Objective:To evaluate the effect of dexmedetomidine on Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in lung tissues in a rat model of cardiopulmonary bypass (CPB).Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, weighing 320-350 g, aged 12-16 weeks, were randomly divided into sham operation group (group S), CBP group, and dexmedetomidine group (group Dex), with 8 rats in each group.In group Dex, dexmedetomidine was intravenously infused in a dose of 5 μg/kg starting from 15 min before CPB followed by infusion of 5 μg·kg -1·h -1 during CPB.Blood samples were collected at 2 h after the end of CPB for blood gas analysis, and oxygenation index (OI) and respiratory index (RI) were calculated.Then the rats were sacrificed by bloodletting.The lung tissues were removed for microscopic examination of the pathological changes which were scored and for determination of wet/dry weight ratio (W/D ratio), contents of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)(by enzyme-linked immunosorbent assay), and expression of JAK2, STAT3, phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) (by Western blot). The p-JAK2/JAK2 and p-STAT3/STAT3 ratios were calculated. Results:Compared with group S, the lung injury score, W/D ratio and RI were significantly increased, OI was decreased, the contents of TNF-α and IL-6, p-JAK2/JAK2 ratio and p-STAT3/STAT3 ratio were increased in the other two groups ( P<0.05). Compared with group CPB, the lung injury score, W/D ratio and RI were significantly decreased, OI was increased, the contents of TNF-α and IL-6, p-JAK2/JAK2 ratio and p-STAT3/STAT3 ratio were decreased in group Dex ( P<0.05). Conclusion:The mechanism by which dexmedetomidine attenuates CPB-induced lung injury may be related to inhibiting JAK2/STAT3 signaling pathway and reducing inflammatory responses in lung tissues of rats.

Objective To evaluate the effect of α7 nicotinic acetylcholine receptor (α7nAChR)agonists on lung injury caused by cardiopulmonary bypass (CPB) in rats.Methods Eighteen healthy clean-grade adult male Sprague-Dawley rats,weighing 350-400 g,were divided into 3 groups (n =6 each)using a random number table method:sham operation group (group S),CPB group and α7nAChR agonist PHA568487 group (group PHA).The rats underwent no CPB and were mechanically ventilated for 60 min in group S.PHA568487 0.8 mg/kg (diluted to 2 ml in normal saline) was intraperitoneally injected at 30 min before CPB,and then CPB was performed for 60 min in group PHA.Normal saline 2 ml was intraperitoneally injected at 30 min before CPB,and then CPB was performed for 60 min in group CPB.Blood samples were collected from the internal jugular vein for determination of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations by enzyme-linked immunosorbent assay.Lung tissues were obtained for microscopic examination of the pathologic changes and for determination of wet/dry weight ratio (W/D ratio) and matrix metalloproteinase-9 (MMP-9) expression (by Western blot).Results Compared with group S,the W/D ratio and serum concentrations of TNF-α and IL-6 were significantly increased,and the expression of MMP-9 was up-regulated in CPB and PHA groups (P＜0.05).Compared with group CPB,the W/D ratio and serum concentrations of TNF-α and IL-6 were significantly decreased,the expression of MMP-9 was down-regulated (P＜0.05),and the pathological changes of lung tissues were significantly attenuated in group PHA (P＜0.05).Conclusion α7nAChR agonists can reduce the acute lung injury caused by CPB in rats,and the mechanism may be related to down-regulating MMP-9 expression and inhibiting systemic inflammatory responses.

