Objective To study the influence of lidocaine on the propofol concentration effect relationships for loss of eyelash reflex and loss of consciousness,hemodynamic function Methods Thirty eight patients were randomly allocated to receiving a computer controlled infusion of lidocaine at target concentration of 0?g?ml -1 (group A,n=9),1 25?g?ml -1 (group B,n=7), 2 5?g?ml -1 (group C,n=7), 5?g?ml -1 (group D,n=8),or 7?g?ml -1 (group E,n=7) respectively While the target concentration of lidocaine was kept stable, propofol was administrated with a computer controlled infusion at an initial target concentration of 0 5 1?g?ml -1 , which was increased every time by 0 5?g?ml -1 until loss of consciousness Plasma concentrations of lidocaine and propofol were measured with high performance liquid chromatography Results 50% of patients lost eyelash reflex and consciousness at plasma propofol concentrations(Cp50) of 1 78 and 3 17?g?ml -1 in the absence of lidocaine In the presence of plasma lidocaine concentration of 1 25 4 3 ?g?ml -1 ,the Cp50 for loss of eyelash reflex was reduced by 42 1% There was a linear regression relationship between plasma lidocaine concentrations from 0 to 7?g?ml -1 and the Cp50 for loss of consciousness (r=-0 69 ) Conclusions The Chinese Cp50 for loss of eyelash reflex and consciousness are lower than those reported abroad Plasma lidocaine concentration at 4?g?ml -1 can potentiate properly the potency of propofol on the sedation and hypnosis during anesthesia induction

Objective To study the influence of age on the pharmacodynamics of propofol including the relationship between plasma concentrations of propofol and the time of loss of consciousness or return of consciousness.Methods Forty-two ASAⅠ-Ⅱ patients were assigned to one of three age groups: group A: age ranged from 18-34 yr(n=14); group B:35-60 yr(n=15); and group C: 61-90 yr(n=13). Once spinal anesthesia was completed, propofol infusion at the rate of 0.5 mg?kg -1?min -1(group A) or 0.4 mg?kg -1?min -1(group B and C )was started until burst suppression of EEG lasting 3s was observed. Venous blood samples were taken at 1, 2, 4, 8,10, 15, 30, 45,60,90,120 and 240 min after the start of propofol infusion for the determination of plasma propofol concentrations. The influence of age on relationship between propofol plasme concentration and loss of consciousness or return of consciousness was analyzed by non-linear regression. The relationships between age and time of loss of consciousness,duration of sleep,the total dose of propofol,the plasma concentration at the time of loss of consciousness or return of consiousness were determined by linear regression.Results As compared with those in group A and B,the time of loss of consciousness and the total dose of propofol required decreased markedly in group C. The observation showed increased sensitivity to propofol in elderly patients. The EC50 values for loss of consciousness were 2.86 (at age of 25 yr),2.26 (at 50yr), and 1.78 (at 75yr) ?g?ml -1,and the EC50 values for return of consciousness of 1.76 (at 25 yr),1.45(at 50yr),1.11(at 75yr)?g?ml -1 respectively.Conclusions Elderly patients are more sensitive to propofol than younger people in terms of hypnosis and EEG effects.

Objective To evaluate the effects of fentanyl and lidocaine on hypnotic effect of propofol in total intravenous anesthesia(TIVA) Methods One hundred and sixty ASAI Ⅲ patients(86 male,74 female) aged (55 0?12 4)yr,weighing (58 0?9 8)kg,scheduled for elective surgery were randomly divided into propofol group(group P,n=30), propofol fentanyl group(group PF,n=52) and propofol lidocaine group (group PL,n=78) Patients with kidney and liver dysfunction, hypertension, neurological and mental disease were excluded All patients were premedicated with intramuscular phenobarbital 0 1g and atropine 0 5mg BP,HR,SpO 2 and BIS were continuously monitored The patients were anesthetized by TIVA with TCI The target plasma concentration for fentanyl was 2?g/L(group PF) and for lidocaine 4mg/L(group PL) The initial target plasma concentration of propofol was set at 1mg/L When pre set concentration was reached, target propofol plasma concentration was increased by increments of 0 5mg/L until loss of consciousness Blood samples were taken before anesthesia(T 0), loss of consciousness(T 1), immediately after intubation(T 2), at skin incision(T 3), 5 and 10 min after skin incision(T 4,T 5), when TIVA was ended (T 6) and when the patient waked up(T 7) for determination of plasma concentrations of propofol, fentanyl and lidocaine Results ED 90 and ED 50 of propofol for loss of consciousness were lower in group PF and PL than those in group P but the difference was of no statistical significance (P

