1.Role of mTOR signaling pathway in dexmedetomidine-induced reduction of renal ischemia-reperfusion injury in rats: the relationship with HIF-1α
Jianbo ZHANG ; Xiaoqiao WANG ; Xiaodi QIU ; Lingzhi WANG ; Huansen HUANG
Chinese Journal of Anesthesiology 2015;35(11):1391-1394
Objective To evaluate the role of mammalian target of rapamycin (mTOR) signaling pathway in dexmedetomidine-induced reduction of renal ischemia-reperfusion (I/R) injury in rats and the relationship with hypoxia-inducible factor 1 (HIF-1α).Methods Seventy-two male Sprague-Dawley rats, aged 10-12 weeks, weighing 220-260 g, were randomly divided into 4 groups (n=18 each) using a random number table: sham operation group (group S), group I/R, dexmedetomidine group (group Dex) ,and rapamicyn + dexmedetomidine group (group Rpm+Dex).Renal I/R was produced by occlusion of bilateral renal pedicles for 35 min follow by reperfusion in anesthetized rats in I/R, Dex and Rpm+Dex groups.Bilateral renal pedicles were only exposed, and then the abdominal cavity was closed in group S.Dexdetomidine 50 μg/kg was injected intraperitoneally at 30 min before I/R in group Dex.In group Rpm+Dex, rapamicyn 1.5 mg/kg and dexdetomidine 50 μg/kg were injected intraperitoneally, and renal I/R model was established 30 min later.Immediately after onset of reperfusion, and at 4 and 24 h of reperfusion (T1-3) , blood samples were collected from the caudal vein for measurement of serum creatinine and blood urea nitrogen (BUN) concentrations.After blood sampling at T1-3, the rats were sacrificed, and the renal specimens were obtained for detection of HIF-1αt, erythropoietin (EPO) and mTOR expression by Western blot.Their kidneys were removed at T3, and cut into sections which were stained with haematoxylin and eosin and examined under microscope.Acute renal tubular necrosis was scored.The cell apoptosis in renal tissues was detected by TUNEL assay, and apoptosis index (AI) was calculated.Results Compared with group S,the concentrations of serum creatinine and BUN, expression of HIF-1α, EPO and mTOR at T2,3 , AI at T3 and acute renal tubular necrosis score were significantly increased in the other three groups (P< 0.05).Compared with group I/R, the concentrations of serum creatinine and BUN were significantly decreased, and the expression of HIF-1α, EPO and mTOR was up-regulated at T2,3 , and AI and acute renal tubular necrosis score were decreased in group Dex (P<0.05) , and no significant change was found in the parameters mentioned above in group Rpm + Dex (P > 0.05).Conclusion The mTOR signaling pathway is involved in dexmedetomidine-induced reduction of renal I/R injury, which may be related to dexmedetomidine-produced up-regulation of HIF-1α expression in renal tissues of rats.
2.Protection effect of dexmedetomidine against H2O2 injury by up-regulating HIF-1α in human renal tubular epithelial cells
Jianbo ZHANG ; Xiaoqiao WANG ; Xiaodi QIU ; Lin RUAN ; Huansen HUANG
The Journal of Practical Medicine 2016;32(7):1084-1087
Objective To investigate the protection effect of dexmedetomidine against H2O2 injury in Human renal tubular epithelial cells(HK-2 cells). Methods HK-2 cells cultured in vitro were randomly divided into four groups(n = 24): control group, dexmedetomidine pretreatment group, H2O2 injury group, H2O2 injury +dexmedetomidine pretreatment group. Cell viabilities were measured by MTS assay, cell apoptosis were detected using flow cytometry, and expression of HIF-1α protein was quantified by western blot. HK-2 cells were divided into 8 groups by combining with three treatment factors such as PI3K inhibitor LY294002, dexmedetomidine and H2O2 injury. MTS assay was used to detect cell viability and western blot was used to quantify protein expression of HIF-1α,Bcl-2 and Bax after treatment in each group. Results Dexmedetomidine significantly increased the level of HIF-1α、 Bcl-2 in HK-2 cells after H2O2 injury, thus improved viabilities and reduced apotosis of cells. Moreover, effect on H2O2 injury cells of Dexmedetomidine was reversed by PI3K inhibitor LY294002. Conclusion Dexmedetomidine could protect against H2O2 injury by up-regulating HIF-1α expression through activating PI3K/Akt/mTOR signaling pathway in HK-2 cells.
