Acute organophosphorus pesticides poisoning(AOPP)is one of the common critical emergency problems and the fatality is extremely high. Organophosphorus pesticides(OPS)are highly effective acetylcholinesterase(AChE)inhibitors. The AChE inhibition results in accumulation of acetyl?choline and overestimation of acetylcholine receptors in synapses of the autonomic nervous system, central nervous system,and neuromuscular junctions,causing a series of symptoms including musca?rinic,nicotinic,and central nervous system dysfunctions. In the early stage of AOPP,the core treat?ment is the use of anticholinergic drugs coupled with cholinesterase reactivator. Atropine and penehycli?dine hydrochloride(Tuoning)are the most commonly used anticholinergic drugs,which can effectively compete with acetylcholine receptors,block the effect of acetylcholine,and relieve the symptoms of re?spiratory failure,bronchospasm,pulmonary edema caused by AOPP. Oximes are believed to function as AChE reactivators,that can promote enzymatic reactivation and restore the activity of hydrolysis of ace? tylcholine. Recently,new avproaches,such as intravenous lipid emulsion,new detoxification drugs, blood purification,and traditional Chinese medicine,have attracted more attention. Overall,great prog?ress has been made in AOPP treatments. A better understanding of AOPP mechanism,and the support from pharmacology,toxicology,and related fields can contribute to the treatment of AOPP. Improved medical management of AOPP can also result in fewer deaths from poisoning worldwide.

BACKGROUND:Bone marrow mesenchymal stem cells (BMSCs) of mice are different from human and rats.The difficulties of culture,sustaining impermanency activity of BMSCs after passage and short-term effect of stem cells tracking limited the study of mice.OBJECTIVE:To obverse modified isolated culture method of BMSCs of mice and the feasibility of long-term fluorescent labeling stem cells.DESIGN,TIME AND SETTING:The experiments were conducted at the Affiliated Hospital of Academy of Military Medicine Science from June to December in 2008.MATERIALS:C57BL/6 mice,males and females,4-6 weeks of age,mean weighing 20 g,were used.METHODS:Stem cell culture fluid serum and liquid change manner were optimized using adherent screening and Percoll separation method.Rat BMSCs were incubated.In accordance with previous experiences of MSCs between human and macaque,Hyclonehigh-grade fetal bovine serum was selected for mouse MSC incubation.Serum was 10% of the medium.Bone marrow cells were washed out using LG-DMEM to filter bone dregs and small muscle blocks.Subsequently,samples were added on the Percoll separating medium at relative density of 1.082,and then incubated in 75 cm~2 culture flask at the concentration of 1.5×10~6/cm~2.BMSCs at the second passage were labeled with CM-Dil.MAIN OUTCOME MEASURES:Morphological changes in primary cultured and subcultured mouse BMSCs were measured.BMSC surface antigen of the second passage of mice (CD105,CD44,CD25,CD34) were determined using flow cytometry.The modified method was assessed to harvest the purity of stem cells.Activity of mouse BMSCs was identified using adipogenic and osteoplastic differentiation.The strength of fluorescent cells following multiple passage was observed.RESULTS:①The attached cells were observed 48 hours after primary cells culture and changed shuttles,triangles and flats at 7 days after culture.The figure become bunches and radial pattam at 3 passages.②MSCs highly expressed CD105,CD44 phenotypes and seldom expressed CD34 and CD45.③Spindle shape of cells gradually disappeared,with increased cell body.Some cells grew in cluster.MSCs changed figures to multilayer knots 10 days after inducing osteoplastic differentiation.MSCs became roundness and appeared fat drops in cells 9 days after inducing adipogenic differentiation.Red fat particles were shown following oil O staining.④The labeling cells gave out oranges light,and marked rates were over 80% in MSCs under the fluorescent microscope.The labeling cells were over 47% in 4 passages MSCs using flow cytometry.CONCLUSION:The modified method gained high-dosage cells in shorten culture time at passage 2 and made CM-Dil long lime labeling cells,which made more convenient for MSCs experiment on mice and stem cells tracer experiment in vivo.

