Objective To compare the clinical efficacy and adverse effects of pegaspargase (PEGASP) and L-asparaginase (L-ASP) in the treatment of NK/T-cell lymphoma.Methods A retrospective analysis was conducted on the clinical data of 46 patients with NK/T-cell lymphoma in Department of Oncology of Hospital of Qingdao Commercial Staff from September 2009 to July 2015.There were 24 patients treated by PEG-ASP combined with GDP (gemcitabine + cisplatin + dexamethasone) as PEG-ASP group,and 22 patients treated by L-ASP combined with GDP as L-ASP group.The efficacy and adverse reactions were compared between the two groups.Results In the PEG-ASP group,there were 11 patients with complete remission,7 patients with partial remission,and the complete remission rate and objective response rate were 45.83％ and 75.00％.In the L-ASP group,there were 9 patients with complete remission,6 patients with partial remission,and the complete remission rate and objective response rate were 40.91％ and 68.18％.There was no significant difference between the two groups in objective response rate (x2 =0.263,P =0.608).Adverse effects such as myelosuppression (25.00％ vs.22.73％,x2 =0.033,P =0.857),coagulopathy (8.33％ vs.9.10％,x2=0.008,P =0.927),liver and renal dysfunction (8.33％ vs.18.18％,x2 =0.982,P=0.322),gastrointestinal reaction (41.67％ vs.40.91％,x2 =0.003,P =0.958) were similar in the PEGASP group and L-ASP group.But the risk of allergic reaction incurred by PEG-ASP was much lower than L-ASP (4.17％ vs.36.36％),with a significant difference (x2 =7.561,P =0.006).Moreover,the PEGASP group had a shorter duration of hospitalization [(10.04 ± 1.63) d] than the L-ASP group [(13.09 ± 2.76)d],with a significant difference (t=-4.612,P=0.000).Conclusion The efficacy of PEG-ASP and L-ASP in the treatment of NK/T-cell lymphoma is similar,but the rate of allergic reaction of patients treated with PEG-ASP is significantly lower,and the hospitalization time is significantly shorter,which is worthy of further clinical application.

Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use.

Objective To investigate the effects of intrathecal morphine remote preconditioning (MRPC) on protein-serine-threonine kinases-endothelial nitric oxide synthase (Akt/eNOS) signaling pathways and cardiac myocyte apoptosis in rats.Methods Male SD rats weighing 280-320 g were used in this study.A needle was inserted through a surgically created hole into the sub-dural space of spinal cord.Thirty-six rats in which intrathecal needle was successfully placed without complication were randomly divided into 3 groups (n =12 in each).In group Ⅰ sham operation was performed (Sham).In group Ⅱ myocardial I/R was produced (I/R).In group Ⅲ morphine was given intrathecally in 3 repeated doses of 1 μg/kg at 5 min intervals before ischemia (MRPC).Myocardial I/R was produced by occlusion of left anterior descending branch (LAD) of coronary artery for 30 min followed by 120 min reperfusion.The animals were then sacrificed and hearts removed for measurement of area at risk (AAR) and infarct size area (IS).IS/AAR ratio was calculated.Myocardial apoptosis was detected by TUNEL and apoptotic index (the number of apoptotic myocardial cells/the total number of myocardial cells) was calculated.The levels of Akt,phosphorylated Akt (p-Akt) and eNOS was determined by Western blot.Results The infarct size,myocardial cell apoptotic index and pAkt level were higher and eNOS level was significantly lower in I/R group than those in group Sham (P ＜ 0.01).MRPC significantly reduced the infarct size and myocardial cell apoptotic index,and pAkt and eNOS level up-regulated in group RMPC compared with group I/R (P ＜ 0.01).Conclusions Akt/eNOS signaling pathways probably participate in the protective effects of intrathecal morphine remote preconditioning against myocardial I/R injury and myocardial cell apoptosis in rats.

