Effect of Xiaoyao San on the brain-gut axis in rats after chronic immobilization stress

Objective:To investigate the effect of Xiaoyao San on the brain-gut axis in rats exposed to chronic immobilization stress (ClS).Methods:Rats were divided into control,model,and treatment groups.The rats belonging to the model and treatment groups were subjected to CIS for 21 consecutive days,during which they were administered Xiaoyao San decoction [3.854 g/(kg· d)] or vehicle by gavage,and their body weight gain,food intake and water intake were monitored.The rats were subsequently subjected to the open field test (OFT) and D-XyloSe absorption test,and the expression levels of neuropeptides secreted by the hypothalamus and stomach were determined by enzyme-linked immunosorbent assay (ELISA),radioimmune analysis,or real-time fluorescence quantitative polymerase chain reaction.Gastric mucosal morphology was also assessed.Results:The model rats exhibited complex brain-gut axis abnormalities following exposure to CIS,abnormalities signified by decreases in food intake,reductions in digestive absorption,decreases in body weight,decreases in the total distances traveled and increases in the time in the central zone during the OFT,gastric mucosal lesion development and decreases in gastrointestinal hormone secretion.These changes were reversed after treatment with Xiaoyao San,which also regulated the secretion of both peripheral (serum and stomach) and central (hypothalamus) brain-gut peptides.Specifically,the levels of neuropeptide Y (NPY) and neuropeptide Y receptor Y5,which are secreted by the hypothalamus and promote digestive function,were increased in the Xiaoyao San-treated group compared with the model group.Furthermore,the levels of pro-opiomelanocortin (POMC) and its receptor,melanocortin-4 receptor (MC4R),which are secreted by the hypothalamus and inhibit digestive function,were significantly decreased in the treatment group compared with the model group.However,the levels of ghrelin (GHRL),gastrin (GAS) and motilin (MTL),which are secreted by the stomach,were significantly increased in the serum and stomach of the treatment group compared with the serum and stomach of the model group following Xiaoyao San treatment (P <.05 vs.the model group).Conclusion:Xiaoyao San attenuates CIS-induced gastrointestinal dysregulation by regulating the peptides secreted by both the hypothalamus and the gastrointestinal tract (GIT),suggesting that its effects are associated with the brain-gut axis.

Research Progress of Male Osteoporotic Fracture

The diagnosis and recognition of male osteoporosis is still insufficient.The male patients with low-energy fracture were less evaluated and treated for osteoporosis.The risk of osteoporotic fracture in elderly men may be between 13%and 25%.With the extension of men’s life,the risk of fracture increases,which makes the management of men with fracture risk challenging.A consensus is emerging on targeted treatment guidelines for male osteoporosis,especially for elderly patients with high fracture risk.This paper aims to seek evidence through literature review,and put forward the most effective clinical strategies and schemes for the diagnosis and treatment of senile osteoporosis,so as to provide some theoretical guidance for clinical practice.

A comprehensive study on the heat transfer characteristics of windward bend lattice frame structure

The windward bend lattice frame structure(WB structure)is characterized by a high heat transfer coefficient and low friction factor.The WB structure can be applied for ther-mal protection system,protecting outer walls of afterburner and nozzles from being damaged by the heating load of hot gas,for air cooling system of the power battery module,dissipating the heat generated during its charging and discharging.In this paper,the heat transfer charac-teristics of the windward bend lattice frame structure have been comprehensively studied.A systematic 3D numerical simulation has been conducted to investigate the effects of the struc-tural parameters of the WB structure,including the pitches in both flow direction and transverse direction,the diameter and the inclination angle of windward bend ligament,on its flow resis-tance and heat transfer enhancement,which has been evaluated by comparing its Nusselt num-ber under an equal pumping power.Furthermore,the contribution of an important parameter,i.e.,the ratio of the interstitial heat transfer rate to the end-wall heat transfer rate(RQ),to the overall heat transfer rate has been fully discussed.As a result,the case of 6 units in the longi-tudinal direction and 2.5 units in the transverse direction,i.e.(nx Z 6,nz Z 2.5)exhibits the best performance in the light of the value of the Nusselt number. Moreover, the structure with aratio of RQ ranges in 4.5e5.0 achieves a better heat transfer performance. Finally, two colorcontour graphs showing an optimal range of Nusselt number coordinated by unit numbers(nx, nz) for pumping powers of 2500 and 3000 have been presented. The graphs correctly reflectthe variation of Nusselt numbers of structures with different nx and nz, and the conclusionsremain consistent with the discussion in sections 4.2 and 4.3, instructing the reasonable selec-tion of structural parameters of a thermal protection system embedded with WB structure.

CRISPR/Cas9-mediated pou4f3 knockout induces defects in the development of the zebrafish inner ear

Objective:The zebrafish is an excellent model for studying gene function in auditory system development.Pou4f3 plays an important role in mouse hair cell formation.Here,we constructed apou4f3-knockoutTg(Brn3c:GFP)zebrafish to provide an efficient fluorescence-visualized model for studying the molecular mechanisms of ear development.Methods:Cas9/single guide RNAs targeting exon 2 ofpou4f3 were designed and injected into one-cell stage zebrafish embryos(G0 generation).The G0 generation were crossed withTg(Brn3c:GFP)zebrafish to obtainpou4f3-mutantTg(Brn3c:GFP)zebrafish.The targeting efficiency was detected by polymerase chain reaction amplification and Sanger sequencing.Zebrafish hair cells were observed by laser scanning confocal microscopyin vivo.The morphology of the otoliths and semicircular canals were analyzed.All animal experiments were approved by the Animal Care and Use Committee of Shandong Provincial Hospital,Cheeloo College of Medicine,Shandong University(approval No.2016-KY-040)on March 3,2016.Results:Thepou4f3-mutantTg(Brn3c:GFP)zebrafish line was successfully established.Fluorescence observation suggested that hair cell development was delayed inpou4f3-knockout zebrafish.Knockout ofpou4f3 also induced defects in the otoliths and semicircular canals and impaired ear function in zebrafish.Conclusion:A CRISPR/Cas9-mediatedpou4f3 mutantTg(Brn3c:GFP)zebrafish model was established for the first time to demonstrate the essential role ofpou4f3 in zebrafish ear development.Our study provides a highly efficient method for the establishment of a visualized model of gene knockout zebrafish and has the potential to allow high-throughput drug screening to explore therapeutics for related diseases.