocytes (NHAs) were cultured. Cell invasion and migration capacities were detected by transwell assay. KIF23 was predicted and confirmed as a direct target of miR-424 by TargetScan prediction and Dual-luciferase reporter assay. Six-week-old female nude mice were used for Xenograft tumor formation assay. RESULTS: Results of this study demonstrated a significant decrease of miR-424 expressions both in glioma cells and tissues. Moreover, the declined miR-424 expressions were observed to be correlated with the poor OS and worse clinicopathological parameters of glioma patients. Functional assays indicated that miR-424 restoration could inhibit the glioma cell epithelial-to-mesenchymal transition (EMT) and metastasis, as well as the tumor growth rate and tumor size of glioma mice. Additionally, kinesin family member 23 (KIF23) expressions were found to be significantly enhanced in glioma specimens, and KIF23 was considered to be a functional target for miR-424 in glioma. CONCLUSIONS: MiR-424, considered as a tumor-suppressor, inhibited cell metastasis and EMT by targeting KIF23 in glioma, which may provide a novel insight into tumorigenesis and the basis for the development of miRNA-targeting therapies against glioma.

Expression pattern of high-affinity tyrosine kinase Aduring the development of human fetal spinal cord.

High-affinity tyrosine kinase A (TrkA) is responsible for the biological activities of nerve growth factor. Most studies of the molecular mechanisms of TrkA that underlie the development of the spinal cord have been conducted in animals and the expression pattern of TrkA during the development of the human fetal spinal cord is not well characterized. We investigated 45 3-28-week-old (G3W-G28W) human fetuses. We assessed the expression pattern of TrkA in the human fetal spinal cord using immunohistochemistry, western blot and reverse transcription polymerase chain reaction to clarify the spatiotemporal developmental changes and to determine the role TrkA plays in development. TrkA immunoreactive products were detected widely in the alar and basal plates, ependyma, glial cells, gray and white matter, internal limiting membrane, mantle layer, marginal layer, neuroepithelium and neurons during this period of development. Expression levels of TrkA mRNA and protein peaked at G12W and G16W, respectively. The strong expression of TrkA was closely related to the formation of the dorsal and ventral horns, and the differentiation of somatic motor neurons during late embryonic development. Our findings suggest that TrkA receptors play crucial roles during the development of human fetal spinal cord. The characteristic expression patterns may clarify the developmental characteristics of the human spinal cord.

Preparation of an inoculum of Gluconacetobacter xylinus without mutants in shaken culture.

AIMS: A high-quality inoculum of Gluconacetobacter xylinus is important to produce bacterial cellulose (BC), a versatile biomaterial. This work aims to develop a method of preparing an inoculum of this bacterium with high cell density and without mutants. METHODS AND RESULTS: Inocula of G. xylinus ACCC 10220 without and with cellulase or carboxymethyl cellulose (CMC) were prepared in shaken culture. BC pellets and BC-negative mutants were present in the inoculum without additives but absent in the inoculum with additives. Based on BC weights statically produced in fresh BC-producing media initiated by different seed culture, the 24-h-shaken inoculum with 1·50% (w/v) CMC was the best because of high biomass and absence of mutants. The BC weights in fresh media inoculated by the 96-h-static inoculum and 24-h-shaken CMC inoculum at 7% (v/v) were 0·70 and 1·05 g l(-1) , respectively, implying significant difference (P < 0·01) in BC weights. However, structure properties of the two BC samples, including the crystallinity index, mass fraction of cellulose Iα , degree of polymerization (DP) and micromorphology were slightly different. CONCLUSIONS: The 24-h-shaken CMC inoculum was the most suitable for a starter culture of BC. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel method of preparing G. xylinus inoculum in shaken culture was developed, featuring high biomass, absence of mutants and no BC entanglements. Cellulase or CMC added into the medium completely suppressed mutation of G. xylinus, and CMC facilitated to form colloidal BC with the low DP in shaken culture, indicating less BC stress to cells. These findings suggested the mutation could be induced by BC stress, and not by shear stress commonly accepted.

Overexpression of long-noncoding RNA ZFAS1 decreases survival in human NSCLC patients.

