Objective To evaluate the effects of long-term intraperitoneal flurbiprofen axetil on the gastric mucosa and liver function in rats with bone cancer pain (BCP).Methods Thirty-six healthy female Sprague Drawley rats,weighing 200-250 g,were randomly divided into 6 groups (n =6 each):BCP + normal saline group (group BCP),BCP + flurbiprofen axetil 10 mg·kg-1 ·d-1 group (group BF10),BCP + flurbiprofen axetil 25 mg· kg-1 · d-1 group (group BF25),BCP + flurbiprofen axetil 50 mg· kg-1 · d-1 group (group BF50),flurbiprofen axetil 50 mg·kg-1 ·d-1 group (group F50),and sham operation + normal saline group (group S).BCP was induced by injecting Walker 256 mammary gland cancer cells into the bone marrow of the left tibia.In BCP and S groups,paw withdrawal threshold to mechanical stimulation (MWT) was measured at 1 day before inoculation of cancer cells (T0) and 3,5,7,10,14,17 and 21 days after inoculation (T1-7).The corresponding doses of flurbiprofen axetil or normal saline were administered intraperitoneally twice a day at 12 h intervals starting from T7 for 7 consecutive days.Blood samples were obtained from the abdominal aorta to determine the levels of alanine transaminase (ALT),aspartate transaminase (AST),total protein (TP),and albumin (ALB) in serum.The rats were then sacrificed and stomach and livers were removed for microscopic examination of pathological changes.The ulcer index (UI) was calculated.Results Compared with group S,MWT was significantly decreased at T2-7,no significant changes were found in the other parameters mentioned above in BCP group,the serum levels of TP and ALB were decreased in BF50 and F50 groups,and UI was increased in BF25,BF50 and F50 groups.Compared with BCP group,the serum levels of TP and ALB were decreased in BF50 and F50 groups,and UI was increased in BF25,BF50 and F50 groups.No significant changes were found in each parameter between BF50 and F50 groups.Microscopic examination showed that the epithelium of gastric mucous membrane became defect in partial region of the stomach and showed damage to gastric glands in the deep part and massive inflammatory cell infiltration in BF50 and F50 groups.Microscopic examination showed mild damage to the integrity and continuity of gastric mucosa and did not show any abnormality in livers in BF25 group.Conclusion Long-term intraperitoneal flurbiprofen axetil can cause damage to the gastric mucosa dose-dependently and has no effect on liver function in rats with BCP.

AIM:To compare the effects of remifentanil and fentanyl for posterior scoliosis correction and the influences on postoperative pain.METHODS:Forty patients scheduled for posterior scoliosis correction(ASAⅠ-Ⅱ,aged 11-18 years)were randomly divided into group remifentanil(group R)and group fentanyl(group F).Anesthesia was maintained with propofol,vecuronium bromide and sevoflurane.Intravenous remifentanil(0.2 ?g?kg-1?min-1)and fentanyl(1 ?g?kg-1?h-1)were continuously administered for analgesia.Vecuronium bromide and analgesics were discontinued around 30 min before the wake-up test.The wake up time from propofol and sevoflurane discontinuation to movement of the patient's toe were recorded.In group R,once remifentanil infusion was stopped before surgery ended,the patients were injected with fentanyl 2 ?g/kg.All of the patients received intravenous fentanyl(10 ?g?kg-1?min-1)for postoperative analgesia and were interviewed for pain degree during the first 24 h after surgery.RESULTS:The wake-up time were(12.3?5.7)min in group R and(21.6?6.5)min in group F(P

Objective To investigate the effects of intrathecal injection of α-cyano-4-hydroxy-cinnamate (4-CIN) in rats with neuropathic pain induced by chronic constriction injury of sciatic nerve (CCI).Methods Eighteen male SD rats were divided randomly into 3 groups(n=6):sham group (group S),CCI model group (group C0) and 4-CIN group (group C1).Group C0 and C1 were operated with the model of neuropathic pain induced by chronic constriction injury of sciatic nerve ; and group S were treated as sham operated rats.Two days after operation,group C1 received intrathecal injection of 100 μmol 4-CIN dissolved in 10％ DMSO 10 μl,while group C0 received intrathecal injection of 10％ DMSO 10 μl only.The paw withdrawal thermal latency(PWTL) and paw withdrawal mechanical threshold(PWMT) were tested 1 d before operation and 1 d,3 d,7 d,10 d,14 d after operation(T0-5).Results The basic values of PWMT and PWTL before operation showed no statistically significant differences among the three groups.On T1-5,the PWMT((11.71 ±2.81) g,(9.76± 1.00) g,(8.22± 1.33) g,(6.50± 1.48) g,(4.67± 1.03) g) and PWTL((11.36±2.18) s,(11.60±2.54) s,(8.54± 1.42) s,(7.59± 1.00) s,(6.88± 0.42) s) in group C0 were significantly lower than those in group S (P＜0.05).However,there were no significant differences between group S and C1 on T2-5(P＞0.05).Conclusion Intrathecal administration of 4-CIN can attenuate neuropathic pain in rats induced by CCI.

