1.Lipoxygenase-mediated oxidative metabolism and oxidative stress
Chinese Journal of Pharmacology and Toxicology 2014;(3):449-454
There is a close relationship between oxidative stress induced tissue damage and many diseases.As a multi-function oxidase,lipoxygenase can generate reactive oxygen species (ROS)by oxidatively metabolizing various endogenous and exogenous chemicals such as drugs and environmental pollutants.Lipoxygense can catalyze endogenous che mical reaction,such as arachidonic acid and pro-duce ROS.Lipoxygenase can be also activated in other ways to generate ROS by activating signal trans-duction.Moreover,some exogenous chemicals can be metabolized into highly reactive radical intermedi-ates by lipoxygenase,inducing ROS generation.The accumulation of intracellar ROS can damage intra-cellar redox balance and induce oxidative stress.That may be one of the possible toxic effect mecha-nis ms of che mical agents.
2.Intermittent exercise promotes collateral circulation in ischemic myocardial tissue
Xiao LU ; Jianan LI ; Tao WU ; Peng HUANG ; Feng QIU ; Xiangbo MENG ; Jing GAO
Chinese Journal of Physical Medicine and Rehabilitation 2009;31(9):587-592
Objective To observe whether appropriate intermittent exercise at the ischemic threshold can safely promote collateral circulation in an ischemic area of the myocardium through the increased expression of vascular endothelial growth factor(VEGF)and its receptor fetal liver kinase-1(Fik-1). Methods A balloon constrictor was surgically implanted in the first obtuse marginal coronary artery(OM1)of miniature pigs.The subjects were divided into 3 groups:a sham-operation group,a pure ischemia group,and an exercise training group.Subjects in the exercise training group performed individualized treadmill programs 30 min daily,5 d per week,for 8 weeks,including 2 two-minute episodes of exercise-induced ischemia.Two pre-exercise episodes of pure ischemia induced by brief OM1 occlusion were also conducted.Only pure ischemia was induced in the pure ischemia group,and the sham-operation group remained sedentary for the experimental period.Relative myocardial blood flow(RMBF)was measured using microspheres.VEGF and Flk-1 expression levels were measured by Western blotting and real time RT-PCR analyses.Cardiac troponin I(ctnI)levels were determined using an enzyme-linked immunosorbent assay(ELISA). Light and electron microscopy were employed to examine myocardia damage in the ischemic area.Results RMBFs in the exercise training group were significantly higher than those in the pure ischemia and sham-operation groups. RMBFs in the pure ischemia group were significantly higher than those in the sham-operation group.The expression of VEGF and Flk-1 proteins and mRNAs in the exercise training group were significantly higher than those in the pure ischemia and sham-operation groups,and the levels in the pure ischemia group were also significantly higher than those in the sham-operation group.After training,no myocardial damage and no ctnI increase was observed in the pure ischemia group.Microscopy revealed no obvious structural changes. Conclusion Intermittent exercise at the isehemia threshold intension can safely promote coronary collateral formation through upregulation of VEGF and Flk-1 expression in the ischemic myocardial area of a porcine model.
3.Influence of frequency of ventilator pipe replacement on bacterial colonization in patients with abdominal infection
Taohua ZHENG ; Xianghong YE ; Weiqin LI ; Nanhai PENG ; Yunzhao ZHAO ; Jianan REN
Chinese Journal of Practical Nursing 2010;26(25):17-19
Objective To discuss the frequency of ventilator pipe replacement in ICU ward for reducing the frequency of VAP occurrence caused by bacterial colonization in ventilator-line. Methods 30 patients hospitalized to ICU ward from Janurary,2008 to June, 2009 who had mechanical-ventilation above 48h were randomly divided into group A, B and C with 30 patients in each group, then bacteria culture and strain analysis were employed for the pipeline sample of ventilator inspiratory side at the time point to be use and used mechanical ventilation for 1 day, 3 days and 7 days. Results There was no bacteria grew after ventilator-line sterilization, and positive ratio of bacterial culture in 1d, 3d and 7d were 46.66%,53.33% and 100.00%, respectively. Conclusions The frequency of ventilator pipe replacement should be shortened in patients with abdominal infection, to replace every 3 days is suitable in ICU where infectious patients gathered.
