Objective To investigate the effect of high-frequency oscillatory ventilation (HFOV) on inflammatory responses in lung tissues of dogs with severe acute respiratory distress syndrome (ARDS).Methods Healthy mongrel dogs of both sexes,weighing 13.7-16.2 kg,in which severe ARDS was induced by intravenous infusion of the mixture of oleic acid 0.2 ml/kg and autologous blood (equal to the volume of oleic acid).Twenty-four dogs with severe ARDS were randomly divided into 4 groups (n=6 each) using a random number table:conventional mechanical ventilation with low tidal volume group (group CMV),HFOV-9 Hz group,HFOV-12 Hz group and HFOV-15 Hz group.In HFOV-9 Hz,HFOV-12 Hz and HFOV-15 Hz groups,the frequency was 9,12,and 15 Hz,respectively,mean airway pressure 20 cmH2O,oscillation pressure 70 cmH2O,and inspired oxygen fraction ratio 1.0.In group CMV,the animals were mechanically ventilated in volume-controlled mode,with positive end-expiratory pressure 5 cmH2O,tidal volume 6 ml/kg,respiratory rate 30 breaths/min,inspiratory/expiratory ratio 1:2,and inspired oxygen fraction ratio 1.0.At 4 h of ventilation,the animals were sacrificed,and lungs were removed for determination of wet/dry weight (W/D) ratio,contents of tumor necrosis factor-alpha (TNF-α),interleukin-6 (IL-6) and IL-10 (by enzyme-linked immunosorbent assay),and expression of vascular endothelial (VE)-Cadherin (by Western blot) and for microscopic examination.Lung injury scores were assessed.Results Compared with group CMV,the lung injury scores,W/D ratio,and contents of TNF-α and IL-6 were significantly decreased,the content of IL-10 was significantly increased,and the expression of VE-Cadherin was significantly up-regulated in the other three groups (P＜0.05).Compared with group HFOV-9Hz,the lung injury scores,W/D ratio and contents of TNF-α and IL-6 were significantly decreased,the content of IL-10 was significantly increased,and the expression of VE-Cadherin was significantly up-regulated in group HFOV-15 Hz,and the content of IL-6 was significantly decreased in group HFOV-12 Hz (P＜0.05).Conclusion HFOV can significantly inhibit inflammatory responses in lung tissues of dogs with severe ARDS as compared with mechanical ventilation with low tidal volume,which may be involved in the mechanism of lung-protective ventilation effect.

Objective To explore the effect of different positive end expiratory pressures (PEEP) on oxygen delivery (DO2) after recruitment maneuvers (RM) in dogs with acute respiratory distress syndrome (ARDS). Method After ARDS models established in 15 dogs by oleic acid, static P-V (pressure-volume) curves were determined by low flow technique. Lower inflection point (LIP) was set by two-way linear regression methods. RM was operated with the pressure control method. ARDS dog models were randomly divided into three groups, namely PEEP 8 cmH2O group (group A), 12 cmH2O group (group B) and 16cmH2O group (group C) after RM (equivalent to pressure at4 cmH2O under LIP, 4 cmH2O near LIP, and 4 cmH2O above LIP, respectively). Hemodynamics and arterial blood gas analysis were monitored before RM, 0, 5, 10 and 15 min after RM. The recruited volume was measured by P-V curve method 15 min after RM and respiratory mechanics was also observed at the same time. Then DO2 was calculated. The quantitative variables were summarized as the mean and SD. The t-test was used to compare continuous variables between the two independent samples. One-way analysis of variance was used to compare variables among three groups. The level of significance was set at P＜0.05 for all the tests. Results In group A, the levels of PaO2 were significantly reduced 5 min, 10 min and 15 min after RM[(257 ± 23 )mmHg, (253±21)mmHg, and (255±19)mmHg] compared with PaO2 at 0 min [(322 ± 20) mmHg] (P＜0.05).But in group B and group C, the levels of PaO2 5 min, 10 min and 15 min after RM were not lower than level of PaO2 at 0 min after RM (P＞0.05 ). The levels of PaO2 in groups B and C were higher than that in group A at the same time (P＜0.05). The recruited volume distinctly increased with PEEP levels escalated [(50±12 ) mL, (124 ±15) mL, and ( 157 ±10)mL](P＜0.05). However, the increment in the recruited volume from PEEP 8 cmH2O to 12 cmH2O was dramatically greater than that from PEEP 12 cmH2O to 16 cmH2O.There was no significant difference in static compliance between group A and B [(14.3 ± 2.2) mL/cmH2O vs. (17.2±1.4)mL/cmH2O] (P ＞ 0.05 ). But compared with groups A and B, the static compliance in the group C significantly reduced(10.5 ± 0.9) mL/cmH2O ( P ＜ 0.05 ). The ratios of DO2 after RM to DO2 before RM were different at different levels of PEEP. The levels of DO2 after RM[( 1.15 ± 0. 11 ),( 1. 14 ± 0.12), ( 1.14 ± 0. 12) and ( 1.16 ± 0.11 )] increased more greatly than that before RM ( 1.00 ±0.09) in the group B (P ＜ 0.05 ). It did not occurred in the groups A and C. Conclusions The PEEP 12 cmH2O set at near the LIP after RM could be the optimal PEEP. Not only can it improve DO2 and the static compliance, but also maintain oxygenation and the recruited volume after RM.

