Key Genes Involved in the Beneficial Mechanism of Hyperbaric Oxygen for Glioblastoma and Predictive Indicators of Hyperbaric Oxygen Prolonging Survival in Glioblastoma Patients

Objective The prognosis of glioblastoma is poor,and therapy-resistance is largely attributed to intratumor hypoxia.Hyperbaric oxygen(HBO)effectively alleviates hypoxia.However,the sole role of HBO in glioblastoma remains controversial.We previously reported that HBO can promote apoptosis,shorten protrusions,and delay growth of glioblastoma,but the molecular mechanism is unclear.We aimed to test candidate genes in HBO-exposed glioblastoma cells and to analyze their correlation with the survival of glioblastoma patients.Methods Glioblastoma cell lines exposed to repetitive HBO or normobaric air(NBA)were collected for RNA isolation and microarray data analysis.GO analysis,KEGG pathway analysis and survival analysis of the differentially expressed genes(DEGs)were performed.Results HBO not only inhibited hypoxia-inducing genes including CA9,FGF11,PPFIA4,TCAF2 and SLC2A12,but also regulated vascularization by downregulating the expression of COL1A1,COL8A1,COL12A1,RHOJ and FILIP1L,ultimately attenuated hypoxic microenvironment of glioblastoma.HBO attenuated inflammatory microenvironment by reducing the expression of NLRP2,CARD8,MYD88 and CD180.HBO prevented metastasis by downregulating the expression of NTM,CXCL12,CXCL13,CXCR4,CXCR5,CDC42,IGFBP3,IGFBP5,GPC6,MMP19,ADAMTS1,EFEMP1,PTBP3,NF1 and PDCD1.HBO upregulated the expression of BAK1,PPIF,DDIT3,TP53I11 and FAS,whereas downregulated the expression of MDM4 and SIVA1,thus promoting apoptosis.HBO upregulated the expression of CDC25A,MCM2,PCNA,RFC33,DSCC1 and CDC14A,whereas downregulated the expression of ASNS,CDK6,CDKN1B,PTBP3 and MAD2L1,thus inhibiting cell cycle progression.Among these DEGs,17 indicator-genes of HBO prolonging survival were detected.Conclusions HBO is beneficial for glioblastoma.Glioblastoma patients with these predictive indicators may prolong survival with HBO therapy.These potential therapeutic targets especially COL1A1,ADAMTS1 and PTBP3 deserve further validation.

The neuroprotective effects of oxygen therapy in Alzheimer’s disease:a narrative review

Alzheimer’s disease(AD)is a degenerative neurological disease that primarily affects the elderly.Drug therapy is the main strategy for AD treatment,but current treatments suffer from poor efficacy and a number of side effects.Non-drug therapy is attracting more attention and may be a better strategy for treatment of AD.Hypoxia is one of the important factors that contribute to the pathogenesis of AD.Multiple cellular processes synergistically promote hypoxia,including aging,hypertension,diabetes,hypoxia/obstructive sleep apnea,obesity,and traumatic brain injury.Increasing evidence has shown that hypoxia may affect multiple pathological aspects of AD,such as amyloid-beta metabolism,tau phosphorylation,autophagy,neuroinflammation,oxidative stress,endoplasmic reticulum stress,and mitochondrial and synaptic dysfunction.Treatments targeting hypoxia may delay or mitigate the progression of AD.Numerous studies have shown that oxygen therapy could improve the risk factors and clinical symptoms of AD.Increasing evidence also suggests that oxygen therapy may improve many pathological aspects of AD including amyloid-beta metabolism,tau phosphorylation,neuroinflammation,neuronal apoptosis,oxidative stress,neurotrophic factors,mitochondrial function,cerebral blood volume,and protein synthesis.In this review,we summarized the effects of oxygen therapy on AD pathogenesis and the mechanisms underlying these alterations.We expect that this review can benefit future clinical applications and therapy strategies on oxygen therapy for AD.

