Safety and Preliminary Efficacy of Ceritinib 450 mg with Food in Chinese ALK-positive Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#Anaplastic lymphoma kinase (ALK) rearrangement is a common driver gene of non-small cell lung cancer (NSCLC). Ceritinib is a second-generation ALK inhibitor, which can bring survival benefits to ALK-positive metastatic NSCLC. However, few studies focus on the safety and efficacy of ceritinib in China. Therefore, this study intends to investigate the safety and preliminary efficacy of ceritinib 450 mg with meals in Chinese patients with ALK-positive NSCLC through a real world study.@*METHODS@#From October 2018 to December 2019, patients with ALK-positive NSCLC from 8 medical centers in Sichuan province were recruited in this study. All of these participants received ceritinib 450 mg/d with food. The basic characteristics, adverse effects (AEs) and responses were collected and analyzed in order to evaluate the safety and efficacy of ceritinib.@*RESULTS@#A total of 109 patients were included in this study. Data cutoff was January 23, 2020. The median duration of treatment exposure was 5.87 mon (range: 0.4 mon-15.7 mon). Total AEs were reported in 98 (89.9%) of 109 patients and grade 3 or 4 AEs were reported in 22.9% of patients. Most common AEs (mainly grade 1 or 2) were diarrhea (60.6%), elevated alanine aminotransferase (ALT)(38.5%) and aspartate aminotransferase (AST)(37.6%). As of data cutoff, 45 patients discontinued ceritinib. The overall response rate (ORR) was 37.6% (95%CI: 28.5%-47.4%) and disease control rate (DCR) was 86.2% (95%CI: 78.3%-92.1%).@*CONCLUSIONS@#The treatment of ceritinib 450 mg with food for Chinese ALK-positive NSCLC patients had a good safety profile and favorable DCR in real-world setting. However, this conclusion needs to be further verified by large sample, prospective trials.

Efficacy of "over iliac crest method" for ultrasound-guided posterior lumbar plexus block: a comparison with manual palpation and sagittal positioning / 中华麻醉学杂志

Objective To evaluate the efficacy of "over iliac crest method" for ultrasound-guided posterior lumbar plexus block by comparing with manual palpation and sagittal positioning.Methods A total of 75 patients,aged 25-64 yr,weighing 42-90 kg,with body mass index of 17-32 kg/cm2,of American Society of Anesthesiologists physical status Ⅰ-Ⅲ,scheduled for elective lower extremity surgery under ultrasound-guided posterior lumbar plexus block combined with parasacral sciatic nerve block,were divided into 3 groups (n =25 each) using a random number table method:manual palpation group (group M),sagittal positioning group (group S) and "over iliac crest method" group (group O).Patients received ultrasound-guided posterior lumbar plexus block with in-plane technique using the corresponding positioning method in M,S and O groups.Successful blockade of each level was recorded at 30 min after injection.Time to determine the lumbar intervertebral space,puncture time for lumbar plexus block,the requirement for adjuvant drugs and block efficacy were recorded.The development of complications related to puncture and nerve block was also recorded.Results Compared with group M,the success rates of blockade at levels L1 and L2 were significantly increased,the success rates of blockade at levels L4 and L5 were decreased (P＜0.05),no significant difference was found in the success rate of blockade at level L3 (P＞0.05),the time to determine the lumbar intervertebral space was prolonged,and the requirement for adjuvant drugs was decreased during surgery in O and S groups,and the efficacy of block was significantly enhanced in group O (P＜0.05).Compared with group S,the success rates of blockade at levels L1 and L2 were significantly increased,the success rates of blockade at level L4 were decreased,the time to determine the lumbar intervertebral space was shortened (P＜0.05),and no significant change was found in the efficacy of block in group O (P＞0.05).There was no significant difference in the puncture time for lumbar plexus block between the three groups (P＞0.05).Complications related to puncture and nerve block were not found in three groups.Conclusion "Over iliac crest method" provides higher success rate and better efficacy than manual palpation and sagittal positioning when used for lumbar plexus block.

