With wide applications of radiation therapy in the treatment of cancer and other diseases and amid the in-creasing concerns about global nuclear safety,the research and development of drugs against radiation damage has become a hot spot.Thanks to its high energy properties,ionizing radiation can not only directly damage cell DNA through targeted effects,but also indirectly affect the cell environment through non-targeted effects,leading to cell dysfunction and even death.In this paper,the mechanism of ionizing radiation damage was analyzed,and the mechanisms of action and clinical applications of four types of anti-radiation drugs,namely,antioxidant,apoptosis inhibitor,cytokine and natural radiation protection agent were discussed.These drugs have huge implications for alleviating the targeted and non-targeted effects caused by ionizing radiation.

Objective To evaluate the effect of sevoflurane preconditioning on high-mobility group box 1 protein ( HMGB1) ∕Toll-like receptor 4 ( TLR4) ∕nuclear factor kappa B ( NF-κB) signaling pathway during lung ischemia-reperfusion ( I∕R) in rats. Methods Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group ( group S) , lung I∕R group ( group I∕R) and sevoflu-rane preconditioning group ( group SP ) . The right pulmonary hilum was only isolated but not ligated in group S. Lung I∕R was induced by clamping the right pulmonary hilum for 60 min followed by 120 min of reperfusion in anesthetized rats in group I∕R. In group SP, 2. 1％ sevoflurane was inhaled for 30 min to per-form sevoflurane preconditioning, and the lung I∕R model was established at 10 min after the end of inhala-tion. The rats were sacrificed at 120 min of reperfusion, and the lungs were removed for examination of the pathological changes which were scored and for determination of wet to dry weight ratio ( W∕D ratio) , con-tent of tumor necrosis factor-alpha ( TNF-α) in lung tissues ( by enzyme-linked immunosorbent assay) and expression of HMGB1, TLR4 and NF-κB protein in lung tissues (by Western blot). Results Compared with group S, the pathological scores, W∕D ratio and content of TNF-α were significantly increased, and the expression of HMGB1, TLR4 and NF-κB was up-regulated in I∕R and SP groups ( P<0. 05) . Compared with group I∕R, the pathological scores, W∕D ratio and content of TNF-αwere significantly decreased, and the expression of HMGB1, TLR4 and NF-κB was down-regulated ( P<0. 05) , and the pathological changes of lung tissues were significantly attenuated in group SP . Conclusion Sevoflurane preconditioning reduces lung I∕R injury probably through inhibiting HMGB1∕TLR4∕NF-κB signaling pathway in rats.

Objective To evaluate the role of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway in propofol-induced reduction of lung ischemia-reperfusion (I/R) injury in aged rats.Methods Thirty-two clean healthy male Sprague-Dawley rats,aged 18-22 months,weighing 450-600,were divided into 4 groups (n =8 each) using a random number table:sham operation group (group S),I/R group (group I/R),I/R plus propofol group (group I/R+P) and all-trans retinoic acid (ARTA) plus I/R plus propofol group (group ARTA+I/R+P).Lung I/R was induced by occlusion of the right hilum of lung for 60 min followed by 120 min of reperfusion in anesthetized rats.In group ATRA+I/R+P,Nrf2/ARE signaling pathway blocker ARTA 6 mg/kg was intraperitoneally injected once a day for 3 consecutive days,and the model of lung I/R injury was established at 2 h after the last administration.In group I/R+P and group ARTA+I/R+P,while the model of lung I/R injury was established,propofol 30 mg · kg-1 · h-1 was infused via the caudal vein until 120 min of reperfusion.The rats were sacrificed at 120 min of reperfusion and then the lungs were removed for examination of the pathological changes which were scored and for measurement of wet/dry weight ratio (W/D ratio),superoxide dismutase (SOD) activity (by xanthine oxidase method),malondialdehyde (MDA) content (using thiobarbituric acid method) and expression of Nrf2 and heme oxygenase-1 (HO-1) protein (by Western blot).Results Compared with group S,the pathological scores,W/D ratio and MDA content were significantly increased,and the activity of SOD was decreased in I/R and ATRA+I/R+P groups,and the expression of Nrf-2 and HO-1 was significantly up-regulated in I/R,I/R+P and ATRA+I/R+P groups (P＜0.05).Compared with group I/R,the pathological scores,W/D ratio and MDA content were significantly decreased,the activity of SOD was increased,and the expression of Nrf-2 and HO-1 was up-regulated in group I/R+P (P＜0.05),and no significant change was found in the indexes mentioned above in group ARTA+I/R+P (P＞0.05).Compared with group I/R+P,the pathological scores,W/D ratio and MDA content were significantly increased,the activity of SOD was decreased,and the expression of Nrf-2 and HO-1 was down-regulated in group ARTA+ I/R+P (P＜0.05).Conclusion Nrf2/ARE signaling pathway activation is involved in propofol-induced reduction of lung I/R injury in aged rats.

