Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

The looming stimulus-evoked flight response to approaching predators is a defensive behavior in most animals. However, how looming stimuli are detected in the retina and transmitted to the brain remains unclear. Here, we report that a group of GABAergic retinal ganglion cells (RGCs) projecting to the superior colliculus (SC) transmit looming signals from the retina to the brain, mediating the looming-evoked flight behavior by releasing GABA. GAD2-Cre and vGAT-Cre transgenic mice were used in combination with Cre-activated anterograde or retrograde tracer viruses to map the inputs to specific GABAergic RGC circuits. Optogenetic technology was used to assess the function of SC-projecting GABAergic RGCs (scpgRGCs) in the SC. FDIO-DTA (Flp-dependent Double-Floxed Inverted Open reading frame-Diphtheria toxin) combined with the FLP (Florfenicol, Lincomycin & Prednisolone) approach was used to ablate or silence scpgRGCs. In the mouse retina, GABAergic RGCs project to different brain areas, including the SC. ScpgRGCs are monosynaptically connected to parvalbumin-positive SC neurons known to be required for the looming-evoked flight response. Optogenetic activation of scpgRGCs triggers GABA-mediated inhibition in SC neurons. Ablation or silencing of scpgRGCs compromises looming-evoked flight responses without affecting image-forming functions. Our study reveals that scpgRGCs control the looming-evoked flight response by regulating SC neurons via GABA, providing novel insight into the regulation of innate defensive behaviors.
Animals ; Superior Colliculi/physiology* ; Retinal Ganglion Cells/physiology* ; GABAergic Neurons/physiology* ; Mice, Transgenic ; Mice ; Optogenetics ; Visual Pathways/physiology* ; Mice, Inbred C57BL ; Photic Stimulation/methods* ; gamma-Aminobutyric Acid/metabolism* ; Male

【Objective】 Tostudy the effect of ABO blood group on the FⅧ∶C and Fib content in human plasma, so as to provide the oretical guidance for the quality control of fresh plasma products and the establishment of relevant quality standards. 【Methods】 Samples determined included fresh plasma collected and fresh plasma separated manually. The FⅧ∶C and Fib content were determined by coagulation method. The exon6 of ABO gene was amplified and sequenced to determine the genotype. 【Results】 The FⅧ∶C in fresh plasma collected was (147.421±45.773)%, and that in fresh plasma separated manually was (119.083±35.130)%, showing significant differences(P<0.05). The Fib content in fresh plasma collected was (2.252±0.381)g/L, and that in fresh plasma separated manually was (2.324±0.470)g/L, with no significant differences observed (P>0.05). The FⅧ∶C in non-O type (A, B, AB type) fresh plasma collected and fresh plasma separated manually were (167.048±40.862)% and (129.251±33.503)%, respectively, significantly higher than that in O type fresh plasma collected and fresh plasma separated manually as(121.386±38.632)% and (91.589±22.328)%, respectively. The Fib contents in non-O type fresh plasma collected and fresh plasma separated manually were (2.242±0.385)g/L and (2.329±0.472)g/L, respectively. The Fib contents in O type fresh plasma collected and fresh plasma separated manually were (2.287±0.370)g/L and (2.307±0.462)g/L, respectively, and no significant difference was noticed (P>0.05). 【Conclusion】 There was no significant correlation between Fib content and ABO blood group, while FⅧ∶C was significantly correlated with ABO blood group. In the preparation and quality control of FⅧ related blood products, the effect of ABO blood group on the FⅧ∶C should be considered, and the quality standard of FⅧ in plasma products should be established based on the ABO blood group.

Objective To observe the effect of surface electromyographic biofeedback (sEMG BFB) combined with routine swallow training in treating dysphagia among those with nasopharyngeal carcinoma after radiation therapy.Methods Fifty dysphagic patients with nasopharyngeal carcinoma after radiation therapy were randomly divided into a biofeedback training group and a routine treatment group,each of 25.Both groups were given routine training including orofacial function training,sensory irritation,behavioral swallowing training,and electrical stimulation.The biofeedback group was additionally given behavioral swallowing training based on sEMG BFB.Before and 4 weeks after the treatment,a videofluoroscopic swallowing study was performed to observe the opening of the upper esophageal sphincter (UES).The penetration aspiration scale (PAS) and the functional oral intake scale (FOIS) were used to evaluate the subjects' swallowing function.Results Before the treatment there were no significant differences between the two groups in terms of UES opening,average PAS score or average FOIS score.Everyone improved significantly after the treatment,but compared with the routine treatment group,UES opening was significantly better after the treatment,the average PAS score was lower and the average FOIS score was higher in the biofeedback training group.Conclusion sEMG BFB combined with routine swallowing training can improve the UES opening and swallowing ability of dysphagic patients with nasopharyngeal carcinoma after radiation therapy.