3.Effects of shenshuning recipe on expression of hepatocyte growth factor in rats with glomerulosclerosis
Lifen ZHANG ; Shili CAO ; Wenzheng HUANG ; Yaoguang WANG ; Xiaodi ZHU
Journal of Integrative Medicine 2006;4(3):289-92
OBJECTIVE: To investigate the effects of Shenshuning Recipe (SSNR) on gene expression of hepatocyte growth factor (HGF) in renal tissues in rats with glomerulosclerosis. METHODS: Glomerulosclerosis was induced in 42 rats by unilateral nephrectomy and intravenous injection of doxorubicin. Then these 42 rats were randomly divided into three groups: untreated group, SSNR-treated group and benazepril-treated group. Another eight rats were included into sham-operation group. The rats in the SSNR-treated group and the benazepril-treated group were fed SSNR or benazepril respectively for 8 weeks. The levels of 24 h urine protein (Upr), serum creatinine (Cr) and blood urea nitrogen (BUN) of rats in each group were examined. The renal morphological changes were observed under microscope, and the diameter of glomerular capillary, mesangial matrix and glomerulosclerosis index were analyzed by image analysis software. Reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect the gene expression of HGF in the renal tissues. RESULTS: The levels of 24 h Upr, serum Cr and BUN in the untreated group were remarkably increased than those in the sham-operation group (P<0.01). The pathological morphological changes in the untreated group showed that the glomerulosclerosis was diffused around the renal tissue and the capillaries were shrunk. The expression level of mesangial matrix was up-regulated and the glomerulosclerosis index was 3.32+/-0.35. The expression level of HGF mRNA in the untreated group was obviously lower than that in the sham-operation group (P<0.05). The levels of 24 h Upr, serum Cr and BUN in the SSNR-treated group and the benazepril-treated group were remarkably decreased as compared with those in the untreated group, while the expression levels of HGF mRNA were both obviously higher than that in the untreated group (P<0.01). The pathological morphological changes in the SSNR-treated group and the benazepril-treated group were both alleviated. There was no significant difference in therapeutic effect between the SSNR-treated group and the benazepril-treated group. CONCLUSION: Shenshuning Recipe can up-regulate the expression of HGF mRNA, decrease the mesangial matrix, and improve the renal function, so that it may retard the development of glomerulosclerosis.
4.Screening and analysis of Chinese herbs with liver channel tropism acting on human liver cancer cell differential expressed protein tyrosine kinase
Xuefei TIAN ; Xiaodi HUANG ; Qing ZHOU ; Zhiqi WANG ; Sha TIAN ; Yuan CHEN
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2015;22(3):227-233
Objective To screen the Chinese drugs with liver channel tropism acting on the characteristic differential expressed protein of human liver cancer cell protein tyrosine kinase (PTKs) system by protein chip technology, and to analyze the difference in different Chinese drugs with liver channel tropism in relation to PTKs regulation. Methods Forty BALB/C nude mice were chosen; a piece of subcutaneous tumor mass was implanted into the left lobe of liver parenchyma to reduplicate the orthotopically implanted tumor models. After modeling for 10 days, the tumorigenicity was confirmed, and all the nude mice models were divided into four groups; different Chinese medicine extracts were injected intra-peritoneally into corresponding treatment groups respectively, and the methods of treatment in the 4 groups were as follows: In liver channel tropism drug pair of Huayu Xiaozhen group, rhizoma sparganii and curcuma zedoary with dosage containing crude drug 4.5 g·kg-1·d-1 was given, in liver channel tropism drug pair of Gongdu Sanjie group, the extract of centipede and scorpion with dosage containing crude drug 0.3 g·kg-1·d-1 was intra-peritoneally injected, in spleen channel tropism drug pair control group, astragalus and rhizoma atractylodis macrocephalae with dosage containing crude drug 6.3 g·kg-1·d-1 