BACKGROUND: Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient's medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu's Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion. METHODS: Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration <10 g/dL were randomly assigned to an individualized strategy, a restrictive strategy following China's guideline or a liberal strategy with a transfusion threshold of hemoglobin concentration <9.5 g/dL. We evaluated two primary outcomes: the proportion of patients who received red blood cells (superiority test) and a composite of in-hospital complications and all-cause mortality by day 30 (non-inferiority test). RESULTS: We enrolled 1182 patients: 379, 419, and 384 received individualized, restrictive, and liberal strategies, respectively. Approximately 30.6% (116/379) of patients in the individualized strategy received a red-cell transfusion, less than 62.5% (262/419) in the restrictive strategy (absolute risk difference, 31.92%; 97.5% confidence interval [CI]: 24.42-39.42%; odds ratio, 3.78%; 97.5% CI: 2.70-5.30%; P <0.001), and 89.8% (345/384) in the liberal strategy (absolute risk difference, 59.24%; 97.5% CI: 52.91-65.57%; odds ratio, 20.06; 97.5% CI: 12.74-31.57; P <0.001). No statistically significant differences were found in the composite of in-hospital complications and mortality by day 30 among the three strategies. CONCLUSION: The individualized red-cell transfusion strategy using the West-China-Liu's Score reduced red-cell transfusion without increasing in-hospital complications and mortality by day 30 when compared with restrictive and liberal strategies in elective non-cardiac surgeries. TRIAL REGISTRATION ClinicalTrials.gov, NCT01597232.
Humans ; Adult ; Postoperative Complications ; Erythrocyte Transfusion/adverse effects* ; Blood Transfusion ; Hospitals ; Hemoglobins/analysis*

Objective To investigate the expression of alpha 7 nicotinic acetylcholine receptor (α7 nAchR), cholinesterase (AChE), choline acetyl translocase (ChaT) after sevoflurane anesthesia. Methods A total of 120 healthy Sprague-Dawley rats with both two genders, aged 1 week, were randomly divided into 5 groups: blank group; air/O2 group; sevoflurane group (group SEV); α7 nAchR agonist group (group PUN); α7 nAchR antagonist group (group MLA), 24 in each group. Blank group received free feeding, air/O2 group was inhaled 60％ oxygen (carrier gas: 1 L/min O2+1 L/min air) 2 h; group SEV was inhaled 3.4％ sevoflurane and carrier gas for 2 h; group PUN and group MLA were injected with PNU-282987 and methyllycaconitine, respectively, after 24 h inhaled of 3.4％ sevoflurane and carrier gas for 2 h. After that, hippocampus dissection carried out in 2 h, 1 w, 4 w, and Western blot method was used to detect α7 nAchR, AChE, ChaT proteins expression. Results Two hours after anesthesia recovery, α7 nAchR in groups SEV, PNU and MLA was significantly lower than that in air/O2 group (P ＜ 0.05); AChE in groups PNU and MLA was significantly lower than that in air/O2 group (P ＜ 0.05); ChaT in groups SEV, PNU and MLA was significantly lower than that in air/O2 group (P ＜ 0.05). One week after anesthesia recovery, α7 nAchR in blank group and groups SEV and PNU was significantly higher than that in air/O2 group (P ＜ 0.05), α7 nAchR in group MLA was significantly lower than that in air/O2 group (P ＜ 0.05); AChE in blank group and and group PNU was significantly higher than that in air/O2 group (P ＜ 0.05), ChaT in blank group was significantly higher than that in air/O2 group (P ＜ 0.05), ChaT in group SEV was significantly lower than that in air/O2 group (P ＜ 0.05). Four weeks after anesthesia awake, AChE in each group was not statistically significant; α7 nAchR in group SEV was significantly higher than that in blank group (P ＜ 0.05), α7 nAchR in group PNU and MLA was significantly lower than that in blank group (P ＜ 0.05); ChaT in blank group and group PNU was significantly lower than that in air/O2 group (P ＜ 0.05), ChaT in group MLA was significantly higher than that in air/O2 group (P ＜ 0.05). Conclusion Sevoflurane inhalation can inhibit ChaT, α7 nAChR, which had no direct effect on AChE; α7 nAChR agonist can effectively help α7 nAChR and ChaT inhibition inhaled sevoflurane, and reached a peak at about 1 week; oxygen concentration around 60％ can increase α7 nAChR expression quantity, to a certain extent against sevoflurane inhibition.