Comparison of different anesthesia techniques on early prognosis in patients undergoing hip joint re-placemen / 中华麻醉学杂志

Objective To compare the effects of different anesthesia techniques on early prognosis in patients undergoing hip joint replacement. Methods The demographic, preoperative and postoperative data of 478 patients, aged 18-95 yr, of American Society of Anesthesiologists physical statusⅠ-Ⅳ, who underwent elective unilateral hip joint replacement in Tongji Hospital from May 2014 to December 2016, were retrospectively analyzed. Patients were divided into general anesthesia group (group GA, n=197), peripheral nerve block group ( group PNB, n=147) and peripheral nerve block combined with general an-esthesia group ( group PNB+GA, n=134) . The amount of crystalloid solution and colloid solution infused, consumption of sufentanil and requirement for vasoactive agents were recorded during operation. The dura-tion of anesthetic recovery room stay, length of hospital stay before and after operation and total length of hospital stay were recorded. The development of complications within 48 h after operation, therapy after ad-mission to intensive care unit and in-hospital fatality were also recorded. Results Compared with group GA, the intraoperative consumption of sufentanil was significantly decreased in group PNB+GA, and the a-mount of crystalloid solution infused, urine output, consumption of sufentanil, requirement for vasoactive agents and incidence of postoperative hypoxemia, pulmonary infection and acute cerebral infarction were significantly decreased in group PNB+GA ( P<0. 05) . Compared with group PNB+GA, the consumption of sufentanil, requirement for vasoactive agents and incidence of postoperative hypoxemia, pulmonary infec-tion and acute cerebral infarction were significantly decreased in group PNB (P<0. 05). Conclusion Compared with general anesthesia or with peripheral nerve block-general anesthesia, peripheral nerve block is more helpful in improving early prognosis in patients undergoing hip joint replacement.

A risk analysis of acute kidney injury after orthotropic liver transplantation for benign end-stage liver disease in adults / 临床麻醉学杂志

Objective To analyze the risk factors of acute kidney injury after orthotropic liver transplantation for adult benign end-stage liver disease.Methods A retrospective analysis was conducted in 30 recipients (18 males,12 females,aged 23-68 years,ASA grade Ⅲ or Ⅳ) who underwent orthotropic liver transplantation for benign end-stage liver disease at Tongji Hospital from May,2014 to December,2014.Both demographic characteristics and perioperative parameters were collected,including general condition,surgery and anesthesia factors and intraoperative salvage autotransfusion or not.Perioperative laboratory findings related to renal function including urine volume,serum creatinine (Scr) and urea nitrogen (BUN) were collected,too.All variables tested in the univariate analysis with a P<0.10 were included in a multiple logistic regression analysis.Results There were less intraoperative salvage autotransfusion,more platelet transfusion and a higher using rate of vasopressors in the AKI group after surgery than those did not.Patients who received intraoperative salvage autotransfusion had 0.058 time odds (95%CI 0.005-0.649) of AKI than those did not;patients who required platelet transfusion had 10.706 times higher odds (95%CI 1.212-94.963) of AKI than those did not.Conclusion It is likely that intraoperative salvage autotransfusion was able to decrease the morbidity of AKI,while platelet transfusion and vasopressor administration to maintain blood pressure could increase the possibility of AKI.

Effect of ketamine on mitochondrial function of rat neurons subjected to anoxia / 中华麻醉学杂志

Objective To investigate the effect of ketamine on the mitochondrial function of rat neurons subjected to anoxia. Methods Primarily cultured rat hippocampal neurons were seeded in culture dishes (35 mm in diameter) at the density of 5×105-1×106 cells∕ml, and divided into 3 groups (n=11 each) using a random number table: control group, anoxia group and ketamine group. The neurons were exposed to 90% N2 plus 10% CO2 50 ml∕min for 5 min in anoxia group. In ketamine group, ketamine was added to the culture medium with the final concentration of 20 μmol∕L at 1 h before anoxia, and then the neurons were exposed to 90% N2 plus 10% CO2 50 ml∕min for 5 min. After the end of treatment in each group, the dead neurons were detected using trypan blue staining, the ATP content was determined by ATP bioluminescence assay, and mitochondrial membrane potential was measured by rhodamine 123 staining. Results Compared with control group, the mortality rate of hippocampal neurons was significantly in?creased, and the ATP content and mitochondrial membrane potential were significantly decreased in anoxia group and ketamine group ( P<0.05) . Compared with anoxia group, the mortality rate of hippocampal neu?rons was significantly decreased, and the ATP content and mitochondrial membrane potential were signifi?cantly increased in ketamine group (P<0.05). Conclusion The mechanism by which ketamine amelio?rates anoxia?induced damage to rat neurons is related to improved mitochondrial function.

