One of the most promising antimalarial drugs which are widely used throughout the world is the artemisinin (ARS)and its derivatives,e.g.,artemether,arteether,and artesunate.Their true potential lies in broader anti-disease applications.The mechanism of action of these compounds appears to involve the endoperoxide bridge to produce carbon-centred free radicals.Large clinical studies did not show serious side effects,however,there is a paucity of large-scale clinical trials suitable to detect rare but significant toxicity.Therefore,a final and definitive statement on the safety of artemisinins still cannot be made.In contrast,animal experiments at high doses shown considerable toxicity upon application of artemisinins.In the present review,the authors give a comprehensive overview on toxicity studies in cell culture and in animals (mice,rats,rabbits,dogs,and monkeys)as well as on toxicity reported in human clinical trials.The authors emphasize the current knowledge on neurotoxicity,embryotoxicity, genotoxicity,hemato-and immunotoxicity and cardiotoxicity.Rapid elimination of artemisinins after oral intake represents a relatively safe route of administration compared to delayed drug release after intra-muscular (im ) injection. There are drug-related differences, i.e., intramuscular application of artemether or arteether,but not to artesunate,which is safe and gives good profiles after im administra-tion in severe malaria.It might also be important in determining dose limitations for treatment of other diseases such as cancer.Questions about dosing regimens,safety of long-term use and possible inter-actions with existing therapies and toxicities that might be related to the treatment of tumors should be answered by appropriate clinical and preclinical studies.

OBJECTIVE To investigate the change of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),intercellular adhesion molecules(ICAM-1),matrix metalloproteinases 2 (MMP-2) and MMP-9 contents in cultured pulmonary microvascular endothelial cells (PMVECs) in rats after perfluoroisobutylene (PFIB) exposure. METHODS PMVECs were separated and purified using a modified method of implantation of pulmonary tissues. After identification,PMVECs were divided into the normal control group and the PFIB-exposed groups(n=3). The PFIB-exposed groups inhaled PFIB at the concentration of 200 mg · m-3 for 5 min in a flow-past header,while the normal control group were PMVECs in quiescent condition. The supernatants and lysates of PMVECs were harvested at 0.5,1,2,4 and 8 h,respec?tively, after execution. The contents of TNF-α,IL-1β,ICAM-1,MMP-2 and MMP-9 were measured by ELISA,and the activity of MMP-2 and MMP-9 was measured by gelatin zymography. RESULTS① According to the morphologic characteristics of cell growth and the expression of specificity antigens and the bind experiment of phytohemagglutinin,the cells separated and purified by modified method shared the characteristics of PMVECs.②TNF-αwas rapidly expressed by PMVECs at 0.5 h post PFIB stimulation and the maximum value was achieved at 2 h post PFIB stimulation(P<0.05). The newly synthesized TNF-α was slowly released out of the cells. The maximum TNF-α in the supernatant was achieved at 4 h post stimulation.③Within 2 h of stimulation,PMVECs synthesized a large amount of IL-1β and peaks at 2 h. However,IL-1βwas never released to the extracellular milieu.④The amount of ICAM-1 was rapidly synthesized by PMVECs after PFIB stimulation,but at a low level.⑤After stimulation with PFIB,MMP-2 in the supernatant of PMVECs culture was gradually increased,peaked at 2 h and then decreased subsequently. The biological activity of MMP-2 in the supernatant was also enhanced after PFIB stimulation. PFIB did not stimulate synthesis or secretion of MMP-9,indicating that PMVECs were not the main source of MMP-9 during PFIB inhalation-induced acute lung injury. CONCLUSION PFIB stimulates the surviving PMVECs to synthesize a large amount of TNF-α,IL-1β, MMP-2 and conjunctive ICAM-1.