Changes of plasma C-reactive protein in patients with craniocerebral injury before and after hyperbaric oxygenation: A randomly controlled study

Changes of plasma C-reactive protein in patients with craniocerebral injury before and after hyperbaric oxygenation： A randomly controlled study BACKGROUND： Plasma inflammatory factor, such as C-reactive protein, whose content is regarded as a sensitively pathological marked protein and quantitative indexes of central nervous system injury, has been paid more and more attention in clinic. OBJECTIVE： To observe the effects and clinical significance of C-reactive protein in patients with craniocerebral injury after hyperbaric oxygenation. DESIGN： Randomized controlled study. SETTING： Departments of Neurosurgery, Laboratory and Hyperbaric Oxygen, the Second Affiliated Hospital, Medical College of Shantou University. PARTICIPANTS： A total of 60 patients with craniocerebral injury were selected from Department of Neurosurgery, the Second Affiliated Hospital, Medical College of Shantou University from October 2006 to April 2007. There were 37 males and 23 females and the mean age was 26 years. All subjects were certainly diagnosed as history of craniocerebral injury. Patients hospitalized at 24 hours after injury, Glasgow Coma Score ranged from 3 to 12 points, and all patients were certainly diagnosed with CT or MR scanning. Patients and their relatives provided confirmed consent. All the subjects were randomly divided into hyperbaric oxygenation group and control group with 30 in each group. METHODS： Patients in the control group were treated with routinely neurosurgical therapy after hospitalization; however, based the same basic treatment in the control group, patients in the hyperbaric oxygenation group received hyperbaric oxygenation by using iced-wheel four-door 2-cabin air-compression chamber （made in Yantai） from 24 hours to 10 days after operation or injury. After entering the cabin, patients who had a clear consciousness breathed the oxygen by using face mask; contrarily, patients directly breathed the oxygen. Therapeutic project： Expression was increased for about 15–20 minutes, maintained for about 70–80 minutes, and decreased for 20 minutes. Otherwise, pressure was maintained from 0.2 to 0.25 MPa. Hyperbaric oxygenation took an hour for once a day and 10 times were regarded as a course. Venous blood was collected before treatment and on the next day of the first course end. Content of C-reactive protein in plasma was measured with immune turbidimetry in hyperbaric oxygenation group; in addition, content of C-reactive protein in plasma was directly measured with the same method at the corresponding time in the control group. If the content was less or equal to 8 mg/L, it was regarded as normal value. Effects of the two groups were evaluated based on Glasgow Coma Score before and after treatment. MAIN OUTCOME MEASURES： Content of plasma C-reactive protein and Glasgow Coma Score in the two groups before and after treatment. RESULTS： All 60 patients were involved in the final analysis. ① Content of plasma C-reactive protein： The two contents were obviously higher than normal value after craniocerebral injury. There was no significant difference in the two groups before treatment （P 〉 0.05）, but both contents were decreased after treatment, and there was significant difference between HBOT group and control group after treatment （t =4.756, P 〈 0.01）. In addition, there was significant difference in hyperbaric oxygen therapy group before and after treatment （t =5.236, P 〈 0.01）. ② Glasgow Coma Score： There was no significant difference in the two groups before treatment （P 〉 0.05）, but scores were increased in both groups after treatment （t =9.92, 2.51, P 〈 0.01, 0.05）; on the other hand, therefore, there was significant difference between the two groupsafter treatment （t =9.21, P 〈 0.01）. CONCLUSION： Hyperbaric oxygenation can remarkably decrease content of plasma C-reactive protein in patients with craniocerebral injury at the phase of stress.

Hyperbaric Oxygen Treatment for Long COVID:From Molecular Mechanism to Clinical Practice

Long COVID symptoms typically occur within 3 months of an initial COVID-19 infection,last for more than 2 months,and cannot be explained by other diagnoses.The most common symptoms include fatigue,dyspnea,coughing,and cognitive impairment.The mechanisms of long COVID are not fully understood,but several hypotheses have been put forth.These include coagulation and fibrosis pathway activation,inflammatory and autoimmune manifestations,persistent virus presence,and Epstein-Barr virus reactivation.Hyperbaric oxygen therapy(HBOT)is a therapeutic method in which a person inhales 100%oxygen under pressure greater than that of the atmosphere.HBOT has some therapeutic effects,including improvement of microcirculation,inhibition of cytokine release leading to a reduction in inflammatory responses,inhibition of autoimmune responses,and promotion of neurological repair.Several clinical trials have been carried out using HBOT to treat long COVID.The results suggest that HBOT helps to improve symptom severity,reduce symptom duration,and enhance patients’quality of life.It is believed that HBOT is an effective option for patients with long COVID,which is worth actively promoting.

