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1.
Artigo em Inglês | MEDLINE | ID: mdl-31442554

RESUMO

Auditory verbal hallucination (AVH), defined as the auditory perception of speech in the absence of a real external stimulus, occurs in individuals with and without mental illness. The distribution of functional abnormalities in patients with AVH suggests aberrant brain network connectivity. However, no study has measured the global functional connectivity density (gFCD) associated with AVH in patients with major depressive disorder (MDD); gFCD is used widely to examine the density distribution of whole-brain resting-state functional connectivity and can serve as an index reflecting brain metabolism disturbance. In this study, we involved drug-naïve patients with first-episode MDD with (n = 35) and without (n = 40) AVH and healthy controls (n = 50).Whole-brain resting-state functional magnetic resonance imaging data were acquired and gFCD was calculated and compared among groups. We found the following gFCD alterations that were shared by both MDD groups: (1) decreased gFCD in the bilateral postcentral gyrus, precentral gyrus, insular cortices and occipital lobe; and (2) increased gFCD in the left middle cingulate cortex. More importantly, we found AVH-specific gFCD changes in patients with MDD: increased gFCD in the left Wernicke's brain regions and bilateral hippocampus and thalamus, and decreased gFCD in the bilateral lateral prefrontal lobule. These findings reflect the disturbance of brain information communication and metabolism in patients with MDD and AVH, related mainly to the language and memory processing circuits, and to some extent provide further support for the "VOICE" model of AVH.

2.
Ageing Res Rev ; : 100965, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678652

RESUMO

Dementia represents one of the most common neurodegenerative disorders in older adults. However, it is still unclear whether non-pharmacological therapies (NPTs) are effective or not and which treatment should be preferred. We applied a series of search strategies to identify eligible randomized controlled trials on 1st October, 2018, investigating the effects of NPTs of dementia in the older persons. Pairwise and network meta-analyses were sequentially performed. A total of 31 trials were included, which enrolled 1895 participants and 7 NPTs. Compared with control group, all the NPTs included were statistically beneficial to cognitive function, and our study indicated Comprehensive Therapy(CT) [the surface under the cumulative ranking curve(SUCRA=92.42%)] might be the best choice for dementia patients. Our study suggests CT might be the optimal NPT for improving the cognitive function of dementia patients. However, the above conclusions need to be further analyzed.

3.
IEEE Trans Cybern ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31689228

RESUMO

In this article, the dissipativity-based filtering of the Markovian jump neural networks subject to incomplete measurements and deception attacks is investigated by adopting an event-triggered communication strategy, where the attackers are supposed to occur in a random fashion but obey the Bernoulli distribution. Consider that the information of the system mode is transmitted to the filter over the communication network that is vulnerable to external attacks, which may lead to the undesired performance of the resulting system by injecting malicious information from the attackers. As a result, the filter has difficulty completing information from the original system. Besides, an event-triggered communication mechanism is introduced to reduce the communication frequency between data transmission due to the limited network resources, and different triggering conditions corresponding to different jump modes are developed. Then, based on the above considerations, the sufficient condition is derived to ensure the stochastic stability and dissipativity of the resulting augmented system although the deception attacks and incomplete information exist. A numerical simulated example is provided to verify the theoretical analysis.

4.
Medicine (Baltimore) ; 98(44): e17686, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689791

RESUMO

RATIONALE: Ependymomas are neuroepithelial tumors that typically occur in the central nervous system. Ependymomas arising in the mediastinum are exceedingly rare, with only approximately 9 isolated cases reported in the literature to date. PATIENT CONCERNS: A 35-year-old woman was referred to our hospital with complaints of progressive back pain for 3 months. Physical examination revealed decreased breathing sounds and tenderness. Contrast-enhanced computed tomography showed a soft tissue mass with heterogeneous enhancement in the right posterior mediastinum. DIAGNOSES: The diagnosis of primary mediastinal ependymomas (PMEs) was confirmed by postoperative histopathologic examination. INTERVENTIONS AND OUTCOMES: The patient underwent surgical resection of the tumor and experienced local recurrence with neck metastasis 2 years postoperatively. She underwent reoperation for the recurrent tumors and received postoperative radiotherapy and adjuvant chemotherapy. Two years later, the patient is doing well, with no evidence of tumor progression or recurrence. LESSONS: Since PMEs are exceedingly rare, treatment options are limited. Surgical resection seems to be the mainstay of treatment. Further evidence-based studies are required to prove the benefit of radiotherapy and chemotherapy in the treatment of PMEs.

