Although penehyclidine hydrochloride (PHC) has been identified to alleviate myocardial injury induced by ischemia/reperfusion (I/R), the regulatory molecules and related mechanisms are unknown. In this study, bioinformatics, molecular biology, and biochemistry methods were used to explore the molecular mechanisms and targets of PHC. In the myocardial ischemia-reperfusion injury (MIRI)-induced rat model, PHC pretreatment significantly improved cardiac function (p < 0.01). Multiple differentially expressed genes, including Z-DNA binding protein 1 (ZBP1), were identified through mRNA sequencing analysis of myocardial ischemic penumbra tissue in MIRI rats. The transduction of the ZBP1 adenovirus vector (Ad-Zbp1) in PHC-pretreated rats exhibited a reversible augmentation in myocardial infarct size (p < 0.01), pronounced pathological damage to the myocardial tissue, as well as a significant elevation of serum myocardial enzymes (p < 0.05). The interaction among ZBP1, fas-associating via death domain (FADD), and receptor-interacting serine/threonine-protein kinase 3 (RIPK3) leads to a remarkable up-regulation of cleaved-Caspase-1 (Cl-Casp-1), N-terminal gasdermin D (N-GSDMD), phospho-mixed lineage kinase domain-like Ser358 (p-MLKLS358), and other regulatory proteins, thereby triggering pyroptosis, apoptosis, and necroptosis (PANoptosis) in cardiomyocytes of MIRI rats. Moreover, the transduction of Ad-Zbp1 in the oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced H9c2 cell model also dramatically augmented the number of cell deaths. However, the intervention of PHC considerably enhanced cell viability (p < 0.01), effectively mitigated the release of myocardial enzymes (p < 0.05), and markedly attenuated the expression levels of PANoptosis regulatory proteins through restraint of ZBP1 expression. Therefore, the therapeutic efficacy of PHC in improving MIRI might be attributed to targeting ZBP1-mediated PANoptosis.

OBJECTIVE: The aim of this research was to examine how penehyclidine hydrochloride (PHC) impacts the occurrence of pyroptosis in lung tissue cells within a rat model of lung ischemia-reperfusion injury.
METHODS: Twenty-four Sprague Dawley (SD) rats, weighing 250 g to 270 g, were randomly distributed into three distinct groups as outlined below: a sham operation group (S group), a control group (C group), and a test group (PHC group). Rats in the PHC group received a preliminary intravenous injection of PHC at a dose of 3 mg/kg. At the conclusion of the experiment, lung tissue and blood samples were collected and properly stored for subsequent analysis. The levels of malondialdehyde, superoxide dismutase, and myeloperoxidase in the lung tissue, as well as IL-18 and IL-1β in the blood serum, were assessed using an Elisa kit. Pyroptosis-related proteins, including Caspase1 p20, GSDMD-N, and NLRP3, were detected through the western blot method. Additionally, the dry-to-wet ratio (D/W) of the lung tissue and the findings from the blood gas analysis were also documented.
RESULTS: In contrast to the control group, the PHC group showed enhancements in oxygenation metrics, reductions in oxidative stress and inflammatory reactions, and a decrease in lung injury. Additionally, the PHC group exhibited lowered levels of pyroptosis-associated proteins, including the N-terminal segment of gasdermin D (GSDMD-N), caspase-1p20, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3).
CONCLUSIONS: Pre-administration of PHC has the potential to mitigate lung ischemia-reperfusion injuries by suppressing the pyroptosis of lung tissue cells, diminishing inflammatory reactions, and enhancing lung function. The primary mechanism behind anti-pyroptotic effect of PHC appears to involve the inhibition of oxidative stress.