was given, and in the model group, equal amount of 0.9% normal saline was intra-peritoneally injected. After the drug treatment for 3 weeks, the mice were sacrificed and the liver cancer tissue was obtained; after its total protein was extracted, protein chip technology was applied to screen the Chinese drug pair with liver channel tropism acting on differential expressed PTKs of human liver cancer cells, and the results were analyzed by cluster analysis.Results After the end of the experiment, there were 6 animals in Huayu Xiaozhen drug pair group, 5 in Gongdu Sanjie drug pair group, 5 in control drug pair group and 7 in model group. The protein chip screening results showed that the adjusting fold greater > 1.50 or < 0.67 was defined as the difference with statistical significance. Compared with model group, there were 42 up-regulated expressions of PTKs in Huayu Xiaozhen drug pair group, including 29 receptor tyrosine kinases (RTKs) and 13 non-receptor protein tyrosine kinases (nrPTKs) of which the erythropoietin having adjusting fold over 5.0 produced liver cell receptor B1 (EphB1), epidermal growth factor receptor (ErbB2, ErbB4) etc. 3 RTKs; there were 7 RTKs with adjusting fold 3.0 - 5.0 including EphA1, EphA3, EphA7, fibroblast growth factor receptor 2-α (FGFR2-α), hepatocyte growth factor receptor (HGFR), macrophage colony-stimulating factor receptor (M-CSFR) and vascular endothelial growth factor receptor 2 (VEGFR2), and 2 nrPTKs with adjusting fold 3.0 - 5.0 were non-receptor tyrosine kinase BMX (BMX) and Janus kinase 1 (JAK1). In the Gongdu sanjie drug pair group, there were 23 up-regulated expressions: 15 RTKs and 8 nrPTKs, and 6 down-regulated expressions; the RTKs with adjusting fold 3.0 - 5.0 were ErbB4, M-CSFR and 1 nrPTKs that was megakaryocyte-associated tyrosine kinase (MATK). In the control drug pair group, there were 28 up-regulated and 8 down-regulated expressions. The results of cluster analysis showed that in Huayu Xiaozhen drug pair group, there were 17 differential expressed PTKs in accord with the screen criteria of which 9 were RTKs [receptor tyrosine kinase-like orphan receptor 2 (ROR2), stem cell factor receptor (SCFR), anaplasia lymphoma kinase (ALK), platelet-derived growth factor receptor β (PDGFR-β), insulin-like growth factor-IR receptor (IGF-IR), ErbB2, ErbB3, EphB1 and EphA2], 1 nrPTKs [fps/fes related tyrosine kinase (FER)] and 7 PTKs 3 RTKs (M-CSFR, FGFR2-α, EphA3) and 4 nrPTKs [acetate kinase 1 (ACK1), bruton tyrosine kinase (Btk), non-receptor tyrosine kinase ABL1 (ABL1) and BMX]. In Gongdu Sanjie drug pair group, there were 7 differential expressed PTKs in accord with the screen criteria 5 RTKs (M-CSFR, FGFR1, ROR2, EphB1, ErbB2) and 2 nrPTKs [src-related kinase lacking C-terminal regulation and N-terminal myristylation sites (SRMS), FER]. Conclusions The drug pair of centipede and scorpion with Gongdu Sanjie action possesses a more effective anti-HCC role than the drug pair of rhizoma sparganii and curcuma zedoary with Huayu Xiaozhen action, the mechanism is possibly via the regulation of PTKs signal pathway. The liver channel tropism drug pair of rhizoma sparganii and curcuma with action of promoting blood circulation and removing blood stasis possibly has an independent anti-HCC effective pathway outside the PTKs signal system.
5.Experience and analysis of excellent works of human parasitology in nation-al medical colleges and universities
Xiaodi YANG ; Qiang FANG ; Yang CHENG ; Xuelian CHANG ; Zhiyong TAO ; Yuanyuan WANG ; Xiaoli WANG ; Jiangyan LI ; Shiya HUANG ; Yumeng JIAO ; Xuemei WANG ; Hui XIA ; Xingzhi CHEN
Chinese Journal of Schistosomiasis Control 2017;29(3):369-371,376
Teaching competition is an effective way for college and university teachers to improve their teaching skills. Based on the teaching practice and experience in medical parasitology,this paper discusses several key issues in teaching competition including topics,teaching designs and teaching methods. It provides references for the teachers in department of parasitology of universities and colleges to improve the quality of classroom teaching.