Influence of hyperbaric oxygen on the differentiation of hypoxic/ischemic brainderived neural stem cells

BACKGROUND： It has been previously shown that hyperbaric oxygen may promote proliferation of neural stem cells and reduce death of endogenous neural stem cells （NSCs）. OBJECTIVE： To explore the effects of hyperbaric oxygen on the differentiation of hypoxic/ischemic brain-derived NSCs into neuron-like cells and compare with high-concentration oxygen and high pressure. DESIGN, TIME AND SETTING： An in vitro contrast study, performed at Laboratory of Neurology, Central South University between January and May 2006. MATERIALS： A hyperbaric oxygen chamber （YLC 0.5/1A） was provided by Wuhan Shipping Design Research Institute; mouse anti-rat microtubule-associated protein 2 monoclonal antibody by Jingmei Company, Beijing; mouse anti-rat glial fibrillary acidic protein monoclonal antibody by Neo Markers, USA; mouse anti-rat galactocerebroside monoclonal antibody by Santa Cruz Biotechnology Inc., USA; and goat anti-mouse fluorescein isothiocyanate-labeled secondary antibody by Wuhan Boster Bioengineering Co., Ltd., China. METHODS： Brain-derived NSCs isolated from brain tissues of neonatal Sprague Dawley rats were cloned and passaged, and assigned into five groups： normal control, model, high-concentration oxygen, high pressure, and hyperbaric oxygen groups. Cells in the four groups, excluding the normal control group, were incubated in serum-containing DMEM/F12 culture medium. Hypoxic/ischemic models of NSCs were established in an incubator comprising 93% N2, 5% 002, and 2% 02. Thereafter, cells were continuously cultured as follows： compressed air （0.2 MPa, 1 hour, once a day） in the high pressure group, compressed air ＋ a minimum of 80% 02 in the hyperbaric oxygen group, and a minimum of 80% Q2 in the high-concentration oxygen group. Cells in the normal control and model groups were cultured as normal. MAIN OUTCOME MEASURES： At day 7 after culture, glial fibrillary acidic protein, microtubule-associated protein 2, and galactocerebroside immunofluorescence staining were examined to observe differentiation and calculate the percentage of NSCs differentiating into neuron-like cells or neuroglia-like cells. RESULTS： Neuron-like cells or neuroglia-like cells were visualized in all five groups. There were no significant differences in the percentage of differentiating cells between the hyperbaric oxygen group and the normal control group （P 〉 0.05）. The percentage of NSCs differentiating into neuron-like cells in the hyperbaric oxygen group was significantly greater than model, high-concentration oxygen, and high pressure groups; however, the percentage differentiating into neuroglia-like cells was significantly lower （P 〈 0.01 ）. CONCLUSION： Hyperbaric oxygen promotes the differentiation of brain-derived neural stem cells into neuron-like cells but inhibits differentiation into neuroglia-like cells. Furthermore, the efficacy of hyperbaric oxygen is superior to high-concentration oxygen and high pressure.

Neuroprotective effect of high-dose hyperbaric oxygenation on rats with acute cerebral infarction in super-early stage:Curative comparison between 9-hour and 18-hour therapeutic protocols