Objective To investigate the effects of different methods of volume therapy on the inflammatory response in patients undergoing liver cancer resection.Methods Forty ASA Ⅰ or Ⅱ patients,aged 40-60 yr,with body mass index 20-25 kg/m2,undergoing liver cancer resection,were randomly divided into 2 groups ( n =20 each):routine fluid replacement group (group Ⅰ ) and goal-directed fluid replacement group (group Ⅱ ).The fluid replacement regime in group Ⅰ =compensatory volume expansion (CVE) + physiological requirements + cumulative loss + confinued loss + the third space losses.CVE was replaced with lactated Ringer's (LR) solution 5 mg/kg before anesthesia induction.The physiological requirements and cumulative loss were replaced with LR solution according to the principle of 4-2-1.The continued loss equal to the intraoperative blood loss was replaced with the equal volume of 6％ hydroxyethyl s tarch ( HES 130/0.4).The 3rd space losses were replaced with LR solution 5 ml·kg-1 ·h-1.In group Ⅱ,CVE was replaced with LR sol6ution as in group Ⅰ.LR solution was infused after anesthesia induction at 5 ml·kg-1 ·h-1.6％ HES was infused to maintain left ventricular ejection time (LVETc) between 350-400 ms.When 350 ms ＜ LVETc ＜ 400 ms and the amplitude of stroke volume ( SV ) increased by ＞ 10％,6％ HES was infused continuously until the amplitude of SV increased by ≤ 10％.Blood samples were taken before anesthesia induction and at the end of operation for measurement of serum TNF-α,IL-2,IL-4,IL-6 and IL-8 concentrations.The adverse cardiovascular reactions were recorded.Results Compared with group Ⅰ,the serum TNF-α,IL-6,IL-8 concentrations were significantly decreased,the serum IL-2 and IL-4 concentrations were significantly increase,and the incidence of hypotension and tachycardia was significantly decreased in group Ⅱ ( P ＜ 0.05).No adverse cardiovascular reactions were found in both groups.Conclusion LVETc and SV-guided volume therapy can maintain the blood volume and inhibit the inflammatory response and is suitable for the patients undergoing liver cancer resection.

Objective To evaluate the protective effects of different modes of ventilation on the lungs on the operated side during one-lung ventilation (OLV ) in patients undergoing thoracic surgery .Methods Forty-five ASA physical status Ⅰ or Ⅱ patients of both sexes ,aged 45-64 yr ,weighing 65-80 kg ,were randomly divided into 3 groups (n=15 each) using a random number table :group A ,group B and group C .After induction of anesthesia ,the patients were intubated with double-lumen tube and OLV was performed .During OLV ,the lung on the operated side was collapsed naturally in group A ,positive pressure ventilation (FGF 2 L/min) was applied in the lung on the operated side in group B ,and high-frequency jet ventilation (frequency 100 beats/min ,driving pressure 0.5 kg/cm2 ) was used in the lung on the operated side in group C .Immediately after intubation (T0 ) , and at 1.5 h (T1 ) and 2 h (T2 ) of OLV ,blood samples were taken from the central vein and radial artery for determination of the serum interleukin-6 (IL-6 ) and IL-8 concentrations .The net release of IL-6 and IL-8 was calculated .Blood samples were taken from the radial artery at T0-2 for blood gas analysis and for determination of surfactant protein A (SP-A) concentration in the serum .Respiratory index (RI) was calculated .The non-cancer tissues 1.0 cm × 1.0 cm × 1.0 cm which were extracted from the lung cancer specimens were used for microscopic examination of the pathological changes of lungs which were scored .Results Compared with group A ,the net release of IL-6 and IL-8 ,serum SP-A concentration ,RI and pathological scores were significantly decreased at T1 ,2 in B and C groups ( P<0.05) .Compared with group B ,the serum SP-A concentration and RI were significantly decreased at T1 ,2 , and the net release of IL-6 was increased at T2 in group C ( P< 0.05 ) .Conclusion Continuous positive ventilation and high-frequency jet ventilation both can effectively protect the lungs on the operated side during OLV in patients undergoing thoracic surgery ,and the efficacy of high-frequency jet ventilation is better .

