Objective To evaluate the efficacy of intra-articular dexmedetomidine mixed with ropivacaine for postoperative analgesia after arthroscopic knee surgery.Methods Sixty ASA physical status Ⅰ or Ⅱ patients,aged 20-64 yr,weighing 50-90 kg,with body height 160-180cm,scheduled for elective arthroscopic knee surgery,were randomly assigned into 2 equal groups using a random number table:ropivacaine group (group R) and dexmedetomidine mixed with ropivacaine group (group RD).In group R,the mixture of noraml saline 1 ml and 19 ml of 0.25％ ropivacaine was injected intra-articularly at the end of surgery.In group RD,the mixture of dexmedetomidine 1 μg/kg and 19 ml of 0.25％ ropivacaine was injected intra-articularly at the end of surgery.VAS scores at rest and during activity were observed and recorded at 1,2,4,8,12,20 and 24 h after surgery.The duration of analgesia after sugery (from the time immediately after intra-articular administration to the time of first administration of fentanyl as an adjunct to analgesia) and consumption of fentanyl at 24 h after surgery were recorded.Results Compared with group R,VAS scores were significantly decreased at 1,2,4 and 8 h after surgery,the duration of analgesia after sugery was prolonged,and the consumption of fentanyl at 24 h after surgery was reduced in group RD (P ＜ 0.05 or 0.01).There was no significant difference in VAS scores at 12-24 h after surgery between the two groups (P ＞ 0.05).Conclusion Intra-articular dexmedetomidine can significantly improve the efficacy of ropivacaine for postoperative analgesia after arthroscopic knee surgery.

Objective To evaluate the role of extracellular signal-regulated protein kinase 5 (ERK5) in the spinal cord in withdrawal responses in morphine-dependent rats.Methods Ninety-six adult male SpragueDawley rats in which intrathecal catheters were successfully placed,weighing 200-250 g,were randomly divided into 4 groups (n =24 each) using a random number table:normal saline group (group A),withdrawal group (group B),dimethyl sulfoxide (DMSO) group (group C) and ERK5 inhibitor BIX02188 group (group D).Morphine dependence (MD) was induced by increasing doses of subcutaneous morphine for 6 days.The initial dose of morphine was 10 mg/kg once a day and was increased by 10 mg/kg once a day from the 2nd to 5th days until 50 mg/kg on the 6th day in B,C and D groups.Morphine withdrawal response (MW) was induced by intraperitoneal naloxone 4 mg/kg at 4 h after last morphine administration in B,C and D groups.In addition,BIX02188 and 1％ DMSO 10 μl were injected intrathecally at 1 h before naloxone injection in D and C groups,respectively.MW and morphine withdrawal-induced hypemlgesia were scored.The rats were then sacrificed after hyperalgesia was scored and the spinal cord was removed for determination of ERK5 and phosphorylated ERK5 (p-ERK5) expression.Results Compared with group A,MW and hyperalgesia scores were significantly increased and the expression of pERK5 was up-regulated in B,C and D groups (P ＜ 0.05).Compared with group B,MW and hyperalgesia scores were significantly decreased and the expression of p-ERK5 was down-regulated in D group (P ＜ 0.05),and no significant change was found in group C (P ＞ 0.05).Conclusion ERK5 in the spinal cord is involved in withdrawal responses in morphine-dependent rats.

Background Elevated intraocular pressure leads to the loss of retinal ganglion cells and vigorous reaction of retinal glial cells.The expression of nestin in retinal glial cells secondary to hypertention and its significance are unclear.ObjectiveThis study aim to investigate the expression of nestin in retinal glial cells (RGCs) in ocular hypertention rats.Methods The ocular hypertention models were established by cauterizing the limbus-draining veins in the right eyes of 42 SD rats,and a conjunctival incision in the left eyes of the rats served as the sham group.The intraocular pressure (IOP) was measured with the Tono-Pen XL tonometer.The number of RGCs in the rats with ocular hypertention was counted.The expression of the nestin protein in RGCs was semi-quantitatively analyzed using Western by immunochemistry.Double immunofluorescence was carried out to evaluate the the confocal laser scaning microscope.Results Significant differences were found in the IOP between the model group and the sham group at various time points (P＜0.05).In 1 week to 3 weeks after operation,the number of RGCs significantly declined in the model group compared with the sham group (P＜0.05).Immunochemistry showed that from 2 hours through 1 week after operation,the expression of nestin was gradually enhanced in the model group in comparison with the sham group.Western blot revealed that the expression of the nestin protein reflected a similar tendency to that of immunofluorescence.The increased introcular pressure as manifested by the induced expression of nestin.Immunoelectron microscopy also confirmed the induced expression of nestin especially at their end-feet suggests a potential neuroprotective mechanism in neuronal degeneration.Nestin may be a useful biomarker for retinal injury study.