BACKGROUND： Previously, only single short-time low-dose hyperbaric oxygenation （HBO） protocol was administrated to treat acute ischemic stroke in early stage and the conflicting results were obtained. There are few studies to report the outcome of administering long-time （can cover all the natural pathologic progression period） high-dose HBO to treat the disease. OBJECTIVE： To evaluate the therapeutic effect between two kinds of high-dose hyperbaric oxygenation on super-early stage of acute permanent middle cerebral artery occlusion （MCAO） in rats. DESIGN： A randomized controlled experimental study. SETTING： Beijing Tiantan Hospital, Capital Medical University; Beijing Research Institute of Neurosurgery. MATERIALS： Seventy-four male SD rats, aged 2.5 months old, weighing （ 280 ＋ 20） g, were provided by the Animal Institute, Chinese Academy of Medical Sciences. Hyperbaric oxygenation device was hyperbaric air cabin in which there was a self-made pure oxygen animal experimental cabin （made in China）. METHODS： This experiment was carried out in the municipal laboratory of Beijing Tiantan Hospital affiliated to Capital Medical University and Beijing Research Institute of Neurosurgery. ① Experimental intervention： All the rats were developed into models of permanent MCAO by suture embolism. Then, they were randomly divided into two HBO groups （9 hours and 18 hours） and control group, with 24 rats in each as well as 3-hour ultrastructure control group, with 2 rats. After being modeled for 3 hours, rats in the two HBO groups stayed in the hyperbaric cabin for 9 hours and 18 hours, separately. Rats in the 9-hour HBO group inhaled pure oxygen at hours 1, 3, 5, 7 and 9, and hyperbaric air at hours 2, 4, 6 and 8. Rats in the 18-hour HBO group inhaled pure oxygen at hours l, 3, 5, 7, 9, 11, 13, 15 and 17, and hyperbaric air at hours 2, 4, 6, 8, l0 12, 14, 16 and 18. After being created into models, rats in the control group and 3-hour ultrastructure control group breathed room air. ② Experimental evaluation： Neurologic functions of rat models in the 9-hour and 18-hour HBO groups as well as control group were scored by Bederson and Garica two neurological grading systems at hours 14 and 28 and on day 5; Infarct volume of rat models in the two HBO groups and control group was measured at hour 24 and on day 5 with NIH image processing software Image J; The pathological changes of brain tissue in the brain infarct region and its opposite region of rat models in the two HBO groups and 3-hour ultrastructure control group were observed with a Philips EM 208S transmission electron microscope. MAIN OUTCOME MEASURES： ① Neurobehavioral outcome. ② Rat brain infarct volume. ③ Ultrastructure of brain tissue in the ischemic penumbra of infarct models at the different time points RESULTS： ① Neurobehavioral outcome： After treatment, Garica score in the 9-hour and 18-hour HBO groups was significantly higher than that in the control group （P 〈 0.01）. Bederson score on day 5 after modeling in the 9-hour and 18-hour HBO groups was significantly lower than that in the control group （P 〈 0.01）. ② Cerebral infarct volume： Cerebral infarct volume in the 9-hour and 18-hour HBO groups was significantly smaller than that in the control group at hour 24 and on day 5 after modeling （P 〈 0.01）. In the 18-hour HBO group, infarct volume on day 5 after modeling was significantly larger than that at hour 24 after modeling （P 〈 0.05）. ③In the 3-hour ultrastructure control group, astrocyte edema and neuron damage around the capillary in the infarct cerebral tissue significantly relieved in the rats which were subjected to HBO. CONCLUSION： High dose of HBO is highly efficient in reducing infarct volume and improving neurobehavioral outcome of rats with acute cerebral infarction, and also has an important role in inhibiting the pathological progression of ischemic brain tissue after cerebral infarction.

Effect of hyperbaric oxygen therapy on BI index, GCS, SAS and SDS in patients with craniocerebral injury

Objective: To research and analyze the effect of psychological nursing intervention on self-rating depression (SDS), self-rating anxiety scale (SAS), Glasgow Score (GCS), Barthel index (Barthel, index, BI) of patients. Methods: From September 2015 to September 2016, 84 patients with craniocerebral injury admitted to our hospital were divided into observation group (n = 42) and control group (n = 42) according to randomized single blindness method. All patients were treated with hyperbaric oxygen therapy. The control group was given routine nursing care, while the observation group was treated by psychological nursing intervention. Results: The scores of GCS in the observation group after 2 weeks and 8 weeks of treatment were respectively (7.79±1.42), (11.86±2.56) which were higher than those in the control group (6.23±1.01), (8.21±1.65) the data show significant difference. After treatment, the scores of SDS and SAS in the observation group were respectively (39.14±1.21), (41.67±1.12) which were lower than those in the control group (45.56±2.50), (56.89±2.47) the data show significant difference. The BI index of the observation group was (43.29±4.63), which was higher than that of the control group (36.83±3.10), the scores of NFD was (23.12±1.01) in the observation group, which was lower than that in the control group (28.45±1.67), the data were statistically significant. Conclusion: Psychological care intervention in patients with craniocerebral injury treated by hyperbaric oxygen therapy is helpful to improve the adverse psychological state and consciousness state, improve the ability of daily living activities and promote the recovery of neurological function. It can be actively promoted and applied in clinical practice.