5.
Arch Biochem Biophys ; : 108181, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31704096

RESUMO

Isoflurane, one of the commonly used inhalation anesthetics worldwide in clinical practice, may generate substantial risks of neurotoxicity in the developing brains. The present study aimed to illustrate the effects and underlying mechanisms of miR-214 on isoflurane-induced neurotoxicity in human neuroblastoma cell line SH-SY5Y. SH-SY5Y cells were transfected with miR-214 or miR-con alone or in combination with pcDNA empty vector or pcDNA-PTEN in the presence of 3% isoflurane and incubated for 48 h. Cell viability, lactate dehydrogenase (LDH) release, apoptosis, and caspase-3/7 activity were evaluated using CCK-8, LDH release assay, flow cytometry analysis, and caspase-3/7 activity assay, respectively. The superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) activities were measured using commercial kits. miR-214 expression and alterations of the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway were detected by qRT-PCR and Western blot, respectively. The interaction between miR-214 and PTEN was explored by luciferase reporter assay. We found that isoflurane exposure induced neurotoxicity in SH-SY5Y cells, as evidenced by the reduced cell viability, increased LDH release, apoptotic rate, caspase-3/7 activity, and oxidative stress levels. Moreover, isoflurane exposure decreased the expression of miR-214 and affected the PTEN/PI3K/Akt pathway in SH-SY5Y cells. miR-214 overexpression significantly suppressed isoflurane-induced viability reduction, LDH release, apoptosis and oxidative stress, as well as inactivation of the PI3K/Akt pathway in SH-SY5Y cells. Interestingly, PTEN was identified as a target of miR-214. Moreover, PTEN upregulation blocked the effects of miR-214 on isoflurane-induced neurotoxicity in SH-SY5Y cells. In conclusion, miR-214 protected against isoflurane-induced neurotoxicity in SH-SY5Y cells via regulation of PI3K/Akt pathway by targeting PTEN, contributing to better understanding the underlying mechanisms of anesthetics-induce neurotoxicity.

6.
Cell Signal ; 65: 109422, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31672604

RESUMO

Docetaxel resistance remains one of the main problems in clinical treatment of metastatic prostate cancer (PCa). Previous studies identified differently expressed lncRNAs in docetaxel-resistant PCa cell lines, while the potential mechanisms were still unknown. In the present study, we found NEAT1 was expressed at high levels in docetaxel-resistant PCa clinical samples and related cell lines. When knockdown NEAT1, cell proliferation and invasion in docetaxel-resistant PCa cells in vitro and in vivo were downregulated. Our further researches explained that NEAT1 exerts oncogenic function in PCa by competitively 'sponging' both miR-34a-5p and miR-204-5p. Inhibition of miR-34a-5p or miR-204-5p expression mimics the docetaxel-resistant activity of NEAT1, whereas ectopic expression of miR-34a-5p or miR-204-5p attenuates the anti-drug function of NEAT1 in PCa cells. Besides, we also found ACSL4 is a target of both miR-34a-5p and miR-204-5p, and ACSL4 was also inhibited by miR-34a-5p and miR-204-5p. Moreover, suppression of miR-34a-5p or/and miR-204-5p greatly restrained the expression of ACSL4 upon NEAT1 overexpression. Joint expression of miR-34a-5p and miR-204a-5p synergistically decreased the expression of ASCL4, indicating miR-34a-5p and miR-204a-5p collaboratively inhibit the expression of ACSL4. Innovatively, we concluded that NEAT1 contributes to the docetaxel resistance by increasing ACSL4 via sponging miR-34a-5p and miR-204-5p in PCa cells.

7.
IEEE Trans Cybern ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31670689

RESUMO

The problem of quasi-synchronization (QS) for the Markovian jump master-slave neural networks with time-varying delay is studied in this article, where the mismatch parameters and unreliable communication channels are considered as well. A set of stochastic variables with different expectations are used to describe the fading phenomena of parallel communication channels. An impulsive-driven transmission strategy is designed to reduce the communication load, and a corresponding impulsive controller is then designed. A synchronization error system (SES) is obtained, and a convex QS condition is established for the SES. A linear matrix inequality-based iterative algorithm is proposed to reduce the bound of the SES, and the corresponding controller gains are calculated. A numerical example is provided to illustrate the effectiveness of the developed result.

