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Objective:To compare the recovery effect of continuous infusion of dexmedetomidine combined with oxycodone or sufentanil in the anesthesia intensive care unit (AICU) in elderly patients after thoracoscopic radical surgery for lung cancer.Methods:Using the method of prospective study, 80 elderly lung cancer patients underwent selective thoracoscopic radical surgery under general anesthesia in Nanjing First Hospital from February 2021 to May 2022 were selected. The patients were divided into dexmedetomidine combined with sufentanil group (S group) and dexmedetomidine combined with oxycodone group (Q group) by random digits table method with 40 cases each group. On the basis of routine monitoring and treatment after operation, the patients in Q group were continuously injected with oxycodone 0.03 mg/(kg·h) and dexmedetomidine 0.4 μg/(kg·h) through analgesia pump, the patients in S group were continuously injected with sufentanil 0.03 mg/(kg·h) and dexmedetomidine 0.4 μg/(kg·h) through analgesia pump. The wake-up time, extubation time, awakening quality (Aldrete score and bucking score) and comfort level (Bruggrmann comfort scale score, BCS score) after entering the AICU were record; the sedation score (Ramsay score) and pain relief score (numerical rating scale score, NRS score) and hemodynamic changes (mean arterial pressure and heart rate) 3, 5, 7, 10 and 14 h after entering the AICU were record; the level of serum inflammatory factors, including tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) immediately, 5 h and 14 h after entering the AICU; press times of analgesia pump, adverse events, bleeding volume of drainage tube during AICU and overall satisfaction score when leaving the AICU were record.Results:The bucking score in Q group was significantly lower than that in S group: (1.02 ± 0.77) scores vs. (1.88 ± 0.34) scores, the Aldrete score and BCS score were significantly higher than those in S group: (8.93 ± 0.25) scores vs. (5.97 ± 0.32) scores and (3.03 ± 0.32) scores vs. (0.93 ± 0.52) scores, and there were statistical differences ( P<0.01); there were no statistical difference in wake-up time and extubation time between two groups ( P>0.05). There were no statistical difference Ramassy score, NRS score 3 and 5 h after entering the AICU, mean arterial pressure and heart rate between two groups ( P>0.05); the Ramassy score 7, 10 and 14 h after entering the AICU in Q group was significantly lower than that in S group, the NRS score, mean arterial pressure and heart rate were significantly lower than those in S group, and there were statistical differences ( P<0.01). There were no statistical differences in TNF-α, IL-6 and CRP immediately after entering the AICU between two groups ( P>0.05); the TNF-α, IL-6 and CRP 5 and 14 h after entering the AICU in Q group were significantly lower than those in S group, and there were statistical difference ( P<0.01). The press times of analgesia pump, bleeding volume of drainage tube and the incidences of nausea vomiting, respiratory depression, lethargy, restlessness, fever and lung infection in Q group were significantly lower than those in S group: (4.63 ± 1.10) times vs. (18.80 ± 1.54) times, (129.67 ± 4.14) ml vs. (164.00 ± 8.14) ml, 10.0% (4/40) vs. 52.5% (21/40), 2.5% (1/40) vs. 25.0% (10/40), 7.5% (3/40) vs. 47.5% (19/40), 0 vs. 20.0% (8/40), 2.5% (1/40) vs. 22.5% (9/40) and 2.5% (1/40) vs. 20.0% (8/40), and there were statistical differences ( P<0.01 or <0.05); there was no severe hypotension, severe bradycardia and delirium in both groups. The overall satisfaction score in Q group was significantly higher than that in S group: (3.53 ± 0.63) scores vs. (2.70 ± 0.65) scores, and there was statistical difference ( P<0.01). Conclusions:Continuous micro-pump infusion of dexmedetomidine combined with oxycodone in AICU elderly patients with lung cancer after thoracoscopic radical surgery can significantly improve the quality of recovery and comfort during extubation, without affecting the extubation time, and can effectively reduce the degree of pain, stress and inflammatory reaction in the early recovery period, and reduce the incidence of adverse events after surgery.
