Objective To evaluate the effect and safety of small dose ketamine combined with morphine for postoperative analgesia in elderly patients undergoing total knee replacement.Methods Sixty-two elderly (≥ 65 years old) patients undergoing total knee replacement under combined spinal-epidural anesthesia were randomly divided into two groups.In group MK,morphine (0.4 mg/ml) and ketamine (0.4 mg/ml) were used for postoperative analgesia.While in group MO,only morphine (0.4 mg/ml) was used for postoperative analgesia.Visual analogue scale (VAS) pain score,comfort level,Ramsay sedation level,cumulative morphine consumption,changes in vital signs (blood pressure,heart rate,respiration,blood oxygen saturation,etc) and occurrence of side-effects (pruritus,nausea and vomiting,psychiatric symptoms,etc) were recorded up to 48 h after surgery.Results The VAS pain scores were significantly lower in group MK than in group MO at time points of 4,8,12,24,36,48 h (Wald x2=16.713,P＜0.05),while the comfort levels were significantly higher in group MK than in group MO after surgery (Wald x2 11.238,P＜0.05).The total morphine consumption after 48 h was significantly lower in group MK than in group MO (t=3.807,P＜0.001).The incidence of postoperative nausea and vomiting was significantly lower in group MK than in group MO (x2 =4.356,P＝0.036).There were no significant differences in sedation level (Wald x2＝ 3.303,P＞0.05) and changes in vital signs (P＞0.05) between the two groups.No case with psychiatric symptoms was found in both groups.Conclusions When used for postoperative intravenous analgesia in elderly patients after total knee replacement,small-dose ketamine combined with morphine can provide better analgesic effects,decrease total consumption of morphine and the incidence of side-effects.

Objective To evaluate the effects of limb ischemic preconditioning (LIP) on the intestinal injury during release of hepatic portal occlusion (RHPO) in rats.Methods Thirty-six male Sprague-Dawley rats,aged 6-7 weeks,weighing 200-250 g,were randomly divided into 3 groups using a random number table:sham operation group (group S,n =12),RHPO group (n =39) and LIP+ RHPO group (n =20).Hepatic ischemia/ reperfusion was produced by occluding portal vein and hepatic artery for 30 min followed by 6 h reperfusion according to Pringle's method.LIP was produced by tourniquet occlusion of the right femoral artery and vein for 10 min followed by 24 h reperfusion before hepatic ischemia.The animals were sacrificed at 6 h after hepatic portal occlusion was released and the mucous membrane of small intestine was obtained for microscopic examination and for determination of malondialdehyde (MDA) content,superoxide dismutase (SOD) activity,myeloperoxidase (MPO)activity,total antioxidant capacity (T-AOC) and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein expression.The degree of damage to intestinal mucous membrane was scored according to Chiu.Results Compared with group S,Chiu's score and levels of MDA and MPO were significantly increased,SOD activity and TAOC were decreased,and ICAM-1 mRNA and protein expression was up-regulated in group RHPO (P ＜ 0.05 or 0.01).Compared with group RHPO,Chiu's score and levels of MDA and MPO were significantly decreased,SOD activity and T-AOC were increased,and ICAM-1 mRNA expression was down-regulated in group LIP + RHPO (P ＜ 0.05).Conclusion LIP can alleviate the intestinal injury during RHPO in rats by enhancing the antioxidant function and down-regulating the expression of ICAM-1.