The effect of analgesia with dezocine on CD4+ and CD8+ T lymphocytes in patients after pulmonary lobectomy / 中国医师进修杂志

Objective To investigate the effect of analgesia with dezocine on CD4+ and CD8+ T lymphocytes in patients after pulmonary lobectomy.Methods Seveuty patients with early non-small-cell lung cancer were selected,and they were scheduled the pulmonary lobectomy.The patients were divided into control group and dezocine group by random digits table method with 35 cases each.The patients in dezocine group were given 0.5 mg/ml dezocine by patient-controlled analgesia (PCA) pump,and the patients in control group were given 0.9％ sodium chloride by PCA pump.The peripheral blood lymphocytes count and percentages of CD4+ T lymphocytes,CD8+ T lymphocytes,natural killer cell (NK cell) before anesthesia induction and 4,24,48 h after operation were detected.Results In control group,the peripheral blood lymphocytes count and NK cell 24 h after operation were (1.08 ± 0.21) × 109/L and 0.141 4 ± 0.021 8,which before anesthesia induction were (1.71 ± 0.33) × 109/L and 0.190 9 ± 0.022 8,and there were statistical differences (P ＜ 0.05).In dezocine group,the peripheral blood lymphocytes count and NK cell 24 h after operation were (1.14 ±0.28) × 109/L and 0.124 9 ± 0.027 6,which before anesthesia induction were (1.69 ± 0.28) × 109/L and 0.198 6 ± 0.027 5,and there were statistical differences (P ＜ 0.05).The CD4+ T lymphocytes 24 h after operation in dezocine group was significantly higher than that in control group (0.355 6 ±0.031 1 vs.0.273 5 ±0.029 4),and there was statistical difference (P ＜0.05).There was no statistical difference in CD8+ T lymphocytes between the 2 groups (P ＞ 0.05).Conclusion Analgesia with dezocine can notably improve immunosuppression in patients after pulmonary lobectomy.

Effect of betulinic acid preconditioning on oxidative stress response during cerebral ischemia-reperfusion in mice / 中华麻醉学杂志

Objective To evaluate the effects of betulinic acid preconditioning on oxidative stress response during cerebral ischemia-reperfusion (I/R) in mice.Methods Seventy-two male Kunming mice,aged 3 months,weighing 25-35 g,were randomly divided into 3 groups (n =24 each) using a random number table:sham operation group (group S),I/R group,and betulinic acid preconditioning group (group BP).Cerebral I/R was induced by middle cerebral artery occlusion in mice anesthetized with 10％ chloral hydrate 40 ml/kg.In group BP,betulinic acid 50 mg/kg was administered by intragastric gavage everyday for 7 days before ischemia,while the equal volume of solvent dimethyl sulfoxide was given in S and I/R groups.At 22 h of reperfusion,neurological function was assessed and scored.The mice were then sacrificed and brains were removed for determination of infarct size,expression of NADPH oxidase (Nox1,Nox2 and Nox4) and p22phox mRNA,activity of ROS and apoptosis rate in the infarcted zone.Results Compared with S group,neurological score,cerebral infarct size,activity of ROS and apoptosis rate in the infarcted zone were significantly increased,and the expression of Nox1,Nox2,Nox4 and p22phox mRNA was up-regulated in group I/R.Compared with group I/R,neurological score,cerebral infarct size,activity of ROS and apoptosis rate in the infarcted zone were significantly decreased,and the expression of Nox1,Nox2,Nox4 and p22phox mRNA was down-regulated in group BP.Conclusion Betulinic acid preconditioning mitigates cerebral I/R injury through inhibiting oxidative stress response in mice.