OBJECTIVE: The purpose of the current study was to characterize the expression of long-noncoding-RNA ZFAS1 (ZFAS1) and assess the clinical significance of ZFAS1 in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 173 patients with NSCLC were addressed in the present retrospective study. Expression levels of ZFAS1 were detected by quantitative real-time PCR. We further analyzed the correlation between ZFAS1 and clinicopathologic features of NSCLC with X2-test. Survival rate was determined with Kaplan-Meier and statistically analyzed with the log-rank method between groups. Univariate and multivariate analyses were performed to analyze the prognostic significance of ZFAS1 expression. RESULTS: ZFAS1 was upregulated in NSCLC tissues (p < 0.01) and higher expression levels of ZFAS1 were found in more advanced tumor tissues (All p < 0.05). ZFAS1 expression levels were significantly associated with tumor differentiation grade (p = 0.028), lymph node metastasis (p = 0.001) and TMN stage (p = 0.001). Furthermore, we found that patients with higher ZFAS1 expression level are associated with a poorer overall survival. Univariate and multivariate analyses indicated that high ZFAS1 expression was an independent prognostic factor for poor survival of NSCLC patients. CONCLUSIONS: Our results illustrated the potential role of ZFAS1 as a prognostic marker for NSCLC patients.

Traumatic spinal cord injury in Tianjin, China: a single-center report of 354 cases.

STUDY DESIGN: Hospital-based retrospective study. OBJECTIVES: The objective of this study was to describe the epidemiological profile of traumatic spinal cord injury (TSCI) in Tianjin Medical University General Hospital, China, from 2009 to 2014. SETTING: Tianjin Medical University General Hospital. METHODS: Hospital medical records of patients with TSCI admitted to hospital from 1 January 2009 to 31 December 2014 were reviewed. Collected variables included gender, age, marital status, ethnic group, occupation, etiology, neurological level of injury, American Spinal Injury Association (ASIA)-ISCoS impairment scale at admission, the severity, death and its cause, concomitant injuries and treatment choice. RESULTS: During the study period, 354 cases were identified. Male-to-female ratio was 2.34:1, with a mean age of 50.1±15.5 years. Falls (55.1%), comprising low falls and high falls (33.6% and 21.5%, respectively), were the leading cause, followed by motor vehicle collisions (MVCs) (35.9%). The most common injury site was the cervical spinal cord, especially C4-C6, accounting for 59.3%. Surgery was the major treatment choice (57.6%). CONCLUSION: The number of TSCI patients increased annually in our center. The mean age at the time of injury was older, and the proportion of males was higher. The leading two causes were falls and MVCs. The SCIs caused by MVCs were increasing. Peasants, workers and unemployed individuals were those at higher risk. Surgery was the major treatment choice. These data may be useful to implement those preventive strategies focused on the characteristics of different groups and pay more attention to high-risk populations.

Microsurgery for ruptured cerebellar arteriovenous malformations.

OBJECTIVE: To summarize the clinical features of ruptured cerebellar arteriovenous malformations (AVMs) and to explore surgical methods and outcomes in ruptured cerebellar AVM patients. PATIENTS AND METHODS: In the past 14 years, 67 patients with cerebellar AVMs were treated at our institution, accounting for 14.9% of the total vascular malformation patients in our department. In this study, we retrospectively analyzed the clinical characteristics, operation indication, surgery techniques, and prognoses of these cases. RESULTS: Among the 67 AVM cases, the distribution of Spetzler-Martin grades was 32 Grade I, 14 Grade II, 13 Grade III, 5 Grade IV, and 3 Grade V cases. Microsurgical treatment was carried out via the retrosigmoid approach or suboccipital midline approach. After the surgery, the distribution of GOS grades was 60 Grade V, 3 Grade IV, 1 Grade III, 2 Grade II, and 2 Grade I cases. CONCLUSIONS: Microsurgical removal should be performed in ruptured cerebellar AVM patients as early as possible once the preoperative and postoperative preparations were done. Good surgical effects were obtained by using proper surgery techniques and the right protection of critical cerebral structures. Patients with a GCS grade of ≥ 8 showed good recovery, but patients with a grade of < 8 had poor prognoses.