Relationship of Hyperbaric Oxygen Therapy of Acute Compartment Syndrome with Changes of Plasma Fibronectin Concentration

This report describes for the first time the effects of hyperbaric oxygen therapy with 253kPa on patients(n=24) with post - trauma acute compartment syndrome, and the relationship be-tween the prognosis of the syndrome and the changes of plasma fibronectin. Plasma fibronectin wasmeasured using single radial immunodiffusion both before and after therapy with hyperbaric oxygen,with 30 healthy people as control for plasma fibronectin. The results showed that the clinical symp-toms and signs of all 16 patients with acute compartment syndromes in early stage were significantlyimproved after 3 times of hyperbaric oxygen therapy and disappeared after 5 times withoutfasciotomy. Six patients who were treated with hyperbaric oxygen after fasciotomy showed reductionin the infection, and, edema of the injured limb However, the effects were less favorable for 2 pa-tients with necrosis although their clinical symptoms and signs were partially improved. Besides,we found that these patients’ plasma fibronectin concentrations were significantly afterhyperbaric oxygen therapy. The mean increase was 43 (18. 9％; P【0. 01), 61( 24. 7%, P【0. 01),49 (17. 2%, P【0. 01), 57 (17. 4%; P【0. 05) and 55 mg/L ( 16. 6%; P【0. 05) after 1, 2, 3, 4and 5 times of therapy, respectively. Plasma fibronectin concentrations returned to the level of thecontrols after 3 times of therapy (P】0. 05). After fourth and fifth therapy plasma fibronectin lev-els of the patients rose higher than those of the controls (P【0.05). The results suggest that hyperbaric oxygen therapy has a beneficial effect on patients withacute compartment syndrome in the early stage Hyperbaric oxygen therapy can reduce edema andskeletal muscle necrosis The method can be used to treat patients with acute compartmentsyndrome in early stage and as an effective adjunctive treatment after fasciotomy.

Hyperbaric oxygen protects against PC12 and H9C2 cell damage caused by oxygen-glucose deprivation/reperfusion via the inhibition of cell apoptosis and autophagy

In this study,we investigated the protective effect of hyperbaric oxygen(HBO)on PC12 and H9C2 cell damage caused by oxygen-glucose deprivation/reperfusion and its possible mechanism.PC12 and H9C2 cell oxygen-glucose deprivation/reperfusion model were established.Cells were divided into a control group,model group,hyperbaric air(HBA)group and HBO group.The cell viability was detected by the CCK8 assay.Hoechst 33342 and PI staining assays and mitochondrial membrane potential(MMP)assays were used to detect cell apoptosis.The ultrastructure of cells,including autophagosomes,lysosomes,and apoptosis,were examined using a transmission electron microscope.The expression of autophagy-related proteins was detected by cellular immunofluorescence and immunocytochemistry.Our results showed that HBO can significantly improve the vitality of damaged PC12 and H9C2 cells caused by oxygen–glucose deprivation/reperfusion.HBO can significantly inhibit apoptosis of PC12 and H9C2 cells caused by oxygenglucose deprivation/reperfusion.Importantly,we found that the protective mechanism of PC12 and H9C2 cell damage caused by oxygen-glucose deprivation/reperfusion may be related to the inhibition of the autophagy pathway.In this study,the results of cellular immunofluorescence and immunocytochemistry experiments showed that the 4E-BP1,p-AKt and mTOR levels of PC12 and H9C2 cells in the model group decreased,while the levels of LC3B,Atg5 and p53 increased.However,after HBO treatment,these autophagy-related indexes were reversed.In addition,observation of the cell ultrastructure with transmission electron microscopy found that in the model group,a significant increase in the number of autophagic vesicles was observed.In the HBO group,a decrease in autophagic vesicles was observed.The study demonstrated that hyperbaric oxygen protects against PC12 and H9C2 cell damage caused by oxygen-glucose deprivation/reperfusion via the inhibition of cell apoptosis and autophagy.

