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Objective:To study the expression and significance of long noncoding RNA (lncRNA) LINC00657 in diffuse-type adenocarcinoma of esophagogastric junction (AEG).Methods:RT-PCR was used to determine the expression of LINC00657 in AEG tissues and AEG patient-derived tumor cells (PDCs). The expression of E-cadherin in AEG tissues and PDCs was detected. The Kaplan-Meier method was used to evaluate the correlation of LINC00657 expression with the overall survival (OS) of patients.Results:LINC00657 was highly expressed in AEG tissues [(1.41±0.12) vs. (0.61±0.11), t=276.038, P<0.01] and PDCs, while E-cadherin was significantly down-regulated. The expression of LINC00657 was retated to tumor diamer, invassion depth, lymph node metastasis, TNM staging (all P<0.05) In Kaplan-Meier analysis, high levels of LINC00657 were associated with poor prognosis for patients with diffuse-type AEG. In addition, a significant inverse relationship was observed between LINC00657 and E-cadherin expression ( r=-0.529, P<0.001). Conclusions:Elevated expression of LINC00657 in diffuse-type AEG tissues is associated with poor prognosis and may confer a malignant phenotype upon tumor cells.
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Tianjin Port 8 · 12 Catastrophic Explosion Accidentis making us alert. And how to learn lessons from the acci?dent,how to form effective prevention and control strategies,which make us much ponder over. Based on summarizing the experiences of the previous chemical emergencies,from the aspects of monitoring and early warning,disaster assessment,on-site detection,and remote telemetry,this paper expounds the importance of the related mechanism and the hardware construction. Then the seriousbot?tleneckin the construction of Chinese chemical defense was pointed out as well as introducing the new development direction of for?eign military monitoring and detecting equipments. Our aim is attracting much attention of peers within the discipline ,so as to effec?tively enhance the abilities of monitoring and early warning and emergency handling for chemical defense in China.
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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.
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OBJECTIVE To establish a model for chlorpyrifos(CPF)whole-body dynamic inhalation exposure in SD rats and investigate the injury effects after acute exposure by CPF. METHODS By optimizing the aerosol parameters ,the animal acute dynamic inhalation exposure of CPF was established. Absorption sampling-gas phase detecting technology was used to monitor the concentration of CPF in the whole-body dynamic-inhalation exposure cabin by exploring the relationship between the concentration , particle size of CPF aerosol and the CPF inhalation time in the exposure cabin via a particle size detector. Using Bliss method,specific pathogen free SD male rats were allocated to the environment of CPF exposure at different lethal concentrations and time points. The symptoms and deaths of these SD male rats in different groups were recorded within the following 10 d. Based on the median lethal concentra?tion time(LCt50),the values of plasma cholinesterase(ChE)were checked at different time points after being exposed at different doses. RESULTS The mean concentrations of CPF aerosol at nine time points was 160.6 mg · m-3,the relative standard deviation value was 6.9%;the geometrical mean of aerosol particle size was 1.1 μm,and the geometric standard deviation was 1.8. The results met the technical requirements of Organization for Economic Cooperation and Development regarding acute inhalation exposure. Under these equipment conditions,the LCt50 of CPF acute inhalation of SD male rats was 1654.2 mg · m-3 · h,suggesting that plasma ChE inhibitory rate was higher with the increase in the exposing dose,and that there was a significant difference as compared with the controls(P<0.05). CONCLU?SION The model for whole-body dynamic-inhalation exposure of CPF is applicable to rats,which can serve as an experimental platform and technical support to inhalation vulnerability and the research on prevention and cure of organophosphate industrial products and nerve agents.
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As an important measure to reduce casualties and prevent secondary pollution, decontamination is an impor-tant link in the process of emergency response during chemical accidents.The decontamination effect is closely related to decontamination technology and equipment.Decontamination agent selection and development are an important part of a decontamination technology.In this paper, the development and use of cleaning agents, such as alkaline, oxidation and chlorination, adsorption (degradation), metal oxide and oxygen acid salt, chemical compounds, biological (enzymatic), and individual disinfection package, light decontamination equipment, multifunctional integrated large-scale decontamination equipment at home or abroad, are reviewed.By laying bare the gap between China and advanced countries in the related field, we hope to raise the concern of relevant professional counterparts and promote the development of domestic decontami-nation technology and equipment with decontaminant agents at the core.