Objective To investigate the changes in myocardial proteomics in the late phase of limb ischemic preconditioning (LIP) in rats.Methods Twelve pathogen-free adult male Sprague-Dawley rats,aged 8-9 weeks,weighing 260-280 g,were randomly assigned into LIP group (n=6) and control group (group C,n=6) using a random number table.Limb ischemia was preceded by 3 cycles of 5-min ischemia which was induced by ligation of the root of the right hindlimb with a rubber band followed by 5-min reperfusion in group LIP.At 24 h after LIP,the tissues were obtained from the left ventricle,and the isobaric tags for relative and absolute quantification technique and liquid chromatography-mass spectrometry were applied to detect the differences in protein expression profiles between the two groups (the difference in expression between the two groups＞ 1.2 times and P＜0.05).The identified differentially expressed proteins were analyzed using the bioinformatics,and some were further verified by Western blot.Results A total of 55 proteins were identified to be differentially expressed,and among the 55 proteins,the expression of 35 proteins was up-regulated,and the expression of 20 proteins was down-regulated.Bioinformatics analysis showed that most of the 55 proteins were organelles,cell membrane or macromolecular compounds,were involved in the process such as metabolism,biological regulation,stress response and signal transduction,and showed functions such as the binding affinity to molecules,catalytic activity,anti-oxidant activity,and modulation of the activity of enzyme.The results verified by Western blot were consistent with those shown by using the isobaric tags for relative and absolute quantification analysis.Conclusion The late phase of LIP can induce changes in the expression of the 55 proteins involving regulation of energy metabolism,anti-oxidant action,regulation of gene expression,and protein folding and degradation in the myocardium,which may be the mechanism of myocardial protection in rats.

Objective To evaluate the effects of limb ischemic preconditioning on intestinal injury and brain injury induced by hepatic ischemia?reperfusion(I∕R)in rats. Methods Healthy male Wistar rats, aged 6-8 weeks, weighing 200-250 g, were divided into 3 groups(n=16 each)using a random number table: sham operation group(Sham group), hepatic I∕R group(I∕R group)and limb ischemic preconditioning group(LIP group). In LIP group, the lower limb blood flow was blocked for 10 min with an elastic rubber tourniquet at the right groin followed by 30?min reperfusion through releasing the tourni?quet. Hepatic I∕R injury was induced by occlusion of the portal vein, hepatic artery and common bile duct for 30 min followed by reperfusion in I∕R and LIP groups. Eight rats in each group were selected at 6 h of reperfusion and samples from the cardiac apex were taken for determination of plasma concentrations of tumor necrosis factor?alpha(TNF?α)and interleukin?10(IL?10)by radioimmunoassay. Then the rats were sacrificed and the small intestine tissues and brain tissues were removed. Intestinal damage was as?sessed and scored according to Chiu. The activity of myeloperoxidase(MPO)in intestinal mucosa was de?tected by colorimetric method. The pathological changes of brain tissues were examined under a light micro?scope. The ultrastructure of brain tissues was observed under an electron microscope. Eight rats in each group were randomly selected at 6 h of reperfusion, and Evans blue(EB)2 mg∕kg was injected through the caudal vein over 1 min. Then the rats were sacrificed, brain tissues were removed for measurement of EB content, and the brain water content was calculated. Results Compared with Sham group, Chiu′s score and MPO activity in intestinal tissues were significantly increased, the brain water content and EB content were increased, and the concentrations of TNF?α and IL?10 in plasma were increased in I∕R group and LIP group(P <0.05). Compared with I∕R group, Chiu′s score and MPO activity in intestinal tissues were significantly decreased, the brain water content and EB content were decreased, and plasma IL?10 concentrations were increased(P <0.05), no significant change was found in plasma TNF?α concentra?tions(P>0.05), and the pathological changes of brain tissues were significantly attenuated in LIP group. Conclusion Limb ischemic preconditioning can attenuate intestinal injury and brain injury induced by he?patic I∕R, and the mechanism may be related to inhibiting systemic inflammatory responses of rats.