Practice of the fourth national hyperbaric oxygen medicine week publicity campaign in China

Objective:We launched the fourth national hyperbaric oxygen(HBO)medicine week publicity campaign in China to increase patients’and medical professionals’understanding of HBO medicine and expand the influence of HBO.Methods:The theme of 2019 was“Oxygen protects life,healthy China”.The main components of the campaign were free medical consultation,free HBO experience,and telemedicine lectures.At least one component was required for each participating hospital.Results:(1)In total,195 hospitals in 26 provinces,autonomous regions,and municipalities directly under the central government participated in the campaign.Shandong province of China had the highest number of hospitals in a single area(48 hospitals);(2)The free medical consultation was organized by the HBO department.In some hospitals,other medical professionals were also invited.Among all hospitals,up to 13 different HBO-related departments participated;(3)The free HBO experiences were held in some hospitals,and the number of experiences ranged from one to three per person;(4)Three telemedicine lectures involving a total of 8 live interactions were held in 55 different hospitals.Lecture videos were provided to play locally in hospitals without the setting necessary for live interactions.Conclusion:Our campaigns created a brand effect beginning in 2016.In the herein-described 2019 study,we considered the previous three campaigns and explored different methods of publicizing HBO medicine in China,including telemedicine.

Effect of hyperbaric oxygen therapy on SAS and SDS in children with ischemic encephalopathy

Objective: To study and analyze the effect of early psychological intervention on the scores of SAS and SDS in children with hypoxic-ischemic encephalopathy undergoing hyperbaric oxygen therapy. Methods: A total of 64 children with hypoxic - ischemic encephalopathy enrolled in our hospital from July 2015 to July 2016 and their parents were selected as study subjects. The patients were treated with hyperbaric oxygen therapy, while their parents were given early psychological intervention. By the way of increasing parents' awareness of the disease, helping parents build confidence in their children's treatment and encouraging them to participate in daily training for their children to relieve their anxiety and depression. The parents' knowledge of the disease before and during treatment, the treatment of hyperbaric oxygen therapy and the change of SAS and SDS were observed. Results: After effective intervention, the scores of SAS and SDS of 64 patients' parents were significantly lower than those before treatment. After 1 courses of intervention, the score of SAS was (43.36 ± 1.27) points, and the score of SDS was (45.22 ± 8.13) points. After 2 courses of intervention, the score of SAS was (41.07 ± 1.21) and the score of SDS was (42.35 ± 7.44) points, and parents' awareness of hypoxic-ischemic encephalopathy was significantly increased, and the differences between the two groups were statistically significant. Conclusion: Early psychological intervention on parents of children with hypoxic-ischemic encephalopathy can effectively improve the awareness of parents on the disease, so as to improve their acceptance of hyperbaric oxygen therapy;significantly reduce the parents' SAS, SDS score. It is beneficial to build a good doctor-patient and nurse-patient relationship, improve the treatment effect and shorten the treatment time.

The new insights of hyperbaric oxygen therapy:focus on inflammatory bowel disease

Inflammatory bowel diseases(IBD),with an increasing incidence,pose a significant health burden.Although there have been significant advances in the treatment of IBD,more progress is still needed.Hyperbaric oxygen therapy(HBOT)has been shown to treat a host of conditions such as carbon monoxide poisoning,decompression sickness,and gas gangrene.In the last few years,there has been an increase in research into the use of HBOT as an adjunct to conventional treatment for IBD.Related research has shown that HBOT may exert its therapeutic effects by decreasing oxidative stress,inhibiting mucosal inflammation,promoting ulcer healing,influencing gut microbes,and reducing the incidence of IBD complications.This paper aims to provide a comprehensive review of experimental and clinical trials exploring HBOT as a supplement to IBD treatment strategies.

Hyperbaric Oxygen Treatment Improves Hearing Level via Attenuating TLR4/NF-κB Mediated Inflammation in Sudden Sensorineural Hearing Loss Patients

Objective Hyperbaric oxygen treatment(HBOT)has demonstrated efficacy in improving hearing levels of patients with idiopathic sudden sensorineural hearing loss(ISSHL);however,the underlying mechanisms are not well understood.HBOT alleviates the inflammatory response,which is mediated by Toll-like receptor(TLR)4 and nuclear factor(NF)-κB.In this study we investigated whether HBOT attenuates inflammation in ISHHL patients via alteration of TLR4 and NF-κB expression.Methods ISHHL patients(n=120)and healthy control subjects(n=20)were enrolled in this study.Patients were randomly divided into medicine group treated with medicine only(n=60)and HBO group receiving both HBOT and medicine(n=60).Audiometric testing was performed pre-and posttreatment.TLR4,NF-кB,and TNF-αexpression in peripheral blood of ISSHL patients and healthy control subjects was assessed by ELISA before and after treatment.Results TLR4,NF-κB,and TNF-αlevels were upregulated in ISSHL patients relative to healthy control subjects;the levels were decreased following treatment and were lower in the HBO group than that in the medicine group post-treatment(P<0.05 and P<0.01).Conclusion HBOT alleviates hearing loss in ISSHL patients by suppressing the inflammatory response induced by TLR4 and NF-κB signaling.