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OBJECTIVE@#To investigate the effects of gene of phosphate and tension homology (PTEN)-induced putative kinase 1 (PINK1)/Parkin pathway on hippocampal mitophagy and cognitive function in mice with sepsis-associated encephalopathy (SAE) and its possible mechanism.@*METHODS@#A total of 80 male C57BL/6J mice were randomly divided into Sham group, cecal ligation puncture (CLP) group, PINK1 plasmid transfection pretreatment groups (p-PINK1+Sham group, p-PINK1+CLP group), empty vector plasmid transfection control group (p-vector+CLP group), with 16 mice in each group. The mice in CLP groups were treated with CLP to reproduce SAE models. The mice in the Sham groups were performed laparotomy only. Animals in the p-PINK1+Sham and p-PINK1+CLP groups were transfected with PINK1 plasmid through the lateral ventricle at 24 hours before surgery, while mice in the p-vector+CLP group were transfected with the empty plasmid. Morris water maze experiment was performed 7 days after CLP. The hippocampal tissues were collected, the pathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining, and the mitochondrial autophagy was observed under a transmission electron microscopy after uranyl acetate and lead citrate staining. The expressions of PINK1, Parkin, Beclin1, interleukins (IL-6, IL-1β) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blotting.@*RESULTS@#Compared with the Sham group, CLP group mice in Morris water maze experiment had longer escape latency, shorter target quadrant residence time, and fewer times of crossing the platform at 1-4 days. Under the light microscope, the hippocampal structure of the mouse was injured, the neuronal cells were arranged in disorder, and the nuclei were pyknotic. Under the electron microscope, the mitochondria appeared swollen, round, and wrapped by bilayer or multilayer membrane structures. Compared with the Sham group, CLP group had higher expressions of PINK1, Parkin, Beclin1, LC3II/LC3I ratio, IL-6 and IL-1β in hippocampus, indicating that sepsis induced by CLP could activated inflammatory response and caused PINK1/Parkin-mediated mitophagy. Compared with the CLP group, p-PINK1+CLP group had shorter escape latencies, spent more time in the target quadrant and had more number of crossings in the target quadrant at 1-4 days. Under the light microscope, the hippocampal structures of mice was destroyed, the neurons were arranged disorderly, and the nuclei were pyknotic. Under transmission electron microscope, swollen and rounded mitochondria and mitochondrial structure wrapped by double membrane or multilayer membrane structure were observed. Compared with the CLP group, the levels of PINK1, Parkin, Beclin1 and LC3II/LC3 ratio in the p-PINK1+CLP group were significantly increased [PINK1 protein (PINK1/β-actin): 1.95±0.17 vs. 1.74±0.15, Parkin protein (Parkin/β-actin): 2.06±0.11 vs. 1.78±0.12, Beclin1 protein (Beclin1/β-actin): 2.11±0.12 vs. 1.67±0.10, LC3II/LC3I ratio: 3.63±0.12 vs. 2.27±0.10, all P < 0.05], while the levels of IL-6 and IL-1β were significantly decreased [IL-6 protein (IL-6/β-actin): 1.69±0.09 vs. 2.00±0.11, IL-1β protein (IL-1β/β-actin): 1.11±0.12 vs. 1.65±0.12, both P < 0.05], suggesting that overexpression of PINK1 protein could further activate mitophagy and reduce the inflammatory response caused by sepsis. There was no statistically significant difference in the above pathological changes and related indicators between Sham group and p-PINK1+Sham group, CLP group and p-vector+CLP group.@*CONCLUSIONS@#PINK1 overexpression can further activate CLP-induced mitophagy by upregulating Parkin, thereby inhibiting inflammation response and alleviate cognitive function impairment in SAE mice.
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Male , Animals , Mice , Mice, Inbred C57BL , Sepsis-Associated Encephalopathy , Phosphates , Actins , Beclin-1 , Interleukin-6 , Autophagy , Ubiquitin-Protein Ligases , Cognitive Dysfunction , Sepsis , Mitochondria , Protein KinasesABSTRACT
Sepsis associated encephalopathy (SAE) is a severe disease secondary to sepsis, which is associated with increased mortality and causes long-term cognitive deficits in survivors. Recently, an increasing body of evidence has shown that gut microbiota is closely related to the central nervous system, and could influence brain function via microbiota-gut-brain axis. Therefore, in the occurrence and development of SAE, cholinergic anti-inflammatory pathway is one of the mechanisms by which gut microbiota could improve cognitive function. Efferocytosis, a process of eliminating apoptotic cells in the body, has anti-inflammatory effects and provides organ protection in sepsis. On the other hand, it could be enhanced by some metabolites of gut microbiota, making it another potential mechanism for gut microbiota regulating SAE. This review summarizes the mutual regulation of gut microbiota, efferocytosis and SAE, to explore potential mechanisms and therapeutic targets of SAE.
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Objective:To investigate the effect of individualized positive end-expiratory pressure (PEEP) on postoperative lung complications in patients undergoing cardiac valve replacement.Methods:Sixty-four patients of both sexes, aged 40-70 yr, with body mass index of 18-26 kg/m 2, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with New York Heart Association class Ⅱ or Ⅲ, undergoing elective cardiac valve replacement (single or double) from July to October 2020, were enrolled in this study.The patients were divided into 2 groups ( n=32 each) using a random number table method: control group (group C) and individualized PEEP group (group P). After recruitment maneuver, group C was set with a fixed PEEP of 4 cmH 2O, group P was titrated using a PEEP-step method, and PEEP was set at 4 cmH 2O after admission to intensive care unit (ICU). Before induction of anesthesia (T 0), before recruitment maneuver (T 1), at 20 min after PEEP ventilation (T 2), at 2 h after surgery (T 3), and at 24 h after surgery (T 4), arterial blood samples were taken for determination of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations.The hemodynamic indicators (heart rate, mean arterial pressure and central venous pressure) at T 1-T 4 were recorded.Pulmonary complications were diagnosed according to clinical manifestations, imaging and blood gas analysis during the postoperative hospitalization.The postoperative length of hospital stay, extubation time and duration of ICU stay were recorded. Results:PEEP in group P [(6.1±1.4)cmH 2O] was significantly higher than that in group C ( P<0.05). Compared with group C, the concentrations of serum IL-6 and TNF-α at T 3 were significantly decreased, central venous pressure at T 2 was increased, and the incidence of postoperative pulmonary complications was decreased ( P<0.05), and no significant change was found in the length of hospital stay, extubation time and duration of ICU stay in group P ( P>0.05). Conclusion:Early application of individualized PEEP after termination of cardiopulmonary bypass can decrease the risk of postoperative pulmonary complications in patients undergoing cardiac valve replacement.
