Objective To observe the effect of febuxostat on IL-1β, TNF-αand COX-2 in gout patients.Methods 82 patients with gout in our hospital from August 2015 to August 2016 were divided into the groups of 40 mg/day of febuxostat and 80 mg/day of febuxostat randomly, 41 cases respectively.Select the same period in our hospital health examination of 41 cases.The levels of serum uric acid were measured before and after one week, two weeks and four weeks after treatment.Serum levels of IL-1β, TNF-αand IL-1βin serum were measured by enzyme-linked immunosorbent assay (ELISA) COX-2 levels.Results The levels of serum uric acid in the group of 40 mg/day vs 80 mg/day of febuxostat were (570.4 ±70.5) μmol/L and (572.8 ±71.2) μmol/L, significantly higher than the normal group (296.5 ±9.7) μmol/L (P<0.05), serum uric acid level decreased gradually with the time of administration, and the serum uric acid levels of the two dosages of fosobutamol at one,two,four weeks were significantly lower than before treatment (P<0.05), but not to below the normal level.The IL-1βof 40 mg/day and 80 mg/day of febuxostat was (40.5 ±6.8) pg/mL and (41.7 ±7.2) pg/mL, COX-2 were (15.5 ±1.7) pg/mL and (15.8 ±1.8) pg/mL respectively, significantly higher than the normal group (8.8 ± 1.7) pg/mL (P<0.05), The expression of IL-1βwas significantly decreased at the second week of IL-1βdecreasing as the time of IL-1βdecreased gradually (P<0.05); TNF-αin 40 mg/day group and 80 mg/day group was significantly lower than that before treatrment (P<0.05), but not to below the normal level.Conclusion Febuxostat can significantly reduce serum uric acid levels in patients with gout, and may reduce IL-1β, TNF-αand COX-2 and other cytokine levels.

BACKGROUND:Hyperbaric oxygen (HBO) can increase oxygen diffusing capacity, thereby, improve hypoxic state of brain edema and brain tissue and promote the recovery of physiological function of brain cells in focal zone, the establishment of bypass circuit, and regeneration and repair of brain cells.OBJECTIVE: To observe the effect of hyperbaric oxygen on c-fos oncogene expression of rats at different time points following acute focal cerebral ischemia/reperfusion(I/R) injury.DESIGN : Randomized grouping animal experiment.SETTING: Department of Emergency, Tangdu Hospital, Fourth Military Medical University of Chinese PLA; Department of Laboratory Medicine, Xi'an Gaoxin Hospital;The General Hospital of the Air Force of Chinese PLA; Hyperbaric Oxygen Treatment Center, Department of Aerospace Medicine, Fourth Military Medical University of Chinese PLA.MATERIALS: This experiment was carried out in the Hyperbaric Oxygen Treatment Center, Department of Aerospace Medicine, Fourth Military Medical University of Chinese PLA in April 2002. Sixty-five 2-month-old healthy male SD rats.METHODS: The involved rats were randomized into: model group (n =20), normal control group (n =5), pure oxygen treatment group (n =20) and HBO treatment group (n =20). In the model group, following the method of Koizumi et al, rat models of middle cerebral artery (MCA) ischemia were developed. In the normal control group, only occlusion of arterial blood flow was omitted; In the pure oxygen treatment group, the operation procedure was the same as that of model group, and embolus being drawn out at ischemia for 1 hour, rats were placed in the hyperbaric cabin at 2,9,21, 45 and 69 hours after embolus being inserted, and they inhaled pure oxygen under the normal pressure; In the HBO treatment group, the operation procedure was the same as that of model group, and rats inhaled pure oxygen for 1 hour under 0.25 MPa pressure. MAIN OUTCOME MEASURES: By means of immunohistochemical and pathohistological methods, neutrophilic infiltration,c-fos oncogene protein and positive cell expression in cerebral cortex, preoptic area and corpora striatum of rats in each group were observed at cerebral I/R 5, 12, 24 and 72 hours; Neuronal necrosis degree in cerebral cortex, medial area of corpora striatum and preoptic area, and cerebrovascular leakage area of left cerebral hemisphere of rats were calculated.RESULTS: Sixty-five rats were involved in the final analysis. ① c-fos positive products mainly focused in the center of the preoptic area, but they were occasionally seen in the contralateral cortex, slightly expressed in the preoptic area and moderately expressed in the corpora striatum, c-fos positive products began to reduce in the above-mentioned area at ischemia 12 hours, and were obviously reduced at ischemia 24 hours; c-fos positive products in the cerebral cortex and preoptic area were obviously weakened in the HBO treatment group than in the simple ischemia group; At I/R 12 hours,neutrophils in the preoptic area and corpora striatum were significantly lower in the HBO treatment group than in the model group, respectively(P ＜ 0.05); At I/R 24 hours, neutrophils in the cerebral cortex, preoptic area and corpora striatum were significantly lower in the HBO treatment group than in the model group (P ＜ 0.05). ② Cerebrovascular leakage area was more significantly contracted in the HBO treatment group than in the model group (P＜ 0.05); At I/R 72 hours, the number of injured nerve cells in the optic chiasm cortex, medial area of corpora striatum and preoptic area was significantly smaller in the HBO treatment group than in the model group (P＜0.05). Neuronal damage was not found in the sham-operation group.CONCLUSION: HBO can markedly contract cerebrovascular leakage area of rats with acute focal cerebral ischemia/reperfusion injury, alleviate the symptoms of nervous system, inhibit neutrophilic infiltration and c-fos oncogene protein expression in the infarct area, and reduce neuronal necrosis in the "penumbral region".