ObjectiveTo observe the effects of norepinephrine and dobutamine (NE+Dobu) on hemodynamics, tissue perfusion and oxygen metabolism in elderly patients with septic shock at different levels of mean arterial pressure (MAP). MethodsAfter aggressive fluid resuscitation,norepinephrine and dobutamine were administered in 18 elderly patients with septic shock to correct hypotension. The rate of dobutamine infusion was 5 ug. kg<'-1>. min<'-1> Norepinephrine was titrated to maintain MAP at levels of 65 mm Hg, 75 mm Hg and 85 mmHg. Four hours later, the changes of hemodynamics, oxygenation index, blood lactate, renal function and gastric pCO<,2> at every MAP level were observed. ResultsThere were no significant differences in heart rate (HR), pulmonary arterial wedge pressure (PAWP), volume of oxygen (VO<,2>), Blood lactate, pH value, △pCO<'2> and creatinine clearance rate (CCr) among the MAP levels of 65 mm Hg, 75 mm Hg and 85 mm Hg ( all P>0.05). Compared with MAP 65 mm Hg, cardiac index (CI), systemic vascular resistance index (SVRI), oxygen delivery over oxygen extraction ratio were obviously higher at MAP 75 mm Hg and 85 mm Hg [4.7±0.6, 5.1±0.7 vs. 4.0±0.6; 1162±278, 1276±319 vs. 1011±225; (697±53) ml. min<'1>. m<'2>,(711±68)ml. min<'-1>. m<'2> vs. (634±70) ml · min<'-1> · m<'2>; (0.28±0.02)%,(0.27±0.02)% vs. (0.25±0.02) %, respectively, all P<0.05). The urinary output at MAP levels of 65 mm Hg, 75 mm Hg and 85 mm Hg were (98±43)ml/h, (91±54) ml/h and(74±49)ml/h repectively, and only the differences between MAP 75 mm Hg and MAP 65 mm Hg had statistical significance (P<0.05).ConclusionsAfter aggressive fluid resuscitation, hemodynamics and renal function are improved at MAP 75 mm Hg after administration of norepinephrine and dobutamine in elderly patients with septic shock. It should be considered that MAP is appropriately increased in elderly patients with septic shock.

