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Objective To evaluate the safety and efficacy of weekly PEGylated-recombinant human growth hormone (PEG-rhGH) in children with idiopathic short stature (ISS) in China. Design and methods This was a multicenter, phase II study in which all subjects were randomized 1:1:1 to weekly s.c. injections of PEG-rhGH 0.1 (low-dose (LD) group) or 0.2 mg/kg/week (high-dose (HD) group) or control for 52 weeks. The primary end point was change (Δ) in height s.d. score (HT-SDS) from baseline to week 52. Secondary end points were height velocity (HV), bone maturity, insulin-like growth factor-1 (IGF-1) SDS, and IGF-1/insulin-like growth factor-binding protein-3 (IGFBP-3) molar ratio. Results A total of 360 children with ISS were recruited in the study (n = 120 in each group). At week 52, ΔHT-SDS was 0.56 ± 0.26, 0.98 ± 0.35, and 0.20 ± 0.26 in the LD, HD, and control groups, respectively (within-group P < 0.0001; intergroup P < 0.0001). Statistically significant values of ΔHV, IGF-1, IGF-1/IGFBP-3 ratio, and IGF-1 SDS at week 52 from baseline were observed in both treatment groups (P < 0.0001). There were clear dose-dependent responses for all auxological variables. PEG-rhGH was well tolerated throughout the treatment period with treatment-emergent adverse events (TEAEs) reported in 86.5%, 84.6%, and 91.3% of children in the HD, LD, and control groups, respectively. The incidence of TEAEs was similar in all treatment groups despite the difference in doses. A total of 27 (8.7%) children experienced drug-related TEAEs. Conclusion Fifty-two-week treatment with PEG-rhGH 0.1 or 0.2 mg/kg/week achieved significant improvement in HT-SDS and other growth-related variables, including HV, IGF-1 SDS, and IGF-1/IGFBP-3 ratio, in a dose-dependent manner. Both doses were well tolerated with similar safety profiles.

Alluvial units are important in understanding the interactions of antecedent drainage evolution with fold growth along the flanks of active orogenic belts. This is demonstrated by the Anjihai River in the northern Chinese Tian Shan foreland, which at present flows northward cutting sequentially through the Nananjihai anticline, the Huoerguos anticline, and the Anjihai anticline. Three episodes of alluviation designated as fans F-a, F-b, and F-c are identified for the Anjihai River. These three alluvial terrain features comprise a series of terraces, where the topographic characteristics, geomorphologic structure, and up-warped longitudinal profiles indicate continuous uplift and lateral propagation of the Halaande anticline and the Anjihai anticline over the past 50 Icy. Shortly after similar to 3.6 ka when the oldest terrace during the period of the fan Fb sedimentation was formed, significant rock uplift at the overlapping zone of the Anjihai anticline and the Halaande anticline led to the eastward deflection of the antecedent Anjihai River. A series of local terraces with elevation decreasing eastward indicate the gradual eastward migration of the channel of the Anjihai River during the period of the fan F-c sedimentation. Finally the Anjihai River occupied the previous course of the Jingou River when the latter was deflected eastward in response to rock uplift of the Anjihai anticline, presently flowing across the eastern tip of the Anjihai anticline. (C) 2017 Elsevier B.V. All rights reserved.

BACKGROUND Glioblastoma multiforme (GBM) is the most common malignant and lethal type of primary central nervous system tumor in humans. In spite of its high lethality, a small percentage of patients have a relatively good prognosis, with median survival times of 36 months or longer. The identification of clinical subsets of GBM associated with distinct molecular genetic profiles has made it possible to design therapies tailored to treat individual patients. METHODS We compared microarray data sets from long-term survivors (LTSs) and short-term survivors (STSs) to screen for prognostic biomarkers in GBM patients using the WebArrayDB platform. We focused on FBLN4, IGFBP-2, and CHI3L1, all members of a group of 10 of the most promising, differentially regulated gene candidates. Using formalin-fixed paraffin-embedded GBM samples, we corroborated the relationship between these genes and patient outcomes using methylation-specific polymerase chain reaction (PCR) for MGMT methylation status and quantitative reverse transcription PCR for expression of these genes. RESULTS Expression levels of the mRNAs of these 3 genes were higher in the GBM samples than in normal brain samples and these 3 genes were significantly upregulated in STSs compared to the levels in LTS samples (P

