UNASSIGNED: Organophosphorus compounds, widely used in agriculture and industry, pose a serious threat to human health due to their acute neurotoxicity. Although traditional interventions for organophosphate poisoning are effective, they often come with significant side effects.
UNASSIGNED: This paper aims to evaluate the potential of enzymes within biological organisms as organophosphorus bioclearing agents. It analyses the technical challenges in current enzyme research, such as substrate specificity, stereoselectivity, and immunogenicity, while exploring recent advancements in the field.
UNASSIGNED: A comprehensive review of literature related to detoxifying enzymes or proteins was conducted. Existing studies on organophosphorus bioclearing agents were summarised, elucidating the biological detoxification mechanisms, with a particular focus on advancements in protein engineering and novel delivery methods.
UNASSIGNED: Current bioclearing agents can be categorised into stoichiometric and catalytic bioclearing agents, both of which have shown some success in preventing organophosphate poisoning. Technological advancements have significantly improved various properties of bioclearing agents, yet challenges remain, particularly in substrate specificity, stereoselectivity, and immunogenicity. Future research will focus on expanding the substrate spectrum, enhancing catalytic efficiency, prolonging in vivo half-life, and developing convenient administration methods.
UNASSIGNED: With the progression of clinical trials, bioclearing agents are expected to become widely used as a new generation of therapeutic organophosphate detoxifiers.

The aim of the study was to systematically evaluate the efficacy and safety of plasma exchange combined with hemoperfusion in the treatment of organophosphorus poisoning.
PubMed, Embase, the Cochrane Library, China National Knowledge Internet, Wanfang database, and Weipu database were searched for articles about this subject. Literature screening and selection were conducted in strict accordance with the inclusion and exclusion criteria.
14 randomized controlled trials with 1,034 participants were included in this meta-analysis study, including 518 cases in plasma exchange combined with hemoperfusion group (the combination treatment group) and 516 cases in hemoperfusion group (the control group). Compared with the control group, the combination treatment group was associated with a higher effective rate (relative risk [RR] = 1.20, 95% confidence interval [CI] [1.11, 1.30], p < 0.00001) and lower fatality rate (RR = 0.28, 95% CI [0.15, 0.52], p< 0.0001); reduced TNF-α (standardized mean difference [SMD] = -1.95, 95% CI [-2.42, -1.48], p < 0.00001), IL-6 (SMD = -1.94, 95% CI [-3.08, -0.80], p = 0.0009), and C-reactive protein (CRP) (SMD = -1.94, 95% CI [-2.86, -1.03], p < 0.0001); shorten coma time (SMD = -1.99, 95% CI [-2.75, -1.24], p < 0.00001), recovery time of cholinesterase activity (SMD = -1.71, 95% CI [-1.90, -1.53], p < 0.00001), and hospital stay (SMD = -1.29, 95% CI [-1.59, -0.98], p < 0.00001). The incidence of complications in the combination treatment group such as liver and kidney damage (RR = 0.30, 95% CI [0.18, 0.50], p < 0.00001), pulmonary infection (RR = 0.29, 95% CI [0.18, 0.47], p < 0.00001), and intermediate syndrome (RR = 0.32, 95% CI [0.21, 0.49], p < 0.00001) was lower than that in the control group.
The current evidence suggests that the combination of plasma exchange with hemoperfusion therapy can reduce the mortality of patients with organophosphorus poisoning, shorten the recovery time of cholinesterase activity and the time of coma, reduce the average length of hospital stay, and reduce the levels of IL-6, TNF-α, and CRP, but high-quality randomized double-blind controlled trials are still required to confirm the current findings in the future.

UNASSIGNED: Acute severe organophosphorus pesticide poisoning (ASOPP) is one of the major diseases that endanger human life and health. However, the effects of conventional therapy including gastric lavages, mechanical ventilation, muscarinic antagonist drugs, and cholinesterase reactivators were uncertain. This meta-analysis aims to investigate the safety and efficacy of hemoperfusion combined with hemofiltration besides routine therapy for ASOPP.
UNASSIGNED: A comprehensive search for candidate publications was performed through PubMed, Medline, Cochrane Library, WanFang, Chinese Biomedical Literature, and China National Knowledge Infrastructure from database inception to May 12, 2020. The retrieved studies were screened by the predefined inclusion and exclusion criteria. The data of important end points were extracted. The risk ratio (RR) and weighted mean difference (WMD) were pooled for categorical variables and continuous variables, respectively. Meta-analyses and publication bias were conducted by using STATA software version 15.1.
UNASSIGNED: A total of 11 randomized controlled trials with 811 patients were included. Compared to conventional therapy group, patients in the hemoperfusion plus hemofiltration group were significantly superior with regard to mortality (RR 0.38, 95% confidence interval [CI] [0.25, 0.57], P < 0.001), total atropine dosing (WMD -147.34 mg, 95% CI [-199.49, -95.18], P < 0.001), duration of mechanical ventilation (WMD -2.34 days, 95% CI [-3.77, -0.92], P < 0.001), cholinesterase recovery time (WMD -2.49 days, 95% CI [-3.14, -1.83], P < 0.001), and length of stay (WMD -4.52 days, 95% CI [-5.31, -3.73], P < 0.001).
UNASSIGNED: Combined hemoperfusion and hemofiltration was a very safe and effective treatment protocol for ASOPP, not only resulting in significantly decreased mortality but also resulting in reduced total atropine dosing, duration of mechanical ventilation, cholinesterase recovery time, and length of stay.