BACKGROUND:Acute carbon monoxide (CO) poisoning may lead to delayed amnesia in rats,and which is similar to delayed neurologic syndrome caused by acute CO in human.So,this experiment is to investigate the pathogenesis of delayed neurologic syndrome by studying acute CO poisoning in the rats.OBJECTIVE:To observe the changes in delayed neuronal damage and memory after acute CO poisoning in the rats,and analyze their correlation.DESIGN:Randomized controlled animal experiment.SETTING:Department of Emergency,Tangdu Hospital,Fourth Military Medical University of Chinese PLA;Department of Laboratory Medicine,Xi'an Gaoxin Hospital;The General Hospital of the Air Force of Chinese PLA,Center for Hyperbaric Oxygen Treatment,Department of Aerospace Medicine,Fourth Military Medical University of Chinese PLA.MATERIALS:This experiment was carried out in the Laboratory of Aviation Pathology and Molecular Biology,Department of Aerospace Medicine.Fourth Military Medical University of Chinese PLA from July to November 2005.Fiftyhealthy male Sprague-Dawley(SD)rats were randomized into control group and CO poisoning group,with 25 rats each.METHODS:The awake rats in the CO poisoning group were placed in self-made jar for poisoning,then which was pumped with 0.999 volume fraction of CO.Rats in the jar inhaled the mixture of CO and air for 60 minutes.The average volume fraction of CO in the jar was 3.451×10-3.Rats in the control group were untouched.MAIN OUTCOME MEASURES:①The step down test was carried out in the rats before and 1,3,5 and 7 days after Coexposure.Escape latency was used as an index for evaluating the ability of memory retention.Shorter escape latencyindicated poor memory ability.②Pathological changes of brain tissue:After step down test was carried out following 1,3,5 and 7 days of CO exposure,6 rats were separately sacrificed in each group,and their brains were harvested.The brain tissue sections were performed haematoxylin & eosin (HE) staining for observing pathological injury degree and the amount of pyramidal neurons in hippocampal CA1 region.③SPSS 10.0 software was used to analyze the relationship of the amount of pyramidal neurons in hippocampal CA1 region and escape latency.RESULTS:Forty-eight rats were involved in the final analysis.①There were no significant differences in escape latencyon the 1"and 3"days after CO exposure between two groups. but escape latency in the CO poisoning group was significantly shorter than that in the control group on the 5th and 7th days after CO exposure(P＜0.05,0.01).②There were no significant changes in the amount of pyramidal neurons in hippocampal CA1 region on the 1st day after CO exposure between CO poisoning group and control group,but pyramidal neurons in hippocampal CA1 region in the CO poisoning group were significantly reduced on the 3rd,5th and 7th days after CO exposure,and 1 5%dead pyramidal neurons were found on the 7th day after CO exposure.③Decrease of pyramidal neurons in hippocampal CA1 region was significantly correlated with shortening of escape latency of rats in the CO poisoning group(r=0.270,P＜0.01).CONCLUSION:Acute CO poisoning leads to delayed neuronal damage,which causes delayed amnesia.

