Histaminergic neurons solely originate from the tuberomammillary nucleus (TMN) in the posterior hypothalamus and send widespread projections to the whole brain. Experiments in rats show that histamine release in the central nervous system is positively correlated with wakefulness and the histamine released is 4 times higher during wake episodes than during sleep episodes. Endogeneous prostaglandin E2 and orexin activate histaminergic neurons in the TMN to release histamine and promote wakefulness. Conversely, prostaglandin D2 and adenosine inhibit histamine release by increasing GABA release in the TMN to induce sleep. This paper reviews the effects and mechanisms of action of the histaminergic system on sleep-wake regulation, and briefly discusses the possibility of developing novel sedative-hypnotics and wakefulness-promoting drugs related to the histaminergic system.

Frailty,a multisystem syndrome in which the decrease of physiological reserve leads to the decrease of anti-stress ability,is highly prevalent among the elderly and is closely associated with ad-verse outcomes in surgical patients.Therefore,it is necessary for anesthesiologists to evaluate frailty during perioperative period.However,how to quantify frailty quickly,accurately,and objectively remains a chal-lenge.As the importance of muscle changes in the pathophysiological changes of frailty has been gradually revealed,bedside muscle ultrasound has attracted widespread attention in the assessment of weakness.This article introduces the parameters of bedside muscle ultrasoundand,the selection of parameters,and muscles for the assessment of frailty in elderly patients,which is expected to provide reference for anesthesiologists in assessing frailty during the perioperative period.

Objective:To evaluate the role of orphan nuclear receptor Nur77 in tunicamycin(TM)-induced injury to hippocampal neurons and the relationship with endoplasmic reticulum stress in mice.Methods:Mouse HT22 cells were divided into 4 groups ( n=10 each) using a random number table method: control group (C group), Nur77 specific agonist Csn-B group (Csn-B group), endoplasmic reticulum stress inducer TM group (TM group), and TM+ Csn-B group. Cells in C group were cultured for 24 h under normal condition. In Csn-B group, Csn-B at a final concentration of 10 μg/ml was added to the culture medium, and the cells were incubated for 24 h. In TM group, TM at a final concentration of 200 ng/ml was added to the culture medium and the cells were incubated for 24 h to induce cell endoplasmic reticulum stress injury. Cells in TM+ Csn-B group were pretreated with Csn-B at a final concentration of 10 μg/ml for 15 min, then TM at a final concentration of 200 ng/ml was added, and the cells were co-incubated for 24 h. The cell viability was examined by CCK-8 assay kit after treatment in each group. The expression of endoplasmic reticulum stress-related protein CCAAT/enhancer-binding protein homologous protein (CHOP), glucose regulated protein 78 (GRP78)and apoptosis-associated protein Bcl-2, Bax, caspase-3 and cleaved-caspase-3 was detected by Western blot. Results:Compared with C group, the cell viability was significantly decreased, and the expression of CHOP, GRP78, Bax and cleaved-caspase-3 was up-regulated, and the expression of Bcl-2 and caspase-3 was down-regulated in TM group ( P<0.05 or 0.01). Compared with TM group, the cell viability was significantly increased, the expression of CHOP, GRP78, Bax and cleaved-caspase-3 was down-regulated, and the expression of Bcl-2 and caspase-3 was up-regulated in TM+ Csn-B group ( P<0.05 or 0.01). Conclusions:Orphan nuclear receptor Nur77 is involved in TM-induced injury to hippocampal neurons, which is related to activation of the endoplasmic reticulum stress in mice.

Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier.Herein,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a pep-tide and a small molecular compound.In this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97-110 amino acids of apoptin(AP)(AA@G))was con-structed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle.As expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma cell.This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced com-bination therapy.

This article mainly elaborated the acupuncture and moxibustion treatment scheme of"eighteen needles for reproduction"based on Professor You Zhaoling's reproductive axis theory of"heart-kidney-Chong Ren-uterus".The"eighteen needles for reproduction"aims to regulate the disordered reproductive axis in gynecological reproductive diseases.It selects the acupoints on the main viscera and meridians of the reproductive axis as the main acupoints,and the acupoints regulating the qi and blood of the related viscera as the matching acupoints.Through specific manipulation,it can regulate the qi and blood,dredge the meridians,and treat the viscera,so as to nourish the essence and help pregnancy,and provide ideas and reference for the treatment of gynecological reproductive diseases with acupuncture and moxibustion.

