OBJECTIVE:To provide reference for improving the data integrity management system of pharmaceutical produc-tion enterprises. METHODS:According to related reports in US Food and Drug Administration(FDA)and China Food and Drug Administration(CFDA),the source of data integrity problems was analyzed,its reasons were summarized and solutions were put forward. RESULTS&CONCLUSIONS:The reasons why there were data integrity problems in enterprises can be attributed to 3 as-pects(staff,hardware/software system and quality management),and the 3 aspects showed large gap with current standards. It is suggested that enterprises evaluate the existing system by adopting the gap analysis,establish a data integrity management project team,strengthen personnel training,upgrade hardware/software system to ensure its safety,stability and effectiveness;and opti-mize the quality management system by developing good ducument specification,special regulation system of data integrity. In addi-tion,the enterprise should establish quality culture,pay attention to industry and regulatory trends in real time to guarantee the data integrity effectively.

Objective To investigate the effects of total nutrient admixture (TNA) on the recovery of patients with gastric cancer after radical gastrectomy.Methods The clinical data of 50 patients with gastric cancer who were admitted to the Affiliated Hospital of Luzhou Medical College between March 2013 and March 2014 were retrospectively analyzed.Among 50 patients receiving radical gastrectomy,26 patients receiving TNA were allocated to the experimental group and 24 patients receiving conventional fluid infusion were allocated to the control group.Patients in the experimental group received the nutritional support therapy using TNA at preoperative day 5 and at postoperative days 1-5,and patients in the control group received the postoperative intravenous rehydration including water,glucose,electrolyte,vitamins and micro elements.The nutritional indexes [albumin (Alb),prealbumin,transferrin and hemoglobin (Hb)],time to anal exsufflation,incidence of complications (wound infection,anastomotic leakage,blooding and intestinal obstruction) and duration of hospital stay were observed before nutritional support therapy and at postoperative day 8.The count data were analyzed using the chi-square test.The chi-square value of correction for continuity was used when 1 ≤ minimum theoretical frequency ≤ 5.The measurement data with normal distribution were presented as (x) ±s and analyzed using the t test or repeated measures ANOVA.The ordinal data were analyzed by the analysis of variance.Results The Alb,prealbumin,transferrin and Hb in the experimental group were (38.6 ± 2.0) g/L,(281 ± 33) mg/L,(2.5 ± 0.9) g/L and (111 ± 20) g/L before nutritional support therapy and (38.2 ± 1.9) g/L,(277 ± 16) mg/L,(2.3 ± 1.1) g/L and (112 ± 37) g/L at postoperative day 8,respectivley.The Alb,prealbumin,transferrin and Hb in the control group were (38.3 ±2.4) g/L,(287 ± 34) mg/L,(2.4 ± 1.1) g/L and (107 ± 21) g/L before nutritional support therapy and (30.3 ±2.3) g/L,(190 ± 41) mg/L,(1.6 ± 0.3) g/L and (93 ± 22) g/L at postoperative day 8,respectivley.There were significant differences in the nutritional indexes at postoperative day 8 between the 2 groups (F =174.042,95.637,9.529,4.919,P ＜ 0.05).The time to anal exsufflation in the experimental group were (52 ± 11) hours,which was significantly different from (70 ± 12) hours in the control group (t =-5.176,P ＜ 0.05).The incidence of complications was 15.4％ (4/26) in the experimental group,which was significantly different from 58.3％ (14/24) in the control group (x2=6.460,P ＜0.05).Patients with complications in the 2 groups were cured by anti-infective or symptomatic treatment.The duration of hospital stay was (9 ± 3) days in the experimental group and (12 ± 4) days in the control group,with a significant difference between the 2 groups (t =-2.912,P ＜ 0.05).Conclusion TNA can improve the nutritional status of patients after radical gastrectomy in a short time.It could help patients to get through the perioperative period smoothly,and enhance the postoperative recovery.