OBJECTIVE:To study the accuracy of infusion of Midazoloam with plasma concentration as target. METHODS:The parameters of Midazoloam obtained from our researches were inputted into target-controlled infusion(TCI) system with C language. The clinical anesthesia of 12 patients undergoing selective operations was completed with plasma concentration as target-controlled infusion. Predicted value of plasma concentration of Midazoloam was compared with measured value. Parameters of Midazoloam sample were calculated such as performance error(PE),absolute performance error(absPE),median performance error(MDPE),median absolute performance error(MDAPE),constancy error(CE),absolute constancy error(absCE),median constancy error(MDCE) and median absolute constancy error(MDACE). RESULTS:PE,absPE,MDPE and MDAPE of plasma concentration were -2.57%,14.16%,-3.28% and 15.34%,respectively. CE,absCE,MDCE and MDACE were 0.06%,1.42%,0.03% and 1.21%,respectively. The measured values were in indirect relationship with predicated values(r=0.986,P

OBJECTIVE　To establish an assay for the simultaneous determination of propofol and lidocaine in human plasma using reversed-phase high performance liquid chromatography（RP-HPLC）.METHODS　With thymol and bupivacaine as the internal standards for propofol and lidocaine respectively,the extraction was performed with cyclohexane.The organic layer was evaporated and the residue was redissolved by mobile phase.The concentrations of propofol and lidocaine were assayed on a hypersil BDS C18 column with a mobile phase consisting of acetonitrile-methanol-water（10∶60∶30）（including 0.14% n-butyamine 0.1% acetic acid）at a flow rate of 1 mL*min-1 and detected at 220 nm during 1～7 min and at 273 nm during 7～16 min.RESULTS　The linearity between concentrations and peak area ratio was obtained from 0.1 μg*mL-1 to 25.6 μg*mL-1（r=0.998，r=0.9995）.The detection limits were 0.1 μg*mL-1 for propofol and 0.05 μg*mL-1 for lidocaine.The within-day and between-day variation coefficients were less than 5%(n=5).The average recoveries were 93.33%,99.4% and 90%,95.67% respectively.CONCLUSION　The method was found to be rapid,accurate and precise.It is suitable for clinical pharmacokinetic and pharmacodynamic study.

To investigate the effect of NVP-DPP728, a DPP-Ⅳ inhibitor on new-onset diabetes and the autoimmune response in non-obese diabetic ( NOD ) mice. Diabetes could be reversed in 75% of NVP-DPP728 treated 20 NOD mice. In these 15 mice with remission, insulitis scores were significantly lower than those of the control group. The percentage of Tregs was increased in the thymus and celiac lymph nodes, plasma TGF-β1 and GLP-1 were also significantly increased ( P＜0. 01 ). NVP-DPP728 treatment may reverse new-onset diabetes in NOD mice by reducing insulitis and increasing Tregs.