Objective Comparing the effect of different anesthetic inductions in pediatric pa-tients undergoing bronchial foreign body removal.Methods Thirty pediatric patients,aged 9-58 months,undergoing emergency bronchial foreign body removal,were randomly into 3 groups (n=10 each):group sevoflurane (group S),group propofol (group P),and group ketamine (group K).Pa-tients in group S were inducted with sevoflurane 8% inhalation,group P with propofol 2.5 mg/kg in-travenous injection,group K with ketamine 5 mg/kg intramuscular injection.Three groups of pa-tients breathed spontaneously during operative period and received topical anesthesia of lidocaine be-fore the placement of rigid bronchoscopy.Combination of intravenous target-controlled infusion of propofol (target plasma concentration of 3-3.5 μg/ml)and remifentanil (target plasma concentration of 2-3 ng/ml)was used for maintenance of anesthesia.The rigid bronchoscopy was inserted after pre-oxygenation for 3 min.Rigid bronchoscopy was performed and the placement time,the first place-ment successfully rate,hypoxemia and side effects as well as postoperative awaking time were recor-ded.Results The first placement successfully rate,group S 90%,group P 70%,group K 40%,with significant difference among three groups (P<0.05).The incidence of side effects were not signifi-cant difference in three groups;In group S and group P,the placement time and the anesthesia awa-king time was significant shorter than that in group K (P<0.05).Conclusion Compared with propo-fol intravenous induction and ketamine intramuscular induction,the high concentration sevoflurane in-duction can provide faster induction,shorter waking time,and reduceside effects in childen undergo-ing bronchial foreign body removal.

ObjectiveTo evaluate the effects of dexmedetomidine on the quality of emergence from general anesthesia in the elderly patients undergoing orthopedic operation.MethodsSixty ASA Ⅰ -Ⅲ patients,aged ≥65 yr,undergoing elective orthopedic operation,were randomly assigned to one of 3 groups ( n =20 each):control group (group C) ; dexmedetomidine 0.25 μg/kg group (group D1 ) and dexmnedetomidine 0.50 μg/kg group (group D2).In groups D1 and D2,15 min befone anesthesia induction,dexmedetomidine 0.25 μg/kg and 0.50 μg/kg were infused over 15 min respectively,while the equal volume of normal saline 15 ml was given instead of dexmedetomidine in group C.After anesthesia induction,tracheal intubation was performed and the patients were mechanically ventilated.General anesthesia was used in the three groups.Flurbiprofen 1 mg/kg was injected intravenously immediately before skin incision.The time for recovery of spontaneous breathing,emergence time,extubation time,and adverse reactions were recorded.Pain was assessed with verbal rating scale (VRS) at 5 min after emergence from anesthesia.ResultsCompared with group C,the incidence of agitation,bucking,and adverse cardiovascular events and VRS score were significantly decreased,and the rate of effective analgesia was significantly increased in groups D1 and D2,and the emergence time and extubation time were significantly prolonged in group D2(P ＜0.05).Compared with group D1,the emergence time and extubation time were significantly prolonged in group D2(P＜0.05).There was no significant difference in VRS score,the rate of effective analgesia and the incidence of adverse renctions between groups D1 and D2(P＞0.05).ConclusionⅣ infusion of dexmedetomidine 0.25 μg/kg before induction of general anesthesia can effectively improve the quality of emergence from general anesthesia in the elderly patients undergoing orthopedic operation.

Objective To investigate the mechanism of the protective effects induced by intrathecally remote morphine preconditioning (RMPC) against myocardial ischemia-reperfusion (I/R) injury in rats.Method Male SD rats weighing 280 ～ 320 g were used in this study. A needle was inserted through a surgically created hole into the spinal cord space. Sixty male SD rats, in which intrathecal needle was successfully placed without complication, were randomly (random number) divided into 10 groups of 6 animals each. In group Ⅰ myocardial I/R was produced (I/R). In group Ⅱ morphine was given intrathecally in 3 repeated doses of 1 μg/kg at 5 mtn intervals before ischemia (RMPC). Antagonists CGRP8-37 (CGRP receptor antagonist), 8-SPT (adenosine receptor antagonist), HOE-140 (bradykinin B2 receptor antagonist) and HEX (autonomic nerve antagonist) were given intrathecally in group Ⅲ , Ⅳ, Ⅴ and Ⅳrespectively at 10 min before RMPC. In group Ⅶ, Ⅷ, Ⅸ and X CGRP8-37, 8-SPT, HOE-140 and HEX were given intrathecally respectively at 40 min before ischemia. Myocardial I/R was produced by occlusion of left anterior descending branch (LAD) of coronary artery for 30 min followed by 120 min reperfusion. At the baseline and the end of 120 min reperfusion venous blood samples were taken for determination of LDH activity. The animals were then killed and hearts removed for measurement of area at risk (AAR) and infarct size area (IS). IS/AAR was calculated. Results The size of infarct area was smaller and IS/AAR ratio lower and significantly less LDH was released at the time of 120 min reperfusion in RMPC group (group Ⅱ) than in group I/R (group Ⅰ). The protective effects of RMPC was abolished by intravenously pretreatment with CGRP8-37, 8-SPT,HOE-140 and HEX. Conclusions CGRP, adenosine, bradykinin and autonomic nerve are involved in the protective effects of intrathecally remote morphine preconditioning against myocardial I/R injury.

