Objective To evaluate the role of calcineurin ( CaN)/nuclear factor of activated T cell cytoplasmic 4 protein ( NFATc4) signaling pathway in inflammatory responses in lung tissues of rats with ventilator-induced lung injury ( VILI) . Methods Twenty-four clean-grade healthy male Wistar rats, aged 5-8 weeks, weighing 220-250 g, were divided into 3 groups ( n=8 each) using a random number table method: control C (group C), VILI group and cyclosporine A plus VILI group (group CsA+VILI). The animals were anesthetized with pentobarbital and tracheostomized. The rats were mechanically ventilated for 6 h with the tidal volume set at 40 ml/kg and respiratory rate at 40 breaths/min to establish the model of VI-LI. The rats kept spontaneous breathing in group C. CaN specific inhibitor cyclosporine A 10 mg/kg was in-traperitoneally injected at 1 h before ventilation in group CsA+VILI. Rats were sacrificed immediately after ventilation, lung tissues were obtained and stained with hematoxylin and eosin to evaluate lung injury, broncho-alveolar lavage fluid was collected for determination of tumor necrosis factor-alpha ( TNF-α) , inter-leukin-1beta ( IL-1β) and IL-6 concentrations by enzyme-linked immunosorbent assay, and the lungs were removed for determination of the wet to dry weight ratio ( W/D ratio) , expression of intercellular adhesion molecule-1 ( ICAM-1) and vascular cell adhesion molecule-1 ( VCAM-1) ( by real-time polymerase chain reaction) , and expression of calcineurin and NFATc4 in lung tissues ( using Western blot ) . Results Compared with group C, the W/D ratio, lung injury scores and concentrations of IL-1β, IL-6 and TNF-αin BALF were significantly increased, and the expression of CaN, NFATc4, ICAM-1 mRNA and VCAM-1 mRNA was up-regulated in group VILI ( P＜0. 05) . Compared with group VILI, the W/D ratio, lung injury scores and concentrations of IL-1β, IL-6 and TNF-αin BALF were significantly decreased, and the expres-sion of CaN, NFATc4, ICAM-1 mRNA and VCAM-1 mRNA was down-regulated in group CsA+VILI ( P＜0. 05) . Conclusion CaN/NFATc4 signaling pathway mediates inflammatory responses in lung tissues of rats with VILI.

Objective To evaluate the accuracy of respiratory variations of internal jugular vein (IJV) in monitoring fluid responsiveness in patients undergoing radical gastrectomy for gastric cancer.Methods Fifty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes,aged 40-64 yr,scheduled for elective radical gastrectomy for gastric cancer,were enrolled in this study.Before induction of anesthesia,the hemodynamic parameters such as heart rate,central venous pressure,cardiac index,stroke volume index (SVI),stroke volume variation and respiratory variation of IJV were recorded after haemodynamics was stable and were recorded again at 10 min after endotracheal intubation,and a loading dose of 6％ 130/0.4 hydroxyethyl starch 7 ml/kg was infused over 15 min.The parameters mentioned above were recorded within 5 min after loading dose.Patients were divided into 2 groups according to the percentage of increase in SVI (△SVI) after volume expansion:△SVI≥ 15％ was considered to be a positive response (responder group) and △SVI＜15％ was considered to be a negative response after volume expansion (non-responder group).Results The area under the receiver operating characteristic curve of respiratory variations of IJV in monitoring fluid responsiveness and 95％ confidence interval were 0.852 (0.744-0.961).Respiratory variation of IJV 24.6％ was considered as the cut-off value and used to monitor fluid responsiveness,and the sensitivity and specificity were 67.6％ and 92.3％,respectively.Conclusion Respiratory variation of IJV can be considered as an effective index in monitoring fluid responsiveness in the patients undergoing radical gastrectomy for gastric cancer.

Objective To evaluate the effect of γ-aminobutyric acid (GABA) preconditioning on pathological stretch-induced damage to type Ⅱ alveolar epithelial cells by mechanical ventilation.Methods A549 cells cultured in vitro (0.2× 106/ml,2.5 ml/well) were randomly divided into 3 groups using a random number table:control group (group C),pathological stretch group (group P) and GABA preconditioning+pathological stretch group (group G).A549 cells were exposed to 20％ cyclic stretch at 0.3 Hz for 6 h in groups P and G;GABA 50 μmol/L was given 30 min before cyclic stretch in group G.After the end of pathological stretch,the cells were collected for determination of the cell viability by methyl thiazolyl tetrazolium assay and lactate dehydrogenase (LDH) release by colorimetricmethod;the expression of F-actin was observed with indirect immunofluorescence;the expression of Rho-associated kinase 1 (ROCK1) and GABAAR were determined by western blot.Results Compared with group C,the cell viability was significantly decreased,the amount of LDH released was increased,the expression of ROCK1 was significantly increased and the expression of GABAAR was significantly decreased in groups P and G (P＜0.05);Compared with group P,the cell viability was significantly increased,the amount of LDH released was decreased,F-actin was re constructed,the expression of ROCK1 was significantly decreased and the expression of GABAAR was significantly increased (P＜0.05) in group G.The reconstruction of F-actin in group P was better than that in group G and worse than that in group C.Conclusion GABA preconditioning can attenuate pathological stretch-induced damage to type Ⅱ alveolar epithelial cells probably through up regulating the expression of GABAA receptor.