Acute ischemic stroke (AIS), as the third leading cause of death worldwide, is characterized by its high incidence, mortality rate, high incurred disability rate, and frequent reoccurrence. The neuroprotective effects of Ginkgo biloba extract (GBE) against several cerebral diseases have been reported in previous studies, but the underlying mechanisms of action are still unclear. Using a novel in vitro rat cortical capillary endothelial cell-astrocyte-neuron network model, we investigated the neuroprotective effects of GBE and one of its important constituents, Ginkgolide B (GB), against oxygen-glucose deprivation/reoxygenation and glucose (OGD/R) injury. In this model, rat cortical capillary endothelial cells, astrocytes, and neurons were cocultured so that they could be synchronously observed in the same system. Pretreatment with GBE or GB increased the neuron cell viability, ameliorated cell injury, and inhibited the cell apoptotic rate through Bax and Bcl-2 expression regulation after OGD/R injury. Furthermore, GBE or GB pretreatment enhanced the transendothelial electrical resistance of capillary endothelial monolayers, reduced the endothelial permeability coefficients for sodium fluorescein (Na-F), and increased the expression levels of tight junction proteins, namely, ZO-1 and occludin, in endothelial cells. Results demonstrated the preventive effects of GBE on neuronal cell death and enhancement of the function of brain capillary endothelial monolayers after OGD/R injury in vitro; thus, GBE could be used as an effective neuroprotective agent for AIS/reperfusion, with GB as one of its significant constituents.
Animals ; Apoptosis ; drug effects ; Brain Ischemia ; drug therapy ; Cell Survival ; Cells, Cultured ; Disease Models, Animal ; Endothelial Cells ; drug effects ; Ginkgolides ; pharmacology ; Glucose ; Lactones ; pharmacology ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; Oxygen ; Plant Extracts ; pharmacology ; Rats ; Stroke ; drug therapy

Objective To evaluate the effect of sevoflurane on liver injury in a pig model of hemorrhagic shock.Methods Twenty-four Bama miniature pigs of both sexes,weighing 20-25 kg,aged 3-5 months,were equally randomized into 3 groups using a random number table:sham operation group (group S);hemorrhagic shock group (group HS);sevoflurane group (group Sev).Hemorrhagic shock was induced by withdrawing 40％ of blood volume from the right femoral artery within 15 min (30 ml/kg) in HS and Sev groups.The animals inhaled 2％ sevoflurane for 30 min after establishment of the model in group Sev.Before hemorrhagic shock (T0),and at 30,60,90,120,180 and 240 min after hemorrhagic shock (T1-6),blood samples were collected from the femoral artery for determination of plasma alaninc aminotransferase (ALT) and betaine-homocysteine S-methyltransferase (BHMT) concentrations (by enzymelinked immunosorbent assay).After blood sampling at T6,the animals were sacrificed,and the right lobes of livers were removed for examination of the pathological changes with light microscope.Results Compared with group S,the plasma ALT concentrations were significantly increased at T4-6,the plasma BHMT concentrations were significantly increased at T3-6 (P＜0.05),and significant liver pathological changes were observed in HS and Sev groups.Compared with group HS,the plasma ALT concentrations were significantly decreased at T4-6,the plasma BHMT concentrations were significantly decreased at T3-6 (P＜0.05),and the liver pathological changes were significantly attenuated in group Sev.Conclusion Sevoflurane can mitigate liver injury in a pig model of hemorrhagic shock.