Role of phosphatidylinositol 3-kinase p110β in spinal dorsal horn neurons in the development of arthritic pain in rats: relationship with TRPV1 and ASIC1a / 中华麻醉学杂志

Objective To evaluate the role of phosphatidylinositol 3-kinase (PI3K) p110β in spinal dorsal horn neurons in the development of arthritic pain (AP) in rats and the relationship with transient receptor potential vanilloid 1 (TRPV1) and acid-sensing ion channel (ASIC)1 a.Methods Forty adult female Sprague-Dawley rats in which intrathecal catheters were successfully placed,aged 3 months,weighing 250-300 g,were randomly divided into 4 groups (n =10 each):control group (group C),group AP,AP + PI3K p110β missense oligo-deoxynucleotide group (group MS) and AP + PI3K p110β antisense oligo-deoxynucleotide group (group AS).AP was induced by injecting complete Freund's adjuvant into the ankle joint cavity of right hindpaw.Normal saline 20 μl,missense oligo-deoxynucleotide 15 μg (20μl) and antisense oligo-deoxynucleotide 15 μg (20 μl) were administered intrathecally once a day for 6 consecutive days starting from the time immediately after arthritis was induced in groups AP,MS and AS,respectively.Mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured 1 day before operation (T0) and on days 4,7,10 after operation (T1-3).The rats were then sacrificed after the last measurement of pain threshold at T3.L4-6 segment of the spinal cord was removed for detection of expression of PI3K p110β (by Western blot),and TRPV1 and ASICla (by immunohistochemistry)in spinal dorsal horn neurons.Results Compared with group C,MWT and TWL were significantly decreased atT1-3,and the expression of PI3K p110β,TRPV1 and ASIC1a was up-regulated in the other 3 groups(P＜ 0.01).MWT and TWL were significantly higher at T1-3,and the expression of PI3K p110β,TRPV1 and ASIC1a was lower in group AS than in groups AP and MS (P ＜ 0.01).Conclusion PI3K p110β in spinal dorsal horn neurons is involved in the development of AP in rats,and the mechanism is related to up-regulation of TRPV1 and ASIC1a expression in spinal dorsal horn neurons.

Analysis of risk factors for postoperative nausea and vomiting in spinal anesthesia patients / 中国医师进修杂志

Objective To investigate the risk factors for postoperative nausea and vomiting (PONV) in spinal anesthesia patients.Methods A total of 841 patients received spinal anesthesia were visited after operation.Data were analyzed using univariate analysis and multivariate Logistic regression to identify risk factors related to PONV.Results PONV occurred in 94 patients (11.2％,94/841).Univariate analysis showed that PONV was unrelated with gender,age,ASA classification,anesthesia mode (P ＞ 0.05),related with operation department (P =0.026),body mass index (P =0.020),education level (P =0.000),history of previous surgery anesthesia (P =0.005),history of PONV (P =0.000),history of kinesia (P =0.002),smoke (P =0.019),intraoperative using of tramadol (P =0.018).Multivariate analysis showed that operation department (OR =4.039,95％ CI 1.331-12.259,P=0.048),education level (OR =3.504,95％ CI 1486-8.260,P=0.015),history of PONV (OR =5.113,95％ CI 1.790-14.606,P =0.002),intraoperative using of tramadol (OR =5.316,95％ CI 1.091-25.908,P =0.039) were identified as independent risk factors for PONV.Conclusions The independent factors associated with PONV following spinal anesthesia include operation department,education level,history of PONV,intraoperative using of tramadol.Identifying patients who are at high risk for PONV will enable the formation of more timely management project.

Inhibition of glial activation in rostral ventromedial medulla attenuates mechanical allodynia in a rat model of cancer-induced bone pain / 华中科技大学学报（医学）（英德文版）

Descending nociceptive modulation from the supraspinal structures plays an important role in cancer-induced bone pain (CIBP). Rostral ventromedial medulla (RVM) is a critical component of descending nociceptive facilitation circuitry, but so far the mechanisms are poorly known. In this study, we investigated the role of RVM glial activation in the descending nociceptive facilitation circuitry in a CIBP rat model. CIBP rats showed significant activation of microglia and astrocytes, and also up-regulation of phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) and pro-inflammatory mediators released by glial cells (IL-1β, IL-6, TNF-α and brain-derived neurotrophic factor) in the RVM. Stereotaxic microinjection of the glial inhibitors (minocycline and fluorocitrate) into CIBP rats' RVM could reverse the glial activation and significantly attenuate mechanical allodynia in a time-dependent manner. RVM microinjection of p38 MAPK inhibitor (SB203580) abolished the activation of microglia, reversed the associated up-regulation of pro-inflammatory mediators and significantly attenuated mechanical allodynia. Taken together, these results suggest that RVM glial activation is involved in the pathogenesis of CIBP. RVM microglial p38 MAPK signaling pathway is activated and leads to the release of downstream pro-inflammatory mediators, which contribute to the descending facilitation of CIBP.

