Lung is the main target of lung-damaging agents(or choking agents,lung irritants)which can result in potential permanent respiratory depression,the rapid development of acute lung injury(ALI)and pulmonary edema,even death in severe cas-es. Recently,with the research progress in the pathogenesis of lung-damaging agents,numerous corresponding experimental studies were carried out and some progress were made. This paper summarizes the progress in the study of lung-damaging agents on the re-search situation,pathogenic mechanism and biomarker,to provide reference for the promotion of ALI prevention,medical antagonis-tic measures and clinical treatment.

Objective: To study the protective effect of N-acetylcysteine on acute lung injury induced by PFIB inhalation and its mechanism. Methods: Survival experiment: 48 male ICR (CD-1) mice were randomly divided into 4 groups, i. e., PFIB control group, NAC prevention group, NAC treatment group, and NAC prevention + treatment group, each group contains 12 animals. The mice of PFIB C group were exposed to PFIB without any treatment. The mice of NAC P group were exposed to PFIB 30min after NAC administration. The mice of NAC T group were exposed to PFIB 1h before NAC administration, The mice of NAC P+T group were administrated with NAC twice (30 min before and 1h after PFIB inhalation) . 150 mg/kg NAC was given by each time. The 7 days survival rate of mice after lethal dose PFIB exposure was observed. 18 male Wistar rats were randomly divided into 3 groups i.e., normal control group (N-C) , PFIB control group (PFIB-C) and NAC prevention group (NAC-P) , with each group contains 6 animals in the second experiment. The rats of N-C group received no treatment. The rats of NAC-P group and PFIB-C group were exposed to PFIB 30min after treatment of NAC (420 mg/Kg, i.p.) and saline, respectively. The respiratory functions of animals were tested before and 24 h after PFIB inhalation. The arterial blood gas was analyzed after rats were anesthetized 24 hours post sublethal dose PFIB exposure. Then samples of BALF, plasma and lung tissue were collected. Wet lung/body weight ratio, protein and phospholipid content in BALF, and T-SOD, GSH, GSH-Px in plasma and lung tissue were measured. The expression of Peroxiredoxin 2 was detected by Westernblot assay. Results: NAC prevention can significantly improve the survival of mice exposed to a lethal dose PFIB while NAC treatment is ineffective. Severe lung edema was observed in rats 24 h after PFIB exposure. Compared to N-C group, the wet lung/body weight ratio, protein and phospholipid content in BALF, and respiratory rate of PFIB control group all increased significantly (P<0.01) . The arterial oxygen partial pressure (PaO₂) reduced significantly (P<0.05) . The GSH-Px activity in lung tissue reduced significantly (P<0.01) while the expression of Peroxiredoxin 2 increased significantly (P<0.01) . NAC prophylaxis significantly reduced the wet lung/body weight ratio, protein and phospholipid content in BALF, respiratory rate of rats exposed to PFIB (P<0.01) . Compared with PFIB-C group, the PaO₂ (P<0.05) and the activity of GSH-Px (P<0.01) and the expression of Peroxiredoxin 2 in lung tissue (P<0.01) were increased significantly. Conclusion Acute lung injury induced by PFIB inhalation is related to oxidative stress caused by the stimulation to lung. induced and pulmonary subjected to stimulate the generation of exposure, NAC prevention can regulation of the redox system in lung tissue and protect target organ of the treated animals effectively.