Objective To explore the possible mechanism and protective effect of mesenchymal stem cell (MSC) on rats with paraquat-induced acute lung injury. Method The solution of 20% paraquat (PQ) in dose of 18 mg/kg was injected intra-peritoneally into rats to induce poisoning,and phosphate buffered solution (PBS) was given to rats instead of PQ in rats of control group. Eighty specific pathogen free (SPF) Wistar rats were randomly divided into four group: PQ plus PBS group (n = 20), PQ plus MSCs group (n = 20), MSCs plus PBS group (n=20), normal group (n = 20). The forth generation of MSCs were transfected with Ad5-EGFP virus vector, and then the MSCs-EGFP was delivered to rats through the tail vein of rats 4h after PQ. Five rats of each group were sacrificed 1 d, 3 d, 7 d and 28 days after MSCs administration, and lung tissues of rats were taken to make sections for histological observation of the migration of MSCs under fluorescence inverted microscope. The lung tissues of rats sacrificed on the 28 th day after PQ poisoning were taken for detecting pulmonary coefficient and the content of hydroxyproline (HYP) in the lung tissue homogenate, and at the same time, the levels of serum transforming growth factor-β1(TGF-β1) were assayed. Results The pathological changes of lung tissue showed that the pulmonary fibrosis and consolidation in the MSCs treatment group were milder than those in PQ poisoning model group. In the MSCs treatment group, the levels of serum TGF-β1 and lung tissue HYP, and pulmonary coefficient were lower than those of PQ poisoning model group (P＜0.05). Conclusions The use of MSCs for treatment of paraquat intoxication can protect pulmonary structure by decrease in TGF-B1 and inhibiting the fibroblast migration, suppressing the production of collagenous protein.

Objective To find the correlative factors which induce breath failure in acute tetramine poisoning cases, and to work out a right treatment scheme for these cases. Methods 47 cases were clinically diagnosed as slight, middling and severe poisoning, separately. The tetramine concentration in blood was compared between the three groups to reveal the relationship between blood concentration of tetramine and breath failure. Patients with breath failure were treated with muscle relaxant plus mechanical ventilation. Repeated hemoperfusions were given to the severe poisoning patients. Results No breath failure occured in both slight and middling groups, while in severe poisoning group, breath failure happened in 33.3% (4/12) patients aged below 15, and in 31.8% (7/22) adult patients aged above 15. Repeated hemoperfusion declined the tetramine concentration in blood, and gave a better effect than with CVVH or CVVHD treatment. muscle relaxant plus mechanical ventilation may control the symptom of twitching completely, and prevent from breath failure effectively. Conclusion Breath failure in acute tetramine poisoning cases was induced by systemic twitching and high blood tetramine concentration. It is very important to grade the poisoning cases according to poisoning degree. Repeated hemoperfusion is the best for blood purification. muscle relaxant plus mechanical ventilation may reduce the mortality effectively.

Objective To explore the prevention and treatment effect and its mechanism of Xuebijing injec-tion combined with dexamethasone on rats' paraqnat-induced acute and chronic pulmonary injury.Method One hundred and twenty of male Wistar rats were randomly divided into six groups:nomud group(A),administrated with saline;model group(B)and treatment groups(group C,D,E,F)were given 20%PQ(100 mg/kg.ip),and 2 hours later the normal and model groups were administrated with the same volume of saline for treatment,rats in group C and group D received 1.25 g/kg and 2.5 g/kg Xuebijing injection respectively.rdts in group E received 25,ng/kg dexamethasone,rats in group F receired 2.5 g/kg Xuebijing injection combined with 2.5 g/kg dexamethasone,one time per day till to be killed,while rats killed at 28 d were treated for 7 days.At 2 d,3 d,4 d after poisoned,five rats in each group were killed,serum SOD,MDA level and arterial gas(at 3 d)were measured.At 28 d,the rest of rats were killed,and serum TGF-β1,lung tissure HYP were measured.The pathology of the lung tissue was ob-served at 3 d and 28 d in guoup A,B,F.Results Compared with group B,poisoning symptoms in the treatment groups were milder and serum.SOD,MDA,TGV-β1,lung tissure HYP level were better,arterial oxygen content were higer.Among treatment groups,the treatment effects in group F were the best,SOD and MDA of 3 d,HYP and TGF-β1 of 28 d in group B and F were respectively(37.47±13.00,91.86±21.35)nmol/mL;(11.34±3.07,5.63±1.58)nmoL/mL;(2.54±0.63,1.32±0.07)mg/g;(484.13±63.79,202.22±49.83)pg/mL.The difference was significant(P＜0.05).The pathology of the lung tissue showed that acute lung hemorrhage,edema or chronic pulmonary fibrosis in group F were milder than that of group B.Conclusions In early stage,Xuebijing injection combined with dexamethasone has a stronger ability to clear out oxidized free radical and inhibit lipid super oxidized reaction.This may ameliorate acute pulmonary blooding and edema.In later stage,they could ameliorate chronic pulmonary fibrosis by inhibiting TGF-β1 secretion and HYP generation.