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Objective:To evaluate the relationship between milk fat globular epidermal growth factor Ⅷ (MFG-E8)-mediated efferocytosis and sepsis-associated encephalopathy (SAE) in mice.Methods:Forty clean-grade healthy male C57BL/6 mice, aged 2-3 months, weighing 18-22 g, were divided into 4 groups ( n=10 each) using a random number table method: sham operation group (group Sham), cecal ligation and perforation (CLP) group (group CLP), sham operation+ phosphate buffer solution (PBS) group (group Sham+ PBS) and CLP+ recombinant mouse MFG-E8 group (group CLP+ rmMFG-E8). SAE was induced by CLP in anesthetized mice.PBS 1 μl and rmMFG-E8 1 μg were injected into the lateral cerebral ventricle in Sham+ PBS and CLP+ rmMFG-E8 groups after operation for 5 consecutive days.Novel object recognition test was performed at 6 days after operation, and the contextual fear conditioning test was performed at 7 and 8 days after operation.The percentage of time spent exploring a novel object, discrimination index and percentage of freezing time induced by condition were calculated.The animals were sacrificed after the end of behavioral tests, and the hippocampus was extracted for determination of the expression of MFG-E8 and GTP-Rac1 (by Western blot), the mRNA expression levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1β (using real-time reverse transcription-polymerase chain reaction) and the apoptosis rate in hippocampus (by TUNEL). Results:Compared with group Sham, the percentage of time spent exploring a novel object, discrimination index and percentage of freezing time were significantly decreased, hippocamcal MFG-E8 expression was down-regulated, GTP-Rac1 expression was up-regulated, mRNA expression of IL-6, TNF-α and IL-1β was up-regulated, and apoptosis rate was increased in group CLP ( P<0.05). Compared with group CLP, the percentage of time spent exploring a novel object and discrimination index were significantly increased, freezing time was prolonged, hippocamcal MFG-E8 and GTP-Rac1 expression was up-regulated, mRNA expression of IL-6, TNF-α and IL-1β was down-regulated, and apoptosis rate was decreased in group CLP+ rmMFG-E8 ( P<0.05). Conclusion:The reduction of hippocampal MFG-E8-mediated efferocytosis may be involved in the pathophysiological mechanism of SAE in mice.
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Objective To investigate the effects of propofol combined with nalbuphine on diaphragmatic movement monitored by ultrasound in patients undergoing colonoscopy.Methods Forty patients, males 21 and females 19, aged 18-65 years, BMI 18-25 kg/m2, ASA physical status I or II, were recruited and scheduled to undergo elective painless colonoscopy.All patients were randomly divided into two groups (n =20):propofol group (group P) and propofol combined with nalbuphine group (group F).Patients in group F received nalbuphine 0.1 mg/kg intravenously 1 min before propofol administration, and patients in group P received same volume of normal saline.Propofol was infused by TCI and the initial target plasma concentration was set at 2μg/ml in all patients.The target concentration was adjusted gradually until the Ramsay sedation score reached 5.Then colonoscopy was started.During the colonoscopy, the propofol concentration was adjusted according to the Ramsay score.Ultrasound was used to monitor the movement of the right diaphragm of the patients.SpO2, MAP, HR, PETCO2, RR, diaphragmatic movement (DM), diaphragmatic thickness at the end of inspiration (TEI) and diaphragmatic thickness at the end of expiration (TEE) were recorded under calm breathing after entering the room (T0), Ramsay sedation score 5 points after propofol administration (T1), and Ramsay sedation score 2 after endoscopy (T2).The diaphragmatic thickening fraction (DTF) was calculated:DTF= (TEI-TEE) /TEI.Adverse reactions such as bradycardia, hypotension, body movement, and respiratory depression were recorded.Results Compared with T0, MAP, SpO2, HR and RR decreased, and PETCO2 increased at T1 time point in patients of the two groups (P<0.05).Compared with group F, the dose of propofol increased in group P (P<0.05).DM at T1 and T2, DTF at T1 were obviously higher in group F than those in group P (P<0.05).There were two cases had body movement in group P, and one case had bradycardia in group F.There was no case suffered from hypotension, respiratory depression and reflux aspiration in two groups.Conclusion Compared with propofol alone, propofol combined with nalbuphine can attenuate the dysfunction of the diaphragm.
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Objective To investigate the effect of ultrasound-guided quadratus lumborum block on cognitive function after laparoscopic colorectal surgery.Methods Seventy-six patients, there is no restriction on gender, aged 50-75 years, falling into ASA physical statusⅡorⅢ, who provided informed consent for their participation in this study and underwent colorectal surgery under general anesthesia were divided into two groups (groups Q and C).Induction of anesthesia was induced by intravenous midazolam 0.03 mg/kg, sufentanil 0.5μg/kg, etomidate 0.3 mg/kg and rocuronium 1 mg/kg in the two groups.Remifentanil 0.2-0.3μg·kg-1·min-1 and propofol 0.10-0.15 mg·kg-1·min-1 were maintained intravenously during anesthesia.0.375％ropivacaine 20 ml was injected between the psoas quadratus muscle and psoas major muscle under ultrasound guidance before extubation in group Q, only equal volume saline was given in group C.Neuropsychological tests were performed preoperatively as well as postoperative day 7.The postoperative pain was evaluated by VAS after surgery.The postoperative sleep quality was measured using a BIS-vista monitor.The changes of serum IL-6, IL-1β, TNF-αand CGRP levels were detected by ELISA at immediately after operation (T0), 1 hour (T1), 2 days (T2), 4 days (T3) and 7 days (T4) after operation.Results Seventy-six patients finished cognitive function tests (38 cases in group Q and 38 cases in group C), 12 cases (31.6％) were diagnosed as POCD in group C, 4 cases (10.5％) in group Q.Compared with group C, the incidence of POCD, VAS scores at 24 and 48 hours after operation in group Q were significantly lower (P<0.05), the sleeping time at night was longer, the serum levels of IL-6, IL-1βand TNF-αwere significantly lower at T2 and T3, and the serum levels of CGRP were significantly higher at T2-T4 (P<0.05 or P<0.01).Conclusion QLB treatment repaired the surgery induced early cognitive dysfunction by inhibiting the postoperative pain, excessive inflammatory response and improving the quality of sleep.
