Longitudinal molecular trajectories of diffuse glioma in adults.

The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear1,2. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner.

PHB2 Maintains the Contractile Phenotype of VSMCs by Counteracting PKM2 Splicing.

BACKGROUND: Phenotypic transition of vascular smooth muscle cells (VSMCs) accounts for the pathogenesis of a variety of vascular diseases during the early stage. Recent studies indicate the metabolic reprogramming may be involved in VSMC phenotypic transition. However, the definite molecules that link energy metabolism to distinct VSMC phenotype remain elusive. METHODS: A carotid artery injury model was used to study postinjury neointima formation as well as VSMC phenotypic transition in vivo. RNA-seq analysis, cell migration assay, collagen gel contraction assay, wire myography assay, immunoblotting, protein interactome analysis, co-immunoprecipitation, and mammalian 2-hybrid assay were performed to clarify the phenotype and elucidate the molecular mechanisms. RESULTS: We collected cell energy-regulating genes by using Gene Ontology annotation and applied RNA-Seq analysis of transforming growth factor-ß or platelet-derived growth factor BB stimulated VSMCs. Six candidate genes were overlapped from energy metabolism-related genes and genes reciprocally upregulated by transforming growth factor-ß and downregulated by platelet-derived growth factor BB. Among them, prohibitin 2 has been reported to regulate mitochondrial oxidative phosphorylation. Indeed, prohibitin 2-deficient VSMCs lost the contractile phenotype as evidenced by reduced contractile proteins. Consistently, Phb2SMCKO mice were more susceptible to postinjury VSMC proliferation and neointima formation compared with Phb2flox/flox mice. Further protein interactome analysis, co-immunoprecipitation, and mammalian 2-hybrid assay revealed that prohibitin 2, through its C-terminus, directly interacts with hnRNPA1, a key modulator of pyruvate kinase M1/2 (PKM) mRNA splicing that promotes PKM2 expression and glycolysis. Prohibitin 2 deficiency facilitated PKM1/2 mRNA splicing and reversion from PKM1 to PKM2, and enhanced glycolysis in VSMCs. Blocking prohibitin 2-hnRNPA1 interaction resulted in increased PKM2 expression, enhanced glycolysis, repressed contractile marker genes expression in VSMCs, as well as aggravated postinjury neointima formation in vivo. CONCLUSIONS: Prohibitin 2 maintains VSMC contractile phenotype by interacting with hnRNPA1 to counteract hnRNPA1-mediated PKM alternative splicing and glucose metabolic reprogramming.

ETCO2 waveforms-assisted awake nasal fibreoptic intubation.

Awake fibreoptic intubation has always been considered the gold standard for expected difficult airway management. However, the use of fibreoptic intubation was limited because it is time-consuming, requires skillful operators and easily affected by blood or secretions in the oral or nasopharynx. We reported a modified technique of awake fibreoptic nasal intubation with the aid of End-tidal carbon dioxide (ETCO2) monitoring, aiming to improve the efficiency and safety of awake fibreoptic intubation.

The roles of the gut microbiota-miRNA interaction in the host pathophysiology.

The gut microbiota regulates the biological processes of organisms acting like 'another' genome, affecting the health and disease of the host. MicroRNAs, as important physiological regulators, have been found to be involved in health and disease. Recently, the gut microbiota has been reported to affect host health by regulating host miRNAs. For example, Fusobacterium nucleatum could aggravate chemoresistance of colorectal cancer by decreasing the expression of miR-18a* and miR-4802. What's more, miRNAs can shape the gut microbiota composition, ultimately affecting the host's physiology and disease. miR-515-5p and miR-1226-5p could promote the growth of Fusobacterium nucleatum (Fn) and Escherichia coli (E.coli), which have been reported to drive colorectal cancer. Here, we will review current findings of the interactions between the gut microbiota and microRNAs and discuss how the gut microbiota-microRNA interactions affect host pathophysiology including intestinal, neurological, cardiovascular, and immune health and diseases.

Back propagation neutral network based signal acquisition for Brillouin distributed optical fiber sensors.

This manuscript proposes a method based on back propagation (BP) neural network and the spectral subtraction method to quickly obtain sensing information in Brillouin fiber optics sensors. BP neural network's characteristics which can realize any complex nonlinear mapping help to determine the frequency shift section(s) information. The training function, transfer function and number of hidden layer nodes of BP neural network are determined with experimental data. The experimental results show that comparing with traditional Lorentz fitting algorithm and edge detection with Sobel operator, the BP neural network is about 1/12 in terms of time complexity with the Lorentz algorithm, about 1/9 with the edge detection based on Sobel operator; while the respective accuracy on determine the frequency shifted section(s) has improved by 79.4% and 27.9%.