Objective To explore the relationship between anxiety sensitivity and psychological stress before parachuting training among parachuting trainees and the mediating role of resilience between them.Methods Anxiety sensitivity index scale(version 3),resilience scale,psychological stress self-evaluation test and self-compiled general information questionnaire were employed for 258 parachuting trainees before training.Pearson correlation analysis was used to analyze the correlations among anxiety sensitivity,resilience and psychological stress.A multiple linear regression analysis was conducted with anxiety sensitivity and resilience as independent variables and psychological stress as dependent variable to explore the relationships among these 3 factors.The mediating effect of resilience on the relationship between anxiety sensitivity and psychological stress was examined using the Hayes Process macro program and bias corrected non-parametric percentile Bootstrap method.Results Before parachuting training,the prevalence of psychological stress among parachuting trainees was 5.0%(13/258).The correlations between anxiety sensitivity,resilience and psychological stress were significant(all P＜0.01).Anxiety sensitivity was positively associated with psychological stress among parachuting trainees(b=0.412,t=7.062,P＜0.01),while resilience was negatively associated with psychological stress(b=-0.187,t=-3.722,P＜0.01).Anxiety sensitivity and resilience were found to explain 31.4%of the total variance.Resilience partially mediated the effect of anxiety sensitivity on psychological stress,accounting for 20.48%of the total effect.Conclusion Parachuting trainees are at a relatively low stress level,with good psychological adaptation.Resilience plays a partial mediating role in the association between anxiety sensitivity and psychological stress.More attention should be paid to parachuting trainees with high anxiety sensitivity,enhancing their resilience,and reducing psychological stress before parachuting training.

One-compartment lumped-parameter models of respiratory mechanics, representing the airflow resistance of the tracheobronchial tree with a linear or nonlinear resistor, are not able to describe the mechanical property of airways in different generations. Therefore, based on the anatomic structure of tracheobronchial tree and the mechanical property of airways in each generation, this study classified the human airways into three segments: the upper airway segment, the collapsible airway segment, and the small airway segment. Finally, a nonlinear, multi-compartment lumped-parameter model of respiratory mechanics with three airway segments was established. With the respiratory muscle effort as driving pressure, the model was used to simulate the tidal breathing of healthy adults. The results were consistent with the physiological data and the previously published results, suggesting that this model could be used for pathophysiological research of respiratory system.

Mechanical ventilation is an importmant life-sustaining treatment for patients with acute respiratory distress syndrome. Its clinical outcomes depend on patients' characteristics of lung recruitment. Estimation of lung recruitment characteristics is valuable for the determination of ventilatory maneurvers and ventilator parameters. There is no easily-used, bedside method to assess lung recruitment characteristics. The present paper proposed a method to estimate lung recruitment characteristics from the static pressure-volume curve of lungs. The method was evaluated by comparing with published experimental data. Results of lung recruitment derived from the presented method were in high agreement with the published data, suggesting that the proposed method is capable to estimate lung recruitment characteristics. Since some advanced ventilators are capable to measure the static pressure-volume curve automatedly, the presented method is potential to be used at bedside, and it is helpful for clinicians to individualize ventilatory manuevers and the correpsonding ventilator parameters.
Humans ; Lung ; Positive-Pressure Respiration ; Respiration, Artificial ; Respiratory Distress Syndrome ; Ventilators, Mechanical

Animals ; Cell Respiration ; Electron Transport Complex III ; metabolism ; Humans ; Iron-Sulfur Proteins ; chemistry ; metabolism ; Mitochondria ; metabolism ; Peptide Fragments ; chemistry ; metabolism ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Subunits ; chemistry

Respirasome, as a vital part of the oxidative phosphorylation system, undertakes the task of transferring electrons from the electron donors to oxygen and produces a proton concentration gradient across the inner mitochondrial membrane through the coupled translocation of protons. Copious research has been carried out on this lynchpin of respiration. From the discovery of individual respiratory complexes to the report of the high-resolution structure of mammalian respiratory supercomplex IIIIIV, scientists have gradually uncovered the mysterious veil of the electron transport chain (ETC). With the discovery of the mammalian respiratory mega complex IIIIIV, a new perspective emerges in the research field of the ETC. Behind these advances glitters the light of the revolution in both theory and technology. Here, we give a short review about how scientists 'see' the structure and the mechanism of respirasome from the macroscopic scale to the atomic scale during the past decades.