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Objective To evaluate the accuracy of different biomarkers for early diagnosis of acute kidney injury ( AKI ) in the patients undergoing cardiovascular surgery under cardiopulmonary bypass ( CPB) . Methods A total of 200 patients, aged 22-86 yr, weighing 46-87 kg, scheduled for elective cardiovascular surgery under CPB, were enrolled in this study. The concentration of serum creatinine was determined at 1 day before operation and 1-7 days after operation. At 1 day before operation and 0, 2, 6 and 12 h after operation, the concentrations of urine neutrophil gelatinase-associated lipocalin (NGAL), cystatin C ( Cys C) , tissue inhibitor of matrix metalloproteinase type 2 ( TIMP-2) and insulin-like growth factor binding protein-7 ( IGFBP-7) were determined. The TIMP-2 and IGFBP-7 product ( TI) was calcu-lated. AKI was diagnosed after surgery according to Kidney Disease Improving Global Outcomes criteria. The receiver operating characteristic curve was plotted, and the area under receiver operating characteristic curve ( AUC) was calculated. Results The incidence of AKI was 20. 5％. The AUC of AKI diagnosed by the concentration of urine NGAL was 0. 689, 0. 709, 0. 713 and 0. 803 at 0, 2, 6 and 12 h after opera-tion, respectively ( P<0. 05) . The AUC of AKI diagnosed by the concentration of urine Cys C was 0. 639, 0. 762, 0. 774 and 0. 812 at 0, 2, 6 and 12 h after operation, respectively ( P<0. 05) . The AUC of AKIdiagnosed by TI was 0. 687, 0. 721, 0. 740 and 0. 779 at 0, 2, 6 and 12 h after operation, respectively ( P<0. 05) . The AUC of AKI diagnosed by combined three indices the parallel test was 0. 694, 0. 773 and 0. 794 at 0, 2 and 6 h after operation, respectively ( P<0. 05) . The AUC of AKI diagnosed by the serial test was 0. 610, 0. 631 and 0. 667 at 0, 2 and 6 h after operation, respectively. Conclusion Urine NGAL or Cys C concentrations or TI single detection and parallel test have a certain accuracy for early diag-nosis of AKI in the patients undergoing cardiovascular surgery under CPB.
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Objective To evaluate the role of C-X-C motif chemokine 13 (CXCL13) in sepsis-associated encephalopathy in mice.Methods A total of 64 healthy male C57BL/6J mice,aged 3-4 months,weighing 20-25 g,were divided into 4 groups (n=16 each) using a random number table method:sham operation group (Sham group),sepsis group (S group),CXCL13 siRNA group (si-CXCL13 group) and negative control siRNA group (si-control group).5-bromo-2-deoxyuridine (BrdU) 50 mg/kg was intraperitoneally injected twice a day for 3 consecutive days in the four groups,and then lipopolysaccharide 500 μg/kg was intraperitoneally injected to establish the sepsis model in S,si-CXCL13 and si-control groups.CXCL13 siRNA 5 μl and siRNA 5 μl were injected into the left lateral cerebral ventricle in si-CXCL13 and si-control groups,respectively,at 3 days before establishing the model.Morris water maze test was performed at 5 days after establishing the model.The escape latency,time spent in the target quadrant,and the number of crossing the platform were recorded.Mice were sacrificed after the end of test,brains were removed and hippocampi were isolated for examination of the pathological changes of the dentate gyrus (with a light microscope) and for determination of the expression of CXCL13,C-X-C motif chemokine receptor 5 (CXCR5) and brain-derived neurotrophic factor (BDNF),and the number of BrdU and BrdU/NeuroD positive cells (by immunofluorescence).Results Compared with sham group,the escape latency was significantly prolonged,the time spent in the target quadrant was shortened,and the number of crossing the platform was reduced on 2nd-4th days,the number of BrdU positive cells in the dentate gyrus was increased,and the number of BrdU/NeuroD positive cells in the dentate gyrus was decreased in S,siCXCL13 and si-control groups,and the expression of CXCL13 and CXCR5 was up-regulated,and the expression of BDNF was down-regulated in LPS and si-control groups (P＜0.05).Compared with S group,the escape latency was significantly shortened,the time spent in the target quadrant was prolonged,and the number of crossing the platform was increased on 2nd-4th days,the number of BrdU positive cells in the dentate gyrus was decreased,the number of BrdU/NeuroD positive cells in the dentate gyrus was increased,and the expression of CXCL13 and CXCR5 was down-regulated,and the expression of BDNF was up-regulated in si-CXCL13 group (P＜0.05),and no significant change was found in the parameters mentioned above in si-control group (P＞0.05).Conclusion CXCL13 is involved in sepsis-associated encephalopathy through regulating hippocampal neurogenesis,and the mechanism may be related to down-regulating the expression of hippocampal BDNF in mice.