Role of protocadherin 20 in spinal cord in development of bone cancer pain in rats / 中华麻醉学杂志

Objective To investigate the effects of protocadherin 20 (PCDH20) in the spinal cord in the development of bone cancer pain (BCP) in rats.Methods Thirty-six SPF female Sprague-Dawley rats,weighing 180-200 g,were randomly divided into 4 groups (n =9 each):sham operation group (group S),BCP group,lentivirus control group (group LC) and PCDH20 siRNA lentivirus group (group P).Control lentivirus and lentivirus containing PCDH20 siRNA 4 μl were injected into the ipsilateral spinal cord in groups LC and P,respectively.One week later,BCP was induced by injection of Walker 256 breast cancer cells into the upper segment of bone marrow of right tibia.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before injection of lentivirus (T1),1 day before BCP (T2),and 7,14 and 21 days after BCP (T3-5).Three rats in each group were sacrificed after measurement of the MWT at 21 day after BCP and the tibia on the operated side was obtained for examination of invasion of the cancer cells with light microscope.The spinal cord was removed for determination of the expression of PCDH20 and postsynaptic density 95 (PSD95) protein (by Western blot) and mRNA (by RTPCR).Results In groups BCP,LC and P,the cancer cells grew out of the bone and destroyed the cortical bone seriously.Compared with group S,the MWT was significantly decreased at T3-5 in groups BCP,LC and P,the expression of PCDH20 and PSD95 protein and mRNA was up-regulated in groups BCP and LC,and the expression of PCDH20 was up-regulated in group P (P ＜ 0.05).Compared with BCP group,no significant change was found in the MWT and expression of PCDH20 and PSD95 protein and mRNA in group LC (P ＞ 0.05),and the MWT was significantly increased at T4,5 and the expression of PCDH20 and PSD95 protein and mRNA was down-regulated in group P (P ＜ 0.05).Conclusion PCDH20 is involved in the development of BCP through regulating the expression of PSD95 in the spinal cord and adjusting the function of excitatory synapse in rats.

Role of ATP-sensitive potassium channel in spinal dorsal horn neurons in hyperalgesia after thoracotomy in rats / 中华麻醉学杂志

Objective To evaluate the role of ATP-sensitive potassium (KATP) channel in spinal dorsal horn neurons in hyperalgesia after thoracotomy in rats.Methods Twenty-eight Sprague-Dawley rats,aged 7-9 weeks,weighing 250-350 g,in which intrathecal catheters were successfully implanted without complications on 14th day after chronic post-thoracotomy pain was induced,were randomly divided into 4 groups (n =7 each):control group,the solvent dimethyl sulfoxide (DMSO) group,KATP channel opener pinacidil group (group P) and KATP channel blocker glibenclamide group (group G).10％ DMSO 10 μl,pinacidil 10 μg/10 μl and glibenclamide 50μg/10μ1 were injected intrathecally in groups DMSO,P and G at 5 day after the intrathecal catheter was implanted,respectively.Paw withdrawal threshold to von Frey filament stimulation was measured before intrathecal administration and at 10,30 and 60 min after intrathecal administration and the acetone test was performed.Coldinduced pain threshold was measured.Results There was no significant difference in paw withdrawal threshold to yon Frey filament stimulation at each time point among the four groups (P ＞ 0.05).Compared with C and DMSO groups,cold-induced pain threshold was significantly increased in group P and decreased in group G (P ＜ 0.05).There was no significant difference in cold-induced pain threshold between C and DMSO groups (P ＞ 0.05).Conclusion KATP channel in spinal dorsal horn neurons is involved in the maintenance of hyperalgesia after thoracotomy in rats.

Effects of pentobarbital sodium on compound muscle action potentials in rats / 中华麻醉学杂志

Objective To investigate the effects of pentobarbital sodium on compound muscle action potentials (CMAPs) in rats.Methods Ten adult Sprague-Dawley rats (5 males,5 females),aged 8 weeks,weighing 240-260 g,were anesthetized with intraperitoneal 1％ pentobarbital sodium 40 mg/kg.The sciatic nerve was stimulated (intensity 0.50,0.55 and 0.60 V,wave length 0.05 ms,frequency 10 Hz) starting from 8 min after administration.Each intensity was repeated three times at 1 s interval.The stimulation mentioned above was repeated every 5 min.CMAPs from the gastrocnemius muscle were recorded starting from 8 min after administration (T1) and then were recorded every 5 min for 9 times (T2-10),Results The peak value of CMAP was significantly decreased at T3-5 when the intensity was 0.50,0.55 and 0.60 V,and CMAP latency was significantly prolonged at T3-6 when the intensity was 0.50 V,and at T4,5 when the intensity was 0.55 and 0.60 V as compared with those at T1 ( P ＜ 0.05 or 0.01 ).Conclusion Pentobarbital sodium can inhibit CMAPs in rats.