Objective To investigate the effects of perioperative parecoxib sodium on serum surfactant protein A and inflammatory response in elderly patients undergoing video-assisted thoracoscopic pneumonectomy,Methods Sixty-two ASA Ⅰ or Ⅱ elderly patients,aged 65-78 years,weighing 51-79 kg,scheduled for elective video-assisted thoracoscopic pneumonectomy under general anesthesia,were randomly divided into 3 groups:0.3 mg/kg parecoxib sodium group (group P1,n=21),0.6 mg/kg parecoxib sodium group (group P2,n =21) and control group (group C,n =20).The patients were given intravenous parecoxib sodium of 0.3 mg/kg immediately before induction of anesthesia and at 12 h after operation in group P1,and also parecoxib sodium of 0.6mg/kg immediately before induction of anesthesia and at 12 h after operation in group P2,while the equal volume of normal saline was given in group C.Blood samples were taken from the central vein before the induction of anesthesia(T0),after operation(T1),12 h after operation(T2) and 24 h after operation(T3).The concentration of serum surfactant protein A (SP-A),TNF-α,IL-6 and IL-8 were determined by ELASA.The incidence of pulmonary complications at 72 h after operation were also recorded.Results Compared with T0,the concentration of serum SP-A,TNF-α,IL-6 and IL-8 increased significantly in all groups at T1-T3 (P＜0.05).Compared with C group,the concentration of serum SP-A,TNF-α,IL-6 and IL-8 in groups P1 and P2 decreased significantly at T1-T3 (P＜0.05),there were no significant differences between groups P1 and P2.The incidence of postoperative pulmonary complications had no statistically significant differences between the three groups.Conclusion Parecoxib sodium can significantly reduce the concentration of serum SP-A and alleviate the inflammatory response in elderly patients undergoing video-assisted thoracoscopic pneumonectomy.

Objective To observe the effect of patient-controlled intravenous analgesia (PCIA)with dezocine combined with sufentanil on inflammatory response and pain after laparoscopic hepatectomy for hepatocellular carcinoma.Methods Sixty patients (43 males,17 females,aged 18-60 years,ASA grade Ⅰ or Ⅱ) scheduled for laparoscopic hepatectomy for hepatocellular carcinoma were divided into sufentanil group (group S) and dezocine+sufentanil group (group DS) according to the random number table,n=30 each.Patients in group S were given 100 ml normal saline containing sufentanil 2.0 μg/kg and tropisetron 5 mg.Patients in group DS were given 100 ml normal saline containing sufentanil 2.0 μg/kg,dezocine 0.5 mg/kg and tropisetron 5 mg.VAS scores and numeric sedation scale (NSS) scores were recorded at 4,24,48 h after operation and patients' satisfaction scores were recorded at 48 h after operation.The levels of serum tumor necrosis factor-α (TNF-α),interleukin-2 (IL-2),interleukin-6 (IL-6) in blood samples harvested before induction of anesthesia and 0,4,24 and 48 h after operation were measured by ELISA.The times of efficient injection and incidence of adverse effect within 48 h after operation were recored.Results Compared with group S,the VAS scores in group DS were decreased significantly while the satisfaction of patients to analgesia were increased significantly at 4,24,48 h after operation (P<0.05).There were no obvious differences in NSS scores between two groups.Compared with before induction of anesthesia,the concentrations of TNF-α and IL-6 were increased significantly while the concentrations of IL-2 was decreased significantly in both groups at 4,24,48 h after operation (P<0.05).Compared with group S,the concentrations of TNF-α and IL-6 were decreased significantly while the concentrations of IL-2 was increased significantly in group DS at 24,48 h after operation (P<0.05).The times of efficient injection in group DS were less than that in group S significantly within 48 h after operation [(2.0±0.7) times vs.(7.2±1.3) times] (P<0.05).There were no obvious differences in adverse effects between two groups.Conclusion PCIA with dezocine 0.5 mg/kg combined with sufentanil 2.0 μg/kg can alleviate the inflammatory response to some extent in patients after laparoscopic hepatectomy for hepatocellular carcinoma,and it can offer a safe and effective analgesic effect.

