Objective To evaluate the behavior and bone destruction of the mouse model of bone cancer pain signs. Method A mouse model of bone cancer pain signs was developed by intra-femur inoculations of Lewis lung carcinoma cells in C57BL/6 mice. Spontane-ous lifting time, ambulatory score and paw withdrawal latencies to radiant heat stimulation were measured in alternative days throughout the experiment. The structural damage of the femur were monitored by radiogram on the 7th, 15th and 23rd day respectively, and the pathohisto-logical changes of the femur bones were observed by hematoxylin-eosin staining (HE) staining on the same days. Meanwhile, the glial fibril-lary acid protein (GFAP) immunohistochemistry changes of the spinal cord in lumbar segments on the 23rd day after inoculation were ob-served. Results Mice received intra-femur inoculation of Lewis lung carcinoma cells gradually developed spontaneous pain, which was be-ginning on the 11th day after inoculation, followed by move-evoked pain and thermal allodynia. On the 23rd day after inoculation, X-ray film showed that medullary cavity of ipsilateral distal femur were filled with tumor cells and full thickness cortical bone was lost. Furthermore, tumor cells invaded peripheral muscles. Astrocytes on the inoculated side of the spinal cord were activated. Conclusion Lewis lung carci-noma cells were a good choice to build a mouse bone cancer pain.

Objective To observe the change of early postoperative cognition in the elderly under low central venous pressure (LCVP) after lobe resection to investigate the safety and feasibility of LCVP in Geriatrics.Methods A total of 45 ASA class Ⅰ ～ Ⅱ old patients (60 ～ 75 y)with elective liver resection were divided into L group and C group.In the LCVP group (L group),CVP was maintained below 5 cmH2O during liver resection until the lobe was done.The patients in the control group (C group) received standard care (The CVP was controlled between 6 cmH2O to 12 cmH2O).To compare the anesthesia recovery after surgery,all patients were tested with a battery of neuropsychologic assessment of cognitive function preoperatively and on the 7th day postoperatively.Results During liver resection,the MAP [(75.8 ±7.9)mmHg] and CVP [(3.1 ±0.4)cmH2O] of experimental group were lower than the control group [MAP (92.3 ± 10.6)mmHg,CVP(9.3 ± 1.4)cmH2O].The difference was statistically significant (t' =20.08,P ＜0.05,t =5.89,P ＜0.01) ;There was no statistically significant difference in postoperative recovery of spontaneous breathing,respiratory,eye opening time,extubation time and leave the operating room time between two groups[(18.1 ±6.7)min,(25.4±8.3)min,(31.9±11.7)min,(42.8±17.8)minvs (15.3 ± 7.0)min,(22.6 ±9.4)min,(30.2 ± 10.8) min,(45.4 ± 13.6) min,P ＞ 0.05].The incidence of POCD was 30.0％ in the experimental group and 27.3％ in the control group.The difference was no statistical significance between two groups(P ＞0.05).Conclusious There was no significant influence of low central venous pressure on anesthesia recovery time and early postoperative cognition in the elderly under hepatic resections.