Effective intracerebral delivery acetylcholinesterase (AChE) reactivator is key for the acute organophosphorus (OPs) poison treatment. However, the blood-brain barrier (BBB) restricts the transport of these drugs from blood into the brain. Herein, we developed transferrin receptor (TfR) aptamer-functionalized liposomes (Apt-LP) that could deliver AChE reactivator (obidoxime) across the BBB to act against paraoxon (POX) poisoning. The aptamer had strong affinity for TfR and was modified with 3\'-inverted deoxythymidine (dT) to improve serum stability. The uptake of Apt-LP by bEnd.3 cells was significantly higher than that of non-targeting liposomes. The ability of Apt-LP to penetrate intact BBB was confirmed in in vitro BBB mice model and in vivo biodistribution studies. Treatment of POX-poisoned mice with Apt-LP-LuH-6 reactivated 18% of the brain AChE activity and prevented brain damage to some extent. Taken together, these results showed that Apt-LP may be used as a promising brain-targeted drug delivery system against OPs toxicity.

Paraoxonase 1 (PON1) is a type of aromatic esterase widely existing in mammals. It can hydrolyze various kinds of compounds effectively in vivo and in vitro. Previous studies have confirmed that PON1 can be used as antidote against organophosphorus poisonings (OPs). In this study, we obtained two subtype isozymes (i.e. rhPON1R192 and rhPON1Q192) by gene recombination and compared their detoxification effects against different OPs in rats. The rhPON1R192 demonstrated better detoxification effect against chlorpyrifos poisoning than the rhPON1Q192, whose detoxification effect against diazinon poisoning was prior to the former. Both of them showed poor detoxification effect against trithion. Therefore, we concluded that, to different OPs, better detoxification effect may be achieved by selecting the PON1 subtype isozyme with higher specific hydrolytic activity.

UNASSIGNED: To observe the clinical efficacy of intravenous infusion of atropine with micropump in combination with hemoperfusion on organophosphorus poisoning patients, and investigate the potential mechanism.
UNASSIGNED: In this study, we enrolled 136 organophosphorus poisoning patients who received treatment in this hospital between January 2009 and December 2017, and they were divided into three groups according to the clinical treatment methods, i.e. Group A (comprehensive treatment with HP, n = 47), Group B (continuous intravenous infusion of atropine with micropump, n = 43) and Group C (regular intravenous infusion of atropine, n = 46). In addition to the close monitoring of vital signs, we recorded the atropinization time (min), cholinesterase reactivation time (h), total dose of atropine, recurrence, incidence rate of atropine poisoning (%), hospitalization time (d) and cure rate (%).
UNASSIGNED: In comparison with Group C, patients in Group A and B manifested more stable vital signs with lower total dose of atropine and incidence rate of atropine poisoning and shorter cholinesterase reactivation time, while the cure rate was remarkably increased (p < 0.05), and no significant differences were observed in atropinization time among three groups (p > 0.05). Compared to Group B and C, total dose of atropine in Group A was significantly decreased with obvious excellence in hospitalization time, reduction of complications and increases in cure rates (p < 0.05). Moreover, patients in Group A had the lowest mortality rate among three groups.
UNASSIGNED: In treatment of organophosphorus poisoning patients, HP and continuous intravenous infusion of atropine using micropump can elevate the survival rate, reduce the incidence of adverse reaction, shorten the reactivation time of cholinesterase and decrease the incidence rate of complications, which are superior to the traditional treatment method.

BACKGROUND: Our study sought to assess the effectiveness of a constant micropump infusion of atropine and pralidoxime chloride compared with repeated-bolus doses in patients with severe acute organophosphorus insecticide poisoning (AOPP).
METHODS: A total of 60 patients with severe AOPP, defined as cholinergic crisis with respiratory failure or cerebral edema, were randomly divided into two groups of 30 patients each. In the experimental group, patients received a continuous micropump of atropine and pralidoxime chloride; in the control group, patients were given intermittent injections of atropine and pralidoxime chloride. Primary outcome measures were the dose of atropine required for atropinization, Acute Physiology and Chronic Health Evaluation II (APACHE II) score at atropinization, time to atropinization and acetylcholinesterase (AchE) recovery time. Additionally, the case fatality rate was measured as a secondary outcome.
RESULTS: Compared to patients in the control group, the time to atropinization, AchE recovery time, dose of atropine when atropinization occurred, and APACHE II score in the experimental group showed a statistically significant therapeutic effect (p < 0.05), and the case fatality rate of the experimental group was lower than that of the control group (p < 0.05).
CONCLUSIONS: Continuous micropump of atropine and pralidoxime chloride combined is more effective than the use of repeated-bolus injection in the treatment of severe acute organophosphorus insecticide poisoning.