Effects of CX3CR1 on expression of μ-receptor and TRPV1 in spinal dorsal horn of morphine-tolerent rats with bone cancer pain / 中华麻醉学杂志

Objective To investigate the effects of intrathecal(IT)CX3 CR1 neutralizing antibody(antiFKR)on morphine tolerance in rats with bone cancer pain(BCP)and the unlerlying mechanism.Methods Forty-eight adult female SD rats aged 3 months weighing 180-200 g were randomized into 4 groups(n =12 each):group I sham operation(S); group Ⅱ BCP + normal saline(NS); group Ⅲ BCP + IgG(IgG)and group ⅣBCP + anti-FKR.Bone cancer pain(BCP)was induced by injecting Walker 256 cancer cells 10 μl(400 cells/ μl)into the medullary cavity of right tibia in groups Ⅱ,Ⅲ and Ⅳ.Ten days later morphine 20 μg/kg was administered IT twice a day for 7 consecutive days.Starting from the 8th day NS,IgG and anti-KFR 10 μl was administered IT once a day for 3 consecutive days in groups Ⅱ,Ⅲ and ⅣⅣ respectively.Paw withdrawal threshold to yon Frey filament stimulation(MWT)and paw withdrawal duration(MWD)were determined bcfore(To,baseline)and at 3,6,9 day after intra-tibial cancer cell inoculation(T1.2,3),on the 3rd and 7th day of IT morphine(T4.5)and on the 3rd day of IT NS/lgG/anti-KFR(T6).The animals were killed at T6 after last pain behavior assessment.The lumbar segment(L4-6)of the spinal cord was removed for determination of the expression of CX3 CR1 protein(by Western blot),μ-opioid receptor and TRPV1 receptor(by immuno-histochemistry)in the dorsal horn of spinal cord.Results IT morphine significantly eased BCP at T4,but morphine analgesia was significantly reduced on the 7th day of IT morphine in the 3 groups indicating morphine tolerance which was significantly relieved by anti-KFR in group Ⅳ.IT anti-KFR significantly down-regulated CX3CR1 prolein and TRPVI receptor expression and up-regulated μ-opioid receptor in group Ⅳ as compared with IT NS and lgG in groups Ⅱ and Ⅲ.Conctusion IT anti-KFR can relieve morphine tolerance in the rats with bone cancer pain by up-regulating μ-opioid receptor and down-regulating CX3 CR1 protein and TRPVI receptor expression.

Comparison of subgluteal and sub-subgluteal-fold approach for ultrasound-guided sciatic nerve block / 中华超声影像学杂志

Objective To compare the effects of subgluteal(SG) and sub-subgluteal-fold(SSGF)approach for ultrasound-guided siatic nerve block. Methods One hundred forty-eight patients undergoing lower limb surgery were randomly divided into two groups to receive SG approaches and SSGF approaches to sciatic nerve block under real time ultrasound guidance. A combined posterior lumbar plexus block under ultrasound guidance was performed for sufficient surgery anesthesia. 20 ml of 0. 5% ropivacaine was used for sciatic nerve and lumbar plexus block separately. Measurements included skin-to-nerve distance,reorientation of the needle during block and execution time,rates of sensory and motor blockade after 15 min and 30 min of injection, quality of surgery blockade, duration of the sensory and motor block, and postoperative complications related to sciatic nerve block. Results In SSGF group, execution time and reorientation of needle for sciatic nerve block was significantly less than those of the SG group( P ＜0.01).But motor blockade in the SG group was quicker when compared with SSGF group ( P ＜0.01). There were no significant differences in the quality and duration of blockade between the two groups. Conclusions Both SG and SSGF approach can be used for sciatic nerve block with equal sensory and motor block rate,whereas sciatic nerve block via SSGF approach was faster and easy to perform than the SG one.