OBJECTIVE:To explore the content variation rule and influencing factors of 5-hydroxymethylfurfural(5-HMF)in the extraction process of the herbs Schisandra chinensis and improve the quality of monitoring the extract of Schisandra chinensis. METHODS:High performance liquid chromatography was adopted to determine the contents of 5-HMF in the extracts during the extraction process (decoction,vacuum concentration,alcohol precipitation,vacuum drying,alkali adjustment),and the content variation rule was found out. For vacuum drying during which the content of 5-HMF reduced obviously,the effects of the tempera-ture and time of drying on the content of 5-HMF were studied,and the effects of vacuum drying and freeze drying on the 5-HMF contents were compared. RESULTS:The content variation trend in the extraction process of Schisandra chinensis was as follows as a large amount of 5-HMF was produced in the herbs decoction process;the content of 5-HMF increased during concentration,re-duced during the alcohol precipitation and the vacuum drying of the extracts by three times concentrate,and maintained substantial-ly unchanged during alkali adjustment. In the process of vacuum drying,the content of 5-HMF decreased with temperature rise and time extension. Freeze drying had no effect as good as that of vacuum drying in the reduction in the content of 5-HMF. CON-CLUSIONS:It is suggested that the vacuum drying of the extracts by three times concentrate at higher temperature,which may pro-duce the extract of Schisandra chinensis with lower content of 5-HMF and thus improve the quality of Schisandra chinensis extract.

Objective To summarize the experience of general anesthesia management in pregnant women with pulmonary hypertension who had to undergo cesarean section. Methods Clinical data, anesthesia methods and outcome of 6 pregnant women with pulmonary hypertension were analyzed. Among them, 1 case of patent ductus arteriosus had to undergo cesarean section twice, because the interval time of twice cesarean section was longer (2 years), and the number of pregnant women was counted to 7 cases. Results Seven patients had to undergo cesarean section with general anesthesia, and all the pregnant women′s hemodynamic were stable during the operation. After operation, 1 pregnant woman discharged from hospital against the doctor′s advices because of massive brain infarction, and the others were all rehabilitated. Seven newborns status:preterm in 3 cases, cardiopulmonary resuscitation in 2 cases, the Apgar score of the others newborns was 9-10 scores. Conclusions Pregnant women with pulmonary hypertension have high peri-operative risk, especially those who undergo general anesthesia. To improve the survival rate, anesthetist should reinforce the perioperative care, maintain oxygen supply, reduce the stress response, maintain the preload and blood pressure, and avoid the increasing of pulmonary pressure.

Objective To investigate the analgesic efficacy of intrathecal injection of RC-13,a competitive kinesin superfamily protein 17 antagonist,in a mouse model of bone cancer pain.Methods Forty male C3H/HeJ mice,aged 6-8 weeks,weighing 20-25 g,were randomly divided into 5 groups (n=8 each): sham operation group (group S); bone cancer pain + 5 μl dimethyl sulfoxide (DMSO) group (group R0); bone cancer pain + 2.5 μg RC-13 group (group R1); bone cancer pain + 5 μg RC-13 group (group R2) and bone cancer pain + 10 μg RC-13 group (group R3).In groups R0-3,bone cancer pain was induced by implantation of α-min-imal essence medium (α-MEM) containing osteosarcomaNCTC 2472 cells into the intramedullary space of right femur.In group S,culture medium α-MEM containing no cancer cell was injected instead.10％ DMSO 5 μl and RC-13 2.5 μg/5 μl,5μg/5μ1 and 10 μg/5 μ1 dissolved in 10％ DMSO were injected intrathecally in groups R0-3,respectively,once a day for 3 consecutive days starting from 14th day after inoculation of the tumor cells.Pain behavior was assessed by the paw withdrawal mechanical threshold (PWMT) and spontaneous lifting times (SLTs) measured at 1 day before inoculation and at 3,5,7,10,14 days after inoculation.The same tests were also performed at 1,3,5 and 7 days after administration in groups R0-3.Results Compared with group S,PWMT was significantly decreased and SLTs were increased at 7-14 days after inoculation in the other groups (P ＜ 0.05).Compared with group R0,PWMT was significantly increased and SLTs were reduced at 1 day after administration in group R1,at 1and 3 days after administration in group R2,and at 1,3 and 5 days after administration in group R3 (P ＜ 0.05).Compared with group R1,PWMT was significantly increased and SLTs were reduced at 3 days after administration in group R2,and at 1,3 and 5 days after administration in group R3 (P ＜ 0.05).Compared with group R2,PWMT was significantly increased and SLTs were reduced at 1 and 3 days after administration in group Rs (P ＜ 0.05).Conclusion Intrathecal RC-13,a competitive kinesin superfamily protein 17 antagonist,has a good analgesic efficacy in a mouse model of bone cancer pain and the efficacy is dose-dependent.