The mechanism by which hyperbaric oxygen treatment alleviates spinal cord injury: genome-wide transcriptome analysis

Accumulating studies have demonstrated that hyperbaric oxygen(HBO)treatment alleviates spinal cord injury(SCI).However,the underlying mechanism by which HBO alleviates SCI remains to be elucidated.In this study,we performed genome-wide transcriptional profiling of the spinal cord between SCI mice and mice that received HBO treatment by high-throughput RNA sequencing at 1 week after SCI.We also compared genome-wide transcriptional profiles from SCI mice and sham-operated mice.We found 76 differentially co-expressed genes in sham-operated mice,SCI mice,and HBO-treated SCI mice.Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis,we identified the biological characteristics of these differentially expressed genes from the perspectives of cell component,biological process,and molecular function.We also found enriched functional pathways including ferroptosis,calcium signaling pathway,serotonergic synapse,hypoxia-inducible factor-1 signaling pathway,cholinergic synapse,and neuroactive ligand-receptor interaction.We performed quantitative reverse transcription-polymerase chain reaction and validated that HBO treatment decreased the expression of Hspb1(heat shock protein beta 1),Hmox1(heme oxygenase 1),Ftl1(ferritin light polypeptide 1),Tnc(tenascin C)and Igfbp3(insulin-like growth factor binding protein 3)and increased the expression of Slc5a7(solute carrier family 5 choline transporter member 7)after SCI.These results revealed the genome-wide transcriptional profile of the injured spinal cord after HBO treatment.Our findings contribute to a better understanding of the mechanism by which HBO treats SCI and may provide new targets for SCI intervention.

Hyperbaric oxygen treatment for experimental intraocular hypertension in rats: An electroretinogram detection

BACKGROUND： Hyperbaric oxygen （HBO） is used for treating glaucoma, and affirmative curative effect has been obtained. HBO can sensitively reflect the obviously heightened b wave of electroretinogram （ERG） of injured tissue. OBJECTIVE： To observe the effect of HBO treatment on retinal function of rats with acute experimental intraocular hypertension with ERG. DESIGN： Randomized controlled experiment. SETTING： Department of Ophthalmology, Third Xiangya Hospital, Central South University; Department of Hyperbaric Oxygen, Xiangya Hospital, Central South University; Department of Anatomy, Xiangya Hospital, Central South University. MATERIALS： Eighteen adult healthy Wistar rats, of either gender, weighing from 150 to 250 g, were provided by the Animal Room of Central South University. Type YLCO. 5/I A baby hyperbaric oxygen chamber, type LMS-2A two-channel physiological recorder, type BG-1 retina exposure system, Jiangwan type Ⅰ stereotaxis instrument. METHODS： This experiment was carried out in the Central South University between March and September 2006. Eighteen healthy Wistar rats were made into models of acute experimental intraocular hypertension. Then, they were divided into two groups： model group and HBO treatment group, with 9 in each group. Following 7 days of HBO treatment, the rats in HBO treatment group were placed in Type YLCO. 5/I A baby hyperbaric oxygen chamber, which was pressurized with pure oxygen（ volume fraction 0.825 ± 0.025）.The treatment pressure was 0.2 MPa. The rats in HBO treatment group daily inhaled HBO for 80 minutes within 7 days; Rats in the model group were untouched. The performance of eyes was observed under the status of intraocular hypertension. ERG was recorded before, during and 7 days after modeling, meanwhile, the recovery rate of b wave from ERG was calculated. Recovery rate of b wave from ERG=（amplitude orb wave 7 days after modeling/amplitude orb wave before modeling）× 100%. MAIN OUTCOME MEASURES： ①Performance of eyes under the status of intraocular hypertension. ②Recovery rate orb wave of ERG. RESULTS： All the 18 rats were involved in the final analysis. ①Performance of eyes under the status of intmocular hypertension.： When intraocular pressure increased until b wave of ERG disappeared, two eyes of rats with corneal opacity, dilated pupils, pale iris and stiffened eyeballs were found. ②Recovery rate of b wave of ERG in the HBO treatment group was significantly higher than that in the model group [（60.04±19.33）% vs. （41.85 ± 13.20）%, t =3.298, P 〈 0,01]. CONCLUSION： HBO treatment can obviously promote the recovery of retinal function following acute intraocular hypertension.