Objective To analyze the ostomy patients' demands, resolve the common problems after discharge by telephone consultation, and supplement the content of specialized health education. Methods The data of 256 telephone consultations from 186 patients with ostomy were retrospectively analyzed. Results Most of the consultations came from patients aged from 61 to 80 years old (64.5%) and patients within one year after surgery (85%). The contents focused on information about ostomy products, care of skin around the stoma and leakage of defecation, which accounted to 32.8%,30.1%,24.6%,respectively.The problems were solved by telephone interview in 201 consultations (78.5%). Conclusion Consultation by telephone is useful to find out the demands of discharged ostomy patients, resolve their problems in time and improve their quality of life. It has great significance for improving health education and extensive services of ostomy patients.

Objective To evaluate the correlation between stroke volume variation (SVV) and blood volume during one-lung ventilation (OLV).Methods Forty ASA Ⅱ male patients,aged 50-60 yr,with body mass index 20-25 kg/m2,scheduled for elective resection of esophageal cancer,were studied.Anesthesia was induced with fentanyl 4 μg/kg,propofol 2 mg/kg,and rocuronium 0.6 mg/kg.Double-lumen tube was inserted.Correct position was verified by fiberoptic bronchoscopy.The patients were mechanically ventilated (VT 8 ml/kg,RR 15 bpm,Ⅰ ∶ E 1 ∶ 2).6％ hydroxyethyl statch (HES) 130/0.4 was infused intravenously at a rate of 0.67 ml· kg-1 · min-1 starting from 30 min of OLV.SVV,cardiac output (CO),SV and cardiac index (CI) were monitored and recorded using the FloTrac/Vigileo (Edwards Lifesciences,USA) system before HES was infused and when the dose of HES reached 2,4,6,8,10 and 12 ml/kg.Spearman rank sum correlation coefficient was used to analyze the data.Results SVV was negatively correlated with the blood volume during OLV and the correlation coefficient was rSVV =-0.249.CI,CO and SV were positively correlated with the blood volume during OLV and the correlation coefficients were rCO =0.570,rSV =0.552 and rCI =0.550,respectively.Conclusion SVV is poorly correlated with the blood volume during OLV and can not reflect the blood volume accurately.

Objective To investigate tentatively the role of angiotensionⅡ( AngⅡ) in perfluoroisobutylene ( PFIB)-in-duced acute lung injury ( ALI) in rats.Methods Twenty-eight male Wistar rats were randomly divided into one control group(0 h) and six PFIB-exposed groups which were executed at 1, 2, 4, 8, 16 and 24 h after PFIB exposure (n=4). The PFIB-exposed groups inhaled PFIB at a concentration of 145 mg/m3 for 8 min in a flow-past header while the control group was exposed to the filtered air in a similar manner .After execution at the corresponding time-point, the samples of the lung, serum and brochoalveolar lavage fluid (BALF) were harvested.The measurement of the lung wet-to-dry weight ratio ( W/D) and total protein content in BALF , and the histopathological examination of the lung were carried out to evalu -ate the degree of lung injury .The over-time changes in the content of AngⅡin the lung homogenates and blood plasma and the activity of angiotensin converting enzyme ( ACE) in the lung tissue were observed .Results The lung W/D and total protein content in BALF were increased significantly at 16 h after PFIB exposure with severe acute lung edema and abun-dant neutrophil exudation to the alveoli , which were alleviated dramatically at 24 h after PFIB exposure .The content of AngⅡin the lung homogenate showed a tendency of increase during the first 8 hours with significant decrease at 16 and 24 h after exposure.However, the content of AngⅡin the plasma and the activity of ACE in the lung experienced of fluctuations , but without significant difference compared to the control group .Conclusion There is no obvious correlation between the extent of lung injury and that of AngⅡin the lung.The pathological significance of AngⅡin PFIB-induced ALI needs to be further clarified.