Objective To evaluate the effect of sevoflurane on the expression of aquaporin 8 (AQP8) in the intestinal mucosa in a pig model of hemorrhagic shock.Methods Twenty-four Bama miniature pigs of both sexes, weighing 22-25 kg, were randomly divided into 3 equal groups using a random number table: sham operation group (group S), hemorrhagic shock group (group HS) and sevoflurane group (group PS).The femoral artery and jugular vein were cannulated for blood pressure monitoring, blood-letting, and blood sampling in anesthetized pigs.Hemorrhagic shock was induced by withdrawing blood from the right femoral artery.Hemorrhagic shock was induced after cannulation in group HS.In group PS, 2％ sevoflurane was inhaled for 30 min after the model of hemorrhagic shock was successfully established.Before anesthesia, and at 0.5, 1, 1.5, 2, 3 and 4 h after hemorrhagic shock, blood samples were collected from the jugular vein for determination of serum D-lactic acid and intestinal fatty acid-binding protein (I-FABP) concentrations.The animals were sacrificed at 4 h after hemorrhagic shock, and the intestinal specimens were obtained for microscopic examination and for determination of AQP8 expression in the intestinal mucosa (by enzyme-linked immunosorbent assay).The intestinal water content was calculated.Results Compared with group S, the serum D-lactic acid and I-FABP concentrations, AQP8 expression, and intestinal water content were significantly increased in HS and PS groups (P＜0.05).Compared with group HS, the serum D-lactic acid and I-FABP concentrations, AQP8 expression, and intestinal water content were significantly decreased in group PS (P＜0.05).The pathological changes of intestinal tissues were significantly reduced in group PS as compared with group HS.Conclusion Sevoflurane can decrease the intestinal mucosal edema through inhibiting AQP8 expression, thus reducing hemorrhagic shockinduced damage to the intestinal mucosa in pigs.

Objective To evaluate the changes in the expression of aquaporin-8 (AQP8) in intestinal mucosa in pigs with hemorrhagic shock.Methods Sixteen Bama miniature pigs,weighing 22-25 kg,were equally and randomly divided into sham operation group (group S) and hemorrhagic shock group (group HS).The animals were fasted for 8 h before operation.The animals were anesthetized with propofol 3 mg/kg injected via the auricular vein,and tracheostomized and mechanically ventilated.In group S,the femoral artery and internal jugular vein were only cannulated.In group HS,the femoral artery and internal jugular vein were cannulated for blood pressure and mean arterial pressure monitoring and blood sampling.Hemorrhagic shock was then induced by removing 40 percent of blood volume over 15 min.Before anesthesia (T0),and at 30 min and 1.0,1.5,2.0,3.0 and 4.0 h after the end of blood-letting (T1.6),blood samples were collected for determination of serum D-lactate and intestinal fatty acid binding protein (I-FABP) concentrations.After blood sampling at T6,the pigs were sacrificed,and intestinal specimens were obtained for microscopic examination and for determination of AQP8 cotent in intestinal mucosa (by ELISA).The water content of intestines was calculated by wet/dry weight ratio.Results Compared with group S,the serum D-lactate concentrations at T2-6,I-FABP concentrations at T1-6,and water content of intestines were significantly increased,and the cotent of AQP8 was up-regulated at T6 in group HS.No changes were found in the intestinal mucosa in group S.In group HS,severe damage to the intestinal mucosa was found,and bleeding,inflammatory cell infiltration,and epithelial cell necrosis were observed.Conclusion The mechanism of hemorrhagic shock-caused damage to intestines is related to up-regulated expression of AQP8 in intestinal mucosa in pigs.

OBJECTIVETo summarize the mid-term follow-up results of revision of total knee arthroplasty and compare the different strategies for infective revisions.

METHODSAll of 45 patients (47 operated knees) lived in Beijing were treated from April 1989 to October 2010 in Arthritis Clinic and Research Center, Peking University People's Hospital. There were 6 male and 39 female patients, who aged from 31 to 77 years (mean (62 ± 11) years). The function of knee, satisfaction and imaging then were compared retrospectively. American Knee Society Scores (KSS), Western Ontario & McMaster University Osteoarthritis Index (WOMAC), the medical outcomes study item short form health survey (SF-36) scales and satisfaction/pain visual analogue scales (VAS) of patients were evaluated. The patients were divided into infection group (33 patients, 34 knees) and non-infection group (12 patients, 12 knees) according to the indication of revision of total knee arthroplasty and compared by t-tests.