Objective To investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on early postoperative lung function in patients undergoing video-assisted thoracoscopic pneumonectomy.Methods Sixty ASA physical status Ⅰ or Ⅱ patients whose preoperative forced expiratory volume in 1 second (FEV1) ＞ 1.5 L,scheduled for elective video-assisted thoracoscopic pneumonectomy under general anesthesia,were randomly divided into 3 groups (n =20 each) using a random number table:control group (group C),Lieque (LU7)-Quchi (LI11)-Neiguan (PC6)-Hegu (LI4) group (group S1),and Xinshu (BL1S)-Feishu (BL13)-PC6-LI4 group (group S2).TEAS was applied to the corresponding acupoints on the operated side for 30 min once a day starting from 30 min before induction of anesthesia until the end of surgery,and on 1 st and 2nd days after surgery in S1 and S2 groups.The frequency was 2/100 Hz,the intensity was the maximum current that could be tolerated,and the intensity was about 6-18 mA for LU7,LI11,PC6 and LI4,or about 20-35 mA for BL15 and BLI3.Patient-controlled intravenous analgesia was performed to maintain the score for the intensity of pain ＜ 4.Before and after surgery,forced vital capacity (FVC) and FEV1 were measured after the chest tube was withdrawn and the changing rate was calculated.Results FEV1 and FVC were significantly lower after surgery than before surgery in all the groups (P ＜ 0.05).There was no significant difference in FEV1 and FVC before and after surgery and the changing rate between the three groups (P ＞ 0.05).Conelusion TEAS (applied during surgery and within 2 days after surgery,30 min/d,2/100 Hz) provides no obvious improvement in early postoperative lung function for the patients undergoing video-assisted thoracoscopic pneumonectomy.

Objective To identify the role of survivin and VEGF in angiogenesis of colorectal tumor by investigating tissue expression of survivin, VEGF and CD34 in human colorectal tumors. Methods Immunohistochemical staining for the paraffin sections by using the polyclonal antibodies of survivin, monoclonal antibodies of VEGF and CD34, was performed by the standard avidin-biotin-peroxidase technique. The percentage of positive cell and quantitative analysis were made by image analysis system, which also helped to calculate the amount of MVD. Results The immunoreactivity of survivin significantly increased in the transition from adenoma with low dysplasia to adenoma with high dysplasia (P <0.01). Similar changes in protein expression were observed for VEGF and MVD. The expression of survivin was closely related with that of VEGF. Both were positively correlated with MVD. Conclusion Survivin promotes angiogenesis of colorectal tumor together with VEGF. VEGF may be the potential causes of reexpression of survivin during colorectal tumorigenesis.

Objective To compare the intraoperative opioids-sparing effects of transcutaneous electrical acupoint stimulation (TEAS) of Lieque (LU7)-Quchi (LI11)-Neiguan (PC6)-Hegu (LI4) versus Xinshu (BL15)-Feishu (BL13)-PC6-LI4 in patients undergoing video-assisted thoracoscopic lobectomy.Methods Sixty ASA physical status Ⅰ or Ⅱ patients,aged 34-83 yr,weighing 50-93 kg,scheduled for elective video-assisted thoracoscopic lobectomy,were randomly divided into 3 groups (n =20 each):control group (group C),LU7-LI11-PC6-LI4 group (group S1),and BL15-BL13-PC6-LI4 group (group S2).TEAS was applied to the corresponding acupoints on the operated side starting from 30 min before induction of anesthesia until the end of operation in S1 and S2 groups.The wave length was 0.6 ms when the frequency was 2 Hz,and the wave length was 0.2 ms when the frequency was 100 Hz.The intensity was the maximum current that could be tolerated,and the intensity was 6-18 mA for LU7,LI11,PC6 and LI4,or 20-35 mA for BL15 and BL13.Anesthesia was induced with iv injection of midazolam,propofol,sufentanil and cisatracurium and maintained with target-controlled infusion of remifentanil and propofol,iv infusion of cisatracurium,and iv boluses of sufentanil when necessary.The plasma concentration of propofol was adjusted to maintain BIS value at 40-60 during operation.The initial effect-site concentration of remifentanil was set at 1 ng/ml and then adjusted to 4 ng/ml at skin incision,and the concentration of remifentanil and consumption of sufentanil was adjusted to maintain Analgesia Nociception Index (ANI) value at 50-70.If the concentration of remifentanil was increased to 4 ng/ml,ANI value was still less than 50,and then sufentanil 0.1 μg/kg was injected intravenously.The time of operation and intraoperative consumption ofremifentanil and propofol were recorded.Results Compared with group C,the intraoperative consumption of remifentanil was significantly decreased in S1 and S2 groups (P ＜ 0.05).There was no significant difference in the intraoperative consumption of remifentanil between group S1 and group S2 (P ＞ 0.05).There was no significant difference in the time of operation and intraoperative consumption of propofol between the three groups (P ＞0.05).Conclusion TEAS of LU7-LI1 1-PC6-LI4 provides similar opioids-sparing effects during operation as TEAS of BL15-BL13-PC6-LI4 in patients undergoing video-assisted thoracoscopic lobectomy.