8.
Chaos ; 29(10): 101102, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31675827

RESUMO

The influences of correlated spatially random perturbations (SRPs) on the first passage problem are studied in a linear-cubic potential with a time-changing external force driven by a Gaussian white noise. First, the escape rate in the absence of SRPs is obtained by Kramers' theory. For the random potential case, we simplify the escape rate by multiplying the escape rate of smooth potentials with a specific coefficient, which is to evaluate the influences of randomness. Based on this assumption, the escape rates are derived in two scenarios, i.e., small/large correlation lengths. Consequently, the first passage time distributions (FPTDs) are generated for both smooth and random potential cases. We find that the position of the maximal FPTD has a very good agreement with that of numerical results, which verifies the validity of the proposed approximations. Besides, with increasing the correlation length, the FPTD shifts to the left gradually and tends to the smooth potential case. Second, we investigate the most probable passage time (MPPT) and mean first passage time (MFPT), which decrease with increasing the correlation length. We also find that the variation ranges of both MPPT and MFPT increase nonlinearly with increasing the intensity. Besides, we briefly give constraint conditions to guarantee the validity of our approximations. This work enables us to approximately evaluate the influences of the correlation length of SRPs in detail, which was always ignored previously.

9.
Nat Genet ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676863

RESUMO

Fruit characteristics of sweet watermelon are largely the result of human selection. Here we report an improved watermelon reference genome and whole-genome resequencing of 414 accessions representing all extant species in the Citrullus genus. Population genomic analyses reveal the evolutionary history of Citrullus, suggesting independent evolutions in Citrullus amarus and the lineage containing Citrullus lanatus and Citrullus mucosospermus. Our findings indicate that different loci affecting watermelon fruit size have been under selection during speciation, domestication and improvement. A non-bitter allele, arising in the progenitor of sweet watermelon, is largely fixed in C. lanatus. Selection for flesh sweetness started in the progenitor of C. lanatus and continues through modern breeding on loci controlling raffinose catabolism and sugar transport. Fruit flesh coloration and sugar accumulation might have co-evolved through shared genetic components including a sugar transporter gene. This study provides valuable genomic resources and sheds light on watermelon speciation and breeding history.

10.
Nat Genet ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676864

RESUMO

Melon is an economically important fruit crop that has been cultivated for thousands of years; however, the genetic basis and history of its domestication still remain largely unknown. Here we report a comprehensive map of the genomic variation in melon derived from the resequencing of 1,175 accessions, which represent the global diversity of the species. Our results suggest that three independent domestication events occurred in melon, two in India and one in Africa. We detected two independent sets of domestication sweeps, resulting in diverse characteristics of the two subspecies melo and agrestis during melon breeding. Genome-wide association studies for 16 agronomic traits identified 208 loci significantly associated with fruit mass, quality and morphological characters. This study sheds light on the domestication history of melon and provides a valuable resource for genomics-assisted breeding of this important crop.

11.
Phys Rev E ; 100(2-1): 022114, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31574709

RESUMO

Fractional Gaussian noise (FGN) with the Hurst exponent H is an important tool to model various phenomena in biophysical systems, like subdiffusion in a single protein molecule. Considering that there also exists a confined structure which can be modeled as a channel in these systems, transport and escape driven by FGN in a deformable channel are investigated in this paper. By calculating the mean velocity, and the mean first passage time (MFPT) for crossing the nearest bottleneck and the probability distribution of the final position, effects of FGN and channel structure on the system dynamics are illustrated. Our results indicate that FGN has a complex influence mechanism under different combinations of H and the noise intensity. For a persistence case (H>0.5), the mean velocity decreases but MFPT increases with the increase of the noise intensity and H. While for an antipersistence case (H<0.5), when H is small, the relationships among the mean velocity, MFPT and the noise intensity are exactly the opposite to persistence cases. When H has a large value, the mean velocity tends to first decrease and then increase. Moreover, effects of the bottleneck and channel asymmetry are investigated. It is shown that a small H and a large channel width can lead to a large mean velocity and fast crossing. Besides, a channel asymmetry can affect the system dynamics by inducing asymmetric structure and adjusting the width of bottleneck. However, the effect of the bottleneck is the main factor. Therefore, a combination of channel with wide bottleneck and FGN in an antipersistence regime is the optimal choice to promote the transport and escape. These results provide a basis for the explanation of molecular activity in living organisms and the design of particle mixture separators.

