Intrinsic Molecular Proton Sensitivity Underlies GPR4 Effects on Retrotrapezoid Nucleus Neuronal Activation and CO-Stimulated Breathing.

An interoceptive homeostatic reflex monitors levels of CO/H to maintain blood gas homeostasis and rapidly regulate tissue acid-base balance by driving lung ventilation and CO excretion-this CO-evoked increase in respiration is the hypercapnic ventilatory reflex (HCVR). Retrotrapezoid nucleus (RTN) neurons provide crucial excitatory drive to downstream respiratory rhythm/pattern-generating circuits, and their activity is directly modulated by changes in CO/H RTN neurons express GPR4 and TASK-2, global deletion of which abrogates CO/H activation of RTN neurons and the HCVR. It has not been determined if the intrinsic pH sensitivity of these proton detectors is required for these effects.

Heterozygous expression of a gain-of-function variant has differential effects on SST- and PV-expressing cortical GABAergic neurons.

More than twenty recurrent missense gain-of-function (GOF) mutations have been identified in the sodium-activated potassium (K) channel gene in patients with severe developmental and epileptic encephalopathies (DEEs), most of which are resistant to current therapies. Defining the neuron types most vulnerable to KCNT1 GOF will advance our understanding of disease mechanisms and provide refined targets for precision therapy efforts. Here, we assessed the effects of heterozygous expression of a GOF variant (Y777H) on K currents and neuronal physiology among cortical glutamatergic and GABAergic neurons in mice, including those expressing vasoactive intestinal polypeptide (VIP), somatostatin (SST), and parvalbumin (PV), to identify and model the pathogenic mechanisms of autosomal dominant GOF variants in DEEs.

Liver-Selective Imidazolopyrazine Mitochondrial Uncoupler SHD865 Reverses Adiposity and Glucose Intolerance in Mice.

Excess body fat is a risk factor for metabolic diseases and is a leading preventable cause of morbidity and mortality worldwide. There is a strong need to find new treatments that decrease the burden of obesity and lower the risk of obesity-related comorbidities, including cardiovascular disease and type 2 diabetes. Pharmacologic mitochondrial uncouplers represent a potential treatment for obesity through their ability to increase nutrient oxidation.

The astrocytic Na -HCO cotransporter, NBCe1, is dispensable for respiratory chemosensitivity.

The interoceptive homeostatic mechanism that controls breathing, blood gases and acid-base balance in response to changes in CO /H is exquisitely sensitive, with convergent roles proposed for chemosensory brainstem neurons in the retrotrapezoid nucleus (RTN) and their supporting glial cells. For astrocytes, a central role for NBCe1, a Na -HCO cotransporter encoded by Slc4a4, has been envisaged in multiple mechanistic models (i.e.

[Development of Nasal Continuum Minimally Invasive Surgical Robot System].

In order to improve the operation difficulties in the narrow space of the nasal maxillary sinus, the nasal continuum minimally invasive surgical robot system is designed. The ball-and-socket joints and NiTiNol tubes are used as the main body of the continuum structure to improve the degree of freedom. The hardware systems and software systems are designed.

Development and experiments of a continuum robotic system for transoral laryngeal surgery.

Purpose: Currently, self-retaining laryngoscopic surgery is not suitable for some patients, and there are dead zones relating to surgical field exposure and operation. The quality of the surgery can also be affected by the long periods of time required to complete it. Teleoperated continuum robots with flexible joints are expected to solve these issues.

TRPM4 Contributes to Subthreshold Membrane Potential Oscillations in Multiple Mouse Pacemaker Neurons.

Select neuronal populations display steady rhythmic neuronal firing that provides tonic excitation to drive downstream networks and behaviors. In noradrenergic neurons of the locus coeruleus (LC), circadian neurons of the suprachiasmatic nucleus (SCN), and CO/H-activated neurons of the brainstem retrotrapezoid nucleus (RTN), large subthreshold membrane potential oscillations contribute to the pacemaker-like action potential discharge. The oscillations and firing in LC and SCN involve contributions from leak sodium (NALCN) and L-type calcium channels while recent work from RTN suggested an additional pivotal role for a secondary calcium-activated and voltage-gated cationic current sensitive to TRPM4 channel blockers.