DNA barcoding of common soft scales (Hemiptera: Coccoidea: Coccidae) in China.

The soft scales (Hemiptera: Coccoidea: Coccidae) are a group of sap-sucking plant parasites, many of which are notorious agricultural pests. The quarantine and economic importance of soft scales necessitates rapid and reliable identification of these taxa. Nucleotide sequences of the mitochondrial cytochrome c oxidase subunit I (COI) gene (barcoding region) and 28S rDNA were generated from 340 individuals of 36 common soft scales in China. Distance-based [(best match, Automated Barcode Gap Discovery (ABGD)], tree-based (neighbor-joining, Bayesian inference), Klee diagrams, and general mixed Yule coalescent (GMYC) models were used to evaluate barcoding success rates in the data set. Best match showed that COI and 28S sequences could provide 100 and 95.52% correct identification, respectively. The average interspecific divergences were 19.81% for COI data and 20.38% for 28S data, and mean intraspecific divergences were 0.56 and 0.07%, respectively. For COI data, multiple methods (ABGD, Klee, and tree-based methods) resulted in general congruence with morphological identifications. However, GMYC analysis tended to provide more molecular operational taxonomic units (MOTUs). Twelve MOTUs derived from five morphospecies (Rhodococcus sariuoni, Pulvinaria vitis, Pulvinaria aurantii, Parasaissetia nigra, and Ceroplastes rubens) were observed using the GMYC approach. In addition, tree-based methods showed that 28S sequences could be used for species-level identification (except for Ceroplastes ceriferus - Ceroplastes pseudoceriferus), even with low genetic variation (<1%). This report demonstrates the robustness of DNA barcoding for species discrimination of soft scales with two molecular markers (COI and 28S) and provides a reliable barcode library and rapid diagnostic tool for common soft scales in China.

Similar survival, but better quality of life after myeloablative transplantation using unrelated cord blood vs matched sibling donors in adults with hematologic malignancies.

This study included data from 185 consecutively treated patients, 16 years of age or older, who underwent myeloablative transplantation using unrelated umbilical cord blood (UCB) (UCB transplantation (UCBT), n=70) or HLA-identical sibling donor peripheral blood stem cells alone or combined with bone marrow (BMT/PBSCT, n=115) from October 2001 to December 2012. All patients received myeloablative regimens, cyclosporin A plus mycophenolate mofetil as prophylaxis for GVHD, and similar supportive care. Although hematopoietic recovery was significantly delayed after UCBT, the rate of neutrophil engraftment was comparable. The median follow-up was 53 months (range, 15-136 months) for BMT/peripheral blood SCT (PBSCT) recipients and 35 months (range, 10-123 months) for UCBT recipients. There were no significant differences in the cumulative incidence of grades III to IV acute GVHD, relapse rate, or 3-year probabilities of disease-free survival between patients receiving UCBT and those receiving BMT/PBSCT. However, the cumulative incidence of chronic and extensive chronic GVHD was lower in UCBT recipients. The rates of long-term survivors returning to school or work and off immunosuppressive therapy were significantly higher after UCBT, which indicated that long-term survivors who underwent UCBT had a higher quality of life.

A ring system detected around the Centaur (10199) Chariklo.

Hitherto, rings have been found exclusively around the four giant planets in the Solar System. Rings are natural laboratories in which to study dynamical processes analogous to those that take place during the formation of planetary systems and galaxies. Their presence also tells us about the origin and evolution of the body they encircle. Here we report observations of a multichord stellar occultation that revealed the presence of a ring system around (10199) Chariklo, which is a Centaur--that is, one of a class of small objects orbiting primarily between Jupiter and Neptune--with an equivalent radius of 124 ± 9 kilometres (ref. 2). There are two dense rings, with respective widths of about 7 and 3 kilometres, optical depths of 0.4 and 0.06, and orbital radii of 391 and 405 kilometres. The present orientation of the ring is consistent with an edge-on geometry in 2008, which provides a simple explanation for the dimming of the Chariklo system between 1997 and 2008, and for the gradual disappearance of ice and other absorption features in its spectrum over the same period. This implies that the rings are partly composed of water ice. They may be the remnants of a debris disk, possibly confined by embedded, kilometre-sized satellites.