RESULTSThe time from operation to follow-up was 1 year and 2 months to 17 years. The mid-term follow-up time was 8 years 3 months. There were significant improvements of KSS clinical and function scores (from 66.9 ± 28.0 and 44.4 ± 37.6 to 25.4 ± 24.2 and 10.0 ± 24.8, t = 7.043 and 3.797, both P = 0.001). Patients of infection group had lower KSS clinical and function scores than non-infection group before operation, and lower Society Function (t = 2.225, 3.520 and 2.885, P = 0.035, 0.002 and 0.007). About the septic group, the II-stage group had significant better post-operation KSS function scores, Society Function, physical component summary, WOMAC functional score and WOMAC score than I-stage group (t = 2.160-3.268, P = 0.004-0.042). The 1-year, 2-year, 6-year, 17-year survival rate were 83.6%, 78.7%, 62.1%, 44.5%.

CONCLUSIONSRevision total knee arthroplasty is an effective method for solving the failure of primary total knee arthroplasty. It can improve the pain and activity difficulty following the failure of primary total knee arthroplasty, and partially improve function along with quality of life. The results of non-infection group are better than infection group. There may be better results for II-stage revision total knee arthroplasty than I-stage revision. Both I-stage and II-stage revision total knee arthroplasty are effective.

Adult ; Aged ; Arthroplasty, Replacement, Knee ; Female ; Follow-Up Studies ; Humans ; Knee Joint ; surgery ; Male ; Middle Aged ; Pain Measurement ; Quality of Life ; Reoperation ; Retrospective Studies ; Surgical Wound Infection ; epidemiology

BACKGROUNDThe thermal injury during bipolar radiofrequercy results in chondrocyte death that limits cartilage repair. The purpose was to determine the effects of various factors of bipolar radiofrequency on human articular cartilage after thermal injury, offering suitable working conditions for bipolar radiofrequency during arthroscopy.

METHODSOsteochondral explants from 28 patients undergoing total knee arthroplasty (TKA) in Department of Orthopaedic, Peking University Reople's Hospital from October 2013 to May 2014, were harvested and treated using bipolar radiofrequency in a light contact mode under the following conditions: various power setting of levels 2, 4 and 6; different durations of 2 seconds, 5 seconds and 10 seconds; irrigation with fluids of different temperatures of 4°C, 22°C, and 37°C; two different bipolar radiofrequency probes ArthroCare TriStar 50 and Paragon T2. The percentage of cell death and depth of cell death were quantified with laser confocal microscopy. The content of proteoglycan elution at different temperatures was determined by spectrophotometer at 530 nm.

RESULTSChondrocyte mortality during the treatment time of 2 seconds and power setting of level 2 was significantly lower than that with long duration or in higher level groups (time: P = 0.001; power: P = 0.001). The percentage of cell death after thermal injury was gradually reduced by increasing the temperature of the irrigation solutions (P = 0.003), the depth of dead chondrocytes in the 37°C solution group was significantly less than those in the 4°C and 22°C groups (P = 0.001). The proteoglycan elution was also gradually reduced by increasing the temperature (P = 0.004). Compared with the ArthroCare TriStar 50 group, the percentage of cell death in the Paragon T2 group was significantly decreased (P = 0.046).

CONCLUSIONSThermal chondroplasty with bipolar radiofrequency resulted in defined margins of chondrocyte death under controlled conditions. The least cartilage damage during thermal chondroplasty could be achieved with lower power, shorter duration, suitable temperature of irrigation solutions and chondroprotective probes. The recommendations for the use of bipolar radiofrequency to minimize cartilage damage could be achieved with a power setting of level 2, treatment duration of 2 seconds, suitable fluid temperature (closer to body temperature of 37°C) and chondroprotective Paragon T2 probes.