Objective To evaluate the effect of ulinastatin on γ-aminobutyric acid (GABA) signal pathway in mice with ventilator-induced lung injury (VILI).Methods Thirty-six male Wister mice were randomly divided into 3 groups using a random number table:control group (group C), ventilator-induced lung injury group (group VILI),and ventilator-induced lung injury+ ulinastatin group (group UTI),n =12 in each group.VILI was induced by 4 h mechanical ventilation with tidal volume 40 ml/kg in groups VILI and UTI.Ulinastatin 1×10 5 U/kg was injected intraperitoneally 1 h before ventilation in group UTI,while the equal volume of normal saline was given in groups C and VILI.The mice were then sacrificed,the left lung was lavaged,and broncho-alveolar lavage fluid (BALF)was collected for determination of concentrations of protein,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and intercellular adhesion molecule-1 (ICAM-1).The lung tissues were re-moved for determination of the wet to dry lung weight (W/D)ratio,the mRNA expression level of IL-1β,TNF-αand ICAM-1.The pathological changes of the lungs were determined under light micro-scope and the lung injury scores were also determined.Immunohistochemistry and Western blot were used to detected the protein expression level of GAD and GABAA R.Results The W/D ratio (6.7 ± 2.4 vs.8.5±2.3)and lung scores [(6.9±2.3)scores vs.(1 1.8±2.7)scores]were significantly de-creased in group UTI than those in group VILI.The concentrations of IL-1β[(56±1 1)ng/L vs.(77 ±1 5)ng/L],TNF-α[(105±29)ng/L vs.(1 58±37)ng/L]and ICAM-1 [(205±46)ng/L vs.(293 ±61)ng/L]in BALF in group UTI were significantly decreased than those in group VILI.The mRNA ex-pression levels of IL-1β(1.81±0.26 vs.2.58±0.34),TNF-α(1.61±0.15 vs.2.94±0.27)and ICAM-1 (1.74±0.27 vs.2.79±0.31)were significantly decreased in group UTI than those in group VILI.The protein expression levels of GAD (0.44±0.08 vs.0.18 ±0.04)and GABAA R (0.30 ±0.09 vs.0.15 ± 0.04)were significantly increased in group UTI than those in group VILI.Conclusion Ulinastatin can at-tenuate VILI probably through activating GABA signaling pathway.

Objective To evaluate the effect of dexmedetomidine on the expression of gamma-aminobutyric acid(GABAA)receptors during ventilator-induced lung injury(VILI)in rats. Methods Thirty pathogen-free adult male Sprague-Dawley rats,weighing 280-320 g,were divided into 3 groups(n=10 each)using a random number table:control group(group C),group VILI and dexmedetomidine group(group Dex).The rats were mechanically ventilated for 4 h with the tidal volume of 40 ml/kg to establish VILI model. Dexmedetomidine 50 μg/kg was injected intraperitoneally after the rats were anesthetized in group Dex,while the equal volume of normal saline was given instead in C and VILI groups. The animals were sacrificed at 4 h of mechanical ventilation,the lungs were removed for examination of pathological changes which were scored,bronchoalveolar lavage fluid(BALF)was collected for determination of concentrations of total protein,interleukin-1 beta(IL-1β),IL-6 and tumor necrosis factor-alpha(TNF-α),and the lung specimens were obtained for determination of the wet/dry weight ratio(W/D ratio),alveolar fluid clearance(AFC)and expression of GABAA receptors,IL-1β,IL-6 and TNF-α mRNA in lung tissues. Results Compared with group C,the W/D ratio,pathological scores,expression of total protein,IL-1β,IL-6 and TNF-α in BALF and expression of IL-1β,IL-6 and TNF-α mRNA in lung tissues were significantly increased,and the GABAA receptor expression and AFC were decreased in VILI and Dex groups(P<0.05).Compared with group VILI,the W/D ratio,pathological scores,expression of total protein,IL-1β,IL-6 and TNF-α in BALF and expression of IL-1β,IL-6 and TNF-α mRNA in lung tissues were significantly decreased,and the GABAA receptor expression and AFC were increased in group Dex(P<0.05).Conclusion The mechanism by which dexmedetomidine reduces VILI is related to up-regulation of GABAA receptor expression in rats.