Objective To investigate the roles of spinal N-methyl-D-aspartic acid receptor-extracellular signal-regulated protein kinases 5 signaling pathway in naloxone-induced withdrawal response in morphine-dependent rats.Methods Ninety-six adult male SD rats weighting 230-250 g were randomly divided into 4 groups:control group,withdrawal group,DMSO group and MK801 group.Rats were subcutaneously injected with morphine.On day 6,rats were injected with naloxone (intraperitoneal) to precipitate morphine withdrawal syndromes.To identify the function of NMDAR-ERK5 signaling pathway in morphine withdrawal,morphine withdrawal-like behavior test and western blot technique were used in this research.The scores of morphine withdrawal symptom,morphine withdrawal-induced allodynia and the activation of ERK5 in spinal cord were observed after intrathecal injection of MK801.Results There was no withdrawal symptoms and withdrawal-induced allodynia in group A after intraperitoneal injection of naloxone.Compared with group A,withdrawal score (45.2±7.3),score of withdrawal-induced allodynia (14.4±3.7) of group B,withdrawal score (44.7±6.2),score of withdrawal-induced allodynia (13.2±2.7) of group C and withdrawal score (28.3±1.6),score of withdrawal-induced allodynia (5.9± 1.1) of group D were significantly increased (P＜ 0.05).Compared with group C,the total withdrawal score (28.3 ± 1.6),score of withdrawal-induced allodynia (5.9± 1.1) of group D were significantly decreased (P＜0.05).Compared with group A,the expression of spinal p-ERK5 of group B (12848±621) and group C (12579±396) were significantly increased (P＜0.05).Compared with group C,the expression of spinal p-ERK5 of group D (5 123±546) was significantly decreased (P＜0.05).Condusion The signaling pathway of spinal N-methyl-D-aspartic acid receptor-extracellular signal-regulated protein kinases 5 contributes to naloxone-induced withdrawal response in morphine-dependent rats.

Objective To evaluate the role of spinal neuronal extracellular signal-regulated protein kinases 5/cAMP response element binding protein (ERK5/CREB) signaling pathway in withdrawal responses in morphinedependent rats.Methods Ninety-six adult male Sprague-Dawley rats in which intrathecal catheters were successfully placed,weighing 200-250 g,were randomly divided into 4 groups (n =24 each):normal control group (group A),morphine withdrawal group (group B),dimethyl sulfoxide (DMSO) + morphine withdrawal group (group C) and ERK5 inhibitor BIX02188 + morphine withdrawal group (group D).Morphine dependence (MD) was induced by increasing doses of subcutaneous morphine for 6 days.The initial dose of morphine was 10 mg/kg once a day and was increased by 10 mg/kg once a day from 2nd to 5th days until 50 mg/kg on 6th day in B,C and D groups.Morphine withdrawal response (MW) was induced by intraperitoneal naloxone 4 mg/kg at 4 h after last morphine administration in B,C and D groups.In addition,BIX02188 10 μg and 1％ DMSO 10 μl were injected intrathecally at 1 h before naloxone injection in D and C groups,respectively.MW and morphine withdrawal-induced hyperalgesia were scored.The rats were then sacrificed after hyperalgesia was scored and the spinal cord was removed for determination of CREB and phosphorylated CREB (p-CREB) expression.Results Compared with group A,MW and hyperalgesia scores were significantly increased and the expression of p-CREB was up-regulated in B,C and D groups.Compared with group B,MW and hyperalgesia scores were significantly decreased and the expression of p-CREB was down-regulated in D group,and no significant change was found in group C.Conclusion The spinal neuronal ERK5/CREB signaling pathway is involved in withdrawal responses in morphine-dependent rats.