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Objective To investigate the role of triggering receptor expressed on myeloid cells 1 (TREM1)in rats with neuropathic pain and its possible mechanism.Methods Forty-eight male a-dult Sprague-Dawley rats,weighing 220-300 g,were successfully placed intrathecal catheters,and then randomly divided into 4 groups (n=1 2 ):sham operation group (group S),neuropathic pain group (group CCI),TREM1 shRNA group (group RNAi)and negative lentivirus group (group Vi-rus).The neuropathic pain was induced by chronic sciatic nerve compression injury (CCI).In group RNAi,30 μl pGLVU6/RFP/Puro-shRNA (1×109IU/ml)was injected intrathecally 1 week before modeling.Group Virus was injected with 30 μl negative lentivirus,whereas group CCI and group S with equal amount of normal saline.MWT and TWL were measured 1 day before (baseline)and 1,3, 7,14 day after modeling.When behavioral test finished,the expression levels of TREM1,TLR4, MyD88,IκBαand p-NF-κB p65 in spinal cord were determined by Western blot.Whereas the mRNA expression levels of IL-1β,TNF-αand IL-6 in spinal cord were measured by RT-PCR.Results Com-pared with group S,the expression levels of TREM1 in groups CCI and Virus significantly increased (P<0.05).While compared with group CCI,the TREM1 expression of group RNAi in spinal cord significantly decreased (P<0.05).Compared with group S,MWT and TWL of groups CCI,Virus and RNAi after modeling and the expression of IκBαsignificantly decreased (P<0.05),whereas the expression of TLR4,MyD88,p-NF-κB p65 increased significantly (P<0.05),as well as the expres-sion of IL-1β,TNFαand IL-6 mRNA (P<0.05).Compared with group CCI,the MWT and TWL of group RNAi after modeling and the expression of IκBαremarkably increased (P<0.05),whereas the expression of TLR4,MyD88 and p-NF-κB p65 in the spinal cord remarkably decreased (P<0.05), as well as the expression of IL-1β,TNF-αand IL-6 mRNA (P<0.05).Conclusion TREM1 knock-down can alleviate neuropathic pain,the underlying mechanism might be the inhibition of TLR4/MyD88/NF-κB signaling pathway.
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Objective To investigate the changes of serum C-X-C motif ligand 13 (CXCL13) concentration in senior patients undergoing total hip replacement and its role in post-operative dys-function(POCD).Methods Eighty consecutive senior patients aged 65-80 years with BMI 18.4-27.3 kg/m2,ASA physical status Ⅱ or Ⅲ,were recruited and scheduled to undergo hip joint replacement operation.Neuropsychological test was performed 1-5 d after operation and patients were divided into POCD group and non-POCD group.Serum C reactive protein (CPR),procalcitonin (PCT),IL-6, TNF-α,CXCL13 concentration were detected 1 d before and 1,2,3,4,5 d after operation. Results A total of 21 (26%)patients developed POCD 1-5 d after operation (recruited in POCD group),and the other 59 patients were recruited in non-POCD group.Compared with the time point of 1 d before operation,serum CRP,PCT,IL-6,TNF-αand CXCL13 concentration were higher 1-5 d after operation in all patients (P<0.05).The concentrationsof these factors were higher in patients from POCD group than in those from non-POCD group 1-5 d after operation (P < 0.05). Conclusion The CXCL13 concentration insenior patients undergoing total hip replacement who devel-oped POCD were higher than in those who did not developed POCD.Whether it is correlated with POCD remains further study.
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Objective:To explore the effect of prostaglandin E2 (PGE2) on the expression of high mobility group box-1 protein (HMGB1) in peritoneal macrophages of septic mice and its possible mechanisms.Methods:Ihe mouse peritoneal macrophages were isolated and cultured by conventional methods.The model of inflammation was established by using lipopolysaccharide (LPS) to incubate with mouse peritoneal macrophages.The PGE2,prostaglandin E receptor (EP) 4 agonist,EP4 RNAi,and DN.CREB inhibitory plasmid were used to interfere with the LPS-treated mouse peritoneal macrophage.The levels of HMGB 1 was determined by Western blot.Results:Compared with LPS alone treatment,the expression of HMGB 1 in peritoneal macrophages was increased obviously after 24 h by treatment with PGE2 and LPS,and it was also increased after the combined treatment of EP4 receptor agonist with LPS for 24 h (both P0.05);compared with LPS alone treatment,the combined treatment of EP4 receptor agonist with LPS for 24 h could up-regulate the phosphorylation of epidermal growth factor receptor (EGFR) and protein kinase B (Akt) thr308 (P<0.05),which were blocked by EGFR inhibitor.Once Akt specific inhibitor was used before EP4 and LPS treatment,the expression of HMGB1 was declined (P<0.05).Conclusion:PGE2 can up-regulate the expression of HMGB1 in sepsis of peritoneal macrophages through EP4 receptor,which may be related to the activation of EGFR/PI3K/Akt signaling pathway.