Objective The purposes of this study were to explore the effect of obstructive sleep apnea-hypopnea syndrome (OSAHS) on the voice by analyzing the acoustic parameters between patients with OSAHS and those without OSAHS and to compare acoustic analyses performed by two software programs (MDVP and Praat). Methods Patients with OSAHS (n = 75) and normal controls (n = 46) were asked to produce a sustained sound of the vowel /i/ and were analyzed with electroglottography (EGG), MDVP, and Praat software. A self-rated scale (Voice Handicap Index, VHI-10) and acoustic parameters were compared. Results There were no statistically significant differences in the fundamental frequency (F0), jitter, shimmer, noise/harmonic ratio (NHR), contact quotient perturbation (CQP), or contact index perturbation (CIP) between the patient group and the normal group. The VHI-10 values were significantly increased in patients with OSAHS. The receiver operating characteristic (ROC) analysis suggested that the shimmer obtained from MDVP and Praat possessed relatively high accuracy in differentiating patients with OSAHS from healthy individuals. The results for F0, jitter, shimmer, and NHR were significantly different between MDVP and Praat in OSAHS patients. In normal persons, there was a significant difference in NHR; however, no significant differences were found for F0, jitter, or shimmer between the two software programs. The results demonstrated that high correlations were found between values obtained by both software programs. Conclusions Patients with OSAHS were prone to vibration irregularity, incomplete glottal closure, hoarseness, and other vocal problems. The two acoustic software programs present different values of acoustic measures. There was a strong correlation and consistency between the parameters calculated by the two software programs.

River-incision rate is widely used to track changes in tectonics or climate over time and space. However, the feasibility of utilizing the spatial variations of river incision to reconstruct past tectonic and climatic processes remains unclear. Here, we focus on the spatial patterns of river incision along the northern Chinese Tian Shan foreland. Three alluvial fans FP, FeH, and FlH are determined as the alluvial fan context of river incision and terrace classification providing the geomorphological framework across the foreland region. Four rivers (i.e. the Kuitun, Jingou, Manas, and Urumqi Rivers from the western, central, and eastern part of the foreland) are used to reconstruct the paleogeomorphology from the reference, which is the best-preserved terrace of each river system with ages clustering in different parts of the Latest Pleistocene-Early Holocene. The depth of incision constrained by the reference terrace of each river is obtained by comparing the present-day topography and the reconstructed one. The resulting profile of channel incision (depth and rate) of each analyzed river displays an overall decreasing-downstream trend from the maximum where the river exits from the mountain range, to zero. Such a trend has been attributed to the progressive lowering of the river gradient that was caused by the adjusted ratio of sediment input versus water discharge induced by climate change. Superimposing on the decreasing-downstream trend, an obvious step can also easily be observed onto the profile of channel incision of each river, downstream of which channel incision is significantly less. The step occurs near the thrust fault controlling growth of the outermost anticline through which each river cuts, thereby implying the key role of local rock uplift in forming the river-incision step. The former observation implies that, at the same timescale, more river incision at the exit from the mountain range does not necessarily mean stronger climatic forcing of incision there. We thus propose that, in a foreland setting, it should be the temporal pattern of river incision rather than its spatial variation that is helpful for unraveling the change in the forcing factor of downcutting.

miR‑152 has been reported to be downregulated in rheumatoid arthritis (RA). However, the functional significance and molecular mechanisms underlying the role of miR‑152 in RA remain largely unknown. The present study aimed to explore the functional role and the underlying mechanisms of miR‑152 in RA. The expression of miR‑152 in serum, synovial tissues, and fibroblast‑like synoviocytes (FLS) from patients with RA and healthy controls was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Cell proliferation, cell cycle phase distribution and apoptosis of FLS were measured by Cell Counting Kit‑8 and flow cytometry assays. The effects of miR‑152 on the production of pro‑inflammatory cytokines, including tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β, IL‑6 and IL‑8, were examined by ELISA. The target gene of miR‑152 was discovered by miRNA‑target prediction bioinformatics analysis, and confirmed by dual‑luciferase reporter assay, RT‑qPCR and western blotting. Spearman's correlation analysis was performed to assess the relationship between miR‑152 expression and a disintegrin and metalloproteinase domain‑containing protein 10 (ADAM10). The results demonstrated that miR‑152 expression levels were significantly decreased in RA serum, synovial tissues and RA‑FLS compared with healthy controls. Overexpression of miR‑152 significantly inhibited cell proliferation, promoted cell apoptosis, and decreased TNF‑α, IL‑1β, IL‑6 and IL‑8 production in RA‑FLS cells. Additionally, ADAM10 was demonstrated to be a target of miR‑152, and expression of the two genes was significantly negatively correlated. Of note, restoration of ADAM10 expression partially reversed the effects of miR‑152 on cell proliferation and apoptosis in RA‑FLS. Thus, miR‑152 may serve as a potential target for therapeutic intervention in RA.