Development and validation of a two-segment continuum robot for maxillary sinus surgery.

Background: Existing rigid instruments have difficulties in backward inspection and operation. Moreover, the pathway to the maxillary sinus is curved and narrow, resulting in complex and repetitive manual operations. There is a necessity to develop a retro-flexing robot and achieve path-following motion.

TRPM4 mediates a subthreshold membrane potential oscillation in respiratory chemoreceptor neurons that drives pacemaker firing and breathing.

Brainstem networks that control regular tidal breathing depend on excitatory drive, including from tonically active, CO/H-sensitive neurons of the retrotrapezoid nucleus (RTN). Here, we examine intrinsic ionic mechanisms underlying the metronomic firing activity characteristic of RTN neurons. In mouse brainstem slices, large-amplitude membrane potential oscillations are evident in synaptically isolated RTN neurons after blocking action potentials.

A brainstem peptide system activated at birth protects postnatal breathing.

Among numerous challenges encountered at the beginning of extrauterine life, the most celebrated is the first breath that initiates a life-sustaining motor activity. The neural systems that regulate breathing are fragile early in development, and it is not clear how they adjust to support breathing at birth. Here we identify a neuropeptide system that becomes activated immediately after birth and supports breathing.

Clinical characteristics and prognosis of community-acquired pneumonia in autoimmune disease-induced immunocompromised host: A retrospective observational study.

Background: Community-acquired pneumonia (CAP) in autoimmune diseases (AID)-induced immunocompromised host (ICH) had a high incidence and poor prognosis. However, only a few studies had determined the clinical characteristics of these patients. Our study was to explore the characteristics and predictors of mortality in CAP patients accompanied with AID-induced ICH.

Effects of Micronucleus Frequencies and Mitochondrial DNA Copy Numbers among Benzene-Exposed Workers in China.

To provide a more comprehensive understanding of genotoxic effects from benzene exposure, its effects on induction of mitochondrial DNA copy number (MtDNAcn) and of micronucleus (MN) were investigated using peripheral blood from workers in China. Changes in mtDNAcn and MN were determined using quantitative real-time polymerase chain reaction (PCR) and cytokinesis-block micronucleus assays (CBMN), respectively, in 58 control and 174 benzene-exposed workers in Shanghai, China. Among the exposed workers, relative mtDNAcn increased and then decreased with increasing doses of benzene exposure.

Clinical characteristics, risk factors, immune status and prognosis of secondary infection of sepsis: a retrospective observational study.

Background: Secondary infection has a higher incidence in septic patients and affects clinical outcomes. This study aims to investigate the clinical characteristics, risk factors, immune status and prognosis of secondary infection of sepsis.

Methods: A four-year retrospective study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between January, 2014 and January, 2018.

[Establishment of pharyngeal 3-dimensional finite element model of patients with isolated cleft palate].

Purpose: The aim of this study was to provide basis for future design and selection of cleft palate surgery through establishing finite element model of pharyngeal cavity which was suitable for biomechanical analysis.

Methods: One patient with isolated cleft palate and 1 normal child underwent multilayer head CT examination. The scanned data of pharyngeal cavity were imported into Mimics software for a 3-D geometric model reconstruction.

Gpr174-deficient regulatory T cells decrease cytokine storm in septic mice.

G protein-coupled receptor 174 (GPR174) is mainly expressed in thymus, spleen, lymph nodes, and leukocytes, and genetic variation in GPR174 is associated with susceptibility to autoimmune diseases, indicating that GPR174 is involved in the immune response. However, the function of GPR174 in regulating inflammatory responses against bacterial infection in sepsis remains unclear. In this study, we investigated the role of GPR174 in regulating suppressive function of regulatory T cells (Treg cells) and the underlying mechanism of Gpr174-deficient Treg cells in controlling cytokine storm of sepsis.

Clinical outcomes of otitis media with effusion following palatoplasty in patients with incomplete cleft palate.

Background: Diagnosis and treatment strategies for CP with OME and the timing of ear tube insertion remain controversial.