Polychlorinated naphthalenes in human serum samples from an industrial city in Eastern China: Levels, sources, and sex differences.

Polychlorinated naphthalenes (PCNs) in the environment in China have been studied extensively. However, there have been no reports on PCNs in human serum samples from China. In this context, we collected 480 serum samples from an industrial city in Eastern China. The concentration range for the sum of the mono-to octa-CNs was 14300-50700 pg/g lipid. The most predominant congener was CN-5/7, which accounted for 21.6%-51.1% of the total PCN concentration. Further analysis indicated that residues of PCN industrial technical products in the local environment appear to be the main source of CN-5/7 in the serum samples. On the other hand, the sum of the tetra-to octa-CNs concentration was obviously higher in males (1390 ±â€¯929 pg/g lipid) than in females (267 ±â€¯25 pg/g lipid). Moreover, the concentrations of combustion-related PCNs in the male 20-24, 25-29 and 30-34 years groups were obviously higher than those in the female samples. Therefore, industrial thermal processes are important sources of PCNs in male serum in addition to PCN products. The toxic equivalent (TEQ) concentrations of PCNs in the pooled serum samples ranged from 0.12 to 0.40 pg/g lipid. CN-10 and CN-66/67 were the dominant TEQ congeners in male serum, and CN-10, CN-1, and CN-2 were the main TEQ congeners in female serum.

Insights into Tissue-specific Specialized Metabolism in Tieguanyin Tea Cultivar by Untargeted Metabolomics.

Tea plants produce extremely diverse and abundant specialized metabolites, the types and levels of which are developmentally and environmentally regulated. However, little is known about how developmental cues affect the synthesis of many of these molecules. In this study, we conducted a comparative profiling of specialized metabolites from six different tissues in a premium oolong tea cultivar, Tieguanyin, which is gaining worldwide popularity due to its uniquely rich flavors and health benefits. UPLC-QTOF MS combined with multivariate analyses tentatively identified 68 metabolites belonging to 11 metabolite classes, which exhibited sharp variations among tissues. Several metabolite classes, such as flavonoids, alkaloids, and hydroxycinnamic acid amides were detected predominantly in certain plant tissues. In particular, tricoumaroyl spermidine and dicoumaroyl putrescine were discovered as unique tea flower metabolites. This study offers novel insights into tissue-specific specialized metabolism in Tieguanyin, which provides a good reference point to explore gene-metabolite relationships in this cultivar.

Metabolite Profiling of 14 Wuyi Rock Tea Cultivars Using UPLC-QTOF MS and UPLC-QqQ MS Combined with Chemometrics.

Wuyi Rock tea, well-recognized for rich flavor and long-lasting fragrance, is a premium subcategory of oolong tea mainly produced in Wuyi Mountain and nearby regions of China. The quality of tea is mainly determined by the chemical constituents in the tea leaves. However, this remains underexplored for Wuyi Rock tea cultivars. In this study, we investigated the leaf metabolite profiles of 14 major Wuyi Rock tea cultivars grown in the same producing region using UPLC-QTOF MS and UPLC-QqQ MS with data processing via principal component analysis and cluster analysis. Relative quantitation of 49 major metabolites including flavan-3-ols, proanthocyanidins, flavonol glycosides, flavone glycosides, flavonone glycosides, phenolic acid derivatives, hydrolysable tannins, alkaloids and amino acids revealed clear variations between tea cultivars. In particular, catechins, kaempferol and quercetin derivatives were key metabolites responsible for cultivar discrimination. Information on the varietal differences in the levels of bioactive/functional metabolites, such as methylated catechins, flavonol glycosides and theanine, offers valuable insights to further explore the nutritional values and sensory qualities of Wuyi Rock tea. It also provides potential markers for tea plant fingerprinting and cultivar identification.

High Level of Spinosad Production in the Heterologous Host Saccharopolyspora erythraea.