Arthroplasty, Replacement, Knee ; methods ; Cartilage, Articular ; surgery ; Catheter Ablation ; methods ; Cell Survival ; physiology ; Chondrocytes ; pathology ; Humans ; Microscopy, Confocal

Objective To evaluate the effect of dexmedetomidine on lung injury induced by renal ischemia/reperfusion (l/R) in rats.Methods Healthy male Sprague-Dawley rats,aged 4-5 months,weighing 250-300 g,were randomized into 4 groups (n =10 each) using a random number table:sham operation group (group S); group I/R; dexmedetomidine pretreatment group (group D1) and dexmedetomidine postconditioning group (group D2).Renal I/R was induced by right nephrectomy and occlusion of the left kidney for 45 min followed by reperfusion in animals anesthetized with intraperitoneal chloral hydrate.In group D1,dexmedetomidine was infused intravenously starting from 30 min before ischemia until beginning of ischemia.In group D2,starting from onset of reperfusion until 30 min of reperfusion,dexmedetomidine was infused intravenously for 10 min at a rate of 1 μg· kg-1 · h-1,and then infused for 20 min at 0.5 μg· kg-1 · h 1.Blood samples were collected at 6 h of reperfusion to determine serum creatinine,blood urea nitrogen,interleukin-1β (IL-1β),IL-6 and tumor necrosis factor-α (TNF-α) concentrations,and IL-1β,IL-6 and TNF-α concentrations in broncho-alveolar lavage fluid (BALF).Lungs were removed for microscopic examination and for determination of wet/dry lung weight ratio.Results Compared with group S,wet/dry lung weight ratio,serum creatinine and blood urea nitrogen concentrations,and IL-1β,TNF-α and IL-6 concentrations in serum and BALF were significantly increased in the other three groups (P ＜ 0.05).The parameters mentioned above were significantly lower in D1 and D2 groups than in I/R group (P ＜ 0.05).Microscopic examination showed that the pathological changes were significantly attenuated in D1 and D2 groups as compared with I/R group.Conclusion Both dexmedetomidine pretreatment and postconditioning can attenuate lung injury induced by renal I/R and inhibition of inflammatory responses is involved in the mechanism.

Objective To evaluate the effects of different sedation depths of propofol on brain injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Forty-five ASA physical status Ⅲ or Ⅳ patients of both sexes,aged 26-64 yr,weighing 50-85 kg,scheduled for elective cardiac valve replacement with CPB,were divided into 3 groups according to intraoperative sedation depths (n =15each):30 ≤ bispectral index (BIS) value ＜ 40 (group A) ; 40 ≤ BIS value ≤ 50 (group B) ; 50 ＜ BIS value ≤ 60(group C).Anesthesia was induced with iv injection of lidocaine,midazolam,sulfentanil,etomidate and vecuronium.The patients were tracheally intubated and mechanically ventilated.PET CO2 was maintained at 35-45 mm Hg.Anesthesia was maintained with iv infusion of propofol at a rate of 7,5 and 3 mg· kg-1 · h-1 in A,B and C groups,respectively,intermittent iv boluses of sulfentanil and pipecuronium,and intermittent inhalation of sevoflurane.The infusion rate of propofol was adjusted to maintain the corresponding anesthesic depth in each group.Before CPB (T1),at 30 min of CPB (T2),immediately after termination of CPB (T3) and at 1 h after the end of CPB (T4),blood samples were obtained from the jugular bulb vein and radial artery for determination of plasma S-100β protein concentration and for blood gas analysis,and the arterial to venous blood oxygen content difference (Dj-aO2),cerebral O2 extraction rate (CERO2) and jugular bulb venous to arterial blood lactic acid content difference (Dj-aL) were calculated.Results Compared with group C,the plasma S-100β protein concentrations were significantly decreased,SjvO2 was increased,and Dj-aO2 and CERO2 were decreased at T3-4,and Da-jL was decreased at T3 in groups A and B (P ＜ 0.05).Compared with group B,the plasma S-100β protein concentrations were significantly decreased at T3-4,SjvO2 was increased at T2,Da-jO2 and CERO2 were decreased at T2,and DajL was decreased at T3 in group A (P ＜ 0.05).Conclusion Moderately deepened anesthetic depth of propofol (30≤ BIS value ＜ 40) is helpful in attenuating the brain injury in patients undergoing cardiac valve replacement with CPB.