Objective To investigate the protective effects of α-1 antitrypsin on human islets injured by protease released from pancreas exocrine cells. Methods ( 1 ) in vivo experiment. Parts of the cadaveric pancreas was digested with collagenase, islets were selected artificially, and pancreatic exocrine cells were collected. 8-9 weeks olds male BALB/c-Nu nude mice were induced into diabetic mice with STZ (240 mg/kg body weight, i. p) and randomly divided into two groups: the control group (n = 6), 250 islets were transplanted into left kidney subcapsule of diabetic nude mice; cotransplant group (n = 7), 250 islets and the equal volume of pancreatic exocrine cells were transplanted into different regions of left kidney subcapsule. Blood glucose level was monitored. Nephrectomies were performed after 28 days. The expression of anti-amylase antibodies in subcapsule was detected by using immunohistochemical staining. (2) Islets culture: Three groups were randomly set up. Group 1: purified islet group, 250 islets were incubated into a 6-well culture plate; Group 2: non-purified islet group, 250 purified islets and equal volume of exocrine cells were incubated; Group 3: nonpurified islet + Al AT group, 250 purified islets and equal volume of exocrine cells were incubated with α-1 antitrypsin added (0. 5 mg/ml). After 48 h, insulin content of islets in each well and trypsin concentration in the supernatant of each well were measured. Results 10000 islets were collected.After islets transplantation, the blood glucose levels in control and co-transplant groups were normal,but a delayed islet function in reversing diabetes was in the co-transplant group, and ehe mice in both groups became hyperglycemic after nephrectomy. A large number of anti-amylase antibody-positive cells were found in renal subcapsule in the co-transplant group while little seen in the control group.Insulin levels in the non-purified islet group were decreased as compared with purified islet group,those in the non-purified islet group + A1AT group were higher than in the non-purified islet group,but lower than in the purified islet groups. Trypsin concentration in the non-purified islet group was increased as compared with purified group, that in the non-purified islet group + A1AT group was lower than the non-purified islet group, but higher than in the purified islets group (all P＜0. 01).Conclusion Protease released from acinar cells during pancreatic digestion has detrimental effect on islet function after transplantation. Co-cultivation of islets and pancreatic exocrine cells with A1AT added can prevent islet cell damage caused by trypsin.

Objective To investigate the sedative and hypnotic interaction between remifentanil and propofol by target-controlled infusion (TCI) during induction of anesthesia.Methods Third-two ASA Ⅰ or Ⅱpatients,aged 22-63 yr,body mass index 18-25 kg/m2,scheduled for elective surgery under general anesthesia,were randomly divided into 4 groups(n=8 each).Group Ⅰ only received TCI pmpofol.GroupⅡ,Ⅲ,and Ⅳreceived a target concentration of 2,4 or 6 ng/ml remifentanil respectively.While the blood-effect site concentrations of remifentanil were equilibrated,patients received TCI of propefol,with an initial target concentration of 0.5μg/ml.After the blood-effect site concentrations of propofol were equilibrated then with 0.5μg/ml increments until the loss consciousness was achieved.The eyelash reflex and state of consciousness were assessed and radial arterial blood sample 6 ml was taken every 3 min to determine the remifentanil and propofol concentrations in blood.Propofol and remifentanil concentrations in blood were measured by reversed-phase high-performance liquid chromatography and high-performance liquid chromatography with ultraviolet detection respectively.The sedative and hypnotic interaction between propofol and remifentanil was determined with a pharmacodynamie interaction model by regression analysis and determined using the isobolographic method.Results Propofol concentrations in blood were lower in group Ⅱ,Ⅲ and Ⅳ than group Ⅰ(P<0.05).The propofol concentratopms in blood were significantly decreased in trun with the increase in the remifentanil concentrations in blood in group Ⅱ-Ⅳ(P<0.05).At loss of eyelash reflex and loss of consciousness of patients,the pharmacodynamic interaction model by curve fitting was superior to linear regression (P<0.05).At loss of eyelash reflex of patients,the curve fitting result showed EC50,prop=2.77μg/ml and EC50,rem=26.67 ng/ml,and the isobolographic method equation is ECprop/2.77+ECrem/26.67=0.69.At loss of consciousness of patients,the curve fitting result showed EC50,prop==3.76μg/ml and EC50,rem=31.56ng/ml,and the isobolographic method equation is Ecprop/3.76+Ecrem/31.56=0.65.Conclusion Remifentanil (Cp 2-6 ng/ml) and propofol by TCI shows a synergistic type of pharmacodynamic interaction on the sedative and hypnotic during induction of anesthesia.