Objective To evaluate the role of neuron-restrictive silencer factor (NRSF) in the spinal cord in remifentanil-induced hyperalgesia in a mouse model of incisional pain (IP) .Methods Fifty-six male Kunming mice were randomly divided into 7 groups (n=8 each):control group (group C) ,IP group (group I) ,IP +remifentanil group (group IR ) , NRSF antisense oligonucleotide group (NAS group ) , IP + NRSF antisense oligonucleotide group (I+NAS group ) ,IP + remifentanil + NRSF mismatch oligonucleotide group (IR+NMS group) , and IP + remifentanil + NRSF antisense oligonucleotide group (IR + NAS group ) . Artificial cerebrospinal fluid 5 μl was injected intrathecally once a day for 3 consecutive days in C ,I and IR groups .NRSF antisense oligonucleotide NAS 10μg was injected intrathecally once a day for 3 consecutive days in NAS ,I+NAS and IR + NAS groups . NRSF mismatch oligonucleotide 10 μg was injected intrathecally once a day for 3 consecutive days in IR+NMS group .A 1-cm longitudinal incision was made through skin ,fascia and muscle of the plantar aspect of the right hindpaw to establish the model of incisional pain in sevoflurane-anesthetized rats .At 30 min after the last injection ,normal saline 0.4 ml was infused subcutaneously in C and NAS groups ,the model was established and normal saline 0.4 ml was subcutaneously infused simultaneously in I and I+NAS groups ,and the model was established and remifentanil 0.04 mg/kg was subcutaneously infused simultaneously in IR ,IR+NMS and IR+NAS groups .At 3 days before operation (T0 ) ,4 h before operation (T1 ) and 4 ,12 ,24 and 48 h after operation (T1-5 ) ,mechanical paw withdrawal threshold to von Frey stimuli (PMWT ) and paw withdrawal latency to thermal nociceptive stimulus (PTWL ) were measured .Results Compared with C group ,the PWMT and PWTL were significantly decreased at T2-5 in I ,IR ,I+NAS ,IR+NMS and IR+NAS groups ( P<0.05) ,and no significant change was found in the PWMT and PWTL at each time point in NAS group ( P>0.05 ) .Compared with I group ,the PWMT and PWTL were significantly decreased at T2-5 in IR and IR+NMS groups ( P<0.05) , and no significant change was found in the PWMT and PWTL at each time point in I +NAS group ( P>0.05) . Compared with IR group ,no significant change was found in the PWMT and PWTL at each time point in IR+NMS group ( P>0.05) ,and the PWMT and PWTL were significantly increased at T2-5 in IR+NAS group ( P<0.05) . Conclusion NRSF in the spinal cord is involved in the development and maintenance of hyperalgesia induced by remifentanil in a mouse model of IP .