Objective To explore the use of pulse indication contour cardiac output (PiCCO) as a guidance for fluid resuscitation and vasopressors employment in patients with septic shock in order to find out the efficacy of this resuscitation strategy in the respect of outcome of patients. Mtthod A total of 30 patients with septic shock were treated with the EDGT fluid treatment protocol as the conventional treatment group from December 2006 to June 2008; and another 26 patients were given fluid treatment under the guidance of PiCCO as PiCCO group from July 2008 to October 2009. Exclusion criteria included patients with history of heart and lung diseases, and liver and kidney dysfunction. The mean arterial blood pressure was maintained above or equal to 65mmHg in PiCCO group,and fluid resuscitation was concluded when global end-diastolic volume index reached 600～750 mL·-2 with the stroke volume variation in ＜ 10% and without auricular fibrillation. Nor-epinephrine was administrated to adiust the systemic peripheral vascular resistance index during 1300～1500 d·s·cm-5·m-2.Dobutamine was empoyed when global ejection fraction was compromised. The options of liquid and diuretics depend upon the presence d extra-vascular lung water. Central venous oxygen saturation and the level of lactate were observed 6hours after resuscitation. The liquid equilibrium for 3 days and the dosage of vasopressors were also recorded. The rate of survival, the time taken for weaning from mechanical ventilation, the days of ICU stay and rate of intact organ function within 28 days were compared between two groups. Results The demphics of patients of two goups were similar. There were no significant difference between PiCCO and the conventional group in values of central venous oxygen saturation and lactate 6 hours after admission to ICU (P ＞ 0.05). And 6 h and 1d after fluid resuscitation, the dosages of dobutamine and the dosages of nor-epinephrine used in PiCCO group were significantly higher than those in conventional group in which the dosages of dobutamine in two groups were [(145.4±24.5)mg vs. (104.2 ± 46.3) mg and (330.2 ± 30.3) mg vs. (202.4 ± 40.3) mg], respectively, and the dosages of nor-epinephrine [(14.5±3.8) mgvs. (10.2±5.6) mgand (38.2±4.2) rng vs.(20.1±6.2) mg], respectively. However, the dosages of vasopressors were similar between two groups 2 d and 3 d later. The amounts of liquid administered to get equilibrium in 6 h and the 3 d in PiCCO group were significantly less than those in conventional group [(2121±578) mL vs. (2910±987) mL and (3845±435) mL vs. (4545 ± 765) mL and (2467±510) mLvs. (2867±618) mL and (951±332) mLvs. (1472±533) mL], respectively. The days required to get free from mechanical ventilation within 28d were significantly longer in PiCGO group[(19.7 ± 8.3) d vs.(15.1±9.1) d], but the days of ICU stay were significantly shorter in PiCCO group [(7.5 ± 3.5) d vs. (9.5±3.2) d] (P＜0.05). The rates of survival and days free from organ failure within 28 days of two groups were similar(P＞0.05). Conclusions When the early fluid management guided with PiCCO in septic shock patients,the fluid management can be implement more safely and precisely. It can shorten the days of ICU stay and days of mechanical ventilation support with avoidance of fluid resuscitation.

AIM: To explore whether necroptosis contributes to the high glucose (HG)-induced damage in hu-man umbilical vein endothelial cells (HUVECs).METHODS: The protein levels of receptor-interacting protein 3 (RIP3) and cleaved caspase-3 were detected by Western blot.The intracellular levels of reactive oxygen species (ROS) were deter-mined by DCFH-DA staining followed by photofluorography.Mitochondrial membrane potential (MMP) was measured by rhodamine 123 staining followed by photofluorography.RESULTS: Treatment of HUVECs with HG at different concentra-tions (10, 20 and 40 mmol/L glucose) for 24 h gradually enhanced the expression levels of RIP3.Treatment of HUVECs with HG (40 mmol/L glucose) for different time (3 h, 6 h, 9 h, 12 h and 24 h) also up-regulated the expression levels of RIP3, peaking at 9 h.Pretreatment of HUVECs with 20 μmol/L Z-VAD-FMK (an inhibitor of caspase) for 30 min before exposure to HG enhanced the expression level of RIP3.Pretreatment of HUVECs with 100 μmol/L necrostatin-1 (an inhi-bitor of necroptosis) for 1 h before exposure to HG alleviated the HG-induced injuries, such as a decrease in cell viability, an increase in ROS generation and dissipation of MMP, but up-regulated the protein level of cleaved caspase-3.CON-
CLUSION: Necroptosis mediates HG-induced injury in HUVECs.There is a negative interacting between necroptosis and apoptosis.