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Objective To investigate the effects of acetylated HMGB1 on cognitive function in rats with sepsis associated encephalopathy (SAE) and the effect of HMGB1 inhibitor.Methods Forty-eight males mice were randomly assigned to three groups (n=16): sham group (group S),cecal ligation puncture group (group C),cecal ligation puncture+sodium butyrate group (group B).Cecal ligation puncture was applied to establish the SAE model,and group S received sham operation.Rats in groups S and C were injected with normal saline 5 ml/kg 30 min and 4 h after CLP,respectively.The rats in group B were intraperitoneally injected with sodium butyrate 500 mg/kg 0.5 h and 4 h after CLP,respectively.All animals were performed Morris water maze test on 4th day after operation,and the exploring time of space exploration experiments were assessed on 7th day after CLP surgery.IL-6,BDNF,HMGB1 and acetylated HMGB1 expression in hippocampus of all rats were determined by Western Blot.Results Compared with group S,the latency of rats in group C was longer and the exploring time was shorter (P<0.05).Compared with group C,the latency of rats in group B was shorter and the exploring time was longer (P<0.05).Compared with group S,the expression of IL-6,HMGB1 and acetylated HMGB1 in group C increased (P<0.05) and the level of BDNF decreased (P<0.05).Compared with group C,the expression of IL-6,HMGB1 and acetylated HMGB1 in group B decreased (P<0.05) and the level of BDNF increased (P<0.05).Conclusion HMGB1 inhibitor sodium butyrate can inhibit the expression of acetylated HMGB1 in the hippocampus of SAE rats,and reduce the cognitive impairment induced by sepsis.
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Objective To explore the predictive capability of different methods for difficult la-ryngoscopy and analyze its optimal cutoff value.Methods Three hundred consecutive patients (aged 18-65 years,weighing 42-88 kg,ASA physical status Ⅰ or Ⅱ)scheduled to undergo general anesthe-sia and surgery were invited to participate.Difficult airway assessments were performed by thyromen-tal height (TMH),thyromental distance (TMD),sternomental distance (SMD),modified Mallam-pati test (MMT)and ratio of height and TMD (RHTMD)before anesthetic induction.Cormack-Le-hane (C-L)grade of laryngoscopy view was assessed after induction.Sensitivity,specificity,positive predictive value (PPV),negative predictive value (NPV)and accuracy of these tests were calculated. Receiver operator characteristic (ROC)curve of TMH was performed to determine the optimal cutoff value of TMH.Results There were 22 patients diagnosed as difficult airway.Sensitivity,specificity, PPV,NPV and accuracy of TMH were higher than those of TMD,SMD and MMT tests.Sensitivity of RHTMD was lower than that of TMH test,and specificity,PPV,NPV and accuracy of RHTMD were similar to that of TMH.The optimal cutoff value of TMH was 4.9 cm through ROC curve. Conclusion The optimal cutoff value of TMH detecting difficult laryngoscopy was 4.9 cm.Similar to RHTMD,TMH appears to be more effective for prediction of difficult laryngoscopy than TMD, SMD and MMT.
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Objective To investigate the role of hippocampal cyclophilin D (CypD) in sepsis-associated encephalopathy in rats.Methods A total of 36 adult male Sprague-Dawley rats,aged 3-4 months,weighing 300-400 g,were randomly divided into 3 groups (n =12 each) using a random number table:sham operation group (Sham group),sepsis group (S group),and sepsis + CypD inhibitor cyclosporin A group (CsA group).Sepsis was induced by cecal ligation and puncture (CLP).Cyclosporin A 6 mg/kg was injected intraperitoneally at 30 min before CLP in group CsA.All the animals underwent Morris water maze test on 4th day after CLP.The animals were sacrificed after the test,and the hippocampus was isolated for determination of the expression of cytochrome c (Cyt c),CypD,caspase-3,brain-derived neurotrophic factor (BDNF),phosphorylated protein kinase A (p-PKA),and phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB).Results Compared with group Sham,the escape latency was significantly prolonged,the space exploration time was shortened,the expression of Cyt c,CypD,caspase-3,p-PKA and p-CREB was up-regulated,and the expression of BDNF was down-regulated in S and CsA groups (P＜0.05).Compared with group S,the escape latency was significantly shortened,the space exploration time was prolonged,the expression of Cyt c,CypD,caspase-3,p-PKA and p-CREB was down-regulated,and the expression of BDNF was up-regulated in group CsA (P＜0.05).Conclusion Hippocampal CypD may be involved in the pathophysiological mechanism of sepsis-associated encephalopathy,and the downstream mechanism is probably related to promotion of activation of PKA/CREB signaling pathway in rats.
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Objective To investigate the influence of low-dose ketamine and dexmedetomidine on cardiovascular response during. sedative amnesia fiberoptic nasotracheal intubation. Methods Ninety ASA Ⅰ or Ⅱ patients scheduled to recerve general anesthesia were evenly random-ized to dexmedetomidine and ketamine (group DK),dexmedetomidine and propofol (group DP)and dexmedetomidine and remifentanil (group DR).Ten minutes before intubation,the patients in group DK received intravenously dexmedetomidine 1.0 μg/kg plus ketamine 0.5 mg·kg-1 ·h-1 ;those in group DP received intravenously dexmedetomidine 1.0 μg/kg plus propofol 2.0 mg · kg-1 · h-1 ;those in group DR received intravenously dexmedetomidine 1.0 μg/kg plus remifentanil 5.0μg·kg-1 ·h-1 .Nasotracheal intubation was performed with fiberoptic bronchoscopy after dexemeto-midine injection and complete topical anesthesia.HR,MAP,SpO 2 and Ramsay sedation score were re-corded before anesthesia (T0 ,baseline),before intubation (T1 ),immediately intubated (T2 )and five minutes after intubation (T3 ).Side effects such as restlessness,bucking,respiratory depression and cardiovascular event during intubation and awareness of intubation were also recorded.Results All pa-tients in three groups were performed successfully.HR and MAP were significantly decreased in groups DP and DR at T1 (P <0.05),SpO 2 was significantly decreased in group DP at T1 (P <0.05);MAP in group DR were higher than those in group DP,HR in groups DP and DR were significantly increased than those in group DK at T3 (P < 0.05 );Ramsay score were significantly decreased in groups DP and DR at T2 ,significantly lower in group DR at T3 than those in groups DK and DP (P<0.05).The incidences of bradycardia and respriatory depression were significantly higher in group DP than those in group DK,and bucking,restlessness,tachycardia incidence rate in group DR were significantly higher than those in groups DK and DP (P <0.05).Conclusion Dexmedetomidine com-bined with low dose ketamine together with topical anesthesia is an ideal method for sedative amnesia fiberoptic nasotracheal intubation with slighter cardiovascular response and less side effects.