Objective To evaluate the intraoperative opioid-sparing effect of different frequency transcutaneous electrical acupoint stimulation (TEAS) in the patients undergoing video-assisted thoracoscopic pneumonectomy.Methods Eighty patients,aged 40-64 yr,weighing 50-90 kg,of ASA physical status Ⅰ-Ⅲ,scheduled for elective thoracoscopic pneumonectomy under general anesthesia,were randomly divided into 4 groups (n =20 each) using a random number table:control group (group Con),stimulation on Lieque (LU7)-Quchi (LI11)-Neiguan (PC6)-Hegu (LI4) at 2/100 Hz group (group 2/100 Hz),stimulation on LU7-LI11-PC6-LI4 at 2 Hz group (group 2 Hz),and stimulation on LU7-LI1 1-PC6-LI4 at 100 Hz group (group 100 Hz).The patients in group Con had the electrodes applied,but received no stimulation.In 2/100 Hz,2 Hz and 100 Hz groups,the patients received 2/100,2 and 100 Hz TEAS on LU7-LI11-PC6-LI4 acupoints ipsilateral to the surgery site,respectively,starting from 30 min before induction of anesthesia until the end of surgery,and the intensity was the maximum current that could be tolerated.Anesthesia was induced with iv midazolam,propofol,sufentanil and cisatracurim,and maintained with target-controlled infusion of remifentanil and propofol,continuous infusion of cisatracurim,and iv boluses of sufentanil when necessary.The target plasma concentration of propofol was adjusted to maintain BIS value at 40-60 during operation.The initial target effect-site concentration of remifentanil was 1 ng/ml,and adjusted to 4 ng/ml at skin incision.The concentration of remifentanil and consumption of sufentanil were adjusted to maintain Analgesia Nociception Index (ANI) at 50-70.When the concentration of remifentanil was increased to 4 ng/ml,ANI was still less than 50,and then 0.1 μg/kg sufentanil was given.The duration of operation and intraoperative consumption of remifentanil and sufentanil (the consumption of sufentanil was converted to the consumption of remifentanil producing the equivalent effect by 1:10) were recorded.Results The intraoperative consumption of remifentanil was significantly reduced in 2/100 Hz group as compared with Con,2 Hz and 100 Hz groups.There was no significant difference in the intraoperative consumption of remifentanil between Con group,2 Hz group and 100 Hz group.Conclusion The use of 2/100 Hz but not 2 and 100 Hz TEAS on LU7-LI11-PC6-LI4 significantly reduces intraoperative opioid consumption in the patients undergoing video-assisted thoracoscopic pneumonectomy.

Objective To observe reverse effect of anisodamine to the adverse effect of remifentanil during enteroscopy without pain for patients with bradycardia .Methods Sixty‐five patients with bradycardia were selected and divided randomly into group C (n=21 ,control group)、group A1 (n=22 ,anisodamine by instillation) and group A2 (n=22 ,anisodamine by continous infusion) .In‐duction :Intravenous etomidate 0 .08 mg/kg ,propofol 1 .00 mg/kg and remifentanil 0 .10μg/kg in 3 groups .Ten mg anisodamine in‐fused by instillation before induction in group A1 ,5 mg anisodamine infused by instillation before induction and continous infused by 0 .25 mg/min in group A2 .Maintenance:All group received propofol 4 mg · kg‐1 · h‐1 ,remifentanil 0 .05 μg · kg‐1 · min‐1 after un‐dergoing enteroscopy .stopping pumping propofol when colonoscopy reached ileocecal junction ,and we took off remifentanil when colonoscopy withdraw to decending colon .Then we observed and recorded HR ,SpO2 ,MAP ,dosage ,fluid infusion ,induction time , check time ,analepsia time ,degree and of enterospasm and numbers of cases and side effect at T0 (before induction) ,T1 (beginning of operation) ,T2 (into the transverse colon) ,T3 (to the ileocecal junction) ,T4 (exit) .Results There were no significant difference a‐mong 3 groups of induction time .Compared with group A1 and group A2 about check time and analepsia time ,group C was much shorter .The HR of group A1 and A2 were more stable than group C at T2 、T3 .At T1 、T2 ,the fluctuation of HR of group A2 was less than that of group A1 .There was obviously different among 3 groups of propofol′s dosage ,operation time and enterospasm ,the effect of group A1 and group A2 were better .There was statistically significant in number of cases of body movement between group A1 (1/22)and group C(4/21) ,there was also statistical significance between group A1 ,group A2 and group C(P<0 .05) .Conclusion There are no difference between 2 methods about relieving enterospasm ,refraining intestinal angina ,shortening operation time , saving anesthetic dosage .Effect of continous pumping to undulation of HR may be more stable .

