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There is still no consensus on the optimal monitoring method to evaluate the hypothalamic-pituitary-gonadal axis (HPGA) inhibition.There were 124 girls treated with triptorelin depot due to puberty disorders, including 77 central precocious puberty and 47 early puberty. After treatment, triptorelin stimulation tests were performed, and blood samples were collected at 0, 20, 40 and 60 min. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured by immunochemiluminometric assay (ICMA).Peak LH (PLH), peak FSH and estradiol in 124 girls were significantly decreased after treatment, while 2 cases had inadequate treatment efficacy. Areas under the receiver operating characteristic curves (AUC) of PLH and peak FSH after stimulation for the diagnosis of HPGA suppression were 0.984 and 0.121. When the cut-off value of PLH was ≤ 2.25 IU/L, the sensitivity was 96.7% and specificity was 100.0%. There was no difference in AUC between PLH and a single LH at 20, 40, or 60 min (A single blood sample for stimulated LH at 20 min, 40 min, or 60 min assayed by ICMA during triptorelin stimulation test is useful for monitoring the treatment efficacy of triptorelin depot in girls with puberty disorders.

Background Polycystic ovary syndrome (PCOS) is a common female endocrinal disease that may result in excessive androgen, but the mechanism of PCOS remains unclear. Most patients with PCOS suffer from low-grade inflammation, whereas the underlying connection between immune and PCOS is still uncertain. Objective This study aimed to determine the immune-related mechanisms behind PCOS pathogenesis and explore distinct immune-related genes and their functional signatures in PCOS. Methods The microarray dataset GSE155489 was downloaded from the Gene Expression Omnibus (GEO) database. The immune-related genes were downloaded from ImmPort. The immune-related differential expression genes (IRDEGs) in PCOS were screened, and functional and pathway enrichment analyses were applied. The protein-protein interactions (PPI), module analysis, and transcription factor enrichment analysis (TFEA) were used to identify hub genes. The immune profile analysis was depicted, and the expression correlation analysis between hub genes and m6A modifiers in PCOS was constructed. Results 125 IRDEGs were identified, and immune-related pathways included the cytokine-cytokine receptor pathway, T cell receptor signaling pathway, and TNF signaling pathway. All genes were associated with four immune cells (monocyte cells, nTreg, iTreg, and Tcm). Moreover, Major Histocompatibility Complex, Class I, A (HLA-A), Major Histocompatibility Complex, Class I, B (HLA-B), Fos Proto-Oncogene (FOS), Prostaglandin-Endoperoxide Synthase 2 (PTGS2), and C-X-C Motif Chemokine Receptor 4 (CXCR4) were identified as hub genes. Furthermore, N6-Methyladenosine (m6A methylation) mediators could potentially play a pivotal role between the immune system and PCOS. Conclusion This study described the relevance between immune and PCOS. We identified five IRDEGs as hub genes for PCOS. The relationship between the m6A methylation and hub genes indicated that m6A methylation could play a potential role in regulating such hub genes in PCOS. These findings could provide new insights into the molecular mechanisms and diagnosis or treatment strategy for the disease.

As is well known in atomic optics, the nonadiabatic transitions induce the loss of atoms trapped in a magnetic well which seriously affects the formation of the Bose-Einstein condensates. Electrostatic traps have widespread applications in molecular optics. While, for most existing electrostatic traps, the electric field strength in the trap center is nearly zero which may cause the nonadiabatic transitions. Especially for a chip-based microtrap, ingenious design is need to overcome this problem. In the paper, we propose a novel electrostatic microtrap composed of four arc-shaped electrodes. The influences of the voltages and the geometrical parameters of the electrodes on the electric field strength as well as the height of the potential well are studied. The distributions of electrostatic field are numerically calculated. We firstly simulate the trajectory of one molecule in the processes of loading and trapping. After that, we simulate the movements of a large number of molecules using the method of Monte Carlo. Then we calculate the temperature of trapped cold molecules. After that, we analyze the impacts of voltages and the geometrical parameters on the efficiency of our microtrap. At last, we show that our scheme can evolve into electrostatic microtrap arrays which should be a powerful tool for a variety of basic research and applications.