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Objective To evaluate the effect of exogeneous adiponectin on hippocampal advanced glycation end products (AGEs)-reactive oxygen species (ROS)-endoplasmic reticulum stress (ERS) pathway in aged mice with postoperative cognitive dysfunction (POCD).Methods Thirty-two healthy male C57BL/6 mice, aged 18 months, weighing 20-25 g, were randomly divided into 4 groups (n=8 each) using a random number table: control group (group C), POCD group, exogeneous adiponectin group (group APN), and vehicle group (group Veh).Splenectomy was performed to establish the POCD model in aged mice anesthetized with intraperitoneal pentobarbital sodium.In group APN, adiponectin 0.1 μg/g (in 2 μl of phosphate buffer solution) was injected into the lateral cerebral ventricle at 30 min before establishing the model.Phosphate buffer solution 2 μl was given at 30 min before establishing the model in group Veh.Cognitive function was assessed on day 7 after surgery.The mice were then sacrificed, and the hippocampus was harvested for determination of the area of AGE deposition (by immunohistochemistry), levels of ROS (by flow cytometry), and levels of glucose-regulated protein 78 (GRP78), C/EBP-homologous protein (CHOP), caspase-12 and ROS (using Western blot).Results Compared with group S, the freezing time in the contextual fear conditioning test was significantly shortened, the area of AGE deposition and levels of ROS, CHOP and caspase-12 were increased, and the level of GRP78 was decreased in POCD, APN and Veh groups.Compared with POCD and Veh groups, the freezing time in the contextual fear conditioning test was significantly prolonged, the area of AGE deposition and levels of ROS, CHOP and caspase-12 were decreased, and the level of GRP78 was increased in group APN.Conclusion Exogeneous adiponectin decreases the occurrence of POCD probably by blocking hippocampal AGEs-ROS-ERS pathway in aged mice.
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Objective To evaluate the effect of lovastatin on shedding of heparan sulfate proteoglycan (HSPG) and syndecan-1 (SDC-1) in the lung tissues of rats with sepsis-induced acute lung injury.Methods One-hundred and twenty male Wistar rats aged 8-12 weeks,weighing 325-425 g,were randomly divided into 3 groups (n =40 each) using a random number table:sham operation group (group S),cecal ligation and puncture (CLP) group and lovastatin group (group L).Lovastatin 4 mg/kg was injected once a day for 5 consecutive days in S and L groups,while the equal volume of 0.5％ CMC (the solvent) was given in CLP group.Sepsis was produced by CLP on 5th day of administration in CLP and L groups.The left lung was lavaged at 24 h after operation.The broncho-alveolar lavage fluid (BALF) was collected for determination of protein concentrations,white blood cell (WBC) count and percentage of neutrophils.Blood samples were collected for determination of the concentrations of HSPG and SDC-1 in serum (by ELISA).Evans blue was injected at 24 h after operation in the remaining 20 rats of each group.The lungs were removed for examination of the pathological changes and for measurement of HSPG and SDC-1 mRNA and protein expression (using Western blot and PCR),and Evans blue content (reflecting pulmonary capillary permeability) in the lung tissue.Results Compared with group S,the protein concentrations,WBC count and percentage of neutrophils in BALF,Evans blue content in lung tissues and the concentrations of HSPG and SDC-1 in serum were significantly increased,and HSPG and SDC-1 mRNA and protein expression was down-regulated in CLP and L groups.Compared with group CLP,the protein concentrations,WBC count and percentage of neutrophils in BALF,Evans blue content in lung tissues and the concentrations of HSPG and SDC-1 in serum were significantly decreased,and HSPG and SDC-1 mRNA and protein expression was up-regulated in group L.The pathological changes of lungs were significantly attenuated in group L as compared with group CLP.Conclusion The mechanism by which lovastatin attenuates acute lung injury induced by sepsis may be related to reduced shedding of HSPG and SDC-1 in lung tissues and improved function of pulmonary vascular endothelium in rats.