12.
Mol Biol Cell ; : mbcE19050247, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31599700

RESUMO

Microtubule associated proteins (MAPs) are a functionally highly diverse class of proteins that help to adjust the shape and function of the microtubule cytoskeleton in space and time. For this purpose, MAPs structurally support microtubules, modulate their dynamic instability or regulate the activity of associated molecular motors. The microtubule binding domains of MAPs are structurally divergent, but often depend on electrostatic interactions with the negatively charged surface of the microtubule. This suggests that the surface exposure of positive charges rather than a certain structural fold is sufficient for a protein to associate with microtubules. Consistently, positively charged artificial objects have been shown to associate with microtubules and to diffuse along their lattice. Natural MAPs, however, show a more sophisticated functionality beyond lattice-diffusion. Here we asked, whether basic electrostatic interactions are sufficient to also support advanced MAP-functionality. To test this hypothesis, we studied simple positively charged peptide sequences for the occurrence of typical MAP-like behaviour. We found that a multivalent peptide construct featuring four lysine-alanine heptarepeats (starPEG-(KA7)4) - but not its monovalent KA7-subunits - show advanced, biologically relevant MAP-like behaviour: starPEG-(KA7)4 binds microtubules in the low nanomolar range, diffuses along their lattice with the ability to switch between intersecting microtubules and tracks depolymerising microtubule ends. Further, starPEG-(KA7)4 promotes microtubule nucleation and growth, mediates depolymerisation coupled pulling at plus ends and bundles microtubules without significantly interfering with other proteins on the microtubule lattice (as exemplified by the motor kinesin-1). Our results show that positive charges and multivalency are sufficient to mimic advanced MAP-like behaviour. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].

13.
Sensors (Basel) ; 19(20)2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31614560

RESUMO

Glaucoma is a serious eye disease that can cause permanent blindness and is difficult to diagnose early. Optic disc (OD) and optic cup (OC) play a pivotal role in the screening of glaucoma. Therefore, accurate segmentation of OD and OC from fundus images is a key task in the automatic screening of glaucoma. In this paper, we designed a U-shaped convolutional neural network with multi-scale input and multi-kernel modules (MSMKU) for OD and OC segmentation. Such a design gives MSMKU a rich receptive field and is able to effectively represent multi-scale features. In addition, we designed a mixed maximum loss minimization learning strategy (MMLM) for training the proposed MSMKU. This training strategy can adaptively sort the samples by the loss function and re-weight the samples through data enhancement, thereby synchronously improving the prediction performance of all samples. Experiments show that the proposed method has obtained a state-of-the-art breakthrough result for OD and OC segmentation on the RIM-ONE-V3 and DRISHTI-GS datasets. At the same time, the proposed method achieved satisfactory glaucoma screening performance on the RIM-ONE-V3 and DRISHTI-GS datasets. On datasets with an imbalanced distribution between typical and rare sample images, the proposed method obtained a higher accuracy than existing deep learning methods.

14.
Zhongguo Gu Shang ; 32(9): 833-836, 2019 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-31615181

RESUMO

OBJECTIVE: To study the effect of soothing liver, relieving depression, invigorating spleen and reinforcing blood on reducing delirium in elderly patients with hip fracture. METHODS: From December 2014 to June 2018, 180 elderly patients with hip fracture admitted were divided into treatment group and placebo group according to the order of admission:90 patients in treatment group were treated with Jiawei Xiaoyao Powder(JWXYP), including 32 males and 58 females, with an average age of(72.12±4.92), involving 67 cases of femoral trochanter fractures and 23 cases of femoral neck fractures; 35 cases underwent dynamic hip screw fixation, 31 cases underwent intramedullary fixation and 24 cases underwent artificial hip replacement. In the placebo group, 90 patients were treated with placebo, including 37 males and 53 females, with an average age of(72.91±5.43) years old, involving 69 cases of femoral trochanteric fractures and 21 cases of femoral neck fractures, including 37 cases underwent dynamic hip screw fixation, 30 cases underwent intramedullary fixation and 23 cases underwent artificial hip replacement. The age, sex, injury site, intraoperative bleeding volume, postoperative drainage, operation time, anesthesia time, post-operative pain score, post-operative hemoglobin, post-operative CRP, delirium severity(DRS) score and delirium occurrence were observed and compared between the two groups. RESULTS: All patients were followed up until delirium returned to normal, postoperative delirium was found in 12 cases (13.33%) in the treatment group and in 39 cases(43.33%) in the placebo group, the treatment group was significantly better than the placebo group. The monitoring indexes of the two groups were compared:post-operative pain score(P=0.002), post-operative hemoglobin(P=0.012), post-operative CRP(P=0.042). CONCLUSIONS: JWXYP can relieve liver depression, invigorate spleen and invigorate blood circulation, reduce pain, inflammatory stimulation and supplement blood volume after operation, and significantly reduce the incidence of delirium after operation.