Objective Learning and memory function is the form of brain higher nervous activity .Hippocampus is the main parts responsible for learning and memory function .Once damaged , it will seriously affect the quality of life in patients .The purpose of this paper was to observe the effects of neonatal repeated intermittent sevoflurane inhalation on learning-memory function and Tau protein , p-Tau protein in brain hippocampus in juvenile and adult rats . Methods Twenty-four healthy SD rats ( n=24 ) were randomly di-vided into juvenile sevoflurane inhalation group ( n=6) , juvenile con-trol group ( n=6);adult sevoflurane inhalation group ( n=6) , and adult control group ( n=6) .Rats in juvenile sevoflurane inhalation group and adult sevoflurane inhalation group inhaled 2.6%sevoflurane at the postnatal 7th day, 14th day, 21th day ( P7,P14,P21) for 2 hours.Rats in juvenile control group and adult control group inhaled the carrier gas (1L/min Air+1L/min O2) at the same time for 2 hours.During P31~37, Morris water maze test was conducted in juvenile sevoflurane inhalation group and juvenile control group to detect the behavior.During P91~97, Morris water maze test was conducted in adult sevoflurane inhalation group and adult control group to detect the behavior .Then hippocampi were taken out to detect the expression levels of Tau protein and p -Tau protein. Results ( 1) Comparison of escape latency at the same time ① Juvenile period: no statistical difference between sevoflurane inhalation group (52.04±41.90,29.77±14.23, 19.87±5.71,22.74±13.73,21.91±9.07) and control group (47.82±8.06,25.26±12.53,23.79±9.49, 20.00±10.10, 14.03±7.55) had (P>0.05).② Adult period: no statistical difference between sevoflurane inhalation group (42.00± 14.12, 26.87±16.93, 19.80±13.76, 15.06±8.45, 8.66±4.82) and control group (41.97±25.66,22.88±10.04,15.88±5.20,9.26± 3.98,11.33±6.05 (P>0.05).(2) Comparison of spatial probe test results:no statistical difference in the swimming times from original area,swimmingresidencetime,swimmingdistanceandspeedbetweengroups(P>0.05).(3)Tauproteinexpressiondetection ①Juvenile period:In the hippocampal CA1 region, CA3 region, DG region, the expression level of Tau in the sevoflurane inhalation group (0.237±0.015, 0.324±0.024,0.226±0.019) was higher than the control group (0.185±0.024,0.232±0.040, 0.184±0.018) (P>0.01).②Adult peroid:no statistically significant difference between sevoflurane inhalation group and control group (P>0.05). (4)p-Tau(Ser396)proteinexpressiondetection ①Juvenileperiod:nostatisticallysignificantdifferencebetweensevofluraneinhala-tion group and control group ( P>0.05) .②Adult period:The expression level in the hippocampal CA3 region of sevoflurane inhalation group (0.170±0.005) was higher than control group (0.158±0.011) (P<0.05), but in the CA1 and DG regions there was no statisti-cally significant difference (P>0.05). Conclusion Neonatal repeated intermittent sevoflurane inhalation has done no harm to learn-ing and memory function of juvenile and adult rats , however , it can result in the significant increase of hippocampal Tau protein expres-sion level in juvenile rats and the increase of hippocampal p-Tau protein expression level in adult rats .

Objective To observe the correlation of intrapulmonary TREM-1 with endoplasmic reticulum stress in mice with acute lung injury (ALI).Methods Balb/c mice were tracheally injected with lipopolysaccharide(LPS,5 mg/kg) to induce ALI.Real-time PCR and Western blot were used to detect the expressions of TREM-1,CHOP and GRP78.The correlation of TREM-1 with endoplasmic reticulum-related proteins was analyzed.LPS (100 ng/mL) was used to induce inflammation in mouse primary peritoneal macrophages,and expressions of TREM -1,CHOP and GRP78 mRNA were detected by real-time PCR.The effect of TREM-1 activation on the expressions of CHOP and GRP78 was observed in macrophages.Results The expressions of TREM-1,CHOP and GRP78 mRNA were increased in ALI mice.TREM-1 mRNA expression was positively correlated with CHOP and GRP78 mRNA expression.In vitro,LPS up-regulated the expressions of TREM-1,CHOP and GRP78,and TREM-1 was positively correlated with CHOP and GRP78.Activation of TREM-1 increased CHOP and GRP78 mRNA expressions.Conclusions TREM-1 is positively related to the endoplasmic reticulum stress.The activation of TREM-1 enhances endoplasmic reticulum in mouse macrophages.