In general, potent non-ketolide versions of erythromycin possessed conformationally constricted two- or three-atom-length sidechains at 3-OH. Novel 14-membered non-ketolides possessing long spacers beyond three-atom length were evaluated for antibacterial activity. The most potent one is 34a, featuring a five-atom-length flexible linker from of a pyridine ring to the aglycone. Conversion of the pyridine of 34a to other aryl groups, changing the linker's length of 34a to longer or shorter ones, and variation of the linker flexibility to a rigid olefin or alkyne led to decreased antibacterial activity. The hybrids of macrolides and quinolones 28b, 31 and 34b possessing various sidechains, unlike their 15-membered counterparts, were ineffective compared to 34a. Similar to the marketed ketolide telithromycin, the non-ketolide 34a proved to be a time-dependent bactericidal agent, but it exhibited superior in vivo pharmacokinetic properties such as longer half-life, higher plasma concentration, lower clearance and shorter time to reach the highest drug concentration relative to telithromycin. Molecular docking suggested 34a might π - π interact with the bacterial ribosomal RNA base G2505Ec. This study suggested that the bacteriostatic agent erythromycin can be structurally modified to afford a new bactericidal chemotype that targets the ribosome and is superior to ciprofloxacin with regard to its minimum bactericidal concentration.

Constitutively erythromycin-resistant apathogens are more difficult to address than inducibly resistant and efflux-resistant strains. Three series of the 4th generation 2-fluoro 9-oxime erythromycin ketolides were synthesized and evaluated. Incorporation of substituted heteroaryl groups (a - m), in contrast to previously reported the unsubstituted heteroaryl groups, proved to the beneficial for enhancement of the activities of the 9-propgargyl ketolide 8 series and the 9-allyl ketolide 14 series. But these aryl groups (a - m) cannot supply the resulting compounds 8 and 14, unlike corresponding the 6-allyl ketolide 20 series, with activity against constitutively resistant Streptococcus pneumoniae. However, hybrids of macrolides and quinolones (8, 14 and 20, Ar = n - t) exhibited not only high activities against susceptible, inducibly erm-mediated resistant, and efflux-mediated resistant strains, but also significantly improved potencies against constitutively resistant Streptococcus pneumoniae and Streptococcus pyogenes. The capacity was highlighted by introduction of newly designed carbamoyl quinolones (q, r, s and t) rather than commonly seen carboxy quinolones (o and p) as the pharmacophores. Structure-activity relationships and molecular modelling indicated that 8r, 14r and 20q may have different binding sites compared to current erythromycins. Moreover, 8r, 14r and 20q have 2.5–3.6 times prolonged half-life and 2.3- to 2.6-fold longer mean residence time in vivo over telithromycin. These findings pave the way for rational design of novel non-telithromycin macrolides that target new binding sites within bacterial ribosomes.

Cylindrical launcher is widely used on the battlefield. Characteristic is easy handling, facilitate multigang outfit, cluster launch, emission rate and better generalization and standardization, etc. This paper mainly studies the thermal emission process of a cylindrical launch, the unsteady numerical simulation of the process, using computational fluid dynamics software GAMBIT and FLUENT, and the concept of dynamic grid and updating method of a certain type of cylindrical equipment vertical thermal emission process. Through to the launcher unsteady numerical simulation of the flow field of the guide surface pressure distribution contours, which lay a foundation for the study of the structure of this type of equipment. At the same time it is for the equipment launcher applicability related research to provide the reference.