The application of chromosome abnormality chip detection in male infertility / Aplicación de la detección de la anormalidad del cromosoma mediante biochips genéticos en la infertilidad masculina

OBJECTIVE: To discuss the application of microarray technology in the diagnosis of male infertility. METHODS: Sixteen loci, including a sex-determining region on the Y chromosome, were investigated by polymerase chain reaction (PCR) in infertile male patients. Chromosome abnormality chip with 180 000 probes was used to detect small deletion, small amplification and loss of heterozygosity. RESULTS: By PCR, nine of 103 infertile patients were found to have sequence-tagged site microdeletions. Microdeletions were not observed in control samples. The deletions detected by PCR were present in six azoospermic men (6/44, 13.6%) and in three oligoasthenoteratozoospermic (OATS) men (3/59, 5%). The overall frequency of microdeletions in infertile men was 8.7% (9/103). Chromosome abnormality chip detection 500+ detected more amplification or deletion in 51 infertile patients and the overall frequency of microdeletions in infertile men was 49.5% (51/103). CONCLUSION: Chromosome abnormality chip detection system provides a sensitive, economic and high-throughput method for detecting the deletion or amplification of genomic DNA sequences of infertile patients. Not only can it identify Yq deletions, but it can also find other chromosome abnormalities and facilitate the understanding of male infertility.

OBJETIVO: Analizar la aplicación de la tecnología de los microarreglos en el diagnóstico de la infertilidad masculina. MÉTODOS: Dieciséis loci, incluyendo una región determinante del sexo en el cromosoma Y, fueron investigados mediante reacción en cadena de la polimerasa (RCP) en pacientes hombres con problemas de infertilidad. Un biochip de la anormalidad cromosómica, con 180000 sondas, fue utilizado a fin de detectar pequeñas delecciones, pequeñas amplificaciones y pérdidas de heterocigosidad. RESULTADOS: Por medio de la RCP, se halló que nueve de 103 pacientes con infertilidad presentaban microdelecciones de sitios de secuencia marcada. Las microdelecciones no fueron observadas en las muestras de control. Las delecciones detectadas mediante RCP, estuvieron presentes en seis hombres azoospérmicos (6/44, 13.6%) y en tres hombres con oligoastenoteratozoospermia (OAT) (3/59, 5%). La frecuencia general de las microdelecciones en los hombres infértiles fue 8.7% (9/103). La detección con biochip de la anormalidad cromosómica de 500+ detectó más amplificación y delección en 51 pacientes, y la frecuencia general de microdelecciones en los hombres infértiles fue 49.5% (51/103). CONCLUSIÓN: El sistema de detección de la anormalidad del cromosoma mediante biochips genéticos representa un método sensible, económico, y de alto rendimiento, para detectar la delección o amplificación de las secuencias genómicas de ADN de pacientes infértiles. Este método puede no sólo identificar las delecciones Yq, sino también hallar otras anormalidades cromosómicas, facilitando así la comprensión de la infertilidad en los hombres.

The application of chromosome abnormality chip detection in male infertility.

OBJECTIVE: To discuss the application of microarray technology in the diagnosis of male infertility. METHODS: Sixteen loci, including a sex-determining region on the Y chromosome, were investigated by polymerase chain reaction (PCR) in infertile male patients. Chromosome abnormality chip with 180 000 probes was used to detect small deletion, small amplification and loss of heterozygosity. RESULTS: By PCR, nine of 103 infertile patients were found to have sequence-tagged site microdeletions. Microdeletions were not observed in control samples. The deletions detected by PCR were present in six azoospermic men (6/44, 13.6%) and in three oligoasthenoteratozoospermic (OATS) men (3/59, 5%).The overall frequency of microdeletions in infertile men was 8.7% (9/103). Chromosome abnormality chip detection 500+ detected more amplification or deletion in 51 infertile patients and the overall frequency of microdeletions in infertile men was 49.5% (51/103). CONCLUSION: Chromosome abnormality chip detection system provides a sensitive, economic and high-throughput method for detecting the deletion or amplification of genomic DNA sequences of infertile patients. Not only can it identify Yq deletions, but it can also find other chromosome abnormalities and facilitate the understanding of male infertility.