BACKGROUND: Nitric oxide (NO) plays an important role in the ischemic brain injury, and hyperbaric oxygen (HBO) can improve ischemia/reperfusion (I/R)-caused nerve injury. Whether the effect of HBO is associated with NO? Its mechanism needs to be further investigated.OBJECTIVE: To observe the changes of expression of nitric oxide synthase (NOS)-positive neurons of rats following acute focal cerebral I/R injury and HBO treatment.DESIGN: Randomized controlled animal experiment.SETTING: Department of Emergency, Tangdu Hospital, Fourth Military Medical University of Chinese PLA; Department of Laboratory Medicine, Xi'an Gaoxin Hospital; The General Hospital of the Air Force of Chinese PLA.MATERIALS : Sixty-six healthy male Sprague-Dawley rats were chosen and randomized into 5 groups: sham-operation group (n =5), sham-operation +HBO treatment group (n =5), model group (n =28), modeling +HBO treatment group (n =28). Ischemia 5,12, 24 and 72 hours four time points were set in the later 2 groups, 7 rats at each time point.METHODS: ①Rats in the model group and modeling+ HBO treatment group were created into models of middle cerebral artery ischemia according to the method from Koizum. Then, an embolus was inserted for ischemia; One hour later, the embolus was drawn out. Inserting embolus was omitted in the other two groups.②Rats in the sham operation + HBO treatment group and modeling + HBO treatment group were placed in HBO chamber at ischemia 2, 9, 21, 45 and 69 hours, separately, and given HBO treatment for 1 hour (0.25 MPa absolute pressure).MAIN OUTCOME MEASURES: The rats in each group were sacrificed at corresponding time points, and their brains were harvested. The distribution and morphology of NOS positive cells in cortical area, preoptic area, lateral and medial corpora striata of infarct region at the level of optic chiasma were observed with nicotinamide-adenine dinucleotide phosphate -diaphorase (NADPH-d) histochemical method.RESULTS: After supplement, 66 rats were involved in the final analysis. ①After ischemia, NOS-positive neurons changed in morphology, mainly presenting prominences were reduced or disappeared, neurons changed from ellipse or triangle into global shape, and shrank; Body of neuron darkly dyed; Both nucleus and cytoplasm were deeply dyed into dark blue; NOS-positive neurons with changed morphology were mostly in lateral corpora striatum, followed by preoptic area and medial corpora striatum, and those in the cortical area were few. NOS-positive neurons with changed morphology were not found in the sham-operation group and sham-operation + HBO treatment group. ②In the model group, NOS-positive neurons with changed morphology were increased with elongation of I/R time. At each time point, NOS-positive neurons in cortical area, preoptic area and medial corpora striatum in modeling + HBO treatment group were less than those in model group, but NOS-positive neurons in two groups both reached their peaks at ischemia 72 hours [Cortical area: (15.46±3.02) vs.(30.52±4.73)/visual field; Preoptic area:(28.56±4.05) vs. (68.81±7.84)/visual field; medial corpora striatum:(21.09±3.83) vs.(45.71±5.24)/visual field; all P＜0.01].CONCLUSION: HBO obviously inhibits the degeneration of NOS-positive neurons in acute focal cerebral I/R injury regions of rats, such as cortical area, preoptic area, medial corpora striatum, and so on