4.Effect of asymptomatic hyperuricemia on the postoperative functional recovery in patients with knee joint re-placement
Zhikui YANG ; Jianan DAI ; Xi CAO ; Yonggang LI ; Peng LI ; Xin GAO ; Chong LIU
Journal of Regional Anatomy and Operative Surgery 2016;25(11):834-836,837
Objective To evaluate the effect of asymptomatic hyperuricemia on the postoperative functional recovery in osteoarthritis (OA)patients with knee joint replacement.Methods Among the 294 patients who recieved knee joint replacement in our hospital from Feb-ruary 2013 to September 2015,a total of 187 patients were included in this study with 79 cases in the hyperuricemia group and the other 108 cases in the control group.The WOMAC index of the two groups were analyzed before the surgery,2 weeks,3 months,and 6 months after the knee joint replacement surgery.Multivariable linear regression was performed to test the effect of impact factors on the variation of WOMAC index.Results The WOMAC index of the two groups significantly increased 2 weeks after surgery,and the difference was statistically signifi-cant(P <0.05).And the WOMAC index of the control group was higher than that in the hyperuricemia group 2 weeks and 3 months after sur-gery with statistically significant difference(P <0.05).Conclusion The uric acid level before surgery was a influence factor of WOMAC index, and high uric acid level before knee joint replacement has negatively impact for the postoperative functional recovery in the osteoarthritis patients.
5.Follow-up study on pedicle fixation for treatment of thoracolumbar burst fractures in patients with osteoporosis
Zhikui YANG ; Jianan DAI ; Xi CAO ; Yonggang LI ; Peng LI ; Xin GAO ; Chong LIU ; Mei ZHENG
Journal of Regional Anatomy and Operative Surgery 2017;26(8):581-585
Objective To explore the effect of pedicle fixation for treatment of thoracolumbar burst fractures in patients with osteoporosis,and to provide more evidence for the treatment.Methods Retrospectively analyzed the clinical data of 121 patients with osteoporotic vertebral burst fracture from June 2012 to October 2015.And these patients were divided into two groups according to different operation methods, namely the control group (n=56) who were given short segment fixation and the observation group (n=65) who were given single segment fixation.The visual analogue scale(VAS),Oswestry disability index(ODI),vertebral height,kyphotic angle and bone mineral density of the two groups were analyzed before surgery and 3 days,1 month,3 months and 12 months after surgery.Results The VAS score,ODI score,vertebral height,and Cobb angle of the injured vertebra were significantly improved in both of the two groups,and the difference was statistically significant (P<0.05).The VAS score of the observation group was better than that of the control group 3 days after surgery with statistically significant difference (P<0.05).But there was no significant difference 3 months,6 months and 12 months after surgery(P>0.05).The ODI score of the observation group was better than that of the control group 3 days and 3 months after surgery with statistically significant difference (P<0.05),and there was no significant difference between the two groups till the end of follow-up.Pedicle fixation at the injured vertebra significantly improved the vertebral height and Cobb angle with statistically significant difference (P<0.05).And the anti-osteoporosis treatment significantly increased the bone mineral density (P<0.05).Conclusion Pedicle fixation at the injured vertebra is useful in pain relief as well as function and anatomical structure restoring.And anti-osteoporosis treatment is necessary for the bone mineral density increase.
6.Lycium barbarum polysaccharides alleviate kidney injury and oxidative stress in unilateral ureteral obstruction rats
Huan ZHOU ; Na TIAN ; Lihua WU ; Jianan PENG ; Yi DING ; Menghua CHEN
Chinese Journal of Nephrology 2018;34(5):377-384