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Objective To evaluate the effects of adiponectin on the mitochondrial damage in septic rats with lung injury .Methods Sixty male Wistar rats ,aged 7-8 weeks ,weighing 180-220 g ,were randomly divided into 3 groups (n=20 each) using a random number table :sham operation group (S group) ,sepsis group (SEP group) and adiponectin group (APN group) .The animals were anesthetized with intraperitoneal 2% pentobarbital sodium 50 mg/kg .Sepsis was produced by cecum ligation and puncture (CLP) .In APN groups ,gene recombinant adiponectin 6 mg/kg was injected intraperitoneally at 12 h after CLP .At 24 h after the operation ,10 rats from each group were chosen and sacrificed ,and lungs were removed for detection of interleukin-6 (IL-6 ) and high-mobility group box-1 (HMGB1 ) contents . The mitochondria of lung samples were isolated for measurement of the malondialdehyde (MDA ) content and degree of mitochondrial swelling and mitochondrial activity . The survival rates within 7 days after operation were recorded in the left 10 rats in each group .Results Compared with S group , IL-6 and HMGB1 contents in lung tissues and MDA content in the mitochondria were significantly increased ,the degree of mitochondrial swelling was increased , and the mitochondrial activity and survival rates within 7 days after operation were decreased in SEP group ( P<0.05 ) . Compared with SEP group , IL-6 and HMGB1 contents in lung tissues and MDA content in the mitochondria were significantly decreased ,the degree of mitochondrial swelling was reduced ,and the mitochondrial activity and survival rates within 7 days after operation were increased in APN groups ( P< 0.05 ) .Conclusion Adiponectin can attenuate lung injury and raise the survival rates in septic rats ,and reduction of mitochondrial damage in lung tissues is involved in the mechanism .
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Objective To observe the protective effects of lovastatin against lung injury and the expression changes of adiponectin in the septic rats.Methods Fifty four male Wistar rats weighting 250-300g were randomly divided into the three groups:sham operation group ( group Sham) ,sepsis group ( group CLP) and lovastatin interven tion group (group LOV).Rats were injected with lovastatin (4mg/kg) or 0.5%CMC (vehicle) for five days and then subjected to CLP.At 4h,12h and 24h after operation.BALF was collected to determine the levels of TNF-αand IL-6,lung tissue was obtained to observe histopathological changes,and to detect the content of MPO and MDA,the blood sample was obtained to detect the level of adiponectin.Results In the group Sham,at 4h,12h and 24h time points,the levels of TNF-αwere (1.80 ±0.13)pg/mL,(2.04 ±0.15)pg/mL and (1.930.19)pg/mL;the levels of IL-6 were (20.56 ±0.23)pg/mL,(18.35 ±0.15) pg/mL and (21.23 ±0.20) pg/mL;the contents of MPO were (2.82 ±0.14) U/g tissue,(2.88 ±0.07) U/g tissue and (2.76 ±0.18) U/g tissue;and the levels of MDA were (3.32 ±0.12)nmol/mg,(3.09 ±0.11)nmol/mg and (3.21 ±0.08)nmol/mg;the concentrations of adiponectin were (2.68 ±0.14)μg/mL,(2.80 ±0.07)μg/mL and (2.86 ±0.18)μg/mL.Compared with group Sham,both LOV group and CLP group had increased pulmonary damage:(1)the levels of TNF-α[4h,12h and 24h were (4.23 ± 0.18)pg/mL,(5.62 ±0.24)pg/mL and (5.14 ±0.10)pg/mL,t=28.41,30.98 and 36.62]and IL-6[4h,12h and 24h were (39.12 ±0.17) pg/mL,(47.25 ±0.21) pg/mL and (44.690.27) pg/mL,t =158.90,273.40 and 127.28] of the CLP group in BALF were both increased,and MPO[4h,12h and 24h were (4.85 ±0.13) U/g tissue, (6.17 ±0.08)U/g tissue and (7.84 ±0.10)U/g tissue,t=26.39,79.40 and 60.43]and MDA[4h,12h and 24h were (6.24 ±0.06)nmol/mg,(7.56 ±0.15)nmol/mg and (8.43 ±0.10)nmol/mg,t=53.31,58.86 and 90.06] concentrations in lung homogenate were raised with the decreased expression of serum adiponectin[4h,12h and 24h were (1.35 ±0.10)μg/mL,(1.17 ±0.07)μg/mL and (1.24 ±0.11)μg/mL,t=19.86,12.75 and 18.81](all P<0.05);(2) meanwhile the levels of TNF-α[4h,12h and 24h were (2.85 ±0.17) pg/mL,(3.720.13) pg/mL and (3.240.09)pg/mL,t=12.02、20.73 and 16.68]and IL-6[4h,12h and 24h were (30.75 ±0.22)pg/mL, (37.52 ±0.29)pg/mL and (32.43 ±0.26)pg/mL,t=78.42,68.29 and 83.67]in BALF of the LOV group were all increased,the contents of MPO[4h,12h and 24h were(3.59 ±0.05)U/g tissue,(4.67 ±0.11)U/g tissue and (5.33 ± 0.05)U/g tissue,t=12.03,33.63 and 33.70]and MDA[4h,12h and 24h were (4.45 ±0.10)nmol/mg,(5.01 ± 0.11)nmol/mg and (5.83 ±0.04) nmol/mg,t =17.72,30.23 and 71.75] were also increased with the serum adiponectin concentrations[4h,12h and 24h were (2.09 ±0.08)μg/mL,(2.07 ±0.05)μg/mL and (2.03 ± 0.10)μg/mL,t=8.96,20.79 and 6.30]dicreased(all P<0.05).There were less histopathological changes in the LOV group,and the levels of TNF-α(t=13.46,17.05 and 15.43),IL-6(t=73.70,64.10 and 80.12),MPO(t=22.16,27.01and 32.86) and MDA(t=37.59,42.72 and 59.13) were lower than those in CLP group,also the level of adiponectin(t=14.15,8.10 and 3.19) increased siginificantly(all P<0.05).Conclusion Administration of lovastatin could attenuate lung injury of the sepsis by down-regulate the level of TNF-αand IL-6,with reduced inflam-matory response and oxidative stress,and could upregulate the level of adiponectin in serums of rats with sepsis.