Objective To analyze the epidemiologic data of patients withClostridium botulinum food poisoning, and to improve the understanding, diagnosis and treatment of food borne botulism.Methods A retrospective study was conducted. Fifty-three patients withClostridium botulinum food poisoning admitted to Chinese PLA Center of Poisoning and Treatment from January 2009 to December 2016 were enrolled, and they were divided into mild, moderate, and severe groups according to the severity of disease. The clinical data including medical history, epidemiology data, routine blood test and blood biochemistry at hospital admission, the vital signs and arterial blood gas analysis before and after treatment, as well as the occurrence frequency of symptom and sign on set were collected.Results Fifty-three patients with food borne botulism were enrolled, with 33 patients in mild group, 13 in moderate group, and 7 in severe group. Most of the patients were female, the age distribution was in large span, the outbreak of disease was in groups mainly with the family, and patients were mainly located in Hebei Province, Beijing and Henan Province. The outbreaks were mainly happened in Spring and Summer, and homemade fermentation products were still the first cause of poisoning with the average latent period of (51.01±4.78) hours. The majority of patients with botulism were in mild resulted from the type A toxin. With the aggravation of disease, hospitalization time was gradually increased, white blood cell (WBC) and neutrophils (NEUT) at hospitalization admission, and respiratory rate (RR), heart rate (HR), fraction of inspired oxygen (FiO2) before the treatment were shown in obviously rising trend, albumin (ALB) at hospitalization admission and pH, arterial partial pressure of oxygen (PaO2), arterial oxygen saturation (SaO2) before treatment were in decline. The parameters in severe group were most severe, and had significant differences as compared with those of mild group [hospitalization time (days): 72.57±39.52 vs. 6.61±3.72, WBC (×109/L): 13.01±6.44 vs. 6.85±2.07, NEUT: 0.85±0.07 vs.0.63±0.14, RR (bpm): 32.14±4.33 vs. 15.18±1.70, HR (bpm): 132.29±5.19 vs. 75.54±8.24, FiO2: 0.32±0.05 vs. 0.21±0.00, ALB (g/L): 38.57±4.65 vs. 42.09±4.57, pH: 7.08±0.10 vs. 7.38±0.07, PaO2 (mmHg, 1 mmHg = 0.133 kPa): 75.16±5.24 vs. 98.39±1.50, SaO2: 0.78±0.06 vs. 0.97±0.02, allP < 0.05]. The symptom and sign on set of 53 patients with food borne botulism was dizziness, followed by fatigue, blurred vision, nausea, and other symptoms and signs were lower than 50%, and the occurrence of dizziness with rank one happen rate was significantly higher than blurred vision and nausea (χ2 values were 7.209 and 10.502 respectively, andP values were 0.007 and 0.004 respectively). After the on time prescription of botulinum antitoxins treatment, the clinical symptoms of patients could be relived quickly. All the patients were discharged without deaths.Conclusion In order to improve the recovery of the food borne botulism poisoning patients, adequate antitoxin and the related organ supports should be prescribed on time.

OBJECTIVETo examine the therapeutic effect of combined use of obidoxime and atropine with artificial ventilation on respiratory muscle paralysis caused by omethoate poisoning in rats.

METHODSRats were exposed to 2 times the dose of LD50 omethoate and treated with atropine (10 mg/kg) to counteract cholinergic symptoms. When the rats' respiratory frequency became slower and breathed with difficulty, the trachea intubation and artificial ventilation was carried out. The rats in group A were continuously treated with atropine. The dose of obidoxime for Group B, C and D were 8, 15, 20 mg/kg respectively, given at the same time as artificial ventilation and 1, 2, 3 hours later. The doses of atropine was reduced to 1/3 - 2/3 of the first dose so as to maintain the rats atropinized. If the rat survival was beyond 60 minutes after withdrawal of artificial ventilation, the combined treatment was considered successful. The function of isolated phrenic diaphragm of the rats was observed with MS-302 physiological and pharmacological analysis instrument.