15.
Phys Rev Lett ; 123(12): 126402, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31633945

RESUMO

Centrosymmetric materials with spin-degenerate bands are generally considered to be trivial for spintronics and related physics. In two-dimensional (2D) materials with multiple degenerate orbitals, we find that the spin-orbit coupling can induce spin-orbital locking, generate out-of-plane Zeeman-like fields displaying opposite signs for opposing orbitals, and create novel electronic states insensitive to the in-plane magnetic field, which thus enables a new type of Ising superconductivity applicable to centrosymmetric materials. Many candidate materials are identified by high-throughput first-principles calculations. Our work enriches the physics and materials of Ising superconductivity, opening new opportunities for future research of 2D materials.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31635808

RESUMO

Liver sinusoidal endothelial cells play a key role maintaining the hepatic homeostasis, the disruption of which is associated with such end-stage liver diseases as hepatocellular carcinoma and cirrhosis. In the present study we investigated the role of brahma-related gene 1 (BRG1), a chromatin remodeling protein, in regulating endothelial transcription and the implication in liver fibrosis. We report that endothelial-specific deletion of BRG1 in mice attenuated liver fibrosis induced by injection with thioacetamide (TAA). Coincidently, alleviation of liver fibrosis as a result of endothelial BRG1 deletion was accompanied by an up-regulation of eNOS activity and NO bioavailability. In cultured endothelial cells, exposure to lipopolysaccharide (LPS) suppressed eNOS activity whereas BRG1 depletion with small interfering RNA restored eNOS-dependent NO production. Further analysis revealed that BRG1 was recruited to the caveolin-1 (CAV1) promoter by Sp1 and activated transcription of CAV1, which in turn inhibited eNOS activity. Mechanistically, BRG1 interacted with the H3K4 trimethyltransferase MLL1 to modulate H3K4 trimethylation surrounding the CAV1 promoter thereby contributing to LPS-induced CAV1 activation. In conclusion, our data unveil a novel role for BRG1 in the regulation of endothelial function and liver fibrosis.

17.
J Cell Physiol ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31637729

RESUMO

Aberrant fibrogenesis impairs the architectural and functional homeostasis of the kidneys. It also predicts poor diagnosis in patients with end-stage renal disease (ESRD). Renal tubular epithelial cells (RTEC) can trans-differentiate into myofibroblasts to produce extracellular matrix proteins and contribute to renal fibrosis. Connective tissue growth factor (CTGF) is a cytokine upregulated in RTECs during renal fibrosis. In the present study, we investigated the regulation of CTGF transcription by megakaryocytic leukemia 1 (MKL1). Genetic deletion or pharmaceutical inhibition of MKL1 in mice mitigated renal fibrosis following the unilateral ureteral obstruction procedure. Notably, MKL1 deficiency in mice downregulated CTGF expression in the kidneys. Likewise, MKL1 knockdown or inhibition in RTEs blunted TGF-ß induced CTGF expression. Further, it was discovered that MKL1 bound directly to the CTGF promoter by interacting with SMAD3 to activate CTGF transcription. In addition, MKL1 mediated the interplay between p300 and WDR5 to regulate CTGF transcription. CTGF knockdown dampened TGF-ß induced pro-fibrogenic response in RTEs. MKL1 activity was reciprocally regulated by CTGF. In conclusion, we propose that targeting the MKL1-CTGF axis may generate novel therapeutic solutions against aberrant renal fibrogenesis.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31612523