6.Mechanism of blood brain barrier in the pathogenesis and therapeutics of multiple sclerosis
Yan JIA ; Yue HUANG ; Jiewen ZHANG ; Junkui SHANG ; Mingfang ZHU ; Xiaodi HAO
Chinese Journal of Neurology 2022;55(6):655-658
Multiple sclerosis (MS) is an idiopathic inflammatory demyelinating diseases of the central nervous system, the underlying cause of which has not been cleared. Previous studies have shown that the pathogenesis of MS is related to the destruction of blood brain barrier, furthermore the drugs used to treat MS have a certain protective effect on the function of blood brain barrier. Therefore, this review combines the research progress at home and abroad to clarify the relationship between the blood brain barrier and MS in pathogenesis and treatment, proposing possible orientation of development.
7.Clinical analysis of critically ill children with heparin-induced thrombocytopenia during extracorporeal membrane oxygenation
Shuyan GAN ; Meixiu LIU ; Saihu HUANG ; Gangfeng YAN ; Xiaodi CAI ; Weiming CHEN ; Guoping LU
Chinese Pediatric Emergency Medicine 2022;29(11):863-867
Objective:To prospectively investigate the prevalence of heparin-induced thrombocytopenia (HIT) in critically ill children during extracorporeal membrane oxygenation(ECMO) and explore the clinical characteristics and prognosis of HIT during ECMO.Methods:A total of 22 critically ill children, who had received ECMO support for more than 96 hours in the Intensive Care Unit at the Children′s Hospital of Fudan University from March 2019 to December 2020, were enrolled.According to the 4T score and the heparin/platelet factor 4(PF4) antibody, children whose 4T scores were not less than 6 and heparin/ PF4 antibodies were positive, were classified into HIT group ( n=6), and non-HIT group ( n=16). The clinical outcomes and the incidence of thrombotic events were compared between two groups. Results:The incidence of HIT during ECMO in critically ill children was 27% in this study.The incidence of thrombosis in the ECMO circuit in the HIT group was higher (100% vs.63%, P=0.133), and the average time to the first thrombosis in ECMO circuit in the HIT group was shorter than that in the non-HIT group (3.70 d vs.5.44 d, P=0.06). During the first 14 days of ECMO, the proportion of children with thrombotic events no less than twice was higher in the HIT group (67% vs.19%, P=0.054). There was no significant difference regarding the survival rate at 28 days after ECMO withdrawal between two groups (33% vs.50%, P=0.664). Conclusion:The prevalence of HIT during ECMO in critically ill children is high.Thrombosis events tend to occur earlier and more extensively in children with HIT during ECMO.No significant effect of HIT on the survival rate of children during ECMO is found.Whether HIT has effect on the survival rate of children with ECMO requires a prospective and large clinical study.
8.Management of acute type A aortic dissection with mesenteric malperfusion
Yueyun ZHOU ; Wei QIN ; Jian LI ; Cunhua SU ; Xiaodi WANG ; Fuhua HUANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2023;39(10):605-609
Objective:To summarize treatment strategies and outcomes of patient suffer from acute Stanford type A aortic dissection(ATAAD) with mesenteric malperfusion.Methods:We collected 13 patients with mesenteric malperfusion among 321 ATAAD patients underwent surgery at Nanjing First Hospital during January 2019 to September 2022. Characteristics of these patients were recorded. We analyzed their early and late clinical outcomes.Results:Two patients underwent revascularization-first strategy in hybrid operation room had no in-hospital mortality or complication related to mesenteric ischemia. There were 11 patients with central repair-first strategy. Eight patients appeared mesenteric complications and 2 of them needed extra gastrointestinal surgery. Six in-hospital mortality were recorded in central repair-first patients.Conclusion:We recommended revascularization-first strategy with followed central repair in hybrid operation room for patients suffered from ATAAD with mesenteric malperfusion. Those who underwent central repair-first strategy because of coronary artery or cerebral malperfusion and unstable hemodynamic needed percutaneous angiography of mesenteric artery.