Objective To observe the effects of isoflurane (ISO) inhale anesthesia on the expression of brain-derived neurotrophic factor (BDNF) and Bcl-2 of hippocampal in rats.Methods A total of 54 SD rats were divided into 3 groups:control group (n=6),O2 group (n=24) and ISO group (n=24).All rats were given 1 week to adapt the environment.Then,rats in the control group were directly sacrificed to collect hippocampi specimens;rats in the O2 group inhaled mixed gas containing 40％ O2 and air for 1 hour;rats in the ISO group anesthetized with 3 ％ ISO and maintained for 1 h with 1.8 ％ ISO after righting reflex disappeared,inhaling 40％ O2 in the whole process of anesthesia.Respiratory rate and percutaneous oxygen saturation (SpO2) of the rats were observed before anesthesia,after induction,30 min after anesthesia,60 min after anesthesia and at the moment of analepsia,respectively.Rats in the O2 group and ISO group were sacrificed to extract hippocampi specimens at 6,12,24 and 72 h after treatment,respectively.The BDNF and Bcl-2 mRNA expression levels in hippocampus of rats were detected using the semi-quantitative reverse transcription PCR (RT-PCR).Results Compared to that before anesthesia,the respiratory rates after induction,30 min after anesthesia and 60 min after anesthesia were decreased (P＜0.05),while no apparent changes was found in the SpO2 (P＞0.05).Compared to the O2 group,the relative expressions of BDNF mRNA in hippocampi of rats in the ISO group were obviously decreased at 12 and 24 h after the treatment (P＜0.05).After anesthesia,the relative expression of BDNF mRNA in rat hippocampus in the ISO group was decreased as time goes on,and the expression levels at 12 and 24 h after the treatment were lower than those in the control group (P＜0.05).Compared to the O2 group and control group,the relative expression levels of Bcl-2 mRNA in hippocampi of the rats in the ISO group were lower at all time points for detection (P＜0.05).Conclnsion ISO can generate transient inhibition effect on expressions of BDNF and Bcl-2 in hippocampus of rat.

Obj cetive A large number of recent studies show that sevoflurane anesthesia may cause learning and memory dysfunction.The aim of this study was to explore changes of learning and memory ability and hippocampal volume in infantile rats after neonatal interrupted and repeated inhalation of 2.6% sevoflurane through detecting the learning and memory ability by Morris water maze and the hippocampus volume by MRI.Method s Thirty two neonatal SD rats were randomly devided into two groups (n=16):experimental group and control group.Rats inhalated 2.6%sevoflurane in the experimental group and 1 L/min O2 +1 L/min Air in the control group at the postnatal days of 7, 14 and 21 (P7, P14, P21). The learning and memory ability was determined by the Morris water maze test from P31 to P37;The brains of rats were scanned by mag-netic resonance imaging ( MRI) machine under anesthesia with 1%sodium pentobarbital at P37, and the brain and bilateral hippocampal volumes were measured. Results ①In the place navigation test, the escape latency had no significant difference between the two groups (P>0.05).In the spatial probe test, the dwelling time, movement distance and number of entering times in platform quadrant decreased slightly in experimental group compared with those in the control group, while there was no significant difference (P>0.05).②The brain volume [(1.53 ±0.18) cm3 vs (1.60 ±0.13) cm3] and right hippocampal volume [(16.15 ±1.76)mm3 vs(16.46 ±1.71)mm3] had no significant difference between the two groups (P>0.05).The left hippocampal volume [(16.46 ±1.71)mm3] was decreased in the experimental group compared with the control group [(18.10 ±2.53)mm3](P<0.05). Conclusion The learning and memory ability has no significant changes in in-fantile rats after neonatal interrupted and repeated sevoflurane inhalation and MRI examination of hippocampal volume is not sufficient for the diagnosis of cognitive dysfunction.

Objective To investigate the expression of NMDAR1 in the hippocampus and cerebral cortex of old rats after 30-min -inhalation of 2% isoflurane, and to investigate the effects of isoflurane on the learning and memory functions of old rats and the underlying mechanism. Methods The healthy old male Sprague Dawley rats (n = 36) were randomly divided into the control group, the oxygen group, the 2-hour post-recovery group, the 1-day post-recovery group, the 3-day post-recovery group, and the 7-day post-recovery group. The morris water maze was used to detect the ethological effect of 30-min inhalation of isoflurane , and the immunohistochemistry assay was used to detect the expression of NMDAR1 in the hippocampus (CA1, CA3) and the cerebral cortex. Results The 30-min inhalation of 2% isoflurane inhibited the learning and memory abilities of old rats at 2 h post-recovery. On 1 d post-recovery, the inhibition of learning and memory began to reduce, then on 3 d and 7 d post-recovery, the learning and memory abilities continously recovered. The expression of NMDAR1 in the rat hippocampus and cerebral cortex decreased at 2 h post-recovery, and reversed on 1 d post-recovery and reached the normal level on 3 d and 7 d post-recovery. Conclusion 30-min inhalation of 2%isoflurane had an inhibitory effect on the learning and memory abilities of old rats, and the attenuation of NMDAR1 in the hippocampus and cerebral cortex may involve in this process.