Objective To analyze the correlation between treatment time and radiotherapy plan of deep inspiration breath-hold (DIBH) technique for the whole breast irradiation (WBI) in the left breast cancer after breast-conserving surgery,verify the inter-fractional reproducibility of radiotherapy,observe the heart location and dosimetric changes and calculate the effect of DIBH upon the WBI setup error after the surgery.Methods We prospectively enrolled 15 patients with left breast cancer undergoing WBI after breast-conserving surgery,who met the requirement of D1BH.Treatment time was recorded,its correlation with the number of field and monitor unit was analyzed.Inter-fractional setup errors and PTV delineation were calculated using cone beam CT (CBCT).The accuracy of the position and dose of the heart during radiotherapy was verified by the imaging fusion of CBCT and CT images.The variables among groups were analyzed by non-parametric Firedman test.Results The average treatment time of DIBH radiotherapy was 4.6 minutes.The treatment time was correlated with the maximal and total number of sub-fields and total monitor units.During DIBH treatment,the mean cardiac displacement volume was 19.1 cm3(3.8％).The mean cardiac dose difference between CBCT and planning CT was 5.1 cGy,and there was no significant difference in the heart V5-V30.The mean inter-fractional system setup error (∑) and random setup error (σ) in the left-right (x),superior-inferior (y) and anterior-posterior (z) direction were ∑x 1.9 mm,∑y 2.1 mm,∑z 2.0 mm,σx 1.3 mm,σy 1.3 mm,σz 1.4 mm,respectively.The corresponding minimal margins for setup error were 5.7 mm,6.2 mm and 6.0 mm,respectively.Conclusion DIBH for WBI after breast-conserving surgery does not significantly prolong the treatment time.Treatment time is related to treatment plan.DIBH yields high inter-fractional reproducibility and protects the heart.

Objective: To analyze the failure patterns of locoregional recurrence (LRR) and investigate the range of radiotherapy in T_1-2N₁ breast cancer patients undergoing modified radical mastectomy. Methods: From September 1997 to April 2015, 2472 women with T_1-2N₁ breast cancer after modified radical mastectomy without neoadjuvant systemic therapy were treated in our hospital. 1898 patients who did not undergo adjuvant radiotherapy were included in this study. The distribution of accumulated LRR was analyzed. The LR and RR rates were estimated by the Kaplan-Meier method, and the prognostic factors were identified in univariate analyses with Log-rank test. Multivariate analysis was performed using Cox logistic regression analysis. Results: With a median follow-up of 71.3 months (range 1.1-194.6), 164 patients had LRR, including supraclavicular/infraclavicular lymph nodes in 106(65%), chest wall in 69(42%), axilla in 39(24%) and internal mammary lymph nodes (IMNs) in 19 patients (12%). In multivariate analysis, age (>45 years vs.≤45 years), tumor location (other quadrants vs. inner quadrant), T stage (T₁ vs. T₂), the number of positive axillary lymph nodes (1 vs. 2-3), hormone receptor status (positive vs. negative) were significant prognostic factors for both LR and RR. Conclusions In patients with T_1-2N₁ breast cancer after modified radical mastectomy, the most common LRR site is supraclavicular/infraclavicular nodal region, followed by chest wall. The axillary or IMN recurrence is rare. The prognostic factors for LR and RR are similar, which indicates that supraclavicular/infraclavicular and chest wall irradiation should be considered for postmastectomy radiotherapy.

OBJECTIVETo observe the clinical effect of ear point embedding on plasma and effect site concentrations of propofol-remifentanil in elderly patients who underwent abdominal external hernia surgery at the time of consciousness and pain disappearing by target-controlled infusion (TCI) and bispectral index (BIS).

METHODSFifty patients who underwent elective abdominal hernia surgery were randomly assigned into an observation group and a control group, 25 cases in each one. In the observation group, 30 minutes before anesthesia induction, Fugugou (Extra), Gan (CO), Pizhixia (AT), and Shenmen (TF) were embedded by auricular needles until the end of surgery, 10 times of counter press each point. In the control group, the same amount of auricular tape was applied until the end of surgery at the same points without stimulation 30 minutes before anesthesia induction. Patients in the two groups were given total intravenous anesthesia, and BIS was monitored by BIS anesthesia depth monitor. Propofol was infused by TCI at a beginning concentration of 1.5μg/L and increased by 0.3μg/L every 30s until the patients lost their consciousness. After that, remifentanil was infused by TCI at a beginning concentration of 2.0μg/L and increased by 0.3μg/L every 30s until the patients had no body reaction to pain stimulation (orbital reflex). Indices were recorded, including mean arterial pressure (MAP), heart rate (HR) and the BIS values, at the time of T(entering into the operation room), T(losing consciousness) and T(pain relief), the plasma and effect site concentrations of propofol at T, the plasma and effect site concentrations of remifentanil at T. After surgery we recorded the total amounts of propofol and remifentanil, surgery time and anesthesia time.