Objective To discuss the short-term curative effect and the safety of percutaneous vertebroplasty using high viscosity bone cement for the treatment of severe osteoporotic vertebral body compression fractures. Methods The clinical data of 100 patients with severe osteoporotic vertebral body compression fractures (compression degree>70%), who received percutaneous vertebroplasty by using high viscosity bone cement during the period from December 2010 to May 2013, were retrospectively analyzed. All the patients were followed up for at least one month. Both preoperative and postoperative visual analogue scale (VAS) and quality of life (QOL) scores, as well as the incidence of bone cement leakage, were recorded and the results were used to evaluate the curative effect and the safety of percutaneous vertebroplasty for severe osteoporotic vertebral body compression fractures. Results One week after the treatment, significant pain relief was obtained in 92 patients (92%), VAS scores decreased from preoperative (7.0 ±1.2) to postoperative (2.0±1.5), and QOL scores increased from preoperative (30±5.0) to postoperative (80±18.0);the differences were statistically significant (P<0.01). One month after the treatment, significant pain relief was seen in 91 patients (91%), VAS scores decreased from preoperative (7.0 ±1.2) to postoperative (1.5 ±1.0) and QOL scores increased from preoperative (30±5.0) to postoperative (80±15.0); the differences were statistically significant (P<0.01). No statistically significant differences in VAS scores and QOL scores existed between the data determined at one week after the treatment and the data determined at one month after the treatment (P>0.05). Leakage of bone cement was observed in 40 patients (40%), resulting no severe neurological symptoms; among the 40 patients, intervertebral disc leakage at above and below the vertebral body was detected in 28 patients (70%), vertebral anterior edge leakage was observed in 11 patients (27.5%) and vertebral posterior edge leakage was seen in one patient (2.5%). Conclusion For the treatment of severe osteoporotic vertebral body compression fractures, percutaneous vertebroplasty by using high viscosity bone cement is safe and effective.

Objective To investigate the effects of xenogenic bone with chitosan/norvancomycin sustained-release biomaterials in treating infectious bone defects in rabbits.Methods Xenogenic bone with chitosan/norvancomycin sustained-release biomaterials was made by electrospinning technique.Rabbit infectious bone defect models were made by Methicillin-resistant Staphylococcus aureus.A successful model was evaluated with the standard of more than three points in Norden score assessment.All models were divided into two groups by random number table method,with eight models in each.The control group was treated with surgical debridement,and the experimental group was implanted with bone particles of xenogenic bone with chitosan/norvancomycin sustained-release system after debridement.Postoperatively,general conditions,X-ray,histological results of HE staining,and bacteriological examination results of the rabbits were observed.Results X-ray showed significant bone defects,sequestration,periosteal reaction,and soft tissue swelling after one month of modeling,with Norden score of (3.84 ± 0.52) points.The general conditions were good and the sinus tracts were healed in experimental group after two months of treatment.The control group demonstrated generally poor conditions with swollen sinus and purulent discharge.Two rabbits were died of sepsis.The pathological scores of tibial were (0.41 ± 0.08) points in experimental group,and (3.27 ± 0.26) points in control group by gross observation.The pathological score of experimental group was significantly lower than control group(P ＜ 0.05).The bone defects were basically repaired in experimental group.The longest diameter of bone defect in experimental group was (0.11 ± 0.02)cm,significantly smaller than (0.48 ± 0.06) cm in control group (P ＜ 0.05).There were no obvious signs of osteomyelitis and the bone defects were well repaired in experimental group.Periosteal reaction,soft tissue swelling,a substantial number of bone destruction,and sequestration were observed in control group.The Norden score was (1.32 ± 0.23) points in experimental group,lower than (5.21 ± 0.48) points in control group(P ＜ 0.05).HE staining showed a large amount of trabecular bone formation,bone cell formation,and fibrous hyperplasia in experimental group,with no obvious signs of infection.On the other hand,infiltration of inflammatory cells,necrotic tissue,and sequestration were observed in control group.The histological score was(0.61 ± 0.10) points in experimental group,lower than (4.21 ± 0.41) points in control group (P ＜0.05).The negative rate of bacterial culture in experimental group was 33％,lower than 100％ in control group (P ＜ 0.05).Conclusion Xenogenic bone with ehitosan/norvancomycin sustained-release biomaterials has excellent effect in infection clearance and bone defect reparation in treatment of infectious bone defects in rabbits.