Mechanism of delayed encephalopathy after acute carbon monoxide poisoning

Many hypotheses exist regarding the mechanism underlying delayed encephalopathy after acute carbon monoxide poisoning(DEACMP),including the inflammation and immune-mediated damage hypothesis and the cellular apoptosis and direct neuronal toxicity hypothesis;however,no existing hypothesis provides a satisfactory explanation for the complex clinical processes observed in DEACMP.Leucine-rich repeat and immunoglobulin-like domain-containing protein-1(LINGO-1)activates the Ras homolog gene family member A(Rho A)/Rho-associated coiled-coil containing protein kinase 2(ROCK2)signaling pathway,which negatively regulates oligodendrocyte myelination,axonal growth,and neuronal survival,causing myelin damage and participating in the pathophysiological processes associated with many central nervous system diseases.However,whether LINGO-1 is involved in DEACMP remains unclear.A DEACMP model was established in rats by allowing them to inhale 1000 ppm carbon monoxide gas for 40 minutes,followed by 3000 ppm carbon monoxide gas for an additional 20 minutes.The results showed that compared with control rats,DEACMP rats showed significantly increased water maze latency and increased protein and m RNA expression levels of LINGO-1,Rho A,and ROCK2 in the brain.Compared with normal rats,significant increases in injured neurons in the hippocampus and myelin sheath damage in the lateral geniculate body were observed in DEACMP rats.From days 1 to 21 after DEACMP,the intraperitoneal injection of retinoic acid(10 mg/kg),which can inhibit LINGO-1 expression,was able to improve the above changes observed in the DEACMP model.Therefore,the overexpression of LINGO-1 appeared to increase following carbon monoxide poisoning,activating the Rho A/ROCK2 signaling pathway,which may be an important pathophysiological mechanism underlying DEACMP.This study was reviewed and approved by the Medical Ethics Committee of Xiangya Hospital of Central South Hospital(approval No.201612684)on December 26,2016.

Oral Epidemic Diseases of Exposure Personnel in Long-term Low Dose Radiation

ORAL epidemic diseases of exposure personnel in long-term low-dose radiation yet have rarely been studied.Referred to WHO oral health survey method and symptom grading standard,data of 341 exposure persons in long-term low-dose radiation including o particle,β particle,and y rays,etc.,were collected from one camp in China in 2011 with cluster sampling and analyzed with Foxpro 6.0 and SPSS 16.0software.

Integrated analysis of micro RNA and m RNA expression profiles in HBx-expressing hepatic cells

AIM To identify the miRNA-mRNA regulatory network in hepatitis B virus X (HBx)-expressing hepatic cells. METHODS A stable HBx-expressing human liver cell line L02 was established. The mRNA and miRNA expression profiles of L02/HBx and L02/pcDNA liver cells were identified by RNA-sequencing analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed to investigate the function of candidate biomarkers, and the relationship between miRNA and mRNA was studied by network analysis. RESULTS Compared with L02/pcDNA cells, 742 unregulated genes and 501 downregulated genes were determined as differentially expressed in L02/HBx cells. Gene ontology analysis suggested that the differentially expressed genes were relevant to different processes. Concurrently, 22 differential miRNAs were also determined in L02/HBx cells. Furthermore, integrated analysis of miRNA and mRNA expression profiles identified a core miRNA-mRNA regulatory network that is correlated with the carcinogenic role of HBx. CONCLUSION Collectively, the miRNA-mRNA network-based analysis could be useful to elucidate the potential role of HBx in liver cell malignant transformation and shed light on the underlying molecular mechanism and novel therapy targets for hepatocellular carcinoma.