Objective To evaluate the efficacy of high frequency two-lung ventilation (TLV) with low tidal volume assisted by CO2 pneumothorax for airway management in patients undergoing thoracoscopic radical resection of esophagus cancer.Methods Thirty patients of both sexes,aged 48-64 yr,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective thoracoscopic radical resection of esophagus cancer,were divided into 2 groups (n =15 each) using a random number table:onelung ventilation group (group O) and TLV group (group T).A left-sided double-lumen tube was inserted orally in group O,and a single-lumen tube was placed orally in group T.During thoracoscopic surgery,the left lung was ventilated,with tidal volume 8 ml/kg and respiratory rate 14 breaths/min in group O.In group T,artificial pneumothorax was induced by continuous CO2 insufflation with CO2 pressure at 10 mmHg,and bilateral lungs were ventilated,with tidal volume 5 ml/kg and respiratory rate 20 breaths/min.Mean arterial pressure and heart rate were recorded before induction of anesthesia,immediately after intubation (T1),at 10 min after intubation (T2),at 30 min after the start of thoracoscopic surgery (T3),immediately after the end of thoracoscopic surgery (T4) and at 30 min of TLV (T5).Arterial blood samples were collected for blood gas analysis at T2,T3,T4 and T5.The exposure of the surgical field and the number of lymph node dissection in the left recurrent laryngeal nerve chain were recorded during surgery.The emergence time,extubation time and time for recovery of consciousness were recorded.Results Arterial oxygen partial pressure was significantly lower at T3,4 than at T2 in the two groups,and arterial carbon dioxide partial pressure was significantly higher,and the pH value was lower at T3,4 than at T2 in group T (P＜0.05).Compared with group O,arterial carbon dioxide partial pressure was significantly increased,the pH value was decreased,and the number of lymph node dissection in the left recurrent laryngeal nerve chain was increased at T3,4 in group T (P＜0.05).There were no significant differences between the two groups in the good exposure of the surgical field,emergence time,extubation time and time for recovery of consciousness (P＞0.05).Conclusion High frequency TLV with low tidal volume when assisted by CO2 pneumothorax can serve as a feasible mode for airway management in patients undergoing thoracoscopic radical resection of esophagus cancer.

Objective To evaluate the effects of penehyclidine hydrochloride on the oxidative stress and cell apoptosis during endotoxin-induced acute lung injury (ALI) in neonatal rats.Methods Forty 7-day-old Wistar rats weighing 12-18 g were randomly divided into 3 groups (n=10 each) using a random number table: penehyclidine hydrochloride group (group PHC), acute lung injury (group AKI) and normal saline group (group NS).The ALI model was induced with intraperitoneal endotoxin 5.0 mg/kg in groups PHC and ALI.In group PHC, penehyclidine hydrochloride 2.0 mg/kg was injected intraperitoneally at 1 h before ALI respectively, while the equal volume of normal saline was administered in groups NS and ALI.At 4 h after endotoxin injection,the rsts were sacrificed.The lungs were collected to determine the wet/dry (W/D) lung weight ratio.The expression of SOD was detected by xanthine oxidase method.The expression of MDA was detected by sulfuretted barbitone method.Levels of cytochrome C (Cyt-C) and Caspase-3 were determined with immunohistochemical method (IHC), and cell apoptosis (by TUNEL).Apoptotic index was calculated.Results Compared with group NS, the W/D ratio and the contents of MDA were significantly increased, the contents of SOD were significantly decreased in groups ALI and PHC (P＜0.05).Compared with group ALI, the W/D ratio and the contents of MDA were significantly decreased, the contents of SOD were significantly increased in group PHC (P＜0.05).Compared with group NS, the contents of Cyt-C, Caspase-3, and apoptotic index were significantly increased in groups ALI and PHC (P＜0.05).Compared with group ALI, the contents of Cyt-C, Caspase-3, and apoptotic index were significantly decreased in group PHC (P＜0.05).Conclusion Penehyclidine hydrochloride ameliorates endotoxin-induced ALI by inhibiting oxidative stress and cell apoptosis in neonatal rats.