Objectives To understand the effects of different doses of vitamin D supplementation on serum calcium,phosphorus,alkaline phosphatase and 25-hydroxyvitamin D levels in very low birth weight infants (VLBWI) and to provide guidance for early prevention of metabolic bone disease in VLBWI.Methods A total of 90 VLBWI hospitalized in the Department of Neonatology,Huzhou Maternal and Child Healthcare Hospital between January 2014 and January 2016 were enrolled and randomly divided into two groups:highdose group and low dose group.High-dose group was given vitamin D 900 U/d orally and low-dose group was given 400 U/d since the eighth day after birth.Serum calcium,phosphorus and alkaline phosphatase levels were detected at 1,7,21 and 42 days of age and serum 25-hydroxyvitamin D levels were detected at 7,21and 42 days of age.Two-sample t-test,Chi-square test,one-way analysis of variance and LSD or Dunnett's T3 test were used for statistical analysis.Results No significant differences in serum calcium,phosphorus and alkaline phosphatase levels were found between the two groups at 1 and 7 days of age,nor were found in serum 25-hydroxyvitamin D level at 7 days of age (all P＞0.05).At 21 days of age,high dose group had higher serum calcium,phosphorus and 25-hydroxyvitamin D levels than low-dose group [(2.38 ± 0.09) vs (2.04 ± 0.15) mmol/L,t=2.421;(1.80±0.50) vs (1.71 ±0.60) mmol/L,t-0.637;(45.58± 18.43) vs (42.53± 16.33) nmol/L,t=0.421],but lower alkaline phosphatase level [(505.12± 185.61) vs (588.32± 168.72) U/L,t=5.314] (all P＜0.05).The same trends were found at 42 days of age.In high-dose group,serum calcium level increased at 7,21 and 42 days of age as compared with that at 1 day of age [(2.43±0.13),(2.38±0.09),(2.39±0.08) vs (2.06±0.57) mmol/L];serum phosphorus level at 7 days of age was lower than that at 1,21 and 42 days of age [(1.31 ±0.26) vs (1.89±0.39),(1.80±0.50),(1.98±0.30) mmol/L];serum alkaline phosphatase level at 7,21 and 42 days of age was higher than that at 1 day of age [(475.18± 133.73),(505.12± 185.61),(538.43 ± 168.16) vs (296.15 ± 99.41) U/L] and a significant increase was observed at 42 days of age as compared with that at 7 days of age;serum 25 hydroxyvitamin D level at 21 days of age was higher than that at 7 days of age,and that at 42 days of age was higher than that at 7 and 21 days of age [(73.55±23.65) vs (30.63± 12.66) and (45.58 ± 18.43) nmol/L];the differences were all statistically significant (LSD or Dunnett's T3 test,all P＜0.05).Conclusions Vitamin D supplementation from the eighth day after birth can improve calcium and phosphorus metabolism in VLBWI and the dose of 900 U/d is more effective than 400 U/d.