Analgesic effect of diprospan in rats with trigeminal neuralgia / 华中科技大学学报（医学）（英德文版）

This study examined the analgesic effect of diprospan in rats with trigeminal neuralgia. Rat model of trigeminal neuralgic pain was established by loosely ligating the left infraorbital branch of the trigeminal nerve. After allodynia developed, the rats were randomly divided into 2 groups (n=20 in each): diprospan group, in which the rats received diprospan (7 mg/mL, 0.1 mL) injected to the left infraorbital foramen area; control group, in which saline (0.1 mL) was administered as the same manner as the diprospan group. The pain threshold (PT) in the left infraorbital area was measured before and 2, 6, and 8 weeks after the administration. The expression of neuropeptides [substance P, preprotachykinin A (PPTA), calcitonin gene-related peptide (CGRP)] in the trigeminal nerve was detected at the same time points as the PT measurement by immunohistochemistry or in situ hybridization method. The results showed that in the diprospan group, the PT was 10.65±1.26, 10.77±1.19 and 14.13±1.34 g 2, 6, and 8 weeks after the administration respectively, significantly higher than that before the administration (PT value: 0.36±0.11) (P0.05). The PT in the diprospan group was significantly greater than that in the saline group 2 and 6 weeks post-administration (P<0.05). In the diprospan group, the expression levels of neuropeptides were significantly reduced as compared with those in the saline group 2 and 6 weeks post-administration (P<0.05). It was concluded that diprospan has an obvious analgesic effect on the trigeminal neuropathic pain partly by reducing the expression of neuropeptides in the trigeminal ganglia.

Change in 5-hydroxytryptamine level in spinal dorsal horn in a rat model of tibial bone cancer pain / 中华麻醉学杂志

Objective To investigate the change in 5-hydroxytryptomine (5-HT) content in spinal dorsal horn in a rat model of tibial bone cancer pain (BCP). Methods Sixty female SD rats weighing 160-180 g were randomly divided into 3 groups ( n = 20 each): control group (group C), sham operation group (group S) and BCP group. BCP was induced by intra-tibial inoculation of 10 μl Walker 256 breast cancer cell suspension in group BCP, while group S received intra-tibial inoculation of 10 μl D-hank solution. Paw withdrawal threshold to mechanical stimulation with yon Frey filaments (MWT) was measured 1 d before (baseline) and at 3, 5, 7, 9, 11,14, 16, 18 and 21 d after breast cancer cell inoculation. At 1 d before and 7, 14 and 21 d after breast cancer cell inoculation, four animals in each group were sacrificed after measurement of MWT. Their lumber segments of the spinal cord were removed for assay of 5-HT content in spinal dorsal horn using HPLC with fluorescence detector.HE staining was used to detect the damage to the tibia. Correlation between the 5-HT content and MWT was analyzed. Results MWT was significantly decreased after breast cancer cell inoculation in group BCP ( P ＜ 0.05).Microscopic examination showed serious bone destruction of tibia at the injection site in group BCP, while no bone destruction was found in groups C and S. 5-HT content in spinal dorsal horn was significantly higher in group BCP than in groups C and S (P ＜ 0.05). There was strong negative linear correlation between 5-HT content in spinal dorsal horn and MWT ( r = - 0.973, P ＜ 0.05 ). Conclusion The 5- HT content in spinal dorsal horn is significantly increased in rats with tibial BCP and is involved in the development of BCP.

Construction of lentivirus vector expressing antigene RNA and ferritin gene / 中华麻醉学杂志

Objective To construct lentivirus vector expressing antigene RNA and ferritin gene.Methods Intermediate plasmid pGC-FU-HF was constructed by transfecting lentivirus vector pGC-FU with heavy chain ferritin subunit gene.The target plasmid pGC-agRNA-HF was subsequently constructed by transfecting the intermediate plasmid with β-arrestin 2 antigene RNA.The NG108-15 cells were transfected with the target plasmid.The titre of lentivirus vector was measured by RT-PCR.The expression of antigene RNA and ferritin gene was determined by Western blot and RT-PCR.Results Lentivirus vector was successfully transfected with antigene RNA and ferritin gene.The titre of lentivirus vector was 2.00 × 109 TU/ml.The expression of β-arrestin2 protein was down-regulated and the expression of ferritin protein up-regulated in the NG108-15 cells after being transfected with the lentivirus vector.Conclusion Lentivirus vector expressing antigene RNA and ferritin gene has been successfully constructed.