Objectives: To analyze the clinical outcomes of otitis media with effusion in children with incomplete cleft palate after palatoplasty prospectively.

Methods: A total of 30 children (10 months-2 years old) with incomplete CP were enrolled in this study and received at least 6 months of follow-up evaluations after palatoplasty.

Clinical characteristics and prognosis of serous body cavity effusions in patients with sepsis: a retrospective observational study.

Background: Cavity effusion is common in patients with infectious diseases. However, the incidence rate and characteristics of serous cavity effusions (SCE) in septic patients are not clear to date. The objective of this study was to investigate the incidence and characteristics of SCE in septic patients and to explore the correlations between the bloody effusions and the illness severity/prognosis in septic patients.

The Role of Ca and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO Chemosensitivity Response of Rats.

The cellular mechanisms by which LC neurons respond to hypercapnia are usually attributed to an "accelerator" whereby hypercapnic acidosis causes an inhibition of K channels or activation of Na and Ca channels to depolarize CO-sensitive neurons. Nevertheless, it is still unknown if this "accelerator" mechanism could be controlled by a brake phenomenon. Whole-cell patch clamping, fluorescence imaging microscopy and plethysmography were used to study the chemosensitive response of the LC neurons.

Protein docking refinement by convex underestimation in the low-dimensional subspace of encounter complexes.

We propose a novel stochastic global optimization algorithm with applications to the refinement stage of protein docking prediction methods. Our approach can process conformations sampled from multiple clusters, each roughly corresponding to a different binding energy funnel. These clusters are obtained using a density-based clustering method.

Distortion product otoacoustic emission together with tympanometry for assessing otitis media with effusion in children.

Objective: To investigate the diagnostic value of distortion product otoacoustic emission (DPOAE) together with tympanometry in assessing otitis media with effusion in children.

Methods: Three hundred and thirty-nine patients, who were diagnosed with obstructive sleep apnea-hypopnea syndrome (OSAHS) and prepared to undergo adenotonsillectomy and had a unilateral or bilateral type 'B' or 'C' tympanogram were enrolled in this study. Patients were divided into the following four groups: Group 1, type 'B' tympanogram with positive DPOAE; Group 2, type 'B' tympanogram with negative DPOAE; Group 3, type 'C' tympanogram with positive DPOAE and Group 4, type 'C' tympanogram with negative DPOAE.

Restoration of orbicularis oculi muscle function in rabbits with peripheral facial paralysis via an implantable artificial facial nerve system.

The purpose of the present study was to restore orbicularis oculi muscle function using the implantable artificial facial nerve system (IAFNS). The part of the IAFNS was implanted into 12 rabbits that were facially paralyzed on the right side of the face to restore the function of the orbicularis oculi muscle, which was indicated by closure of the paralyzed eye when the contralateral side was closed. Wireless communication links were established between the part (the processing chip and microelectrode) and the external part (System Controller program) of the system, which were used to set the working parameters and indicate the working state of the processing chip and microelectrode implanted in the body.

Rigid laryngoscope manifestations of 61 cases of modern laryngeal tuberculosis.

The present study investigated the clinical characteristics and diagnosis of modern laryngeal tuberculosis (TB). A total of 61 patients that were pathologically diagnosed with laryngeal TB between 1998 and 2012 were retrospectively analyzed using laryngoscopy methods. The primary symptoms of laryngeal TB observed in the present study include hoarseness and sore throat, and in the majority of cases, laryngeal TB was not associated with pulmonary TB (ratio 41/61, 67.

Ventilatory and chemoreceptor responses to hypercapnia in neonatal rats chronically exposed to moderate hyperoxia.

Rats reared in hyperoxia hypoventilate in normoxia and exhibit progressive blunting of the hypoxic ventilatory response, changes which are at least partially attributed to abnormal carotid body development. Since the carotid body also responds to changes in arterial CO/pH, we tested the hypothesis that developmental hyperoxia would attenuate the hypercapnic ventilatory response (HCVR) of neonatal rats by blunting peripheral and/or central chemoreceptor responses to hypercapnic challenges. Rats were reared in 21% O (Control) or 60% O (Hyperoxia) until studied at 4, 6-7, or 13-14days of age.