OBJECTIVE: To determine the changes of Mu-opioid receptor (Mor) and neuron-restrictive silencer factor (NRSF) in periaquductal gray (PAG) in mouse models of remifentanil-induced postoperative hyperalgesia. METHODS: Thirty-two Kun-Ming mice were randomly divided into 4 groups (8 mice in each group): Group C (mice underwent a sham procedure and saline was infused subcutaneously over a period of 30 min), Group I (mice underwent a surgical incision and the same volume of saline), Group R (mice underwent a sham procedure and remifentanil was infused subcutaneously at the moment of surgical incision over a period of 30 min), and group IR (mice underwent a surgical incision and remifentanil). Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) tests were performed 24 h before the operation and 2, 6, 24, and 48 h after the operation. The specimens were collected after behavioral testings at 48 h. The expressions of Mor and NRSF in mice's PAG neurons were determined by Western blot. RESULTS: Mechanical allodynia and thermal hyperalgesia developed in Group I, R and IR (P<0.01). Intraoperative infusion of remifentanil enhanced mechanical allodynia and thermal hyperalgesia in mice with planta incision (P<0.01). In Group R and Group IR, the expression of Mor was significantly lower (P<0.01) and NRSF was significantly higher (P<0.01) when compared with Group C and Group I. CONCLUSION Intraoperative infusion of remifentanil induces postoperative hyperalgesia in mouse models, accompanied with decreased expressions of Mor and increased of NRSF level in PAG neurons, which may be involved in remifentanil induced hyperalgesia.
Animals ; Disease Models, Animal ; Hyperalgesia ; chemically induced ; Mice ; Pain, Postoperative ; Periaqueductal Gray ; drug effects ; metabolism ; Piperidines ; administration & dosage ; Receptors, Opioid, mu ; metabolism ; Remifentanil ; Repressor Proteins ; metabolism

Objective To identify the risk factors for in-hospital cardio-cerebrovascular events and 1-year mortality following lower extremity fracture surgery in elderly patients. Methods Four hundred and thirty patients, aged ≥ 65 yr, undergoing elective lower extremity fracture surgery from January 2010 to December 2014, were selected. Age, gender, American Society of Anesthesiologists (ASA) physical sta-tus, preoperative comorbidities (diabetes mellitus, cardio-cerebrovascular events and hemiplegia), preop-erative anemia, surgical site (hip and femur, knee joint and the site below the knee), anesthesia method (general anesthesia, neuraxial anesthesia), surgery time, intraoperative hypertension and hypotension, intraoperative blood loss, postoperative Hb≤90 g∕L in hospital and volume of postoperative drainage, post-operative pneumonia and admission to the intensive care unit after operation were recorded. The patients were divided into either cardio-cerebrovascular event group or non-cardio-cerebrovascular event group ac-cording to whether the patients developed cardio-cerebrovascular events after surgery in hospital. The pa-tients were divided into either survival group or dead group according to the living status 1 yr after surgery. The risk factors of which P values were less than 0. 05 would enter the multi-factor logistic regression analy-sis to stratify the risk factors for in-hospital cardio-cerebrovascular events and 1-year mortality following low-er extremity fracture surgery. Results Three hundred and seventy-two patients completed the study. A-mong the 372 patients, 35 patients developed postoperative cardio-cerebrovascular events in hospital, and the incidence was 9. 4％, logistic regression analysis showed that the preoperative cardio-cerebrovascular diseases and ASA physical status ≥ Ⅲ were risk factors for in-hospital postoperative cardio-cerebrovascular events. Thirty-three patients died within 1 yr after surgery, the mortality rate was 8. 9％, and logistic re-gression analysis showed that age≥75 yr, preoperative hemiplegia and development of cardio-cerebrovascu-lar events after surgery in hospital were postoperative 1-year mortality-related risk factors. Conclusion Preoperative cardio-cerebrovascular diseases and ASA physical status ≥ Ⅲ are the independent risk factors for in-hospital cardio-cerebrovascular events following lower extremity fracture surgery in elderly patients;age≥75 yr, preoperative hemiplegia and in-hospital postoperative cardio-cerebrovascular events are the in-dependent risk factors for 1-year mortality after surgery.

Chronic pain patients are often accompanied with anxiety disorder, which promote the development of each other's disease process to a certain extent and seriously affect the quality of life of patients.However, the mechanism regulating the comorbidity between the two has not been clarified.Synaptic remodeling is the alteration of synaptic structure and function, which affects the transmission of signals between neurons.Synaptic remodeling is a hot topic in the field of chronic pain and anxiety disorders, but only few studies have explored its pathological changes in chronic pain and anxiety disorders.By summarizing the relevant researches in recent years, the occurrence of chronic pain co-anxiety disorder is closely related to changes in synaptic structure, synaptic transmission efficiency and synaptic function in brain regions.Synaptic remodeling could lead to the decline of centra pain regulation ability and aggravate the progression of chronic pain accompanied by anxiety disorder through ionic amino acid receptors, neuronal transmission and interactions between neurons and glial cells.Understanding the latest research progress of the co-morbidity mechanism of chronic pain and anxiety disorder is helpful to provide theoretical basis and potential new targets for its treatment.