RESULTSAt Tand T, MAP and HR of the observation group were higher than those of the control group (<0.05,<0.01). At T, the plasma and effect site concentrations of propofol in the observation group were significantly lower than those in the control group (<0.05,<0.01). At T, the plasma and effect site concentrations of remifentanil in the observation group were significantly lower than those in the control group (<0.05,<0.01). There was no significant difference in BIS values at Tand Tbetween the two groups (both>0.05). There was no significant difference in operation time and anesthesia time between the two groups (both>0.05). The total amount of remifentanil in the observation group was significantly lower than that in the control group (<0.01). There was no significant difference in the total amount of propofol between the two groups (>0.05).

CONCLUSIONSEar points embedding combined with propofol-remifentanil TCI could reduce the plasma and effect site concentrations of propofol and remifentanil and the total amount of remifentanil in elderly patients with extra-abdominal hernia surgery, and had the effect of assisting sedation and analgesia.

Objective To evaluate the clinical efficacy and analyze the prognostic factors of radiotherapy after breast-conserving surgery for stage Ⅰ-Ⅱ breast cancer patients.Methods Clinical efficacy of adjuvant radiotherapy in 1 376 patients with stage Ⅰ and Ⅱ (T1-2 N0-1 M0/T3NoM0) breast cancer after undergoing unilateral breast-conserving surgery between 1999 and 2013 was retrospectively reviewed.Among them,930 patients (67.6％) received radiotherapy combined with chemotherapy including 517 receiving radiotherapy followed by chemotherapy and 413 receiving chemotherapy followed by radiotherapy.In total,1 055 patients (76.7％) were treated with endocrine therapy.Eighty-six patients (39.6％) positive for HER-2 received targeted therapy.The overall survival (OS) and disease-free survival (DFS) rates were calculated using the Kaplan-Meier method.Univariate analysis was performed by Log-rank test and multivariate analysis was conducted by Cox regression method.Results The median follow-up time was 55 months.The quantity of patients receiving follow-up for ≥ 10 years was 90.The 5-and 10-year OS rates for all patients were 98.6％ and 91.5％,and 94.6％ and 82.8％ for 5-and 10-year DFS rates.Mutivariate analysis revealed that age (P=0.016),T staging (P =0.006),N staging (P =0.004),lymphovascular invasion (P =0.038) and time interval between radiotherapy and surgery (P=0.048) were independent prognostic factors for DFS rate.Multivariate analysis demonstrated that N staging (P=0.044) and ER (P=0.026) were independent prognostic factors for DFS in the radiotherapy alone group.Conclusions The radiotherapy-based comprehensive treatment yields favorable clinical outcomes for stage Ⅰ-Ⅱ breast cancer patients after undergoing breast conserving surgery.The prognostic factors for DFS include age,T staging,N staging,lymphovascular invasion and the time interval between radiotherapy and breast-conserving surgery.In the radiotherapy alone group,DFS rate is associated with N staging and ER level.