Objective Several physiological reactions of human periodontal ligament cells (hPDLCs) are effected by a varie-ty of long-chain non-coding RNA , and nicotine as the major risk factor of smoking-related periodontitis , would lead to many cytokines changes in hPDLCs .The aim of the study was to explore the effect of nicotine on the expression of lncRNA NEAT 1 and IL 8 in the nucleus of hPDLCs. Methods We cultured the hPDLCs in vitro and used the 4th generation cells for subsequent experiments .hPDLCs were randomly divided into 4 groups:control group , nicotine group ,α-BTX group, nicotine+α-BTX group.Control group:hPDLCs without any ir-ritation;nicotine group: 10-5 mol/L nicotine stimulated hPDLCs for 4h;α-BTX group:10-8 mol/Lα-BTX stimulated hPDLCs; nicotine+α-BTX group:10-5 mol/L nicotine+10-8 mol/Lα-BTX stimulated hPDLCs .Real-time quantitative PCR was taken to detect the expres-sion level of NEAT1 and downstream IL 8 mRNA.In addition, the protein expression of IL-8 was tested by ELISA. Results After we primary cultured the periodontal ligament tissue for 3 weeks, the cells around the tissue were arranged radially .After a stable passage, microscopic observation showed that hPDLCs were long spindle-shape or spindle-shape with clear contour and adherent growth .Com-pared with nicotine group , the expression of NEAT1-1, NEAT1-2, IL-8 mRNA in hPDLCs in other three groups were all decreased ( P<0.05) .The expression level of IL-8 protein in the supernatant of the nicotine group was significantly higher than the control group , about 4.8 times higher than the control group ( P<0.05) , while theα-BTX group and nicotine+α-BTX group were not significantly dif-ferent from the control group (P>0.05). Conclusion Nicotine can promote the expression of NEAT1 and IL-8 in hPDLCs, which suggets that NEAT 1 may be involved in the development of smoking-related periodontitis by promoting early inflammatory reaction .

Objective To explore the effects of general anesthesia combined thoracic paraverte-bral block on postoperative pain and fast track single-port video-assisted thoracoscopic surgery (VATS).Methods Thirty patients,including male 20 and female 10,received single-port VATS were randomly and equally divided into two groups:group C received general anesthesia only,and group T received ultrasound-guided thoracic paravertebral nerve block combined with general anesthe-sia.Both groups did not use the patient-controlled analgesia,if insufficient analgesia happened (rest-ing VAS scores>4),than used dezocine intravenously as additional analgesia (a single-dose 5-20 mg, no more than 120 mg per day).The Ramsay scores at 1,4,8,12 h after the surgery and the mechani-cal withdrawal threshold on the day before the surgery,at 4,8,12,24 h after the surgery were recor-ded.The first time of post-operation pain feedback,the consumption of dezocine in the first 24 h after surgery,the incidence rates of side effects,the first time off-bed and the hospital stays were also re-corded.Results Compared with group C,the Ramsay scores at 8,12 h postoperatively in group T significantly decreased (P <0.05),and the mechanical withdrawal threshold at 4,8 h postoperatively significantly increased (P <0.05).The first time of post-operation pain feedback in group T was sig-nificantly longer than group C (P <0.05).The consumption of dezocine in the first 24 h after surgery significantly decreased in group T (P <0.05).The first time off-bed and the hospital stays in group T were shorter than group C (P <0.05).Also,the incidence rates of nausea,vomiting in the first 24 h postoperatively were lower in group T (P < 0.05 ).Conclusion General anesthesia combined with single-injected thoracic paravertebral nerve block can effectively relieve the postoperative pain in pa-tients undergoing single-port VATS,reduce the consumption of opioids in the first 24 h postopera-tively,cutting down the occurring rates of adverse reactions,which was beneficial to early ambulate and shortened the hospital stays.