BACKGROUND: Hyperbaric oxygen(HBO) is the first choice in the treatment of acute carbon monoxide(CO) poisoning. However,the mechanism of HBO in the treatment of CO poisoning,especially the mechanism in the treatmentof CO poisoning-induced delayed encephalopathy,is unclear at present.OBJECTIVE: To observe the pathological changes of hippocampal neurons in rats after acute CO poisoning to investigate the impacts of HBO therapy on Bcl-2 protein expression in hippocampal neurons in rats after CO poisoning.DESIGN: A completely randomized controlled experimental study based on the experimental animals.SETTING: Emergency department in a military medical university of Chinese PLA affiliated hospital,department of laboratory medicine in a municipal hospital,and the center of HBO therapy in a military medical university of Chinese PLA.MATERIALS: The study was conducted in the Laboratory of HBO Therapy Center,Faculty of Aerospace Medicine,the Fourth Military Medical University of Chinese PLA. Sixty male SD rats were selected.INTERVENTIONS: Sixty rats were randomly divided into 3 groups: normal control group(control group),CO poisoning group(CO group),and HBO therapy group(HBO group) with 20 rats each. Rats of each group were exposed under air or CO gas(volume fraction was 3.2 × 10-3) respectively for 60 minutes,and rats of CO-HBO group were treated by HBO. Cerebral pathological slices of hippocampus were prepared for routine HE and Bcl-2 staining to observe the characteristics of the changes of hippocampal neuronal injury and the Bcl-2protein expression on the 1st,3rd,5th and 7th day after CO poisoning.MAIN OUTCOME MEASURES: Changes of pathomorphology and Bcl-2protein expressionRESULTS: It could be seen lot of degenerated and necrotic neurons in hippocampus of rats in CO group. Degenerated and necrotic neurons decreased and the expression of Bcl-2 protein increased in CO-HBO group,especially on the 3rd and 5th day after poisoning( P ＜ 0. 05).CONCLUSION: HBO therapy can promote Bcl-2 protein expression in hippocampus after acute CO poisoning,so it can protect neurons.

Objective To study the efficacy of hyperbaric oxygen(HO)for the delayed encephalopathy after acute carbon monoxide poisoning(DEACMP)Method One hundred and eleven patients who were diagnozed as the DEACMP from November 2000 to March 2007 in Tangdu Hospital the Fourth Military Medical University were randomly divided into two groups.Thirty-six cases were treated by onventional approach(group A),and 76 cases by HO besides conventional treatment(group B).The efficacy of HO was evaluated after 4courses of treatment. The curative effects were evaluated as(1)cured:clinical symptoms and signs fully disappeared,abnormal electroencephalogram recovered,patients were completely self-help and competent enough for routine work.(2)improved:chnical symptoms and signs partly disappeared,abnormal electroencephalogram partly recovered,patients were partial self-help and incompetent enough for routine work.(3)inefficacy:patient's condition didn't changed.Data were expressed as((x)±s)and analyzed with the chi-quare test and t-test.The statistical significance was established as P＜0.05.Results In group B,62(81.58%)were in good recover,9(11.84%)improved and 5(6.94%)were inefficacy;while in group A:21(58.33%)were in good recover,5(13.89%)were improved and 10(27.78%)were inefficacy.The effciency rate in group B was significantly higher(93.42%)than that(72.22%)in group A(P＜0.05),and the required time for the therapeutic effect noticed time in group B were significantly shorter(P＜0.05)Conclusions HO Can improve the therapeutic effects on DEACMP

Objective To observe the injury of some chief organ induced by paraquat (PQ) poisoning in rats, and to explore the mechanism. Method A total of 60 inbred line SD rats were randomly divided into experimental group (n = 30) and control group (n = 30), and each group was further divided into 6 subgroups (n =5) as per the sacrifice of rats at different intervals. The rats of experimental group received the intra-abdominal injection of paraquat (1 mg/mL, 18 mg/kg), and the rats of control group were treated with the same amount of saline solution instead. The rats of each subgroup were sacrificed separately 2 h,6 h, 12 h,24 h,72 h and 120 h after administration of PQ or saline. Lungs, livers and kidneys were taken for histopathological study. Results There was noticeable exudate in lung tissue of rats in experimental group in the early stage. And then the cystic changes in the liver of rats in experimental group were found. A noticeable hemoglobin was found in the renal tubules 24 h after modeling. But the exudation in lung decreased 24 h later, and in the mean time, the disorganization of pulmonary alveoli was obvious and some remarkable collagen appeared in the interstitial tissue of lung, and it was significantly obvious 72 h after modeling. In the liver of rats in experimental group, the injured tissue had some extent of repair in 72 h after modeling, and recovered gradually. But the injury of kidney was exacerbated 72 h after modeling. In the control group, the lung, liver and kidney were not changed in all stages after modeling.Conclusions The paraquat could induce failure of some chief organs in SD rats. The injury was most remarkable in the lung in a progressive way. The kidney injury was not more severe than that of lung tissue, but the pathological changes of the kidney became worse and worse as time taken. The injury of liver induced by paraquat was slight, and the injury could heal up gradually.