Objective To quantify the setup errors measured with kV cone-beam CT (CBCT) using breast board with or without a thermoplastic head mask in breast cancer patients who received whole breast and supraclavicular nodal region irradiation.Clinical target volume (CTV) to planning target volume (PTV) in 3 directions were also calculated.Methods The study included thirty patient receiving both whole breast and supraclavicular nodal region irradiation on Elekta Versa HD linear accelerators (Elekta Oncology Systems,Crawley,UK) between June 2016 and January 2018.The setup error data were retrospectively analyzed.All the patients were immobilized in the supine position on a breast board system (Carbon fibre breast board,Civco,Iowa,USA) with both arms raised.Twenty of the patients added an extra thermoplastic head mask to immobilize the neck.A CBCT scan was taken before treatment at the first 3 to 5 fractions and then once every week.Registration with the planning CT was performed and adjusted to match the target volume of the supraclavicular nodal region and the cervical vertebra by experienced medical staff,the position of the arms and the breast were also considered.For all patients the couch shifts in left-right (x),superior-inferior (y),anterior-posterior (z) were recorded.Statistical analysis included two-tails significance tests (t-Student and Manne-Whitney test for means,x2 test for variances).Population of the two groups was compared in terms of distribution of the mean shift (systematic error) and their standard deviations (random error).Van Herk's setup margin defined as MPTV =2.5Σ + 0.7δ was calculated in patients with or without mask immobilization.Results Altogether,56 images and 109 images were acquired in breast board only group and head mask group,respectively.Shifts of the breast board only group and the head mask group in x,y,z were 0.212±0.174 cm vs.0.272±0.242 cm (P=0.070);0.364±0.246 cm vs.0.242±0.171 cm (P=0.001);0.423±0.302 cm vs.0.364±0.269 cm (P=0.204).Proportion of the shift less than 5 mm in the breast board only group and the head mask group were 91.07％ vs.85.32％ (P=0.294);67.86％ vs.89.91％ (P=0.001);67.86％ vs.74.31％ (P=0.381).The CTV to PTV margin in x,y,z were 0.645 cm,0.981 cm,1.317 cm in breast board only group and 0.873 cm,0.709 cm,0.961 cm in head mask group,respectively.Setup error in the x direction was significantly correlated with BMI (P=0.001).Conclusions For the alignment and immobilization of patients who received whole breast and supraclavicular nodal region irradiation,using a breast board in combination of a thermoplastic head mask may significantly help to reduce the shift variance in superior-inferior direction compared to using breast board only.The anterior-posterior error is relatively large,other immobilization device or patient alignment methods are needed to be further explored to improve the accuracy.

Objective:To compare magnetic resonance imaging (MRI)-based and computed tomography (CT)-based target volume delineation and dose coverage in partial breast irradiation (PBI) for patients with breast cancer, aiming to explore the application value of MRI localization in PBI after breast-conserving surgery.Methods:Twenty-nine patients with early breast cancer underwent simulating CT and MRI scans in a supine position. The cavity visualization score (CVS) of tumor bed (TB) was evaluated. The TB, clinical target volume (CTV), planning target volume (PTV) were delineated on CT and MRI images, and then statistically compared. Conformity indices (CI) between CT- and MRI-defined target volumes were calculated. PBI treatment plan of 40 Gy in 10 fractions was designed based on PTV-CT, and the dose coverage for PTV-MRI was evaluated.Results:The CVS on CT and MRI images was 2.97±1.40 vs. 3.10±1.40( P=0.408). The volumes of TB, CTV, PTV on MRI were significantly larger than those on CT, (24.48±16.60) cm 3vs. (38.00±19.77) cm 3, (126.76±56.81) cm 3vs. (168.42±70.54) cm 3, (216.63±81.99) cm 3vs. (279.24±101.55) cm 3, respectively, whereas the increasing percentage of CTV and PTV were significantly smaller than those of TB. The CI between CT-based and MRI-based TB, CTV, PTV were 0.43±0.13, 0.66±0.11, 0.70±0.09( P<0.001), respectively. The median percentage of PTV-MRI receiving 40 Gy dose was 81.9%(62.3% to 92.4%), significantly lower than 95.6%(95.0%~97.5%) of PTV-CT. Conclusions:The CVS between CT and MRI is not significantly different, but the MRI-based TB, CTV, PTV are significantly larger than CT-based values. The PTV-MRI is of underdose if PBI treatment plan is designed for PTV-CT. As a supplement of CT scan, MRI can enhance the accuracy of TB delineation after breast-onserving surgery.