UNLABELLED: Spinosad, a highly effective insecticide, has an excellent environmental and mammalian toxicological profile. Global market demand for spinosad is huge and growing. However, after much effort, there has been almost no improvement in the spinosad yield from the original producer, Saccharopolyspora spinosa Here, we report the heterologous expression of spinosad using Saccharopolyspora erythraea as a host. The native erythromycin polyketide synthase (PKS) genes in S. erythraea were replaced by the assembled spinosad gene cluster through iterative recombination. The production of spinosad could be detected in the recombinant strains containing the whole biosynthesis gene cluster. Both metabolic engineering and UV mutagenesis were applied to further improve the yield of spinosad. The final strain, AT-ES04PS-3007, which could produce spinosad with a titer of 830 mg/liter, has significant potential in industrial applications. IMPORTANCE: This work provides an innovative and promising way to improve the industrial production of spinosad. At the same time, it also describes a successful method of heterologous expression for target metabolites of interest by replacing large gene clusters.

Antitumor Activity of a Novel Sphingosine-1-Phosphate 2 Antagonist, AB1, in Neuroblastoma.

The bioactive lipid sphingosine-1-phosphate (S1P) and its receptors (S1P1-5) play critical roles in many pathologic processes, including cancer. The S1P axis has become a bona fide therapeutic target in cancer. JTE-013 [N-​(2,​6-​dichloro-​4-​pyridinyl)-​2-​[1,​3-​dimethyl-​4-​(1-​methylethyl)-​1H-​pyrazolo[3,​4-​b]pyridin-​6-​yl]-​hydrazinecarboxamide], a known S1P2 antagonist, suffers from instability in vivo. Structurally modified, more potent, and stable S1P2 inhibitors would be desirable pharmacological tools. One of the JTE-013 derivatives, AB1 [N-(1H-4-isopropyl-1-allyl-3-methylpyrazolo[3,4-b]pyridine-6-yl)-amino-N'-(2,6-dichloropyridine-4-yl) urea], exhibited improved S1P2 antagonism compared with JTE-013. Intravenous pharmacokinetics indicated enhanced stability or slower clearance of AB1 in vivo. Migration assays in glioblastoma showed that AB1 was slightly more effective than JTE-013 in blocking S1P2-mediated inhibition of cell migration. Functional studies in the neuroblastoma (NB) cell line SK-N-AS showed that AB1 displayed potency at least equivalent to JTE-013 in affecting signaling molecules downstream of S1P2. Similarly, AB1 inhibition of the growth of SK-N-AS tumor xenografts was improved compared with JTE-013. Cell viability assays excluded that this enhanced AB1 effect is caused by inhibition of cancer cell survival. Both JTE-013 and AB1 trended to inhibit (C-C motif) ligand 2 expression and were able to significantly inhibit subsequent tumor-associated macrophage infiltration in NB xenografts. Interestingly, AB1 was more effective than JTE-013 in inhibiting the expression of the profibrotic mediator connective tissue growth factor. The terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine nick-end labeling assay and cleaved caspase-3 detection further demonstrated that apoptosis was increased in AB1-treated NB xenografts compared with JTE-013. Overall, the modification of JTE-013 to produce the AB1 compound improved potency, intravenous pharmacokinetics, cellular activity, and antitumor activity in NB and may have enhanced clinical and experimental applicability.

Gene Replacement for the Generation of Designed Novel Avermectin Derivatives with Enhanced Acaricidal and Nematicidal Activities.

Avermectin (AVM) and ivermectin (IVM) are potent pesticides and acaricides which have been widely used during the past 30 years. As insect resistance to AVM and IVM is greatly increasing, alternatives are urgently needed. Here, we report two novel AVM derivatives, tenvermectin A (TVM A) and TVM B, which are considered a potential new generation of agricultural and veterinary drugs. The molecules of the TVMs were designed based on structure and pharmacological property comparisons among AVM, IVM, and milbemycin (MBM). To produce TVMs, a genetically engineered strain, MHJ1011, was constructed from Streptomyces avermitilis G8-17, an AVM industrial strain. In MHJ1011, the native aveA1 gene was seamlessly replaced with milA1 from Streptomyces hygroscopicus. The total titer of the two TVMs produced by MHJ1011 reached 3,400 mg/liter. Insecticidal tests proved that TVM had enhanced activities against Tetranychus cinnabarinus and Bursaphelenchus xylophilus, as desired. This study provides a typical example of exploration for novel active compounds through a new method of polyketide synthase (PKS) reassembly for gene replacement. The results of the insecticidal tests may be of use in elucidating the structure-activity relationship of AVMs and MBMs.