Objective To investigate the roles of spinal extracellular signal-regulated protein kinases 5 (ERK5) on morphine withdrawal in rats.Methods Ninety-six male and adult SD rats weighting 230-250 g were randomly divided into saline-naloxone-DMSO group (group A),saline-naloxone-BIX02188 group (group B),morphine-naloxone-DMSO group (group C) and morphine-naloxone-BIX02188 group (group D).To set up morphine dependent model,rats were subcutaneously injected with morphine in the increasing dosage method.On day 6,4 h after the injection of morphine,rats were injected with naloxone (intraperitoneal) to precipitate morphine withdrawal syndrome.The scores of morphine withdrawal symptom and morphine withdrawal-induced allodynia were observed after intrathecal injection of ERK5 inhibitor BIX02188.Result There were not withdrawal symptoms and withdrawal-induced allodynia in group A and B after intraperitoneal injection of naloxone.Compared with group A,teeth chatting (7.5± 1.1),wet dog shacks (4.6± 0.7),jump (5.3± 0.7),abnormal position (8.9± 1.9),diarrhea (7.1 ± 1.6),salivation (2.8±0.6),weight loss (7.9±0.9),total withdrawal score (44.8±5.9),score of withdrawalinduced allodynia (14.6±2.4) of group C and teeth chatting (3.1±0.5),wet dog shacks (1.5±0.4),jump (2.2± 0.5),abnormal position (7.9± 1.6),diarrhea (1.8±0.5),salivation (2.8±0.9),weight loss (3.7±0.6),total withdrawal score (23.1± 1.3) and score of withdrawal-induced allodynia (3.5± 1.1) of group D were significantly increased (P＜0.05).Compared with group C,teeth chatting (3.1±0.5),wet dog shacks (1.5±0.4),jump (2.2±0.5),diarrhea (1.8±0.5),weigbt loss (3.7±0.6) and total withdirawal score (23.1±1.3),score of withdrawal-induced allodynia (3.5±1.1) of group D were significantly decreased (P＜0.05).But there was not significant change in abnoral position (7.9±1.6) and salivation (2.8±0.9).Conclusion Inhibition of the activation of spinal cord ERK5 can significantly alleviate withdrawal symptoms of morphine dependent rats by intrathecal injection BIX02188.

Objective To evaluate the changes in the activity of extracellular signal-regulated kinase 5 (ERK5) in the distal cerebrospinal fluid contacting neurons (CSF-CNs) in the mid-brain of morphine dependent rats.Methods Forty-eight male adult Sprague-Dawley rats weighing 230-270 g,were randomly divided into 2 groups (n =24 each) using a random number table:control group (group A) and morphine dependence group (group B).Morphine dependence was induced by increasing doses of subautaneous morphine for 5 consecutive days.The initial dose of morphine was 10 mg/kg twice a day and was increased by 10 mg/kg everyday until 50 mg/kg on 5th dav.The equal volume of normal saline was injected subcutaneously instead of morphine in group A.On 3rd day after morphine dependence was induced,the distal CSF-CNs in the mid-brain was labeled with 30％ cholera toxin subunit B and horseradish peroxidase compound (CB-HRP) 3 μl injected in the lateral cerebral ventricle in the morning.At 4 h after the last injection of morphine,the segments in which CSF-CNs were located were removed,and CB-HRP positive neurons,phosphor-ERK5 (p-ERK5) positive neurons and CB-HRP/p-ERK5 positive neurons were counted.Results Compared with group A,the number of p-ERK5 and CB-HRP/p-ERK5 positive neurons in the mid-brain was significantly increased (P ＜ 0.05),and no significant change was found in CB-HRP positive neurons in group B (P ＞ 0.05).Conclusion The enhanced activity of ERK5 in the distal CSFCNs in the mid-brain may contribute to the development of morphine dependence in rats.

Objective: Based on the analysis of the ancient literatures about chest stuffiness and pains in Chrono-Medicine of traditional Chinese medicine,to study the content of timing medication in chest stuffiness and pains. Methods: According to the database of Chinese Medical Code, searching the ancient literatures and establishing the database, extracting the contents of chest stuffiness and pains’s prescription which covering timing medication. And the statistical analysis and content discussion were carried out according to the choice of taking medicine. Results: The 67 kinds of traditional Chinese medicine included were qi regulating agent, dispelling cold agent, expectorant agent and blood regulating agent. Besides,the time of taking medicine is used to be3:00-5:00,7:00-9:00,11:00-13:00,17:00-19:00, 19:00-21:00, 21:00-23:00.Take medicine once a day in the morning, twice a day, three times a day, three times a day and once a night. It is recommended that timing medication in clinical should be increased in time of 21:00-23:00 and 11:00-13:00, and paying more attention to the heart channel corresponding and the heart pericardium channel in time of 11:00-13:00 and 19:00-21:00. Conclusion Timing medication is beneficial to the optimization of therapeutic effect and minimization of toxicity of traditional Chinese medicine, which needs to provide the best evidence for further multi-center clinical trial research, and promote the popularization of timing medicine in clinical practice.