9.Expression and localization of the nuclear factor-κB classical signaling pathway in the radial artery of diabetic patients.
Lei HUANG ; Wen CHEN ; Yifan ZHU ; Xiaodi WANG ; Liming WANG ; Xin CHEN
Chinese Journal of Surgery 2014;52(8):617-621
OBJECTIVETo observe the expression and localization of the nuclear factor-κB (NF-κB) classic signaling pathway in the radial artery of the coronary artery bypass grafting (CABG) patients with diabetes and non-diabetes.
METHODSSamples of radial artery from 36 cases of diabetic and non-diabetic patients were randomly collected from January 2012 to December 2012.In the diabetic group there were 13 male cases, 5 female cases, with an average age of (69 ± 6) years.In non-diabetes group there were 13 male cases, 5 female cases, with an average age of (70 ± 6) years.HE staining techniques was used to test the morphology of radial artery. Immunohistochemical techniques was then used to test the expression and localization of key factors (inhibitor of kappa B kinase β (IKKβ), P50, P65, tumor necrosis factor-α (TNF-α) and endothelial nitric oxide synthase (eNOS)) in the NF-κB classical signaling pathway in the two groups of patients.
RESULTSThe radial artery intima was signifiantly thickened in the diabetic patients when compared with non-diabetic patients by HE staining. And there wss a lot of inflammation and foam cell infiltration in the radial artery intima of the diabetic patients. Using immunohistochemical techniques the expression of IKKβ, P50, P65 in diabetic group were obviously higher than non-diabetic group (4.4 ± 0.5 vs. 1.1 ± 0.6, 4.8 ± 0.7 vs. 1.2 ± 0.7, 4.2 ± 0.4 vs. 1.6 ± 0.7, t = 18.238, 15.052, 13.535, all P < 0.01).In the aspect of inflammatory cytokines, the expression of TNF-α and eNOS factors in diabeics group were significantly higher than non-diabetic group (5.5 ± 0.5 vs.1.4 ± 0.7, 3.3 ± 0.5 vs. 0.8 ± 0.4, t = 20.118, 16.764, all P < 0.01) also. And the five kinds of protein were mainly located in radial artery intima layer cells in diabetic patients.
CONCLUSIONSExpression levels of 5 key factors in NF-κB classic signaling pathway are significantly higher in radial artery intimal layer of diabetic patients than non-diabetic patient's. And Positive signals are more concentrated in the radial artery intima layer of cells.
Aged ; Case-Control Studies ; Coronary Artery Bypass ; Diabetes Mellitus ; metabolism ; Female ; Humans ; Male ; Middle Aged ; NF-kappa B ; metabolism ; Radial Artery ; metabolism ; Signal Transduction
10.Expert consensus on implementation strategy of awake prone positioning for non-intubated patients in China (2023).
Yuanyuan MI ; Zheyi CAI ; Jing LIU ; Fei TIAN ; Liping YANG ; Lei BAO ; Shanbing HOU ; Su GU ; Li LI ; Xueli ZHOU ; Yun XU ; Shumei ZHANG ; Xiaoxia FU ; Xiaodi LI ; Chuansheng LI ; Liang SUN ; Xiaohong ZHANG ; Hong QI ; Shiying YUAN ; Liqun ZHU ; Haiyan HUANG ; You SHANG
Chinese Critical Care Medicine 2023;35(4):337-351
The awake prone position plays an important role in the treatment of hypoxemia and the improvement of respiratory distress symptoms in non-intubated patients. It is widely used in clinical practice because of its simple operation, safety, and economy. To enable clinical medical staff to scientifically and normatively implement prone position for awake patients without intubation, the committees of consensus formulation, guided by evidence-based methodology and Delphi method, conducted literature search, literature quality evaluation and evidence synthesis around seven topics, including indications and contraindications, evaluation, implementation, monitoring and safety management, termination time, complication prevention and health education of awake prone position. After two rounds of expert letter consultation, Expert consensus on implementation strategy of awake prone positioning for non-intubated patients in China (2023) was formulated, and provide guidance for clinical medical staff.
Humans
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Consensus
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Prone Position
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Wakefulness
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China
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Dyspnea