RESULTSNone of the rats in Group A was successful after withdrawal from artificial ventilation and the function of phrenic diaphragm appeared poor; whereas > 80% of the rats in B, C, D Group were successful after withdrawal from artificial ventilation in 3 h and the function of phrenic diaphragm remained well. The survival rate in B, C and D groups were higher after withdrawal from artificial ventilation than that in Group A(P < 0.01). The function of phrenic diaphragm in Group B, C and D were gradually decreased after ACh was added into the container.

CONCLUSIONSCombined use of suitable dose of obidoxime and atropine with artificial ventilation for respiratory muscle paralysis caused by omethoate poisoning could promote the recovery of diaphragm function and reduce the death rate in poisoned rats.

Animals ; Atropine ; administration & dosage ; Dimethoate ; analogs & derivatives ; poisoning ; Drug Therapy, Combination ; Obidoxime Chloride ; administration & dosage ; Rats ; Respiration, Artificial ; Respiratory Paralysis ; drug therapy

Mercury is one of the common heavy-metal toxins,which can cause damage throughout the body in a variety of ways. Cases of renal toxicity of mercury poisoning are increasing clinically. However,little is known about nephrotoxicity mechanisms,and treatment remains unsatisfactory. The mechanism of mercury toxic nephropathy is reviewed in this paper,including the direct toxic effect on the kidney,the injury to the biomembrane system,generation of Hg-metallothionein,imbalance of intra?cellular calciumion,oxidative damage,induced apoptosis,and immune injury. Besides,the mechanism and limitation of common therapies,potential developments of the field are discussed. This review will facilitate further investigations therapies about both the mechanism and treatment of mercury toxic nephropathy.

A rapid and simple method for the determination of cyanide in blood was developed based on pinhole shell-isolated nanoparticles (pinSHINs)-enhanced Raman spectroscopy and an online lysis-purging and trapping approach.In the online lysis-purging and trapping device, the bound cyanide in blood can be cleaved through sulfuric acid acidification, and transferred into HCN volatile gas, then purged into alkaline solution to form NaCN solution, thus high-efficient liberation and entrapment of cyanide from the methemoglobin-bound form can be achieved.The pinSHINs substrate is quite stable to weaken the gold-dissolution effect caused by cyanide under strong alkaline condition, and therefore the detection window can be prolonged to 1 h comparing with 5 min of AuNPs.A limit of detection down to 10 μg/L and a linear range from 100-2000 μg/L in blood were achieved in this method.This method was further applied to rapid measurement of blood samples of cyanide exposed rats and clinic poisoned patients, which provided a sensitive, selective and reliable way for rapid detection of cyanide poisoning.

ObjectiveTo determine thallium in whole blood by atomic absorption detection method, and to investigate the eliminating effect of hemoperfusion (HP) for thallium in blood.Methods The blood of Beagle dogs which had not exposed to thallium before were obtained for preparation of thallium nitrate (TlNO3)-containing solution in three concentrations according to the conversion formula based on animal weight and volume of blood. HP was performed in the simulated in vivo environment. The content of TlNO3 in blood of the next group was determined on the amount of TlNO3 for the last HP of the former dose group. Thallium quantity in different samples was measured with atomic absorption spectrometer blood samples before and after HP. Finally, the thallium concentration in blood was analyzed statistically.Results Thallium concentrations showed a good linear relationship in the range of 0-200μg/L (r = 0.998 4). The intra-day precision (RSD) was lower than 4.913%, the intra-day recovery rate was 96.2%-111.9%; the inter-day precision (RSD) was lower than 7.502%, the inter-day recovery rate was 89.6%-105.2%. The concentration of thallium in blood was significantly reduced after HP per time in high, middle, and low dose groups [(453.43±27.80) mg/L to (56.09±14.44) mg/L in high dose group,F = 8.820,P = 0.003;(64.51±13.60) mg/L to (3.19±0.23) mg/L in middle dose group,F = 36.312,P = 0.000; (5.40±0.98) mg/L to (0.38±0.25) mg/L in low dose group,F = 46.240,P = 0.000]. The adsorption rate of four times of HP in high, middle and low dose group were (87.63±2.48)%, (95.06±1.54)% and (92.76±4.87)%, respectively, without significant difference (F = 4.231,P = 0.070 ).Conclusions The method for measuring thallium was established, and it shows a very stable, simple, sensitive for determination of thallium. HP can effectively remove thallium from blood. Thallium concentration can be reduced by 90% after four times of HP. HP is also effective even when thallium concentration is not high.