Objective To evaluate the neurotoxicity induced by multiple exposures to sevoflurane anesthesia in the neonatal rats.Methods Thirty-two healthy SPF Sprague-Dawley rats of both sexes,aged 7 days,weighing 15-20 g,were randomly divided into 2 groups (n=16 each) using a random number table:control group (group C) and multiple exposures to sevoflurane anesthesia group (group Sev).On postnatal day 7,14 and 21,2.6％ sevoflurane was inhaled for 2 h in group Sev,while the mixed gas of oxygen and air was inhaled instead of sevoflurane in group C.Morris water maze test was carried out on postnatal day 32-36 to assess the cognitive function.On postnatal day 21 and 36,8 rats in each group were selected and anesthetized,and the cerebrospinal fluid was collected for determination of the concentrations of amyloid β-protein by enzyme-linked immunosorbent assay.Results Compared with group C,no significant change was found in the escape latency,movement time spent in the effective region of the platform,movement distance,the number of entries into the effective region,percentage of residence time,percentage of movement distance,and percentage of the number of entries (P＞0.05),and the concentrations of amyloid β-protein in the cerebrospinal fluid were significantly increased on postnatal day 36 in group Sev (P＜0.05).Conclusion Multiple exposures to sevoflurane anesthesia can induce central neurotoxicity,but do not induce changes in the cognitive function in the neonatal rats.

Objective To evaluate the effects of multiple exposures to sevoflurane anesthesia on the expression of apolipoprotein E (ApoE) in the hippocampus of neonatal rats.Methods Twenty-four pathogen-free Sprague-Dawley rats (12 males,12 females),aged 7 days,weighing 15-20 g,were randomly divided into 2 groups (n=12 each) using a random number table:control group (group Con) and multiple exposures to sevoflurane anesthesia group (group Sev).On postnatal day 7,14 and 21,2.6％ sevoflurane was inhaled for 2 h in group Sev,while the mixed gas of oxygen and air was inhaled instead of sevoflurane in group Con.Morris water maze test was carried out on postnatal day 31-37 to assess cognitive function.The rats were then sacrificed,and the hippocampus was removed to determine the expression of ApoE protein in hippocampal CA1,CA3 and DG regions (by immunohistochemistry) and the expression of ApoE mRNA (by fluorescent quantitative real-time reverse transcriptase polymerase chain reaction).Results There was no significant difference between the two groups in cognitive function (P＞0.05).Compared with group Con,the expression of ApoE protein in hippocampal CA1 and CA3 regions and ApoE mRNA was significantly up-regulated in group Sev (P＜0.05),and no statistically significant change was found in the expression of ApoE protein in hippocampal DG region in group Sev (P＞0.05).Conclusion Multipie exposures to sevoflurane anesthesia can up-regulate the expression of hippocampal ApoE and produce mild neurotoxicity without causing changes in cognitive function in neonatal rats.

Objective To investigate the effect of sevoflurane anesthesia on the expression of hippocampal apolipoprotein E (ApoE) mRNA of rats.Methods Sixty healthy male Sprague-Dawley rats,weighing 300-400 g,aged 15 weeks,were randomly divided into 2 groups (n=30 each) using a random number table:50％ oxygen group (group C) and 3.2％ sevoflurane group (group S).The rats in group C inhaled 50％ oxygen for 2 h,while those in group S inhaled 3.2％ sevoflurane in 50％ oxygen for 2 h.Morris water maze test was carried out before anesthesia and at 24 and 72 h after anesthesia.At 2,24 and 72 h after anesthesia,hippocampal specimens were obtained for determination of the expression of ApoE mRNA by RT-PCR.Results Compared with group C,no significant change was found in the escape latency,time of staying at the original platform quadrant,frequency of crossing the original platform,and swimming distance before and after anesthesia,and the expression of ApoE mRNA was up-regulated after anesthesia in group S.There was no significant difference in the escape latency,time of staying at the original platform quadrant,frequency of crossing the original platform,and swimming distance before and after anesthesia,and expression of ApoE mRNA at each time point after anesthesia between the two groups.Conclusion Cognitive dysfunction induced by sevoflurane has no relationship with the up-regulated expression of ApoE mRNA in the hippocampus of rats.