Objective To evaluate the relationship between the shedding of syndecan-4(SDC-4) in lung tissues and ventilator-induced lung injury in rats. Methods Thirty pathogen-free healthy adult male Wistar rats, weighing 220-250 g, were divided into 3 groups(n=10 each)using a random number table:control group(group C), mechanical ventilation with traditional tidal volume(VT)group(group T-VT) and mechanical ventilation with high VTgroup(group H-VT). The animals were anesthetized with pento-barbital sodium and tracheostomized. The rats kept spontaneous breathing in group C. The rats were me-chanically ventilated for 4 h with the VTset at 6 ml∕kg in group T-VT and with the VTset at 40 ml∕kg in group H-VT. Blood samples were collected immediately after the end of ventilation for measurement of serum SDC-4 concentrations by enzyme-linked immunosorbent assay. The left lung was lavaged, and broncho-alveolar lavage fluid was collected for determination of interleukin-1beta(IL-1β), IL-18, tumor necrosis factor-alpha and SDC-4 concentrations by enzyme-linked immunosorbent assay. The lungs were removed for determination of the wet to dry weight ratio and expression of SDC-4 protein and mRNA in lung tissues(by Western blot and real-time polymerase chain reaction, respectively)and for examination of the pathological changes. The lung injury scores were recorded. Results Compared with group C, the wet to dry weight ratio, lung injury scores, concentrations of IL-1β, IL-18, tumor necrosis factor-alpha and SDC-4 in bron-cho-alveolar lavage fluid and concentrations of SDC-4 in serum were significantly increased, the expression of SDC-4 mRNA was up-regulated, and the expression of SDC-4 was down-regulated in group H-VT(P<005), and no significant change was found in the parameters mentioned above in group T-VT(P>005).Marked pathological changes of lung tissues were found in group H-VT. Conclusion A large shedding of SDC-4 in lung tissues may be involved in the pathophysiological mechanism of ventilatior-induced lung injury in rats.

Objective To evaluate the accuracy of respirophasic variation in carotid artery blood flow peak velocity(ΔVpeak-CA)in predicting fluid responsiveness in the patients undergoing surgery in the prone position. Methods Forty-three American Society of Anesthesiologists physical status Ⅰ-Ⅲ pa-tients of both sexes, aged 45-75 yr, with body mass index of 20-25 kg∕m2, scheduled for elective posteri-or approach lumbar surgery, were enrolled in the study.After induction of anesthesia, hydroxyethyl starch 130∕0.4 sodium chloride injection 7 ml∕kg was intravenously infused over 20 min when the patients were in the prone position.Subjects were classified as responders if stroke volume index increased≥15% after vol-ume expansion.The receiver operating characteristic curve for ΔVpeak-CA in determining positive fluid re-sponsiveness was drawn. Results The results of receiver operating characteristic curve analysis showed that: the cut-off value of ΔVpeak-CA in predicting positive fluid responsiveness was 7.94%, sensitivity 81.8%, specificity 70.0%, and the area under the curve(95% confidence interval)was 0.818 (0.378-0.757). Conclusion Respirophasic ΔVpeak-CA can accurately predict fluid responsiveness in the patients undergoing surgery in the prone position.

Objective To evaluate the effect of goal-directed fluid therapy (GDFT) on postoperative cognitive function in the patients undergoing intracranial tumor resection.Methods One hundred patients of both sexes,aged 45-64 yr,weighing 50-70 kg,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,scheduled for elective cerebral glioma or meningioma resection,were randomly divided into 2 groups (n=50 each) using a random number table:GDFT group (group G) and conventional fluid therapy group (group C).The mean arterial pressure was maintained at 65-110 mmHg,urine volume ＞0.5 ml · kg-1 · h-1,and central venous pressure at 8-12 cmH2O in group C.In group G,GDFT was performed using FloTrac/Vigileo system,and the cardiac index was maintained at 2.5-4.0 L · min-1 · n 2,stroke volume variation≤ 13％,mean arterial pressure at 65-110 mmHg,and stroke volume index at 35-47 ml/m2.The requirement for crystalloid and colloid,urine volume,blood loss,and requirement for vasoactive agents were recorded during operation.Before induction of anesthesia (baseline),when the dura of brain was opened,at the end of tumor removal,at the end of operation,and at 24 h after operation (T0-4),venous blood samples were taken to determine the concentrations of serum neuron-specific enolase (NSE) and S100β protein by enzyme-linked immunosorbent assay.The patient's cognitive function was assessed using Mini-Mental State Examination at T0 and 7 days after operation (T5).Results Compared with the baseline value at T0,the serum NSE and S100β protein concentrations were significantly increased at T24 in the two groups (P＜0.05).Compared with group C,the requirement for colloid,total volume of fluid infused and urine volume during operation were significantly increased,the serum NSE and S100β protein concentrations were significantly decreased at T3,4 (P＜0.05),and no significant change was found in Mini-Mental State Examination score at T0 and T5 in group G (P＞0.05).Conclusion GDFT based on FloTrac/Vililgeo system can reduce the damage to brains after operation,but it has no significant effect on postoperative cognitive function in the patients undergoing intracranial tumor resection.