Objective To analyze the value of the potential risk factors on predicting primary graft dysfunction (PGD) after bilateral lung transplantation for the patients with idiopathic pulmonary fibrosis (IPF).Methods A retrospective study was conducted. Fifty-eight patients with IPF who underwent the bilateral lung transplantation admitted to Wuxi People's Hospital Affiliated to Nanjing Medical University from June 2014 to March 2017 were enrolled. The grade 3 PGD happened within 72 hours after transplantation was taken as the outcome event, and these patients were divided into PGD and non-PGD groups. The age, gender, body mass index (BMI), underlying disease, and N-terminal-probrain natriuretic peptide (NT-proBNP) before operation, pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), and mean pulmonary artery pressure (mPAP) before and after operation, duration of operation, the volume of blood transfusion during operation and postoperation, the use of extracorporeal membrane oxygenation (ECMO) during the operation, blood purification treatment after operation, and shock within 3 days after operation were recorded. The differences of parameters mentioned above between the two groups were compared. The predictive factors of PGD were searched by binary logistic regression analysis, and the receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of preoperative PADP for grade 3 PGD after transplantation.Results Among 58 patients who underwent the bilateral lung transplantation, 52 patients were enrolled. The rest patients were excluded because of incomplete clinical data. There were 17 patients in the PGDgroup, with a mortality rate of 47.06%. The non-PGD group included 35 patients with a mortality rate of 8.57%. PADP and mPAP ahead of operation, the dosage of red cells suspension after the operation, and the total amount of blood transfusion during and after the operation in PGD group were significantly higher than those in non-PGD group [PADP ahead of operation (mmHg, 1 mmHg = 0.133 kPa): 33.7±10.5 vs. 25.3±10.1, mPAP ahead of operation (mmHg): 40.4±14.1 vs. 32.8±11.1, the dosage of red cells suspension after the operation (mL): 700 (300, 1500) vs. 300 (300, 500), the total amount of blood transfusion during and after the operation (mL): 2250 (1850, 4275) vs. 1800 (1550, 2800)], with statistically significant differences (all P < 0.05). There were no significant differences in age, gender, BMI, underlying disease, NT-proBNP before operation, PASP before and after operation, PADP and mPAP after operation, duration of operation, amount of plasma and red cells suspension as well as total amount of blood transfusion during operation, plasma amount and total amount of blood transfusion after operation, amount of plasma and red cells suspension during and after operation, use of ECMO during operation, blood purification treatment after operation, and shock after operation between the two groups (all P > 0.05). It was shown by binary logistic regression analysis that the preoperative PADP was the independent risk factor of grade 3 PGD after lung transplantation [odds ratio (OR) = 1.084, 95% confidence interval (95%CI) = 1.016-1.156,P = 0.015]. It was shown by ROC curve that the area under the ROC curve (AUC) of the PADP before operation for predicting the grade 3 PGD after lung transplantation was 0.728. When the cut-off value was 36 mmHg, the sensitivity was 47.1%, and the specificity was 91.4%.Conclusions Compared with the non-PGD group, the patients with higher preoperative PADP were more common in the PGD group, and the patients in the PGD group were more likely to be characterized by grade 3 PGD after lung transplantation. The preoperative PADP was an effective predictor of grade 3 PGD after lung transplantation.

This study was performed to investigate the impact of nobiletin(NOB)on fracture healing in osteoporosis(OP)rats through the stimulator of interferon gene(STING)/nuclear transcription factor kappa B(NF-κB)signal pathway.A rat model of OP fracture was established by ovariectomy and right femoral shaft fracture intramedullary fixation;the rats after modeling were randomly grouped into model group,high dose(NOB-H,30 mg/kg NOB),medium dose(NOB-M,20 mg/kg NOB),low dose(NOB-L,10 mg/kg NOB)NOB group and NOB-H+ STING activator(DMXAA)group(30 mg/kg NOB+25 mg/kg DMXAA),and 18 rats experienced only ovaries expose were used as sham operation group.After the intervention,the fracture healing status of rats were measured;Micro-CT was used to detect the changes of bone trabecular microstructure in rats;commercial kits were used to detect the serum levels of bone metabolism related indicators(alkaline phosphatase(ALP),calcium,phosphorus)and inflammatory factors(tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β));HE was used to detect the morphological changes and trabecular area of femur,while Western blot was applied to detect the expression of STING/NF-κB pathway related proteins.Compared with the control group,the fracture line in the model group was clear,the trabecular structure was disordered and the gap was large,furthermore,the levels of TNF-α and IL-1β,the expression of STING and p-NF-κB p65/NF-κB p65 were significantly increased,the trabecular area,the levels of ALP,calcium,phosphorus,and bone mineral density(BMD),bone volume fraction(BV/TV),bone trabecular number(Tb.N)and bone trabecular thickness(Tb.Th)were significantly decreased(P<0.05);compared with the model group,the fracture line of NOB-L group,NOB-M group and NOB-H group gradually blurred,the trabecular structure arranged orderly,and the gap gradually decreased,and the trend of the index changes mentioned above were opposite to that of the model group(P<0.05).STING activators attenuated the promotion of fracture healing by NOB in OP rats and increased the inflammatory responses.In conclusion,NOB can reduce inflammatory reaction and promote fracture healing in OP rats,which may be related to the inhibition of STING/NF-κB signal pathway.