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Chemical threat is a serious public safety problem we must be facing. And how to effectively deal with it is a priority. Based on the needs of chemical defence in our country, hierarchical monitoring technology platform is proposed. From three aspects of monitoring and early warning, on-site detecting and laboratory confirmation, and the international development needs and trends, the comparation of domestic and foreign equipment construction and development suggestions in our country are discussed and reviewed. Our aim is to establish effective monitoring mechanism for chemical defence, so as to nip the chemical threat in the bud or reduce the chemical hazards to the minimum.
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″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.
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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.
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OBJECTIVE Based on different drug loading models,three types of nanoparticulated HI-6 were prepared and their reactivations on inhibited acetylcholinesterase (AChE)in peripheral and central nervous syste ms were evaluated and compared in so man-intoxicated mice.METHODS Three kinds of nano-reactivators including HI-6 loaded human serum albunin nanoparticle (HSA-HI-6 NP),HI-6 absorptive mesoporous silica nanoparticle(MSN-HI-6),polylactico-glycolic acid nanoparticle coated HI-6 (PLGA-HI-6 NP)were prepared.The characteristic of all blank nanocarriers was observed through elec-tron microscope.HI-6 release rate of nano-reactivators was also determined in vitro.Then the reactiva-tion rate of nano-reactivators at a constant HI-6 dosage(22 mg·kg -1 )on so man-inhabited AChE both in blood and brain was assessed the so man intoxicated mice(120 μg·kg -1 ,sc).RESULTS All the syn-thetic nanocarriers met the de mand for nanodrug use in vivo.The rate of HI-6 release of nano-reactiva-tors was HI-6 >HSA-HI-6 NPs >MSN-HI-6 >PLGA-HI-6 NP in vitro.On the reactivations of so man-inhibited mice blood AChE,the free HI-6 and HSA-HI-6 NPs,as well as MSN-HI-6 showed co mparable reactivation rates(20% -30%)but were greater than that of PLGA-HI-6 NPs (6.2%)(P <0.01 ). However on the reactivations of so man-inhibited mice brain AChE,the reactivation rate of HSA-HI-6 NP (15.3%)was significantly higher than that of PLGA-HI-6 NP(3.3%)and free HI-6(6.3)(P<0.01 ).In addition,MSN-HI-6 group had a significant reactivation rate compared to PLGA-HI-6 NPs(P <0.01 ). But there was no statistic difference between MSN-HI-6 and free HI-6.CONCLUSION The reactivation potency changed obviously with different drug loading models and HSA-HI-6 NPs had the most potent reactivation on so man-inhibited AChE in both blood and brain.
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OBJECTIVE The antagonism of obidoxi me on sarin induced miosis and visual impair-ment was evaluated and its antagonistic mechanism was investigated.METHODS ① 30 min after sarin (2 μg /0.1 mL per eye)was given as an eyedrop,the ability of the 2.5%,5.0%,7.5% obidoxi me and 1 .0% atropine to reverse effects of sarin on pupil dia meter and light reflex were evaluated at different ti mes.② Another 36 rabbits received sarin and at 30 min afer sarin exposure,the drugs above were ad-ministrated and their effects on pupillary light reflex,as well as the AChE activity of cornea,iris and reti-na were recorded 4h after the treatment.RESULTS ① Miosis and impaired pupillary light reflex oc-curred soon after sarin exposure but the abnormal pupil width and pupillary light reflex had disappeared by 48 h after sarin exposure;Subcequent to 1 .0% atropine treatment,the pupil dilatedinstead while the impaired light reflex did not i mprove significantly;unlike atropine,soon after ad ministration of 2.5%, 5.0%,7.5% obidoxi me,the pupil dia meter and light reflex were significantly increased(P <0.01 )and then had beco me normal totally by 24 h post-dose,much faster than those of the control and atropine treatment group.However,there was no significant difference in the recovery ti me between the different dose groups of obidoxi me.② 4h after treatment,the AChE activity in cornea and irisof sarin-treated group were (42 ±4)%,(26 ±2)%,respectively;the AChE activity in cornea of 2.5%,5.0%,7.5%obidoxi me were (74 ±1 1 )%,(81 ±10)% and (74 ±7)%,respectively,and the AChE activity in iris were(39 ±10)%,(43 ±8)% and (43 ±8)%,respectively ,co mpared with sarin-treated group,AChE activities of cornea and iris as well as light reflex of the obidoxi me-treated group were significantly increased(P<0.01 ).But there was no difference in light reflex and AChE activity between the sarin-treated and atropine-treated groups.CONCLUSION Obidoxi me showed better antagonism of sarin-induced ocular effects than that of the commonly used drug,atropine;the antagonistic mechanism is likely closely related to its rapid reactivation of the inhibited AChE in the cornea and iris.