Objective To investigate the effects of isoflurane preconditioning on renal ischemia reperfusion (I/R) injury in rats and the role of TNF-α plays in the mechanism.Methods Male SD rats were used in the study.The animals were randomly divided into 3 groups ( n =12 each):shame operation group; I/R group; Isoflurane preconditioning group (inhaled 1.5％ isoflurane (1 MAC) for 30 min followed by 10 min washout before I/R).At 2 h reperfusion,blood samples were obtained for urea nitrogen (BUN) concentration and creatinine (Cr) content.The level of TNF-α in renal tissues were determined by enzyme-linked immunosorbent assay (ELISA).Observe the pathological changes in H.E.staining slides under microscope.Results BUN concentration and Cr content and the level of TNF-α in I/R group and isoflurane preconditioning group were significantly higher than in shame operation group[ BUN:( 17.69 ±0.99)mmol/L vs (8.37 ±1.12)mmol/L,t =-23.55,P ＜0.01; ( 12.26 ± 1.11 ) mmol/L vs (8.37 ±1.12 )mmol/L,t =- 19.09,P ＜ 0.01 ;Cr:( 103.22 ± 13.42)μmol/L vs (71.48 ± 8.59) μ mol/L,t =-21.45,P ＜0.01;(86.51 ± 11.49) μmol/L vs (71.48 ±8.59) μmol/L,t =-9.87,P ＜0.01 ;TNF-α:(0.51 ±0.07)ng/ml vs (0.43 ±0.00)ng/ml,t =-5.79,P ＜0.01;(0.47 ±0.03)ng/ml vs (0.43 ±0.00)ng/ml,t =-8.86,P ＜0.01 ].BUN concentration and Cr content and the level of TNF-α in Isoflurane preconditioning group were significantly lower than in I/R group [ BUN:( 12.26 ± 1.1 1 ) mmol/L vs ( 17.69 ± 0.99 ) mmol/L,t =15.67,P ＜ 0.01 ; Cr:( 86.51 ± 11.49) μmol/L vs ( 103.22 ± 13.42 ) μ mol/L,t =6.68,P ＜0.01 ;TNF-α:(0.47 ±0.03) ng/ml vs (0.51 ±0.07) ng/ml,t =2.61,P ＜0.05].Therenal I/R injury which located around kidney tubules was increased in I/R group and isoflurane precondi-tioning group compared to shame operation group [ ( 17.26 ± 1.45 ) vs (0.00 ± 0.00 ),t =- 72.38,P ＜0.01;(12.69±1.83) vs (0.00 ±0.00),t =-39.53,P ＜0.01].The renal I/R injury which located around kidney tubules was decreased in isoflurane preconditioning group compared to I/R group [ ( 12.69 ±1.83) vs (17.26±1.45),t =19.87,P ＜0.01].Conclusions Preconditioning with 1.5％ isoflurane 30 min can protect kidney from I/R injury in rats by regulating the level of TNF-α in renal tissues.

Objective To evaluate the effect of dexmedetomidine on spinal p38 mitogen?activated protein kinase ( p38MAPK) expression during remifentanil?induced hyperalgesia in rats with incisional pain. Methods Forty?eight healthy male Sprague?Dawley rats, aged 6 weeks, weighing 220-250 g, were ran?domly divided into 4 groups ( n= 12 each) using a random number table: control group ( group C) , inci?sion pain group ( group IP ) , incision pain + remifentanil group ( group IP+R ) , and incision pain +remifentanil + dexmedetomidine group ( group IP+R+D) . After successful establishment of the model of in?cisionsal pian, remifentanil 1?0μg∕kg was infused for 4 h via the tail vein in group IP+R; remifentanil 1?0μg∕kg was infused for 4 h via the tail vein, and dexmedetomidine 10μg∕kg was simultaneously infused for 4 h via the jugular vein in group IP+R+D; the equal volume of normal saline was infused for 4 h via the tail and jugular veins in C and IP groups. The mechanical paw withdrawal threshold ( MWT) was measured at 24 h before operation ( T0 ) , and at 4, 6, 24 and 48 h after the end of drug infusion ( T1?4 ) . After meas?urement of MWT at T4 , the expression of p38MAPK was determined using immuno?histochemistry. Results was up?regulated at T4 in IP and IP+R groups ( P<0?05) , and no significant change was found in the MWT and expression of p38MAPK in group IP+R+D (P>0?05). Compared with group IP, the MWT was signifi?cantly decreased at T1?4, and the expression of p38MAPK was up?regulated at T4 in group P+R, and the MWT was significantly increased at T1?4, and the expression of p38MAPK was down?regulated at T4 in group IP+R+D (P<0?05). Compared with group IP+R, the MWT was significantly increased at T1?4, and the expression of p38MAPK was down?regulated at T4 in group IP+R+D ( P<0?05) . Conclusion The mecha?nism by which dexmedetomidine reduces hyperalgesia induced by remifentanil is related to down?regulation of spinal p38MAPK expression in the rats with incisional pain.

