Objective To investigate the influence of left heart function in obstructive sleep apnea by CIH, and explore left heart function before and after CPAP. Methods 75 OSA were divided into two groups. Blood pressures of 40 patients were coincident with diagnostic standard of hypertension and 35 patients did not have hypertension. The control group included 30 healthy adults. The blood pressures before and after sleep, left ventricular ejection fraction(LVEF) ,shortening fraction(FS) , E, A and E/A were compared with those of normal control subjects. BP, LVEF and E/A after CPAP were also analyzed. Results Multiple parameters including LVEF[ ( 56.40 ±9.74)% ] , FS[ (33. 80 ±6.16)% ] and E/A (0. 87 ±0.17) , were impaired in OSA patients relative to the control subjects ( P <0. 05 orP <0.01). E/A was significantly decreased in obstructive sleep apnea unallied hypertension than that in normal control subjects. E/A was conspicuously decreased in obstructive sleep apnea patients associated hypertension comparing with that in obstructive sleep apnea unallied hypertension. After CPAP for 6 months, in these obstructive sleep apnea associated hypertension patients, LVEF [(59.70 ±11. 1)%] was increased than that before treatment[ (56. 40 ± 9.74)% ] ( P <0.05), and E/A (1.16 ± 0. 25 ) was higher than that before treatment (0. 87 ±0. 17) ( P <0.01). Conclusion CIH may affect left heart structure and function. These changes were aggravated with hypertension. CPAP treatment had important effects in the treatment of cardiovascular function, and it could improve the life quality.

Glucagon-like peptide-1 (GLP-1) receptors belong to the class B of G protein coupled-receptors and are expressed in pancreas,lungs,GI tract,kidneys,heart and the central nervous system.During episodes of hyperglycemia activation of GLP-1 receptors located on pancreas islet β-cells facilitates insulin release and increases insulin sensitivity to regulate blood sugar.In the central nervous system,activation of GLP-1 receptors produces neuroprotection and analgesia.In this mini-review,we have summarized our recent work:1) identification of microglial GLP-1 receptor/IL-10/ β-endorphin pathway in the spinal cord;2) discovery of the mechanisms of activation of GLP-1 receptors by which analgesic Lamiophlomis rotata and its effective ingredients iridoid glycosides produce antinociception.Our work highlight that spinal microglial GLP-1 receptor might be a human-demonstrated target for the treatment of chronic pain.

This study was purposed to investigate the significance of genomic comprehensive analysis information in diagnosis, therapy and prognosis of MDS through comprehensive analysis of a patient with MDS. The bone marrow specimen from a patient with MDS was comprehensively analyzed by a combination of genomic approaches, including chromosomal karyotyping, fluorescence in situ hybridization (FISH), genome scanning using Affymetrix high density SNP microarray platform, and next-generation sequencing (NGS) analysis using IonTorrent Cancer Gene Panel. The results showed that an abnormal clone was identified by standard G-banding karyotyping and confirmed by FISH, which contains interstitial deletions on the long arms of chromosome 5 and 11 respectively. SNP-array analysis defined the two genomic deletions to be an 81 Mb interstitial deletion on the long are of chromosome 5 and a 24 Mb interstitial deletion on the long are of chromosome 11. Meanwhile, SNP-array detected two genomic regions with acquired loss of heterozygosity (LOH), a 58 Mb region on the short arm of chromosome 1 and a 39 Mb region on the distal end of the long arm of chromosome 14. In addition, SNP-array identified multiple genomic regions with long stretch of absence of heterozygosity, representing about 5.3% of autosomal genome, indication a certain level of consanguinity between the parents. No clinically significant gene mutation was identified using IonTorrent 50 Cancer Gene Panel while 6 polymorphisms within 6 genes were observed including APC, FGFR3, KDR, KIT, PDGFRA, and RET. It is concluded that the combined genomic techniques are necessary to provide a full picture of the patient's genomic alterations. Some of the acquired genomic findings are important for the diagnosis and therapy selection. Germline genomic alterations warrant genetic counseling and are useful for further studies to explore the mechanisms leading to tumorigenesis of MDS patient.
Female ; Genome, Human ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Karyotyping ; Middle Aged ; Myelodysplastic Syndromes ; diagnosis ; genetics ; therapy ; Oligonucleotide Array Sequence Analysis ; methods

Opioid drugs are the first line of defense in severe pain but the adverse effects associated with opioids are considered as a serious issue worldwide. Acupuncture/electroacupuncture is a type of Chinese medicine therapy which is an effective analgesic therapy, well documented in animals and human studies. Electroacupuncture stimulation could release endogenous opioid peptides causing analgesia in a variety of pain models. It can be used as an alternative therapy to control the opioid crisis.