The objective of this study was two-fold: 1) to investigate the changes of cytokines concentration in relation to severe aplastic anemia (SAA) when treated with immunosuppressants combined with cord blood (IS + CBI). and 2) to assess the curative effect of umbilical cord blood chimerism engraftment.We selected 43 patients with SAA all treated with IS + CBI (newly diagnosed group). Among them, a total of 33 patients were treated effectively (effective group) while 10 cases were treated invalidly (invalid group). An additional 20 healthy individuals were selected as control (control group). The expression levels of IL-17, IL-22 and other cytokines in each group were detected by ELISA. The engraftment of cord blood stem cells was detected by using short tandem repeat-polymerase chain reaction (STR-PCR).1. IL-17, IL-22 and other cytokines expressions in the newly diagnosed group were significantly higher than in the control group. 2. After six months, the levels in the effective group were significantly lower than pre-therapy levels (P0.05). The levels in the invalid group did not differ to those observed prior treatment. 3. After one and three months of treatment, a small amount of engraftment was found in the effective group. However, after six months, transplant rejection was observed in all patients. No effective engraftment was observed in the invalid group.1) Th17 and Th22 producing cells in SAA patients significantly increased indicating a positive correlation between these biomarkers and the progression of SAA. 2) During the IS + CBI treatment the maintenance of a normal hematopoietic function depended on immunesup-pressants. Early umbilical cord blood chimerism engraftment may promote hematopoietic recovery.

Hereditary retinal diseases (HRDs), including retinitis pigmentosa, Leber's congenital amaurosis, congenital stationary night blindness, vitelliform macular dystrophy, Stargardt macular dystrophy, etc., are the most common and severe hereditary ocular diseases, which are closely associated with blindness. With the accomplishment of human genome project and the widespread application of genetic study techniques, the way leading to understanding of gene mutations of HRDs has been paved. Many encouraging breakthroughs of gene therapy studies have been made. Among them, the arrayed primer extension chip (Apex) technology greatly improved the efficiency of mutant gene screening of HRDs. Till now, 46 pathogenic genes and 2497 mutation loci have been identified to be related to HRDs. Gene therapy is one of the key treatments for HRDs. The disease causing mutant gene must be detected before the application of gene therapy. This paper reviews the latest progress in the study of gene mutations in HRDs.

In nine rhesus monkeys, human corneal grafts were used for penetrating keratoplasty in one eye of each. The data were divided into three groups according to the size of grafts. Group 1 (n = 3) received 5.5-mm human corneal grafts in 5.0-mm recipient beds; group 2 (n = 3) received 6.2-mm human corneal grafts in 6.0-mm beds; and group 3 (n = 3) received 7.5-mm grafts in 7.0-mm beds. Five of nine eyes in groups 1 and 2 (55%) maintained graft clarity for more than 1 year, but only two of the three in group 1 maintained clear human corneal grafts for 32 and 36 months, respectively. However, the three grafts in the third group maintained transparency for only 4-7 months. Our findings suggest that xenogeneic corneal grafts may have a greater success rate in humans than previously believed.

Combining the outputs of several neural networks into an aggregate output often gives improved accuracy over any individual output. The set of networks is known as an ensemble. This work presents an ensemble method for regression that has advantages over simple weighted or weighted average combining techniques. Generally, the output of an ensemble is a weighted sum whose weights are fixed. Our ensemble is weighted dynamically, the weights dynamically determined from the predicting accuracies of the trained networks with training dataset. The more accurate a network seems to be of its prediction, the higher the weight. This is implemented by generalized regression neural network. Empirical results show that this method improved on predicting accuracy.

Combining the outputs of several neural networks into an aggregate output often gives improved accuracy over any individual output. The set of networks is known as an ensemble. Neural network ensembles are effective techniques to improve the generalization of a neural network system. This paper presents an ensemble method for regression that has advantages over simple weighted or weighted average combining techniques. After the training of component neural networks, genetic algorithm is used to optimize the combining weights of component networks. Compared with ordinary weighted methods, the method proposed in this paper achieved high predicting accuracy on five test datasets.