Effect of minocycline on spinal CX3 C chemokine receptor 1 mRNA expression in morphine-tolerant rats with bone cancer pain / 中华麻醉学杂志

Objective To investigate the effect of minocycline on spinal CX3 C chemokine receptor 1(CX3 CR1)mRNA expression in morphine-tolerant rats with bone cancer pain.Methods Sixty female SD rats weighing 180-200 g in which intrathecal(IT)catheter was successfully placed at L3,4 interspace without complications were randomly divided into 4 groups:control group(group C,n=10);minocycline group(group M,n=10);bone cancer pain + morphine tolerance group(group BM,n=20)and bone cancer pain+morphine tolerance+ minocycline group(group BM+M,n=20).Bone cancer pain was induced by injection of breast cancer cells(Walker256)10μl(400/μl)into upper segment of bone marrow of right tibia.Morphine tolerance was induced by IT injection of morphine 20 μg/kg twice a day for 7 consecutive days starting from the 10th day after intratibia injection in BM and BM + M groups. Minocycline 0.25 mg/kg was injected IT once a day for 3 consecutive days in group M and after the model of bone cancer pain and morphine tolerance was established in group BM + M. Mechanical withdrawal threshold (MWT) and mechanical withdrawal duration (MWD) were determined before (T0, baseline) and at3, 6 and 9 days after operation (T1-3) and at 4, 7, 10 and 12 days after IT morphine injection was started (T4-7).The animals were sacrificed at T6 and T7 respectively in BM and BM + M groups and at T7 in C and M groups.The lumbar segment of the spinal cord (L4-6) was removed for determination of CX3 CR1 mRNA (by RT-PCR) and OX-42 expression (by immuno-histochemistry) .Results There was no significant difference in MWT and MWD at all time points between group C and group M. MWT was significantly decreased while MWD prolonged in morphine tolerant rats with cancer pain in group BM as compared with C and M groups. The hyperalgesia was significantly attenuated by IT minocycline in group BM + M. Spinal CX3 CR1 mRNA and OX-42 expression was significantly increased in group BM than in C and M groups. IT minocycline attenuated the increase in spinal CX3 CR, mRNA and OX-42 expression induced by bone cancer. Conclusion IT minocycline can inhibit spinal CX3CR1 mRNA expression, thereby antagonizing morphine tolerance in morphine-tolerant rats with bone cancer pain.

Establishment of a rat model of bone cancer pain-chronic morphine tolerance / 中华麻醉学杂志

Objective To establish a rat model of bone cancer pain-chronic morphine tolerance. Methods Thirty-six adult female Sprague-Dawley rats weighing 180-200 g in which intrathecal catheters were successfully placed without complications were randomly divided into 3 groups ( n = 12 each) :group sham operation (group S),group chronic morphine tolerance (group M) and group bone cancer pain + chronic morphine tolerance (group BM). Bone cancer pain was induced by intra-tibia inoculation of Walker256 mammary gland carcinoma cells (4 ×102 cells/μl) in group BM, while in group M heat-inactivated Walker256 mammary gland carcinoma cells were given instead, and then 10 days later, intrathecal morphine 20 μg,/kg was administered twice a day for 9 consecutive days. The mechanical paw withdrawal threshold (MWT) and mechanical paw withdrawal duration (MWD) were measured before inoculation, at day 1, 3, 6 and 9 after inoculation, and at day 1, 3, 5, 7 and 9 of morphine administration. The degree of bone destruction was assessed by radiological analysis at day 9 after inoculation. After the last measurement of pain threshold, the rats were given innoxious touch-stimulus. The rats were sacrificed 3 h after stopping the stimulus, and L4-6 segment of the spinal cord was isolated to determine the expression of Fos protein in the spinal dorsal horn. Results Compared with group S, MWT was significantly decreased, MWD was significantly prolonged and the expression of Fos protein was up-regulated in group M ( P ＜ 0.05 or 0.01 ). MWT was significantly decreased, MWD was significantly prolonged, bone destruction scores were significantly increased,and the expression of Fos protein was up-regulated in group BM compared with group M ( P ＜ 0.05 or 0.01 ). Conclusion A rat model of bone cancer pain-chronic morphine tolerance is successfully established.