Glutamate is the major fast excitatory transmitter in the central nervous system. While normal synaptic transmission is mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors, N-methyl-D-aspartate (NMDA) receptors are thought to selectively contribute to plasticity. Genetically enhancing NMDA receptor functions enhances animal behavior in normal physiological learning and enhances their sensitivity in the case of tissue injury. One major mechanism for NMDA receptors is synaptic long-term potentiation (LTP). Here we present evidence that NMDA receptors not only contribute to normal synaptic responses induced by stimulation of local layer V or white matters, but also contribute to generation of action potentials induced by a depolarizing step applied to the soma. Calcium-calmodulin sensitive adenylyl cyclase 1 and cAMP signal pathways likely mediate these effects. Considering the importance of cingulate neurons in nociception and pain, our results provide a new mechanism for NMDA receptor contributing to neuronal synaptic transmission, spiking properties in forebrains, and possible forebrain-related behavioral nociceptive responses and pain.
Action Potentials ; Adenylyl Cyclases ; metabolism ; Animals ; Cyclic AMP ; metabolism ; Mice ; Prosencephalon ; physiology ; Receptors, N-Methyl-D-Aspartate ; physiology

Despite a large number of rear-end collisions on the road and a high frequency of whiplash injuries reported, the mechanism of whiplash injuries is not completely understood. One of the reasons is that the injury is not necessarily accompanied by obvious tissue damage detectable by X-ray or MRI. An extensive series of biomechanics studies, including injury epidemiology, neck kinematics, facet capsule ligament mechanics, injury mechanisms and injury criteria, were undertaken to help elucidate these whiplash injury mechanisms and gain a better understanding of cervical facet pain. These studies provide the following evidences to help explain the mechanisms of the whiplash injury: (1) Whiplash injuries are generally considered to be a soft tissue injury of the neck with symptoms such as neck pain and stiffness, shoulder weakness, dizziness, headache and memory loss, etc. (2) Based on kinematical studies on the cadaver and volunteers, there are three distinct periods that have the potential to cause injury to the neck. In the first stage, flexural deformation of the neck is observed along with a loss of cervical lordosis; in the second stage, the cervical spine assumes an S-shaped curve as the lower vertebrae begin to extend and gradually cause the upper vertebrae to extend; during the final stage, the entire neck is extended due to the extension moments at both ends. (3) The in vivo environment afforded by rodent models of injury offers particular utility for linking mechanics, nociception and behavioral outcomes. Experimental findings have examined strains across the facet joint as a mechanism of whiplash injury, and suggested a capsular strain threshold or a vertebral distraction threshold for whiplash-related injury, potentially producing neck pain. (4) Injuries to the facet capsule region of the neck are a major source of post-crash pain. There are several hypotheses on how whiplash-associated injury may occur and three of these injuries are related to strains within the facet capsule connected with events early in the impact. (5) There are several possible injury criteria to correlate with the duration of symptoms during reconstructions of actual crashes. These results form the biomechanical basis for a hypothesis that the facet joint capsule is a source of neck pain and that the pain may arise from large strains in the joint capsule that will cause pain receptors to fire.
Biomechanical Phenomena ; Cervical Vertebrae ; physiopathology ; Female ; Humans ; Male ; Neck ; physiopathology ; Shear Strength ; Whiplash Injuries ; classification ; diagnosis ; physiopathology

Animals ; Atherosclerosis ; pathology ; Cell Adhesion ; Cell Division ; Endothelial Cells ; pathology ; Humans ; Models, Biological ; Myocytes, Smooth Muscle ; pathology ; Stem Cells ; pathology

【Objective】To unmask the mechanisms underlying the suppression of infant neuropathic pain after peripheral nerve injury.【Methods】Rats were subjected to spared nerve injury(SNI)at postnatal 10 d or 33 d. Mechanical paw withdrawal thresholds as well as spinal interleukin-10(IL-10)and the β-endorphin precursor gene proopiomelanocortin(POMC)mRNA expression were detected 7 d after surgery. The IL-10 or β-endorphin neutralizing antibody was intrathecally injected for 3 d(the 7 th-9 th day after surgery)and mechanical paw withdrawal thresholds were tested 1 h after each injection. Spinal IL-10 mRNA and POMC mRNA were detected by RT-qPCR.【Results】In contrast to adult rats,infant rats subjected to SNI displayed no mechanical allodynia but an increase in spinal cord IL-10 and POMC mRNA expression. Intrathecal administration of the IL-10 antibody and β-endorphin antibody evoked neuropathic painlike behaviors in infant rats. SNI-induced POMC mRNA increase was blocked by the pretreatment with intrathecal the IL-10 antibody,while the increased IL-10 mRNA expression was not affected by the β-endorphin antibody pretreatment.【Conclusions】The suppression of neuropathic pain in infant rats may be mediated by activation of spinal IL-10/β-endorphin pathway.

The accurate annotation of transcription start sites(TSSs)and their usage are critical for the mechanistic understanding of gene regulation in different biological contexts.To fulfill this,specific high-throughput experimental technologies have been developed to capture TSSs in a genome-wide manner,and various computational tools have also been developed for in silico pre-diction of TSSs solely based on genomic sequences.Most of these computational tools cast the problem as a binary classification task on a balanced dataset,thus resulting in drastic false positive predictions when applied on the genome scale.Here,we present DeeReCT-TSS,a deep learning-based method that is capable of identifying TSSs across the whole genome based on both DNA sequence and conventional RNA sequencing data.We show that by effectively incorporating these two sources of information,DeeReCT-TSS significantly outperforms other solely sequence-based methods on the precise annotation of TSSs used in different cell types.Furthermore,we develop a meta-learning-based extension for simultaneous TSS annotations on 10 cell types,which enables the identification of cell type-specific TSSs.Finally,we demonstrate the high precision of DeeReCT-TSS on two independent datasets by correlating our predicted TSSs with experimentally defined TSS chromatin states.The source code for DeeReCT-TSS is available at https://github.-com/JoshuaChou2018/DeeReCT-TSS_release and https://ngdc.cncb.ac.cn/biocode/tools/BT007316.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.