Aim To explore the effect of miRNA-143 ( miR-1 4 3 ) on homocysteine ( Hcy ) induced-vascular smooth muscle cells ( VSMCs ) proliferation and the mechanism .Methods VSMCs were cultured and in-cubated with Hcy by using primary cultured method . Then, cells were treated with different concentrations of Hcy and folate .VSMCs proliferation was determined with MTT assay , miR-143 was measured by qRT-PCR, and methylation of miR-143 was determined with meth-ylated PCR.Results After cells were treated with dif-ferent concentrations of Hcy , the proliferation of VSMCs was significantly increased , mRNA expression of miR-143 was decreased and methylation of miR-143 was increased .The proliferation of VSMCs was signifi-cantly decreased when transfected VSMCs with miR-143 precursor , and cell proliferation was increased by using miR-143 inhibitor transfection .Conclusion Hy-pomethylation of miR-143 may inhibit VSMCs prolifera-tion.

Aim To investigate the role of miR-125 b and its DNA methylation in homocysteine ( Hcy )-in-duced vascular smooth muscle cells( VSMCs) prolifera-tion. Methods VSMCs were stimulated with 0,50, 100, 200, 500 μmol · L-1 Hcy respectively. Then qRT-PCR was used to detect the mRNA levels of miR-125b,and nested-touchdown methylation-specific PCR ( ntMS-PCR) was used to detect the methylation levels of miR-125b. VSMCs were transfected with miR-125b precursor or the inhibitor of miR-125b ,then 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyl tetrazolium bromide ( MTT ) assay was used to reflect the proliferation of VSMCs. The distribution of CpG islands of miR-125b promoter region was analyzed by bioinformatics meth-ods. VSMCs were stimulated with 100 μmol·L-1 Hcy and transfected with or without DNA methylation inhib-itors 5-nitrogen impurity cytidine ( AZC) , then the ex-pression of miR-125b was detected by qRT-PCR. Re-sults The mRNA levels of miR-125 b were decreased in 100,200,500 μmol·L-1 Hcy group compared with 0 μmol·L-1 Hcy group. The precursor of miR-125b could inhibit the proliferation activity and the inhibitor of miR-125 b could increase the proliferation activity of VSMCs cells. Bioinformatics analysis indicated that MiR-125 b promoter region had a CpG island whose length was 792 bp ( 1881-2672 ) . The miR-125 b pro-moter region methylation levels increased after Hcy in-tervention ( P <0. 01 ) . The expression level of miR-125 b increased after AZC intervention ( P <0. 05 ) . Conclusions ① Hcy promotes vascular smooth mus-cle cell proliferation maybe by down-regulating the ex-pression of miR-125b. ② Hcy down-regulates the ex-pression of miR-125 maybe by up-regulating the methy-lation levels of miR-125b promoter region.

Objective:To investigate whether the lung specific X protein(LUNX)gene can serve as a prognostic biomarker for non-small cell lung cancer related to immune cell infiltration.Methods:A total of 280 non-small cell lung cancer patients admitted to Hengshui People's Hospital from January 2020 to January 2023 were selected to detect the expression of LUNX gene in cancer tissue and adjacent tissues,and to analyze the relationship between LUNX gene and immune cell infiltration and prognosis survival status in the tumor microenvironment.Results:Compared with adjacent tissues,the expression level and positive rate of LUNX gene in non-small cell lung cancer tissue were increased,which were related to differentiation degree,lymph node metastasis and tumor staging(P<0.05).GEPIA database analysis showed that the LUNX gene was only slightly expressed or not expressed in other tissues,while its expression was elevated in LUAD and LUSC(P<0.05).The copy number of LUNX gene and LUNX gene were related to the level of immune cell infiltration(P<0.05).Survival analysis showed that high expression of the LUNX gene was associated with patient survival prognosis(P<0.05).Conclusion:The LUNX gene is specifically expressed in non-small cell lung cancer tissue,affecting the level of immune cell infiltration in non-small cell lung cancer,leading to an imbalance in the immune microenvironment,and is an important mechanism for causing patients prognostic death,which can be used as a prognostic biomarker for evaluating immune cell infiltration.