Objective To evaluate the relationship between vascular endothelial growth factor (VEGF) and extracellular signal-regulated kinase (ERK) signaling pathway in spinal dorsal horns of rats with neuropathic pain.Methods Twenty male Sprague-Dawley rats,aged 2 months,weighing 160-320 g,were randomly divided into 4 groups (n =5 each):sham operation group (group S); chronic constrictive injury (CCI) group; normal saline group (NS group); VEGF antibody group.Neuropathic pain was induced by CCI.The animals were anesthetized with intraperitoneal 10％ chloral hydrate 350 mg/kg.The left sciatic nerve was exposed and 4 ligatures were placed on the sciatic nerve at 1 mm intervals.In group S,the left sciatic nerve was only exposed but not ligated.In VEGF antibody group,VEGF antibody 0.3μg/15 μl was injected intrathecally every 2 days for 4 times starting from 2 h after CCI,while the equal volume of normal saline was injected in NS group.Paw withdrawal threshold to von Frey filament stimulation (PWMT) and paw withdrawal latency to nociceptive thermal stimulation (PWTL) were measured at 1 day before CCI (T1),and 1,3,5 and 7 days after CCI (T2-5).The rats were sacrificed after PWMT and PWTL were measured and the L4-6 segments of the spinal cord were removed for determination of phosphorylated ERK (p-ERK) expression in spinal dorsal horns by immunohistochemistry and Western blot.Results Compared with group S,PWMT and PWTL were significantly decreased at T2-5,and the p-ERK expression in spinal dorsal horns was up-regulated in CCI and VEGF antibody groups (P ＜ 0.05).Compared with CCI group,PWMT and PWTL were significantly increased at T3-5,and the p-ERK expression in spinal dorsal horns was down-regualted in VEGF antibody group (P ＜ 0.05).Conclusion VEGF in the spinal dorsal horn is involved in the development and maintenance of neuropathic pain in rats through activating ERK signaling pathway.

Objective:To observe the effect of esketamine on cardiac index in patients undergoing lumbar surgery in prone position under general anesthesia.Methods:Forty-five patients with prone lumbar surgery after general anesthesia in Hunan Provincial People′s Hospital from March to July 2021 were divided into observation group (24 cases, group A) and control group (21 cases, group B) according to random number table method. Group A received 0.5 mg/kg esketamine intravenously during induction, and 0.15 mg/(kg·h) esketamine intravenously for 2 h after prone position. Group B received the same amount of normal saline. Both groups were given sevoflurane and remifentanil during operation to maintain anesthesia, and sufentanil was given intermittently during operation. The mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic pressure (DBP), cardiac index (CI), and heart rate (HR) before induction (T 0), during endotracheal intubation (T 1), 5 minutes after intubation (T 2), 5 minutes after prone position (T 3), 10 minutes after prone position (T 4), 30 minutes after prone position (T 5), 45 minutes after prone position (T 6), 60 minutes after prone position (T 7), 90 minutes after prone position (T 8), and 120 minutes after prone position (T 9) were recorded; The total dosage of norepinephrine 2 hours after anesthesia to prone position and extubation time after operation were also recorded. The Visual Analogue Scale (VAS) was performed 15 minutes after extubation, 6 and 24 hours after operation. Results:There was no significant difference in CI between T 3-T 9 and T 2 in group A ( P>0.05); the CI of group B at T 3-T 7 was significantly lower than that at T 2 (all P<0.05); there was no significant difference in CI between T 8-T 9 and T 2 in group B (all P>0.05); There was no significant difference in CI between group A and group B at T 0-T 2 (all P>0.05). The CI of group A at T 3-T 9 was significantly higher than that of group B (all P<0.05); The dosage of norepinephrine in group A was significantly lower than that in group B ( P<0.05); There was no significant difference in HR, MAP, SBP and DBP between the two groups at different time points (all P>0.05); there was also no significant difference in extubation time and VAS scores at 15 minutes, 6 hours and 24 hours after extubation between the two groups (all P>0.05). Conclusions:Intraoperative application of esketamine can increase CI after prone position and reduce the amount of norepinephrine during lumbar surgery.

To investigate the effect of prophylactic aucubin (AU) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. 
 Methods: Male BABL/c mice were randomly divided into a control group, an ALI group, and an AU treatment group, 16 mice in each group. ALI mice were injected with LPS (5 mg/kg, intratracheal injection), and AU (10 mg/kg) was injected intraperitoneally 30 min ahead. After LPS injection for 6 hours mice were sacrificed, the morphological changes of lung tissues were detected by HE staining and the lung injury score was obtained. The mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin 10 (IL-10) in lung tissue was detected by real-time PCR. The total protein and lactate dehydrogenase (LDH) activity, the cell count, and the protein content of TNF-α and IL-10 in the mouse bronchoalveolar lavage fluid (BALF) were detected.
 Results: Compared with ALI mice, the pathological damage score of lung tissue was significantly reduced in the AU group, the total number of BALF cells, neutrophils, and macrophages were significantly decreased, LDH activity and the total protein content were also significantly decreased (all P<0.01). In addition, AU can reduce the mRNA and protein expression of TNF-α in lung of ALI mice, and increase the mRNA and protein expression of IL-10 (all P<0.01).
 Conclusion: AU can reduce LPS-induced ALI in mice.
Acute Lung Injury ; chemically induced ; Animals ; Bronchoalveolar Lavage Fluid ; Iridoid Glucosides ; Lipopolysaccharides ; Lung ; Male ; Mice ; Tumor Necrosis Factor-alpha