RESUMO

Morphine is an opioid analgesic drug routinely used to treat pain in several medical conditions including cancer. Increasing evidence has shown that morphine can directly modulate cancer growth via regulating angiogenesis. In this work, we investigated the effect of morphine on angiogenesis under pathological conditions. We showed that morphine, in a concentration typical of that observed in patient's blood, stimulates tumor angiogenesis under serum deprivation and H2 O2 -induced oxidative stress conditions. We found that morphine protected human lung tumor associated-endothelial cell (HLT-EC) against serum deprivation or H2 O2 -induced inhibition of capillary network formation. Furthermore, morphine stimulated other biological functions of HLT-EC under serum deprivation and H2 O2 -induced pathological conditions, such as growth, migration and survival, without affecting HLT-EC adhesion. Interestingly, morphine at the same concentration did not affect lung tumor cell growth and survival, suggesting the specific protective role of morphine at low micromolar concentrations on tumor angiogenesis. Using in vivo Matrigel angiogenesis assay, we found that morphine stimulated in vivo angiogenesis under H2 O2 -induced pathological condition. The opioid receptor antagonist, naloxone, did not inhibit the protective activity of morphine in in vivo angiogenesis, indicating that the effect was less likely to be mediated by the typical opioid receptors. Mechanism analysis indicated that morphine alleviated serum deprivation and H2 O2 -induced angiogenesis inhibition via reducing oxidative stress and damage, and activating Akt/mTOR/eIF4E signaling. We demonstrate the protective role of morphine on tumor angiogenesis under pathological conditions. Our work suggests that clinical use of morphine may be harmful in patients with angiogenesis-dependent cancers.

19.
Brain Behav ; : e01423, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31617335

RESUMO

BACKGROUND: The breakthrough discovery has been made that a single dose of ketamine, an N-methyl-D-aspartate receptor antagonist, achieves rapid and sustained (~7 days) antidepressant activity in patients with major depressive disorder (MDD). This discovery has ushered in an exciting era of research and brought new hope for patients with MDD. However, the mechanisms underlying the specific antidepressant actions of ketamine in humans remain to be elucidated. OBJECTIVES: This study protocol was designed to test the main hypothesis that ketamine could rapidly reverse depression- and stress-associated synaptic loss and deficits in resting-state functional connectivity and that this action could be affected by circadian rhythm, in patients with treatment-resistant depression. METHODS/STUDY DESIGN: In this clinical study, adults (aged 18-65 years) with treatment-resistant depression will be randomized to intravenous administration of placebo (control group) or ketamine (0.5 mg/kg body weight) at 11 a.m. (daytime group), or 6 p.m. (nighttime group) for 24 weeks. The primary outcome will be the change from baseline to 24 weeks in the total Montgomery-Asberg Depression Rating Scale score. Brain imaging, sleep, and genetic studies, including functional magnetic resonance imaging, positron emission tomography, polysomnography, and genetic analyses, will be performed to examine whether and how ketamine can rapidly reverse deficits in synaptic function and to identify objective markers for the assessment of ketamine infusion therapy for treatment-resistant depression. CONCLUSIONS: This clinical study protocol is the first, to our knowledge, to describe the prospective testing of the hypothesis that daytime and nighttime administrations of ketamine would have different antidepressant effects. The brain imaging, sleep, and genetic findings from patients with treatment-resistant depression are expected to shed new light on the mechanisms of ketamine and its interaction with target sites in the brain, which can be used for objective evaluation of the efficacy of ketamine.

20.
Cytogenet Genome Res ; 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31630146

RESUMO

Klinefelter syndrome (KS) is one of the most common congenital disorders of male infertility. Given its high heterogeneity in clinical and genetic presentation, the relationship between transcriptome, clinical phenotype, and associated co-morbidities seen in KS has not been fully clarified. Here, we report a 47,XXY Chinese male with infertility and analyzed the differences in gene expression patterns of peripheral blood mononuclear cells (PBMCs) with regard to a Chinese male and a female control with normal karyotype by single-cell sequencing. A total of 24,439 cells were analyzed and divided into 5 immune cell types (including B cells, T cells, macrophage cells, dendritic cells, and natural killer cells) according to marker genes. Using unsupervised dimensionality reduction and clustering algorithms, we identified molecularly distinct subpopulations of cells between the KS patient and both controls. Gene ontology enrichment analyses yielded terms associated with well-known comorbidities seen in KS as well as an affected immune system and type I diabetes mellitus. Based on our data, we identified several candidate genes which may be implicated in regulating the phenotype of KS. Overall, this analysis provides a comprehensive map of the cell types of PBMCs in a KS patient at the single-cell level, which will contribute to the prevention of comorbidity and improvement of the life quality of KS patients.

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