Objective To compare the biomechanical effects of n-HA/PA66 vertebral body cage and percutaneous vertebroplasty for treating osteoporotic vertebral fracture, so as to provide theoretical foundations for clinically choosing operative approach and numbers of n-HA/PA66 cage. Methods Based on finite element models of normal vertebral T11-L3, four finite element models of vertebral T11-L3 with n-HA/PA66 cage implanted by different approaches (transversus approach A, B and psoas major muscle approach A, B) were established. Two controlled models without intertransverse ligaments were also built. Besides, two finite element models of osteoporotic vertebral T11-L3 with injection of 1.8 mL or 3.6 mL bone cement were built, respectively. The loads of 500 N and force torque of 7 N·m from different directions were applied on nine models, to calculate and analyze the displacement and stress of the osteoporotic vertebrae during standing, extension, anteflexion, lateral bending, and rotation, and to investigate the biomechanical effects from two kinds of osteoporotic vertebral fracture treatment on vertebral body. Results Under the same loading, bone cement could lead to a larger stress increase while a smaller displacement decrease in vertebral body compared with n-HA/PA66 cage. The model with n-HA/PA66 cage implanted by psoas major muscle approach A (namely, a cage was implanted through psoas major muscle) had the minimal increase in vertebral stress while the maximum decrease in displacement. Conclusions In order to reduce the risk of the additional fracture due to stress increment and recover the stiffness of osteoporotic vertebrae, clinicians are suggested to implant one n-HA/PA66 cage through psoas major to treat the osteoporotic vertebral fractures.

Objective To explore the biomechanical effect from different volumes of bone cement on osteoporotic spine T11-L3 at different levels of osteoporosis in vertebroplasty by the finite element method, so as to offer theoretical foundation for the selection of cement volume before vertebroplasty. Methods Based on CT scan images, the finite element models of spine T11-L3 were built and validated. Twelve models of osteoporotic spine T11-L3 without bone cement were developed as the control models. The spine L1 was injected with 1.8 mL and 3.6 mL bone cement, respectively, to strengthen the spine and build 24 models of spine T11-L3 at different levels of osteoporosis. The vertical load (500 N) and the torque (7 N·m) were applied on superior face of the spine T11 to calculate and analyze vertebral stress and displacement under the working conditions of standing, backward extension, anteflexion, lateral bending and rotation, respectively. Results After injection of bone cement, the changes in vertebral stress and displacement under torsional loads were the maximum. For the models with injection of 1.8 mL bone cement, as the levels of osteoporosis increased, the stress of spine L1 increased from 55.0% to 87.7%, and the displacement decreased from 6.5% to 32.0% under torsional loads. The torsional stress of spine T12 and L1 at the highest level of osteoporosis increased by 3.6% and 5.7%, respectively. For the models with injection of 1.8 mL bone cement, as the level of osteoporosis increased, the stress of spine L1 increased from 288.5% to 313.8%, and the displacement decreased from 8.9% to 44.7% under torsional loads. The torsional stress of spine T12 and L1 at the highest level of osteoporosis increased by 7.3% and 7.6%, respectively. Conclusions The deterioration in osteoporosis and the increase in cement volume will lead to the increase in vertebral stress. The vertebral stress and displacement will increase most under torsional loads. Therefore, for patients with vertebral fracture at high level of osteoporosis, low-dosage bone cement should be considered in order to avoid a large increase in stress, and torsional movement of the patients should be restricted.