Objective To evaluate the correlation between stroke volume variation (SVV) and the blood volume. Methods Forty-eight ASA Ⅱ male patients, aged 50-60 yr, scheduled for elective radical operation for gastric cancer, were studied. Anesthesia was induced with fentanyl 4 μg/kg, propofol 2 mg/kg and cis-atracurium 0.15 mg/kg and maintained with inhalation of 2%-3% sevoflurane. 6% HES 130/0.4 was infused intravenously at a rate of 0.67 ml· kg - 1 · min - 1 30 min after induction. SVV,cardiac output (CO),SV and cardiac index (CI) were monitored and recorded using the FloTrac/Vigileo (Edwards Lifesciences, USA) system before HES was infused and when the dose of HES reached 2, 4, 6, 8, 10, 12, 14, 16 and 18 ml/kg. CVP was also recorded at the corresponding time points. Spearman's rank sum correlation coefficient was used to analyze the data. Results Correlation coefficients between the amount of HES infused and CO, SV, CI or CVP were rSVV = - 0.91 ± 0.06,rCO = 0.83 ± 0.04, rSV = 0.86 ± 0.09, rCI = 0.86 ± 0.09 and rCVP = 0.90 ± 0.03. Among the 5 correlation coefficients, rSVV was the highest, rCVP was significantly higher than rCO, rSV and rCI (P ＜ 0.05), and there was no significant difference among rCO, rSV and r CI (P ＞ 0. 05). Conclusion SVV is highly correlated with the blood volume and can be used to guide volume therapy.

Objective To analysis the effect of caffeine citrate on pulmonary function, vascular endothelial growth factor (VEGF)and insulin like growth factor -1 (IGF-1) in the apnea syndrome rats.Methods 80 male Wistar rats were selected, 20 were randomly selected to be the control group, the rest of the rats were replicated of apnea syndrome model.The rats were randomly divided into model group, experiment group and positive drug group, 20 of each group.The experimental group was given caffeine citrate injection of 5 mg/kg intraperitoneal injection, the positive drug group was given intraperitoneal injection of aminophylline 3 mg/kg, the model group was given intraperitoneal injection of normal saline, once a day, continuously for 1 week.Pulmonary function, serum VEGF, IGF-1 levels and sleep apnea were compared after the experiment.ResuIts Compared with the positive drug group, the related indexes of pulmonary function of the experimental group increased significantly ( P<0.05 ) .Serum VEGF levels decreased significantly (P<0.05).The serum IGF-1 level increased significantly (P<0.05).The sleep apnea index decreased significantly during the period of NREM and REM.(P<0.05).ConcIusion Caffeine citrate can improve apnea syndrome rats lung function, reduce the serum VEGF level, promote the formation of serum IGF-1, reduce the sleep apnea index.

OBJECTIVE To investigate whether the pulmanary fibrosis formed after a single PFIB exposure.METHODS A total of 70 male mice were exposed to PFIB 130 mg·m-3 for 5 min.Pulmonary edema of 10 mice was evaluated by lung indices at 24 h after PFIB exposure.Pathological changes and collagen deposition were detected by hematoxylin and eosin (HE) and Sirius red stainings in the other mice,changes in collagen content in lungs and plasma by measuring the respective hydroxyproline content at 2,4,6,8,12 and 16 weeks after PFIB exposure.RESULTS Severe pulmonary edema was observed at 24 h after PFIB exposure.At day 14 after PFIB exposure,inflammatory cell infiltration,alveolar septum thickening,interstitial and alveolar edema and protein leakage were noticed.Collagens types Ⅰ and Ⅲ on the wall of vessel and bronchi were severely damaged,but considerable amount of collagen type Ⅲ deposited on the alveolar wall.The content of hydroxyproline considerably decreased in the lungs but increased significantly in the plasma up to six weeks.Hydroxyproline in lungs and plasma began to recover at the end of 8 weeks,and then returned to normal.At 16 weeks,they recovered to normal level.At the end of 4 weeks,the lung lesions and the collagens at the wall of vessel and bronchi began to recover gradually; collagen typeⅢ at the alveolar wall was gradually absorbed,too.At 16 weeks,the lungs almost recovered to normal level.CONCLUSION At earlier phase after PFIB exposure,the excessive collagens destruction in lungs is observed,but no pulmonary fibrosis forms at the later phase.