Objective To propose the method of dose distribution calculated by one-step optimization with 7 shells (Cao method) and compare with that by three-step optimization with 4 shells (Blanck method) and CyberKnife treatment plans for pancreatic cancer. Methods 20 cases of pancreatic cancer who underwent CyberKnife treatment were retrospectively analyzed,and CT was performed to localize and delineate the target area and endangering organs. Dosage was optimized and evaluated with Blanck method and Cao method. The planning target volume (PTV) conformity index (CI), new conformity index (nCI), homogeneity index (HI),gradient index (GI), coverage, dose-volume and doses to organs at risk were compared. Results Compared with Blanck method, CI (1.11 ± 0.05 vs 1.15 ± 0.05), nCI (1.20 ± 0.06 vs 1.23 ± 0.06), coverage [(92.48 ± 1.85)% vs (93.53 ± 2.15)%], volumes encompassed by 100% and 30% prescription dose line (36.46 ± 16.64 vs 38.19 ± 17.68; 286.19 ± 126.52 vs 320.93 ± 154.82) and monitor unit (56 369 ± 20 019 vs 57 814 ± 20 531) were significantly decreased,while GI was increased (3.22 ± 0.19 vs 3.11 ± 0.19), and all the differences were statistically significant (P<0.05). Additionally, Dmax of the intestine (21.17 ± 2.90 vs 20.63 ± 3.13), D10cc of the stomach (12.78 ± 2.57 vs 13.11 ± 2.43), D5ccof the duodenum (11.01 ± 3.45 vs 11.50 ± 3.25), D10ccof the duodenum (9.30 ± 3.31 vs 9.78 ± 3.07) and D0.35ccof the spinal cord (6.09 ± 0.98 vs 6.59 ± 0.92) were all significantly decreased (P<0.05). No significant differences were found on other parameters. Conclusions Better dose distributions are accessible by one-step optimization with 7 shells in CyberKnife treatment plans for pancreatic cancer.

[Abstact] Objective To analyze the related parameters of the treatment plans for the pancreatic cancer with the Cyber-knife system.Methods The clinical data of 129 patients with single-target pancreatic cancer for the first time who underwent CyberkKnife radiosurgery between January 2017 and December 2017 in Shanghai Changhai Hospital were retrospectively analyzed.The parameters were all selected from the MultiPlan @4.0.2 treatment planning system and the data were analyzed.Results The volume of the targets in 129 patients with pancreatic cancer was 3.355-238.936 cm3,with the average volume of 51.43 ± 55.64 cm3.Patients were averagely treated for 5 to 8 sessions,and the average prescription dose was 6 Gy × 6 fraction,which equaled to 58 Gy in the biological equivalent dose (BED).The collimators with 20 mm and 15 mm accounted for up to 31％ and 27％,respectively,which were the top 2 options.The finally designed the conformal index(CI),new conformal index(nCI),and the homogeneity index were 1.14 ± 0.09,1.29 ± 0.09 and 1.42 ± 0.04,respectively.The coverages of tumor target was 80.3％-95.6％,with the average of 90.0 ± 4.6％.The treatment nodes,beams and Mus are 79,180 and 7 060 in average.The estimated treatment time was 42 ± 8 minutes.The organs at risk can be protected very well.Conclusions Reasonable Cyber-knife treatment plan can guarantee that stereotactic body radiation therapy can effectively treat Pancreatic Cancer.