Objective To evaluate the effect of dexmedetomidine on microRNA (miRNA)-155-hypoxia-inducible factor-1α (HIF-1α)-heme oxygenase-1 (HO-1) signaling pathway in a rat model of endotoxin-induced acute lung injury.Methods Forty adult male Wistar rats,weighing 220-250 g,were equally and randomly divided into 4 groups using a random number table:control group (group C),dexmedetomidine group (group D),endotoxin-induced acute lung injury group (group L),and endotoxin-induced acute lung injury+dexmedetomidine group (group LD).Acute lung injury was induced by intraperitoneal lipopolysaccharide (LPS) 5 mg/kg in L and LD groups.In D and LD groups,dexmedetomidine was infused in a loading dose of 1 μg · kg-1 · h-1 for 10 min starting before intraperitoneal injection of normal saline or LPS followed by an infusion of 5 μg · kg-1 · h-1 throughout the operation.At 6 h after normal saline or LPS injection,blood samples were taken from the carotid artery for detection of arterial oxygen partial pressure (PaO2).The left lung was lavaged,and broncho-alveolar lavage fluid (BALF) was collected for determination of concentrations of total protein,interleukin-1β (IL-1β),tumor necrosis factor-α (TNF-α),and intercellular adhesion molecule-1 (ICAM-1).The rats were then sacrificed,and lungs were removed for determination of the wet to dry lung weight ratio (W/D ratio),mRNA expression of miR-155,IL-1β,TNF-α and ICAM-1,and protein expression of HIF-1α and HO-1,and for examination of the pathological changes which were scored.Results Compared with group C,the PaO2 was significantly decreased,and the W/D ratio,lung injury score,concentrations of total protein,IL-1β,TNF-α and ICAM-1 in BALF,mRNA expression of miR-155,IL-1β,TNF-α and ICAM-1,and protein expression of HIF-1α and HO-1 were significantly increased in L and LD groups (P ＜ 0.05).Compared with group L,the PaO2 and protein expression of HIF-1α and HO-1 were significantly increased,and the W/D ratio,lung injury score,concentrations of total protein,IL-1β,TNF-α and ICAM-1 in BALF,and mRNA expression of miR-155,IL-1β,TNF-α and ICAM-1 were significantly decreased in group LD (P＜0.05).Conclusion Dexmedetomidine reduces endotoxin-induced acute lung injury through activating miR-155-HIF-1α-HO-1 signaling pathway in rats.

Objective To evaluate the effect of dexmedetomidine on janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in mice with endotoxin-induced acute lung injury (ALI).Methods Twenty-four male C57BL/6 mice,weighing 20-25 g,were randomly divided into 3 groups (n=8 each) using a random number table:control group (group C),endotoxin-induced ALI group (group ALI),and dexmedetomidine group (group Dex).ALI was induced with lipopolysaccharide (LPS) 5 mg/kg injected intraperitoneally.Dexmedetomidine 40 μg/kg was injected intraperitoneally at 1 h after LPS injection in group Dex,while the equal volume of normal saline was given in C and ALI groups.At 6 h after LPS injection,blood samples were collected from the carotid artery to detect arterial oxygen partial pressure (PaO2).The mice were then sacrificed,and broncho-alveolar lavage fluid (BALF) was collected for determination of the concentrations of total protein,interleukin-1β (IL-1β),IL-6 and tumor necrosis factor-or (TNF-α).The lung tissues were removed for determination of wet to dry lung weight ratio (W/D ratio),and expression of phosphorylated JAK2 (p-JAK2),phosphorylated STAT3 (p-STAT3),IL-1β mRNA,IL-6 mRNA and TNF-α mRNA,and for examination of the pathological changes which were scored.Results Compared with group C,the PaO2 was significantly decreased,and W/D ratio,lung injury score,concentrations of total protein,IL-1β,IL-6 and TNF-α in BALF,and expression of IL-1β,IL-6 and TNF-α mRNA,p-JAK2 and p-STAT3 were increased in ALI and Dex groups (P＜0.05).Compared with group ALI,the PaO2 was significantly increased,and W/D ratio,lung injury score,concentrations of total protein,IL-1β,IL-6 and TNF-α in BALF,and expression of IL-1β,IL-6 and TNF-α mRNA,p-JAK2 and p-STAT3 were decreased in group Dex (P＜0.05).Conclusion The mechanism by which dexmedetomidine attenuates LPS-induced ALI is probably related to inhibition of activation of JAK2/STAT3 signaling pathway in mice.