Objective To investigate the effect of lycium barbarum polysaccharides (LBP) on oxidative stress in renal tissue of rats with renal interstitial fibrosis (RIF).Methods The RIF rat model was established by unilateral ureteral obstruction (UUO).A total of 108 specified pathogen free (SPF) class healthy adult male Sprague-Dawley (SD) rats were randomly divided into sham operation group,UUO model group and treatment group.The treatment group was further divided into low,medium and high dose of LBP groups and benazapril group.From the next day of the operation,the rats were given continuous intragastric administration for 3 weeks.The LBP low,medium and high dose groups were given 400,600,800 mg · kg1 · d-1 LBP,respectively.The benazapril group was administered with 1.05 mg · kg-1 · d-1 benazepril hydrochloride.The sham operation group and UUO model group were daily fed normal saline solution by gavage.Six rats were sacrificed randomly at 7,14 and 21 days after operation.Their blood samples were collected to detect the serum creatinine (Scr) and the kidney organ index was calculated.The pathological changes on the surgical side were observed by both HE staining and Masson staining.Meanwhile,the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the renal tissue were detected by colorimetry detection.The expression of transforming growth factor-β1 (TGF-β1) protein was detected by immunohistochemical staining and the expression of TGF-β1 mRNA was detected by real time PCR.Results (1) Compared with the sham group,the Scr and kidney organ index of the UUO model group and treatment groups increased at each time point (all P < 0.05).Compared with the UUO model group,the kidney organ index of LBP low dose group in the 7th days,the LBP medium and high dose group in the 21st days as well as benazapril group in the 7th and 21st days were significantly lower (all P < 0.05).(2) Renal pathological change:compared with the sham operation group,both the renal tubular interstitial injury index and collagen positive area of the else groups were higher at each time point (all P < 0.05).Compared with the UUO group,the tubulointerstitial injury index and collagen staining positive area of LBP dose groups and benazapril group significantly decreased at different time points (all P < 0.05).(3) Compared with the sham group,in renal tissue of the other groups the level of MDA increased,SOD level decreased,while the expressions of TGF-1 mRNA and protein increased (all P < 0.05).Compared with the UUO model group,LBP low,medium and high dose group as well as benazapril group had lower MDA level,higher SOD level as well as lower expressions of TGF-1 mRNA and protein at each time point (all P < 0.05).Conclusions The pathological injury in UUO rats can be improved by the LBP.The LBP can alleviate the oxidative stress status of the kidney tissue by decreasing MDA and increasing SOD.The further study on the LBP delaying the progression of RIF is to be conducted.
7.Characterization of 19 novel gene mutation sites associated with autosome-dominant polycystic kidney disease
Junlan YANG ; Siqi PENG ; Zhiyuan WEI ; Jianan JIANG ; Bin WANG ; Fengmei WANG ; Xiaotong XIE ; Tian XU ; Xiaoliang ZHANG
Chinese Journal of Internal Medicine 2024;63(9):866-873
By analyzing the of genetic testing data of patients with renal polycystic kidney disease and their relatives, this study aims to identify unreported novel gene mutation sites associated with autosomal dominant polycystic kidney disease (ADPKD). Structural prediction software was employed to investigate protein structural changes before and after mutations, explore genotype-phenotype correlations, and enrich the ADPKD gene database. In this single-center retrospective study, patients with multiple renal cysts diagnosed from January 2019 to February 2023 at the Zhong Da Hospital Southeast University were included. Genetic and clinical data of patients and their families were collected. Unreported novel gene mutation sites associated with ADPKD were identified. The AlphaFold v2.3.1 software was used to predict protein structures. Changes in protein structure before and after mutations were compared to explore genotype-phenotype correlations and enrich the ADPKD gene database. Twelve mutated genes associated with renal cysts were detected in 52 families. Nineteen novel gene mutation sites associated with ADPKD were identified, including 17 mutations in the PKD1 gene (one splicing mutation, seven frameshift mutations, four nonsense mutations, one whole-codon insertion, and four missense mutations); one ALG9 missense mutation; and one chromosomal structural variation. Truncating mutations in the PKD1 gene were correlated with a more severe clinical phenotype, while non-truncating mutations were associated with greater clinical heterogeneity. Numerous novel gene mutation sites associated with ADPKD remain unreported. Therefore, it is essential to analyze the pathogenicity of these novel mutation sites, establish genotype-phenotype correlations, and enrich the ADPKD gene database.