Purpose. Vasculogenic mimicry (VM) was related to invasion and metastasis of head and neck squamous cell carcinoma (HNSCC) patients. This study was designed to investigate the role of EphA2 in VM formation of HNSCC.Methods. The SiRNA technique was used to knock down the expression of EphA2in vitro. The ability of cell migration and invasion were measured by transwell and wound healing assays; three-dimensional culture was used to detect the ability of channel-like structure formation; Western blot was used to detect the expression of epithelial-mesenchymal transition- (EMT-) related moleculesin vitro. Further semiquantitative real-time RT-PCR assays and immunohistochemistry were used to demonstrate expression of EphA2 and EMT-related molecules according to VM presence or not in human tissue.Results. Knocking down EphA2in vitroleads to disabled channel-like structure formation, reduction of invasion and migration ability, and reverse of EMT-related markers. Both semiquantitative real-time RT-PCR and immunohistochemistry showed that expressions of EphA2, Twist, and Vimentin were higher in the VM-positive group than in the VM-negative group significantly, while expressions of E-cadherin, claudin4, and DSG-3 were reverse.Conclusions. EphA2 played a key role in VM formation of HNSCC through regulation of EMT.

To investigate the expression and its significance of interleutin-17 (IL-17) and immunoglobulin E (IgE) in patients with bronchial asthma, sixty adult patients with bronchial asthma and 30 healthy human control were sequentially enrolled in this study. The production of IL-17 was measured by enzyme-linked immunosorbent assay (ELISA) and fluorescent quantitative polymerase chain reaction (qPCR), respectively. The correlation between expression of IgE and IL-17 was analyzed. It was found that IL-17 was significantly up-regulated in bronchial asthma in comparison to the health control on mRNA level, and serum levels of IL-17 and IgE in bronchial asthma were significantly higher than those in health control, respectively (P < 0. 001). Significant positive correlation in bronchial asthma were found between expression of IL-17 and IgE (r = 0.7082, P = 0.0418). The present study implied that expressions of IL-17 and IgE play an important role in the development of bronchial asthma. Key words: Bronchial asthma, immunoglobulin E, interleukin-17, enzyme-linked immunosorbent assay (ELISA).

Background: Hereditary ataxia is a group of hereditary diseases that are characterized by chronic progressive uncoordinated gait and are frequently associated with cerebellar atrophy. Objectives: To investigate evidence-based diagnosis of hereditary ataxia by retrospective analysis of the diagnostic process in one Chinese family. Methods: Clinical records of 15 ataxia patients from one Chinese family with 46 family members were retrospectively reviewed and a tentative diagnosis was made based on clinical manifestations, signs and symptoms, mode of inheritance, and progression. Since hereditary ataxia is a group of heterogeneous diseases having various subtypes and overlapping symptoms, we adopted a stepwise evaluation to achieve a tentative diagnosis. To confirm the diagnosis, we performed polymerase chain reaction (PCR) specific for the suspected causative gene of spinocerebellar ataxia (SCA) subtype 3 (SCA3). Results: Through analysis of hereditary and clinical characteristics of family histories of the patients, we suspected that the family might suffer from SCA, especially, SCA3. The PCR assay for SCA3 showed that, five of the ten samples analyzed had a CAG trinucleotide expansion of the SCA3 gene, and four of the five members developed ataxia. The remaining one, a seven-year-old girl, showed no symptoms or signs except for uvula deviation. No clinical symptoms were found in five other members with negative PCR results. Thus, based on both clinical findings and laboratory results, we further confirmed that the family suffered from SCA3. Conclusion: Hereditary ataxias are disorders sharing overlapping symptoms. Comprehensive analysis of medical and family records together with genetic diagnosis improves diagnostic efficiency of hereditary ataxia and aides in family counseling.