Objective To evaluate the effect of ketamine on the expression of tryptophan hydroxylase 2 (TPH2) in the median raphe nuclei of mentally depressed mice.Methods Thirty-six healthy SPF male C57BL/6J mice,aged 8-12 weeks,weighing 20-26 g,were divided into 3 groups (n=12 each) using a random number table:control group (C group),depression group (D group) and depression plus ketamine group (D+K group).Mental depression was induced by forcing the animals to swim in a narrow cylinder from which they can not escape.Ketamine 15 mg/kg was intraperitoneally injected once a day for 7 consecutive days starting from 1 day after successful establishment of the model in group D+K.The equal volume of normal saline was given instead of ketamine in C and D groups_ Forced swimming test was performed again at 30 min after the last administration,and the immobility time was recorded.Open field test was also performed at 30 min after the last administration,and the total horizontal distance and the number of standing on the back legs were recorded.The mice were sacrificed after the end of the behavioral testing,and the hippocampi and median raphe nuclei were isolated.High-performance liquid chromatography-electrochemical detection assay was used to measure the content of 5-hydroxytryptamine (5-HT) in hippocampi.The expression of TPH2 protein and mRNA in the median raphe nuclei was detected using Western blot and real-time polymerase chain reaction,respectively.Results Compared with group C,the immobility time was significantly prolonged,the total horizontal distance was shortened,the number of standing on the back legs and content of 5-HT in hippocampi were deceased,and the expression of TPH2 protein and mRNA in the median raphe nuclei was down-regulated in group D,and the total horizontal distance was significantly shortened,the number of standing on the back legs was decreased (P＜0.05),and no significant change was found in the immobility time,content of 5-HT in hippocampi or expression of TPH2 protein and mRNA in the median raphe nuclei in group D +K (P＞0.05).Compared with group D,the immobility time was significantly shortened,the content of 5-HT in hippocampus was increased,the expression of TPH2 protein and mRNA in the median raphe nuclei was up-regulated (P＜0.05),and no significant change was found in the total horizontal distance or the number of standing on the back legs in group D+K (P＞0.05).Conclusion The mechanism by which ketamine produces anti-depressant effect may be related to up-regulation of TPH2 expression in the median raphe nuclei and increase in the synthesis of 5-HT in hippocampi of mice.

Objective To study the sleep improvement function of DHA-PC.Methods The mice were randomly divid-ed into control, vehicle, DHA+Lecithin (60+200 mg/kg) and DHA-PC(50,100,200 mg/kg) groups.Ten mice were enrolled in each group .The mice of control were administered with normal food , the vehicle group was orally given normal saline at the dosage of 0.2 ml/10 g, while both DHA-PC and DHA+Lecithin were orally given corresponding drugs at the dosage of 0.2 ml/10 g.All the groups were treated for 30 days except control group .The direct sleep-inducing test, the test of lengthening sleep time induced by pentobarbital sodium , the test of pentobarbital sodium subthreshold-hypnosis and the test of barbital sodium sleep latency were conducted to observe the inductive effect of DHA -PC.Results Neither the effect on mice body mass nor directly-induced sleep was observed .DHA-PC (50,100, and 200 mg/kg) could prolong sleep time to (56.2 ±13.7),(57.9 ±25.4) and(64.1 ±18.4) min, respectively,compared to vehicle(32.9 ±10.8)min (P<0.05).DHA+Lecithin could not prolong sleep time (38.6 ±11.7)min compared to (32.9 ±10.8)min of vehicle.There was significant difference compared with DHA-PC at the dosage of 200 mg/kg (64.1 ±18.4)min (P<0.05).DHA-PC (200 mg/kg) enhanced pentobarbital sodium subthreshold-hypnosis (70%) compared to vehicle (10%) (P<0.05),so did DHA+Lecithin (60%) compared to vehicle (10%) (P<0.05).Both DHA-PC (200 mg/kg)[(22.9 ±4.1)min ] and DHA+Lecithin [(19.5 ±2.7) min ]could shorten sleep latency compared to vehicle (31.3 ±6.9) min(P<0.01), and the sleep latency of DHA +Lecithin (19.5 ±2.7) min was shorter than that of DHA-PC(50,100 mg/kg).Conclusion DHA-PC has some effect some sleep improvement in mice .

Objective To evaluate the role of glycogen synthase kinase-3 beta (GSK-3β) in spinal cord ischemia/reperfusion (I/R) injury in rats.Methods Forty-eight male Sprague-Dawley rats,aged 3 months,weighing 250-300 g,were randomly divided into 3 groups (n =16 each) using a random number table:sham operation group (group S),group I/R and I/R+ GSK-3β inhibitor LiCl group (group LiCl).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 300 mg/kg.Spinal cord ischemia was induced by 45 min occlusion of the abdominal aorta followed by reperfusion.In I/R and LiCl groups,normal saline 5 ml and LiCl 15 mg/kg were injected,respectively,via the caudal vein at 30 min before ischemia.The animals were sacrificed at 48 h of reperfusion and the lumbar segment (L4-6) of spinal cords was removed for microscopic examination and for determination of neuronal apoptosis in the anterior horn of the spinal cord (by TUNEL),and the expression of interleukin-6 (IL-6),IL-8 and IL-10 was detected (by immunohistochemistry).The apoptosis rate was calculated.Results Compared with group S,the apoptosis rate was significantly increased,IL-6 and IL-8 expression was upregulated,and IL-10 expression was down-regulated in I/R and LiCl groups.Compared with group I/R,the apoptosis rate was significantly decreased,IL-6 and IL-8 expression was down-regulated,IL-10 expression was up regulated,and the pathological damage was attenuated in LiCl group.Conclusion Activated GSK-3β is involved in the development of spinal cord I/R injury possibly by promoting synthesis and release of inflammatory factors in rats.