8.Foundation of acute symptomatic osteoporotic thoracolumbar fracture classification system and its validity examination and clinical application evaluation
Dingjun HAO ; Jianan ZHANG ; Junsong YANG ; Tuanjiang LIU ; Xiaohui WANG ; Peng LIU ; Liang YAN ; Yuanting ZHAO ; Qinpeng ZHAO ; Dageng HUANG ; Jijun LIU ; Shichang LIU ; Yunfei HUANG ; Yuan TUO ; Ye TIAN ; Lulu BAI ; Heng LI ; Zilong ZHANG ; Peng ZOU ; Pengtao WANG ; Qingda LI ; Xin CHAI ; Baorong HE
Chinese Journal of Trauma 2021;37(3):250-260
Objective:To establish the acute symptomatic osteoporotic thoracolumbar fracture (ASOTLF) classification system, and to examine the reliability and evaluate the effect of clinical application.Methods:A retrospective case series study was conducted to analyze the clinical data of 1 293 patients with osteoporotic thoracolumbar fracture(OTLF) admitted to Honghui Hospital from January 2016 to December 2018. There were 514 males and 779 females, aged 57-90 years [(71.4±6.3)years]. The T value of bone mass density was -5.0--2.5 SD [(-3.1±-0.4)SD]. According to the clinical symptoms a and fracture morphology, OTLF was divided into 4 types, namely type I(I occult fracture), type II(compressed fracture), type III (burst fracture) and type IV(unstable fracture). The type II was subdivided into three subtypes (type IIA, IIB, IIC), and the Type III into two subtypes (type IIIA, IIIB). of all patients, 75 patients (5.8%) were with type I, 500 (38.7%) with type II A, 134 (10.4%) with type IIB, 97 (7.5%) with type IIC, 442 (34.2%) with type IIIA, 27(2.1%) with type IIIB and 18 (1.4%) with type IV. After testing the validity of the classification, different treatment methods were utilized according to the classification, including percutaneous vertebroplasty (PVP) for Type I, PVP after postural reduction for Type II, percutaneous kyphoplasty (PKP) for Type IIIA, posterior reduction and decompression, bone graft fusion and bone cement-augmented screw fixation for Type IIIB, and posterior reduction, bone graft fusion and bone cement-augmented screw fixation for Type IV. The visual analog score (VAS), Oswestry disability index (ODI), Frankel grade of spinal cord injury, local Cobb Angle, and vertebral body angle (vertebral body angle) were recorded in all patients and in each type of patients before surgery, at 1 month after surgery and at the last follow-up. The neurological function recovery and complications were also recorded.Results:The patients were followed up for 24-43 months [(29.9±5.1)months]. A total of 3 000 assessments in two rounds were conducted by three observers. The overall κ value of inter-observer credibility was 0.83, and the overall κ value of intra-observer credibility was 0.88. The VAS and ODI of all patients were (5.8±0.7)points and 72.5±6.6 before surgery, (1.8±0.6)points and 25.0±6.3 at 1 month after surgery, and (1.5±0.6)points and 19.5±6.2 at the last follow-up, respectively (all P<0.05). The Cobb angle and vertebral body angle of all patients were (13.0±9.1)° and (8.0±4.6)° before surgery, (7.9±5.2)° and (4.6±2.9)° at 1 month after surgery, and (9.1±6.0)° and (5.8±3.0)° at the last follow-up, respectively (all P<0.05). At the last follow-up, VAS, ODI, Cobb Angle and VBA of each type of patients were significantly improved compared with those before surgery (all P<0.05). The spinal cord compression symptoms were found 1 patient with type IV and 5 patients with type IIIB preoperatively. At the last follow-up, neurological function improved from grade C to grade E in 1 patient and from grade D to grade E in 5 patients ( P<0.05). The lower limb radiation pain or numbness in 3 patients with type IV and 22 patients with type III preoperatively were fully recovered after surgical treatment at the last follow-up except for three patients. Conclusions:The ASOTLF classification is established and has high consistency and reliability. The classification-oriented treatment strategy has achieved a relatively satisfactory effect, indicating that the classification has a certain guiding significance for treatment of OTLF.
9.Causes of residual back pain at early stage after percutaneous vertebroplasty
Junsong YANG ; Hao CHEN ; Peng LIU ; Tuanjiang LIU ; Jijun LIU ; Zhengping ZHANG ; Baorong HE ; Liang YAN ; Haiping ZHANG ; Yuanting ZHAO ; Jianan ZHANG ; Dageng HUANG ; Dingjun HAO
Chinese Journal of Orthopaedics 2020;40(10):625-634