OBJECTIVE To clarify the long-term toxicity to the respiratory system in a rat model of acute lung injury (ALI) induced by a single low-dose of perfluoroisobutylene(PFIB) inhalation expo?sure,and observe the possible beneficial effect of early intervention via Qingkailing(QKL) injection. METHODS Totally 224 male Wistar rats were randomly divided into 4 groups:normal control group in which air exposure was followed by a saline 10 mL · kg-1(ip),QKL control group in which QKL 10 mL · kg-1 was ip given after air exposure,PFIB exposure group in which rats were exposed to PFIB 280 mg·m-3 for 5 min only,and QKL treatment group in which QKL 10 mL·kg-1 was given ip at 1 h after PFIB exposure. Lung functions of rats were measured at 24 h,3,6,12,24,36 and 48 weeks after exposure. The arterial blood gas,lung coefficient,protein content in bronchoalveolar lavage fluid(BALF),hydroxy?proline(HYP) content in lung tissue and plasma,and other indicators were detected or analyzed. RESULTS Within 24 h after PFIB exposure,the lung coefficient and protein content in BALF were increased significantly(P<0.01),whereas the PaO2(P<0.01) and SaO2(P<0.05) indices in arterial blood decreased significantly in PFIB group compared with normal control. The inhalation time , exhalation time,tidal volume(TV),expired volume(EV)and relaxed time were reduced significantly (P<0.01). However,all the above indicators returned to normal in 3 weeks,but TV,EV and peak expiratory flow were significantly lower than in normal group at 48 weeks(P<0.05). HYP contents in lung tissues,compared with normal control(P<0.05),were reduced significantly within 24 h after PFIB exposure,increased significantly in 6 weeks(P<0.05),then returned to normal in 12 weeks. HYP contents in plasma increased significantly compared with normal control(P<0.05) within 24 h after PFIB exposure but returned to normal in 3 weeks. The protein contents in BALF of QKL treatment group were significantly lower than those in PFIB group(P<0.01) within 24 h after PFIB exposure. From 24 h to 24 weeks after PFIB exposure,changes of pulmonary functions were similar to those in PFIB group. At 48 weeks,TV and EV in QKL treatment group were more significantly increased than those in PFIB group(P<0.05). CONCLUSION Rats with ALI induced by a single low dose of PFIB exposure undergo compensatory repair except for pulmonary capacity and pulmonary ventilation functions. Early treatment with QKL reduces protein content of BALF and alleviates pulmonary edema,and has some beneficial effect on lung function recovery later.

Vesicants are the main agents used to fill chemical weapons, and chemical weapons abandoned by the Japa-nese Army in China.The mustard-lewisite mixture, which was developed for cold weather or high-altitude use due to its lower freezing point, is a special and important agent.The toxicology, emergency treatment and clinical management of mustard-lewisite mixture poisoning are introduced in this paper.

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.

Acute lung injury ( ALI) is a type of pulmonary excessive inflammation with high morbidity and mortality.It can be induced by multiple causes.There are currently no successful therapeutic or preventive measures because the patho-genesis of ALI has not been completely clarified.Many studies have shown that the activation of complement 5a (C5a) and its receptors is necessary in the process of ALI.Drug development targeting on C5a and its receptors may bring new hope to the treatment of ALI.In this article, the experimental evidence and possible mechanisms are summarized to reveal the rela-tionship between C5a and ALI.

″Tianjin Port 8 · 12 Catastrophic Explosion Accident″ affected the national people′s heart. After the disaster,the chemical defense,medical,explosion and so on various relevant profes?sional experts and rescue teams responded to the national call. Taking the bull by the horns,pooling the wisdom and efforts,the experts and rescue teams carried out and implemented the decision spirit of ″it should not hurt one man,and should not appear serious secondary disasters in the late treat?ment″which put forward by the Party Central Committee and State Council. In order to better learn and sum up experience,the cause of the disaster,the disaster rescue and disposal process,the enlighten?ment brought by the disaster and the recommendations deal with unexpected chemical incidents in the future was discussed in this paper.

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.

Chemical weapons(CW), as weapons of mass destruction on the battlefield , made their debut in the First World War of the last century .To achieve total prohibition on CW , the international community concluded the Chemical Weapons Convention(CWC)in 1993, and it came into force in 1997.So far, only seven countries have been outside the CWC.The offensive and defensive pattern of the world changed then , and the world began to enter the post-CW era.A chemical terrorist attack perspective is needed in consideration of chemical threats facing the world .This article summarizes the experience on specific chemical attacks , analyzes the possibility , sources, types and developments of a chemical terror-ist attack, and puts forward countermeasures for any possible chemical terrorist attack .

The Strategic National Stockpile (SNS) is a national repository of antibiotics, chemical antidotes, antitoxins, life-support medications , intravenous administration , airway maintenance supplies , and medical/surgical items.It is designed to supply and resupply state and local public health agencies in the event of a national emergency anywhere and at any time within the United States or its territories .This article introduces the development , emergency supplies reserve and maintenance of the SNS .