Both FOXO3a and FOXO1 are involved in the HGF-protective pathway against apoptosis in endothelial cells.

Hepatocyte growth factor (HGF) was identified as an endogenous tissue protective agent against apoptosis in many cell types. The mechanism by which HGF protects primary endothelial cells (ECs) has not yet been completely elucidated. FOXO1 and FOXO3a, two members of the FOXO family, are the most abundant FOXO isoforms in mature endothelial cells. In this study, we aimed to explore whether FOXO1 and FOXO3a play similar roles in HGF-mediated protection against apoptosis in mature endothelial cells. Our result showed that HGF prevented ECs from oxidative-stress induced apoptosis in part by inducing the phosphorylation of FOXO proteins. FOXO1 and FOXO3a are equally important in this process by regulating the expression of Bim, PUMA, FasL, and TRAIL.

Metabolites of isocorynoxeine in rats after its oral administration.

This work presents the metabolites of isocorynoxeine (ICOR), which is one of four bioactive tetracyclic oxindole alkaloids isolated from Uncaria hooks used commonly in the traditional Chinese medicines and Kampo medicines. After oral administration of 40 mg kg(-1) ICOR to rats, bile was drained and analyzed by LC-MS. Two phase I metabolites, namely 11-hydroxyisocorynoxeine (M1) and 10-hydroxyisocorynoxeine (M2), and two phase II metabolites, namely 11-hydroxyisocorynoxeine 11-O-ß-D-glucuronide (M3) and 10-hydroxyisocorynoxeine 10-O-ß-D-glucuronide (M4), were isolated from rat excreta and bile, respectively, whose structures were elucidated on the basis of CD, NMR, and MS.

Association between the neutrophil-to-lymphocyte ratio and in-hospital mortality in patients with chronic kidney disease and coronary artery disease in the intensive care unit.

BACKGROUND: The objective of this study was to investigate the correlation between neutrophil-to-lymphocyte ratios (NLR) and the risk of in-hospital death in patients admitted to the intensive care unit (ICU) with both chronic kidney disease (CKD) and coronary artery disease (CAD). METHODS: Data from the MIMIC-IV database, which includes a vast collection of more than 50,000 ICU admissions occurring between 2008 and 2019, was utilized in the study and eICU-CRD was conducted for external verification. The Boruta algorithm was employed for feature selection. Univariable and multivariable logistic regression analyses and multivariate restricted cubic spline regression were employed to scrutinize the association between NLR and in-hospital mortality. The receiver operating characteristic (ROC) curves were conducted to estimate the predictive ability of NLR. RESULTS: After carefully applying criteria to include and exclude participants, a total of 2254 patients with CKD and CAD were included in the research. The findings showed a median NLR of 7.3 (4.4, 12.1). The outcomes of multivariable logistic regression demonstrated that NLR significantly elevated the risk of in-hospital mortality (OR 2.122, 95% confidence interval [CI] 1.542-2.921, P < 0.001) after accounting for all relevant factors. Further insights from subgroup analyses unveiled that age and Sequential Organ Failure Assessment (SOFA) scores displayed an interactive effect in the correlation between NLR and in-hospital deaths. The NLR combined with traditional cardiovascular risk factors showed relatively great predictive value for in-hospital mortality (AUC 0.750). CONCLUSION: The findings of this research indicate that the NLR can be used as an indicator for predicting the likelihood of death during a patient's stay in the intensive care unit, particularly for individuals with both CAD and CKD. The results indicate that NLR may serve as a valuable tool for assessing and managing risks in this group at high risk. Further investigation is required to authenticate these findings and investigate the mechanisms that underlie the correlation between NLR and mortality in individuals with CAD and CKD.

FTY720 inhibits tumor growth and enhances the tumor-suppressive effect of topotecan in neuroblastoma by interfering with the sphingolipid signaling pathway.