Objective To evaluate the clinic efficacy of sufentanil and remifentanil by target- controlled infusion (TCI) combined with propofol in patients undergoing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).Methods Sixty patients,ASA Ⅰ ～ Ⅱ,undergoing elective EBUS-TBNA were randomly divided into group S ( sufentanil group),group R (remifentanil group) and group SR (sufentanil + remifentanil group),each group were twenty patients.The anesthesia of all groups is propofol intravenous anesthesia with 2％ lidocaine topical anesthesia,to controll BIS between 50 and 60 during surgery.Heart rate(HR),mean arterial pressure(MAP) pulse oxygen saturation( SpO2 ) and respiratory rate (RR) were recorded and compared 5mins after entering room(T0),30mins after the beginning of surgery(T1 ) and after surgery(T3).Arterial blood gas and the times of cough during surgery were also recorded and compared in all groups.The use of propofol and lidocaine,the wake-up time,satisfaction with anesthesia and adverse reactions in 6 hrs after surgery were also obtained.Results ( 1 ) RR decreased distinctly in group R and PaCO2 increased distinctly in group S and group R compared with that of group SR (P ＜0.05) during surgery.(2)The times of cough and the wake-up time lessened distinctly in group R and group SR compared with that of group S ( P ＜0.05 ).(3) The use of propofol and lidocaine,satisfaction with anesthesia and adverse reactions in 6 hrs after surgery were similar in all groups ( P ＞ 0.05 ).Conclusion Sufentanil compounded remifentanil by TCI combined with propofol is a safe and feasible anesthesia option for EBUS-TBNA,which provides better efficacy,high satisfaction and less side effects compared with using alone of sufentanil and remifentanil respectively.

Objective To explore the effects of extrinsic and intrinsic recognition loading on gait in patients with Parkinson disease.Methods Eight patients with Parkinson disease and six control subjects were instrutted to walk with extrinsic and intrinsic recognition loading respectively.The gait parameters in two conditions were measured with three-dimension motion analysis equipment.FAB scale and Stroop Test were used as the evaluation of executive function.Results The velocity(cm/s),the cadence(step/min),single support and swing phase(%)in the audition stimulates condition in the patients group((113.4±14.32)step/min,(78.90±16.35)cm/s,(40.50±2.58)%,(40.50±2.58)%)were significantly better than those in the calculation condition(respectively(91.27±15.54)step/min,(63.79±21.49)cm/s,(37.95±2.61)%,(37.95±2.61)%).In the calculation condition,the coefficients of variability in stride length,swing and sinfle support phase were significantly higher in the patient group(respectively(6.69±3.99),(8.56±5.69),(8.56±5.69))than in thecontrol group(respectively(3.23±1.34),(5.02±2.54),(5.02±2.54));in the audition condition,except that,the coefficients of variability in step length and velocity also were significantly higher in the patient group(respeetively(11.92±5.86),(6.89±4.98))than the control group(respectively(7.35±3.32),(2.5±1.53)).In the patients group,the score of FAB(15.63±1.51)was lower and error rates of Stroop test(0.087±0.056)was higher than those in the control group(respectively(17.67±0.52),(0.027±0.03))significantly.The error rate of stroop-3 was significantly negative correlated with the gait variables of patient group in the calculation condition.Conclusion The extrinsic audition stimulates has lower effect on the gait of patients of Parkinson's disease than the intrinsic recognition loading.

Objective To determine the minimum alveolar concentration for endotracheal intu-bation (MACEI )of sevoflurane for curbing the responses to endotracheal intubation in 50% premature infants less than 37 weeks of corrected age.Methods Twenty-seven ASA Ⅰ or Ⅱ premature infants less than 37 weeks of corrected age were enrolled in this study.At first,the anesthesia induction was started by inhaling 6% sevoflurane.After the patient lost consciousness,the end tidal sevoflurane concentration (CET Sev)was adjusted to the target concentration and maintained stable for 1 5 min.En-dotracheal tube was then intubated.The up-and-down sequential method was used to calculate the MAC.The initial CET Sev was 3.0% and it was increased or decreased by 0.2% in the next patient ac-cording to the endotracheal intubation response.If the intubation response was positive,the CET Sev was increased;if the intubation response was negative,the CET Sev was decreased.The midpoint from negative response to positive response was set as a balance point and the mean value of the concentra-tions of sevoflurane at all the balance points were calculated as MACEI .Results The end tidal sevoflurane concentration for blunting the responses to endotracheal intubation in 50% premature in-fants was 2.55%±0.20%,and the MAC9 5 was 2.81% (95% confidence interval 2.67%-3.58%). Conclusion The MACEI of sevoflurane for curbing the responses to endotracheal intubation in 50%premature infants less than 37 weeks of corrected age is 2.55%,which is lower than that in the full-term children.