Objective To explore the effects and mechanisms of prenatal hypoxia on vasomotor functions of fetal rats.Methods Sixteen pregnant Sprague-Dawley rats were randomly divided into two groups:control and hypoxia groups (eight in each group).Rats in the hypoxia group were provided with 10.5％ of oxygen from gestation day 5 to 21,while those in the control group were exposed to normoxic condition.Fetuses were removed from the pregnant rats by cesarean section on gestational day 21.Fetal body weight,blood gas and electrolyte levels were measured.Thoracic aorta rings were separated from fetal rats and used in different vascular function tests.Effects of hypoxia during pregnancy on angiotensin Ⅱ (Ang Ⅱ)-mediated vasoconstrictions and acetylcholine (Ach)-mediated vasodilatations in fetal thoracic aortas were measured.Changes in vasomotor functions were observed after both endothelial nitric oxide synthase (eNOS) inhibitor NG-nitro-L-arginine methyl ester (L-Name) and L-type calcium channel (LTCC) inhibitor nifedipine were administered.T-test and two-way analysis of variance were used for statistical analysis.Results (1) Compared with the control group,fetal body weight [(4.40±0.23) vs (3.33±0.42) g,t=2.871],blood partial pressure of oxygen [(50.64±2.17) vs (42.50-±-2.32) mmHg (1 mmHg=0.133 kPa),t=-2.618] and blood oxygen saturation [(58.95±1.97)％ vs (47.73±2.24)％,t=3.564] in the hypoxia group were significantly reduced (all P＜0.05).(2) Compared with the control group,Ang Ⅱ-mediated vasoconstrictions increased,but Ach-mediated vasodilatations in fetal thoracic aortas decreased in the hypoxia group (both P＜0.05).L Name induced stronger Ang Ⅱ-mediated contractions in thoracic aortas in the control group than that in the hypoxia group (P＜0.05).However,nifedipine decreased Ang Ⅱ-induced contractions,especially in the hypoxia group (P＜0.05).Conclusions Maternal hypoxia during pregnancy not only affects the growth and development of fetuses but also changes their blood vessel functions,which may be related to the change of LTCC and the impairment of eNOS.

This article introduced the main biological mechanisms of acupuncture promoting nerve function recovery after spinal cord injury, which include inhibition of inflammation and oxidative stress, alleviation of neuropathic pain, increase of neurotrophic active sub-stance, regulation of cell survival/apoptosis gene and neural regeneration pathway.

The method of flying through the air is a qi-promoting and qi-circulating technique commonly used in clinical acupuncture. It includes four methods: the blue dragon wagging its tail, the white tiger shaking its head, the green turtle probing the cave and the red phoenix winging to the source and functions to circulate bodily meridian qi. The method of flying through the air was firstrecorded in Golden needle Fu. Later and modern doctors developed it on the basis of Golden needle Fu. This article straightens up the historical origin and development of four methods of flying through the air.

Methotrexate (MTX)has dual effects of anti-inflam-matory and immune suppression,and its pharmacological mecha-nism is complex,diverse and synergistic.This paper summari-zes the main anti-inflammatory mechanism of low-dose MTX,in-cluding inhibition of JAK/STAT pathway,inhibition of inflam-matory reaction and immune response,increasing the accumula-tion of adenosine and the function of intracellular metabolites (methotrexate polyglutamate).In addition,low-dose MTX can inhibit oxidation by decreasing the level of lipid peroxidation, suppress the inflammatory response to secondary spinal cord in-jury,reduce spinal cord ischemia reperfusion injury and neuro-pathic pain,thus playing a neuroprotective role by a series of pharmacological mechanism.The anti-inflammatory mechanism of low-dose MTX and its application in spinal cord injury were reviewed,to guide the further research on the anti-inflammatory effect of MTX,and provide a theoretical basis for new drugs for clinical treatment of spinal cord injury.

Objective To study the effect of the long-term administration of hemocoagulasein vitro and in vivo,whether it may cause hypofibrinogenemia and changes of cytokine interleukin-6(IL-6) expression level which related to fibrinogen synthesis.Methods Totally 50 healthy subjects pooled plasma was chose in vitro experiments,which was divided into 7 groups.After that,added various of dilutions of injection hemocoagulase and incubated at 37 ℃,detected FIB concentration every 12 h.In vivo experiments,80 rats with six-week old were randomly divided into 4 groups:negative control group,high-dose group,middle-dose group,low-dose group,After 3 weeks administration,the serum level of Ⅴfactor,Ⅷ factor,PT,activated partial thromboplastin time (APTT),FIB,IL-6 was detected.Results Hemocoagulase in vitro had a strong role to reduce fibrin,and showed a significant dose-dependent and time-dependent;Hemocoagulase prolonged low-dose use might reduce the concentration of FIB in mice,but theⅤfactor,Ⅷ factor,PT,APTT,TT were not significantly affected.Compared with the negative control group,FIB and IL-6 concentration decreased in high-dose group,middle-dose group,low-dose group and had statistically significant differences (P<0.05);The level of FIB among the groups had statistically significant differences (P<0.05).The APTT of the middle and high dose groups was slightly prolonged,which was significantly different from that of the negative control group (P<0.05).Conclusion Hemocoagulase has a strong effect to reduce the concentration of fibrin,when there is a long-term medication,fibrin concentration of the patient should be closely monitored,hemocoagulase not only directly decomposed fibrin,but also may affect the synthesis of IL-6,the specific mechanism needs further study.