Objective:To explore the risk factors of residual back pain (RBP) in patients undergone PVP within 1 month and further analyze the correlation.Methods:Between March 2013 and January 2015, 1 316 patients with OVCF were treated by PVP. RBP after PVP was defined as a visual analogue scale (VAS) score of > 4 both 1 week and 1 month post-operatively. According to the pain relief, the patients were divided into two groups, the satisfied group and the unsatisfied group. All patients were scheduled for follow-up at1 week, 1 month, 3 months, and 1 year post-operatively, during which radiography and magnetic resonance imaging (T1-weighted, T2-weighted, and short time inversion recovery (STIR) sequences) were recommended to detect the existence of secondary OVCF. VAS scores and Oswestry disability index (ODI) were recorded. Demographic data, surgical information, anesthesia method, number of OVCF, injection amount of cement of single vertebral bone, imaging data and other comorbidity informations of patients in the two groups were analyzed by Logistic regression for the factors related to RBP after PVP.Results:Among 1 316 patients, 60 cases complained RBP, and the prevalence was 4.6%. VAS score and ODI of the two groups were significantly different at 1 week, 1 month and 3 months after surgery, suggesting there was a certain degree of residual pain in the lower back of patients in the unsatisfied group, which was more severe than that in the satisfied group. However, the above differences disappeared in the follow-up of 12 months after surgery.Univariate analysesshowed that preoperative bone mineral density (BMD), number of fracture, cement distribution and volume injected per level and lumbodorsal fascia contusion were associated with RBP after PVP ( P< 0.01, retrospectively). Multivariate analysis revealed that the absolute value of pre-operative BMD(odds ratio ( OR)=3.577, P=0.029), combined withlumbodorsal fascia contusion ( OR=3.805, P=0.002), number of fracture ( OR=3.440, P<0.001), satisfactory cement distribution ( OR=3.009, P=0.013) and combined with depression ( OR=3.426, P=0.028) were positively correlated with RBP after PVP, and these were risk factors. The injection amount of cement of single vertebral bone ( OR=0.079, P<0.001) was negatively correlated with RBP after PVP, which was a protective factor. Conclusion:Pre-operative low BMD, lumbodorsal fascial injury, multiple segment OVCF, insufficient cement injected volume, unsatisfactory cement distribution and depression were risk factors associated with RBP after PVP in patients with OVCF.
10.Effect of crizotinib on TGF-β1 signaling pathway in acute radiation-induced lung injury in mice
Qingqing HANG ; Hangjie YING ; Jianan JIN ; Min FANG ; Yong BAO ; Ming CHEN ; Fang PENG
Chinese Journal of Radiological Medicine and Protection 2022;42(6):408-415
Objective:To study the effect of crizotinib on acute radiation-induced lung injury in mice and its possible mechanism.Methods:A total of 72 mice were randomly divided into 4 groups by the random number table method: healthy control group (NC group, n=12), crizotinib-only group (CRZ group, n=12), radiotherapy-only group (RT group, n=24), and radiotherapy pluscrizotinib group (RT+ CRZ group, n=24). The whole lungs were exposed to a single dose of 12 Gy X-rays. Lung tissue and bronchoalveolar lavage fluid (BALF) were obtained at 1, 2, 4, and 8 weeks after radiotherapy. The total number of nucleated cells was counted under a light microscope, and the total protein content of BALF was detected by bicinchoninic acid (BCA) protein assay. The pathological changes of lung tissue were observed by HE staining and MASSON staining. The expressions of TGF-β1 and ICAM-1 mRNA in lung tissue were detected by real-time quantitative polymerase chain reaction (qPCR), the locations and expressions of MPO and ICAM-1 proteins were observed by immunohistochemical staining, and the expressions of TGF-β1, Smad3, p-Smad3 and ICAM-1 proteins in lung tissue were detected by Western blot. Results:At different time points after irradiation, the pathological manifestations such as inflammation and exudation of lung tissue in the RT+ CRZ group were significantly increased, and the total number of cells and protein content in BALF was higher than that of the other three groups, compared with RT group, the difference was statistically significant at 4 week ( t=-5.031, -2.814, P<0.05). Compared with RT group, the expressions of ICAM-1 and TGF-β1 mRNA in lung tissue of the RT+ CRZ group were significantly increased, while the expression of TGF-β1 increased significantly at 1, 4 and 8 weeks after irradiation ( t=-2.687, -7.032, -5.221, P<0.05), and the expression of ICAM-1 increased significantly at 2 and 4 weeks after irradiation ( t=-4.819, -6.057, P<0.05). The expressions of these two gradually increased from 1 to 4 weeks and peaked in 4 weeks, then decreased at 8 weeks. At the same time, the trend of the expression of MPO mRNA was consistent with ICAM-1 and TGF-β1. At 4 week, there was no difference in the expression of Smad3 protein in these four groups ( P>0.05). The expressions of TGF-β1, p-Smad3, ICAM-1 and p-Smad3/Smad3 proteins of the RT+ CRZ group were all higher than those of the other three groups ( F=14.74, 10.03, 35.29, 22.94, P<0.05). Conclusions:Crizotinib combined with radiotherapy can aggravate acute radiation-induced lung injury, which may due to the increase of ICAM-1 expression by up-regulating the TGF-β1 signaling pathway.