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A sensitive determination method for sulfur mustard ( HD ) metabolites thiodiglycol ( TDG ) in rabbit urine was established and validated using isotope dilution negative ion chemical ionization ( NICI) gas chromatography-mass spectrometry ( GC-MS ) , in which deuterated thiodiglycol ( TDG-d8 ) was used as internal standard. Two solid-phase extraction ( SPE) steps were established and optimized in order to reduce the interfering backgrounds, one was used to extract thiodiglycol ( TDG ) from urine with self-assemblied Florisil SPE cartridges, another cleaning treatment of the by-products after pentafluorobenzoyl chloride (PFBZ) derivatization. The results showed that the limits of detection quantitation of this method were 0. 1 and 0. 3 μg/L, respectively. The exposure time-response relationship and exposure dose-response relationship of TDG in rabbit urine were studied after rabbit skin exposure to sulfur mustard (HD, 0. 02-0. 15 LD50). The TDG levels in the rabbit urine increased rapidly during the first day after application and then decreased over time for all dosage groups. A secondary release was also noted for the high-dose group, and the duration of high TDG excretion levels was correlated positively with the HD dosage levels. We thus concluded that abnormally high levels of TDG in urine could be used as a clear diagnostic indicator of HD exposure.
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Nerve agents (NAs) belong to the class of organic phosphorus compounds which are acetylcholinesterase ( AChE) inhibitors, including soman, sarin, tabun,VX, etc.NAs are extremely toxic and considered as the most danger-ous chemical warfare agents.The current standard treatment for poisoning by nerve agents consists of the combined adminis-tration of anticholinergic drugs such as atropine sulphate, AChE reactivators such as pralidoxime, obidoxime and HI-6 and diazepam for anticonvulsant effects, but oximes are therapeutic antidotes against nerve agent intoxications which exert the therapeutic purposes primarily by reactivating the NAs-inhibited AChE.In this paper, the mechanism of nerve agents, the main working procedure of anti-NAs drugs, the chemical structure of classic reactivator, the corresponding antitoxic action, in vivo and in vitro effects and metabolic kinetics are reviewed.
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Objective To establish a whole-body dynamic inhalation exposure system for toxicological studies on highly toxic chemicals, and to evaluate the safety and applicability of the system.Methods The safety and standardization of the laboratory were ensured after positive and negative pressure protection and airtight protection were finished.By modifying and optimizing the key technological units of the exposure chamber, the relationships between aerosol concentrations in the chamber and the push rate, exposure time and different monitoring points were investigated.Results and Conclusion Multi-protection was achieved, including the independent exposure chamber, negative pressure experiment and positive pressure protection under working conditions.The laboratory meets the demands of safety and specifications.The exposure aerosol concentrations in the chamber are uniform, stable and controllable while the air is dynamically flowing.The whole-body dynamic inhalation exposure system can meet the need for toxicological studies on highly toxic chemicals.
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Objective To observe the effect of neutralizing monoclonal antibodies to antiglomerular basement membrane (GBM) antibody on anti-GBM nephritis rats. Methods Wistar rats were randomly divided into five groups: control group Ⅰ was a negative control and was injected with healthy human IgG via the caudal vein. Control group Ⅱ was injected with neutralizing monoclonal antibodies to anti-GBM antibody only. Anti- GBM nephritis group was injected with human anti-GBM antibody via the caudal vein only. Intervention group Ⅰ was injected with human anti-GBM antibody via the caudal vein and then with neutralizing monoclonal antibodies to anti-GBM antibody at day 7. Intervention group Ⅱ was injected with human antiGBM antibody via the caudal vein and then with neutralizing monoclonal antibodies to anti-GBM antibody at day 14. The blood, urine and kidney tissue were collected at day 7, 14, 21 for analysis of 24-hour urinary protein, BUN, Ser and histological study. Results At day 21, there were significant decreases in intervention group Ⅰ compared with anti-GBM nephritis group in 24-hour proteinuria [(16.62±5.53) g], BUN[(11.53±2.26) mmol/L] and Scr [(102.46±16.86) μmol/L] (P＜0.05), and also in intervention group Ⅱ as compared to anti-GBM nephritis group, but no significant difference was found (P＞0.05) . There was obvious decrease of renal cell proliferation,crescent formation and deposition of immune complexes in intervention group Ⅰ and intervention group Ⅱ compared with anti-GBM nephritis group, while such improvement in intervention group Ⅰ was more significant. There was no significant change in control group Ⅰ and control group Ⅱ.Conclusion The early application of neutralizing monoclonal antibodies to anti-GBM antibodies can effectively improve the kidney lesions of anti-GBM nephritis rats.