Occupational pneumoconiosis (referred to as “pneumoconiosis”) caused by exposure to occupational dust is the most serious occupational disease in China. Biological monitoring on occupational populations exposed to dust is important for the prevention, diagnosis, and treatment of pneumoconiosis. Biological monitoring is a systematic engineering process that includes a series of processes such as biological samples selection, selection of biological monitoring indicators, and selection of detection methods. The biological samples for biological monitoring mainly include urine, blood, exhaled breath gas, bronchoalveolar lavage fluid, saliva, sputum, and more. The indicators of biological monitoring involve multiple pathways such as oxidative stress, inflammatory response, collagen synthesis/degradation, phagocytic cell apoptosis, and pathways related to the formation of pneumoconiosis. Suitable detection methods need to be determined upon different biological monitoring indicators, including enzyme-linked immunosorbent assay, high-performance liquid chromatography, high-performance liquid chromatography-tandem mass spectrometry, inductively coupled plasma mass spectrometry, etc. Currently, there is a lack of true clinically valuable biological monitoring indicators that can indicate the correlation between dust exposure and the hazards of occupational populations, and there are no systematic and complete biological monitoring methods reported. It is necessary to further standardize the biological monitoring process and search for specific biological monitoring indicators.

Objective: To detect of the components and concentration of the metals and metalloids in the lavage fluid of whole-lung lavage (WLL) of the cases of pneumoconiosis, and analyze the characteristics, and explore the method to sample and process the samples of bronchoalveolar lavage fluid (BAL) . Methods: The samples of urine and serum of three cases of pneumoconiosis were collected before WLL, and the samples of BAL were collected during the WLL from the left and right lungs according to the sequence of four pressured gas flow and five negative pressure drainage. Each of 10ml original samples of WLL was collected firstly, and the left was centrifuged to acquire all the sediment samples and each of 10 ml samples from the centrifuge clear liquids, The components and concentration of the metals and metalloids in the samples were measured by Inductively Coupled Plasma mass spectrometer (ICP-MS) . Results: The average volume of BAL from unilat-eral lung for 3 patients was 10 758.3±1518 ml, and the average recovery rate was 89.7%. The average dry weight of sediment samples of BAL of three cases of pneumoconiosis was 0.292 gram with the right lung sam-ples slightly higher than the left lung samples. The detectable elements from the samples included Barium (Ba) , Strontium (Sr) , Calcium (Ca) , Magnesium (Mg) , Manganum (Mn) , Ferrum (Fe) , Cuprum (Cu) , Zinc (Zn) , Kalium (K) , Natrium (Na) , Selenium (Se) , Silicon (Si) and Uranium (U) . Each of concentration dis-tributions of these elements were not normal. Except for Cuprum, Selenium and Uranium, the concentrations of the other ten elements in the supernatant samples, mixture samples and sediments samples were statistical-ly different with the nonparametric test of Kruskal-Wallis. The concentrations of Natrium, Kalium and Barium in supernatant samples were higher, while the others in precipitation samples were higher. The concentration of elements in the sample from the right lung was slightly higher than that from the left lung, but there was no statistically significant difference (P>0.05) . There were statistical difference in term of element concentration of precipitates samples before and after pressured gas flow (P<0.05) . The concentration of K、Ca、Mg、Si and Se in se-rum, urine, supernatant and sediment samples had a good correlation. The correlation coefficient of Silicon between serum and precipitation was 0.676 and that between urine and precipitation was 0.524. Conclusion The concentra-tions of the metals and metalloid in sediment samples were more stable than that of supernatant and mixture samples. The sampling of one-side lung lavage fluid was representative in the detection of metals and metalloid in the BAL. It was the best time for sampling sediment from the BAL after the first pressured gas flow among the WLL.