BACKGROUND: Neuroblastoma (NB) is the most common extra-cranial solid tumor in childhood. Poor outcomes for children with advanced disease underscore the need for novel therapeutic strategies. FTY720, an immunomodulating drug approved for multiple sclerosis, has been investigated in oncology with promising preclinical activities. To date, its effect in NB has not been explored. Herein we describe our preclinical experience with FTY720, alone or in combination with topotecan, and its putative mechanism of action in NB. PROCEDURE: MTT assay was performed to assess the effect of FTY720 on cell viability. A NB xenograft model was employed to assess the efficacy of FTY720 on tumor growth. Quantitative real-time PCR and Western blot were employed to determine changes of mRNA and protein expression, respectively. Liquid chromatography/tandem mass spectrometry was used to measure sphingolipid levels. RESULTS: FTY720, but not FTY720-P induced NB cell death. FTY720 inhibited the growth of NB xenografts and enhanced the tumor-suppressive effect of topotecan both in vitro and in vivo. FTY720 significantly inhibited sphingosine kinase 2 (SphK2) mRNA and protein expression in NB cells. Pro-apoptotic sphingosine levels were increased in NB cells and NB xenografts treated with FTY720. FTY720-induced cell death was caspase-independent and involved the dephosphorylation of Akt and BAD at Ser136. CONCLUSIONS: Our data demonstrate that FTY720 has potent preclinical anti-cancer activity in NB. Its unique death signaling mechanism, interference with the sphingolipid pathway, acts cooperatively with that of topotecan, suggesting that FTY720 related molecules may be useful in NB treatment.

Cytotoxicity of Local Anesthetics on Bone, Joint, and Muscle Tissues: A Narrative Review of the Current Literature.

Background: Local anesthetics are commonly used in surgical procedures to control pain in patients. Whilst the cardiotoxicity and neurotoxicity of local anesthetics have received much attention, the cytotoxicity they exert against bone, joint, and muscle tissues has yet to be well recognized. Objective: This review aimed to raise awareness regarding how local anesthetics may cause tissue damage and provide a deeper understanding of the mechanisms of local anesthetic-induced cytotoxicity. We summarized the latest progress on the cytotoxicity of local anesthetics and the underlying mechanisms and discussed potential strategies to reduce it. Findings: We found that the toxic effects of local anesthetics on bone, joint, and muscle tissues were time- and concentration-dependent in vitro. Local anesthetics induced apoptosis, necrosis, and autophagy through specific cellular pathways. Altogether, this review indicates that toxicity of local anesthetics may be avoided by rationally selecting the appropriate anesthetic, limiting the total amount, and determining the lowest effective concentration and duration.

Sciatic Nerve Block Combined with Flurbiprofen Inhibits Spinal Cord Inflammation and Improves Postoperative Pain in Rats with Plantar Incision.

Background and Purpose: Peripheral nerve block is often used to relieve postoperative pain. But the effect of nerve block on inflammatory response is not fully understood. Spinal cord is the primary center of pain processing. This study is to investigate the effect of single sciatic nerve block on the inflammatory response of the spinal cord in rats with plantar incision and the combined effect with flurbiprofen. Methods: The plantar incision was used to establish a postoperative pain model. Single sciatic nerve block, intravenous flurbiprofen or the combination of both were used for intervention. The sensory and motor functions after nerve block and incision were evaluated. The changes of IL-1ß, IL-6, TNF-α, microglia and astrocytes in the spinal cord were examined by qPCR and immunofluorescence respectively. Results: Sciatic nerve block with 0.5% ropivacaine in rats induced sensory block for 2h and motor block for 1.5h. In the rats with plantar incision, the single sciatic nerve block did not alleviate postoperative pain or inhibit the activation of spinal microglia and astrocytes, but the levels of IL-1ß and IL-6 in spinal cord were decreased when the nerve block wore off. The combined effect of a single sciatic nerve block and intravenous flurbiprofen not only decreased the levels of IL-1ß, IL-6, and TNF-α, but also relieved the pain and alleviated the activation of microglia and astrocytes. Conclusion: The single sciatic nerve block cannot improve postoperative pain or inhibit the activation of spinal cord glial cells, but can reduce the expression of spinal inflammatory factors. Nerve block combined with flurbiprofen can inhibit spinal cord inflammation and improve postoperative pain. This study provides a reference for rational clinical application of nerve block.

Novel electrochemical sensing platform basing on di-functional stimuli-responsive imprinted polymers for simultaneous extraction and determination of metronidazole.