OBJECTIVES: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common operative neurocognitive disorders, which places a heavy burden on patients, families and society. Therefore, it is very important to search for preventive drugs. Previous studies have demonstrated that perioperative use of dexmedetomidine resulted in a decrease the incidence of POD and POCD. But the specific effect of dexmedetomidine on elderly patients undergoing hepatic lobectomy and its potential mechanism are not clear. This study aims to evaluate the efficacy of intraoperative use of dexmedetomidine on preventing POD and POCD in elderly patients undergoing hepatic lobectomy and the influence on the balance between proinflammation and anti-inflammation. METHODS: This trial was designed as a single-center, prospective, randomized, controlled study. One hundred and twenty hospitalized patients from January 2019 to December 2020, aged 60-80 years old with American Society of Anesthesiologists (ASA) II-III and scheduled for hepatic lobectomy, were randomly allocated into 3 groups (n=40) using a random number table: A C group, a Dex1 group, and a Dex2 group. After anesthesia induction, saline in the C group, dexmedetomidine [0.3 μg/(kg·h)] in the Dex1 group, and dexmedetomidine [0.6 μg/(kg·h)] in the Dex2 group were infused until the end of operation. The incidences of hypotension and bradycardia were compared among the 3 groups. Confusion Assessment Method (CAM) for assessing POD and Mini Mental State Examination (MMSE) for evaluating POCD were recorded and venous blood samples were obtained for the determination of neuron specific enolase (NSE), TNF-α, IL-1β, and IL-10 at the different time below: the time before anesthesia (T0), and the first day (T1), the third day (T2), the fifth day (T3), and the seventh day (T4) after operation. RESULTS: Compared with the C group, the incidences of bradycardia in the Dex1 group or the Dex2 group increased (both P<0.05) and there was no difference in hypotension in the Dex1 group or the Dex2 group (both P>0.05). The incidences of POD in the C group, the Dex1 group, and the Dex2 group were 22.5%, 5.0%, and 7.5%, respectively. The incidences of POD in the Dex1 group or the Dex2 group declined significantly as compared to the C group (both P<0.05). However, there is no difference in the incidence of POD between the Dex1 group and the Dex2 group (P>0.05). The incidences of POCD in the C group, the Dex1 group, and the Dex2 group were 30.0%, 12.5%, and 10.0%, respectively. The incidences of POCD in the Dex1 group and the Dex2 group declined significantly as compared to the C group (both P<0.05). And no obvious difference was seen in the incidence of POCD in the Dex1 group and the Dex2 group (P>0.05). Compared with the C group, the level of TNF-α and IL-1β decreased and the level of IL-10 increased at each time points (from T1 to T4) in the Dex1 group and the Dex2 group (all P<0.05). Compared with the Dex1 group, the level of IL-1β at T2 and IL-10 from T1 to T3 elevated in the Dex2 group (all P<0.05). Compared with the T0, the concentrations of NSE in C group at each time points (from T1 to T4) and in the Dex1 group and the Dex2 group from T1 to T3 increased (all P<0.05). Compared with the C group, the level of NSE decreased from T1 to T4 in the Dex1 group and the Dex2 group (all P<0.05). CONCLUSIONS Intraoperative dexmedetomidine infusion can reduce the incidence of POCD and POD in elderly patients undergoing hepatic lobectomy, and the protective mechanism appears to involve the down-regulation of TNF-α and IL-1β and upregulation of IL-10 expression, which lead to rebalance between proinflammation and anti-inflammation.
Aged ; Aged, 80 and over ; Bradycardia ; Cognitive Dysfunction/prevention & control* ; Delirium/prevention & control* ; Dexmedetomidine/therapeutic use* ; Humans ; Hypotension/drug therapy* ; Interleukin-10 ; Middle Aged ; Postoperative Cognitive Complications/prevention & control* ; Postoperative Complications/epidemiology* ; Prospective Studies ; Tumor Necrosis Factor-alpha