A novel magnetic-controlled electrochemical sensor has been fabricated by combined photo-responsive surface molecular imprinted polymers (P-SMIPs) and electrochemical sensor. In particular, the P-SMIPs were obtained by living radical polymerization of photo-responsive functional monomer onto the magnetic Fe3O4 modified multi-walled carbon nanotubes nanocomposites. The magnetic glassy carbon electrode was introduced to make the anchoring and removal of P-SMIPs onto the magnetic-controlled glassy carbon electrode easy to manipulate. Driven by UV/vis light, the platform performs releasing and absorption of metronidazole basing on conformational variations of the photo-responsive monomer at the receptor sites part in the P-SMIPs. This process can be tested by the photo-responsive variations of metronidazole electrochemical signal. As the consequence, extracting of P-SMIPs sensor can be conveniently triggered by the controllable UV light intervention measure, leading to effectively improve in both analytes mass transfer rate to the receiving media and extraction efficiency. The experimental result indicated that the excellent recoveries of metronidazole were varied between 77.9% and 89.9% with RSDs ≤4.87% in the biological samples. Therefore, the P-SMIPs sensor shows satisfactory potential in reusable extractions that can be recycled several times with no significant loss of activity, and this utilization strategy can be extended to other analytes, achieving manifold applications of pharmaceutical and environmental.

An allelic series of spontaneous Rorb mutant mice exhibit a gait phenotype, changes in retina morphology and behavior, and gene expression signatures associated with the unfolded protein response.

The Retinoid-related orphan receptor beta (RORß) gene encodes a developmental transcription factor and has 2 predominant isoforms created through alternative first exon usage; one specific to the retina and another present more broadly in the central nervous system, particularly regions involved in sensory processing. RORß belongs to the nuclear receptor family and plays important roles in cell fate specification in the retina and cortical layer formation. In mice, loss of RORß causes disorganized retina layers, postnatal degeneration, and production of immature cone photoreceptors. Hyperflexion or "high-stepping" of rear limbs caused by reduced presynaptic inhibition by Rorb-expressing inhibitory interneurons of the spinal cord is evident in RORß-deficient mice. RORß variants in patients are associated with susceptibility to various neurodevelopmental conditions, primarily generalized epilepsies, but including intellectual disability, bipolar, and autism spectrum disorders. The mechanisms by which RORß variants confer susceptibility to these neurodevelopmental disorders are unknown but may involve aberrant neural circuit formation and hyperexcitability during development. Here we report an allelic series in 5 strains of spontaneous Rorb mutant mice with a high-stepping gait phenotype. We show retinal abnormalities in a subset of these mutants and demonstrate significant differences in various behavioral phenotypes related to cognition. Gene expression analyses in all 5 mutants reveal a shared over-representation of the unfolded protein response and pathways related to endoplasmic reticulum stress, suggesting a possible mechanism of susceptibility relevant to patients.

The advantages of penehyclidine hydrochloride over atropine in acute organophosphorus pesticide poisoning: A meta-analysis.

Background: Penehyclidine hydrochloride (PHC) has been used for many years as an anticholinergic drug for the treatment of acute organophosphorus pesticide poisoning (AOPP). The purpose of this meta-analysis was to explore whether PHC has advantages over atropine in the use of anticholinergic drugs in AOPP. Methods: We searched Scopus, Embase, Cochrane, PubMed, ProQuest, Ovid, Web of Science, China Science and Technology Journal Database (VIP), Duxiu, Chinese Biomedical literature (CBM), WanFang, and Chinese National Knowledge Infrastructure (CNKI), from inception to March 2022. After all qualified randomized controlled trials (RCTs) were included, we conducted quality evaluation, data extraction, and statistical analysis. Statistics using risk ratios (RR), weighted mean difference (WMD), and standard mean difference (SMD). Results: Our meta-analysis included 20,797 subjects from 240 studies across 242 different hospitals in China. Compared with the atropine group, the PHC group showed decreased mortality rate (RR=0.20, 95% confidence intervals [CI]: 0.16-0.25, P <0.001), hospitalization time (WMD=-3.89, 95% CI: -4.37 to -3.41, P <0.001), overall incidence rate of complications (RR=0.35, 95% CI: 0.28-0.43, P <0.001), overall incidence of adverse reactions (RR=0.19, 95% CI: 0.17-0.22, P <0.001), total symptom disappearance time (SMD=-2.13, 95% CI: -2.35 to -1.90, P <0.001), time for cholinesterase activity to return to normal value 50-60% (SMD=-1.87, 95% CI: -2.03 to -1.70, P <0.001), coma time (WMD=-5.57, 95% CI: -7.20 to -3.95, P <0.001), and mechanical ventilation time (WMD=-2.16, 95% CI: -2.79 to -1.53, P <0.001). Conclusion: PHC has several advantages over atropine as an anticholinergic drug in AOPP.