BACKGROUND: Inflammation is a biological response of the immune system to harmful stimuli. Penehyclidine hydrochloride (PCH) can alleviate inflammation and oxidative stress by activating reactive oxygen species (ROS), nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase 1 (HO-1) in animal models, but there is a lack of cellular evidence.
OBJECTIVE: This study investigated the effects of PHC on lipopolysaccharide (LPS)-induced inflammation response and oxidative stress in RAW264.7 cells.
METHODS: RAW264.7 cells were treated with 1 μg/mL or 5 μg/mL of PHC, with interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), IL-1β, and prostaglandin E2 (PGE2) levels measured with enzyme-linked immunosorbent assay (ELISA) and nitric oxide (NO) measured using the Griess test. Reactive oxygen species were examined with flow cytometry and immunofluorescence, and b-related factor 2 (BRF-2) and NAD(P)H-quinone oxidoreductase 1 (NQO1) using western blot.
RESULTS: Penehyclidine hydrochloride partly, but substantially, reversed LPS-related NO and PGE2 production by RAW264.7 cells in a dose-dependent manner and suppressed LPS-induced expression of IL-6, TNF-α and IL-1β messenger ribonucleic acid (mRNA), secretion of IL-6, TNF-α and IL-1β, and ROS production. Lipopolysaccharide stimulation did not affect Nrf2, heme oxygenase 1 (HO-1) or NQO1 protein expression in RWA264.7 cells not treated with PHC. However, PHC treatment significantly elevated Nrf2, HO-1 and NQO1 protein in LPS-treated RWA264.7 cells, an effect that was dose-dependent. The ROS scavenging using N-acetyl-L-cysteine abolished the PHC-induced upregulation of Nrf2 and HO-1.
CONCLUSIONS: Penehyclidine hydrochloride may alleviate LPS-induced inflammation and oxidative stress by activating Nrf2 signaling in RAW264.7 macrophages. These findings suggest that PHC could alleviate inflammation by targeting activated macrophages.

Penehyclidine hydrochloride (PHC) has been shown to be effective in the treatment of rhabdomyolysis (RM)-induced acute kidney injury (AKI). Our research sought to investigate the pharmacological effects and mechanisms of PHC on RM-induced AKI.
RM-induced AKI models were established by FeG treatment and glycerol injection. Cell viability was analyzed by cell counting kit-8 assay. Reactive oxygen species (ROS) levels were examined by flow cytometry. The LDH, Fe2+, MPO, MDA, and GSH levels were measured using the corresponding kits. The interaction between HIF-1α and MT1G was analyzed by dual-luciferase reporter gene and chromatin immunoprecipitation assays. The kidney pathological alterations were examined by hematoxylin-eosin staining. The levels of serum creatinine, uric acid, and blood urea nitrogen were examined using ELISA. Ferroptosis-related proteins (SLC7A11, GPX4, and ACSL4) were analyzed by Western blot.
PHC administration increased FeG-treated HK-2 cell viability, reduced ROS, LDH, Fe2+, MPO, MDA, and ACSL4 levels, and raised GSH, SLC7A11, and GPX4 levels in cells, suggesting that PHC improved FeG-induced HK-2 cell ferroptosis and injury. PHC protected against AKI primarily by suppressing ferroptosis. HIF-1α blocked the SLC7A11/GPX4 pathway by transcriptionally activating MT1G. PHC alleviated glycerol-induced kidney injury in rats by inhibiting ferroptosis.
PHC improved RM-mediated AKI by inhibiting ferroptosis through the HIF-1α/MT1G/SLC7A11/GPX4 axis.

Penehyclidine hydrochloride (PHC) is an anticholinergic drug with cardioprotective effects. Ferroptosis is closely related to myocardial ischaemia-reperfusion injury (MIRI). In the present study, MIRI was induced in rats by left anterior descending coronary artery ligation. PHC pretreatment increased haemodynamic parameters and histopathological damage and reduced myocardial infarction size in the MIRI model. PHC pretreatment also inhibited ferroptosis, which was characterized by the decreased levels of Fe2+, 4-hydroxynonenal and ACSL4, and increased levels of GPX4, GSH-Px and GST. In response to 6 h of oxygen-glucose deprivation and 18 h of reoxygenation, PHC pretreatment had the same effects on these factors in H9c2 cells and reduced lipid ROS levels. Furthermore, ACSL4 overexpression reversed the protective effects of PHC on H9c2 cells. These results indicated that PHC inhibited MIRI through ACSL4-mediated ferroptosis. This study demonstrated that PHC could inhibit ferroptosis in MIRI and the relationship among PHC, ACSL4, ferroptosis and MIRI. This study demonstrated the inhibitory effect of PHC on ferroptosis and showed that PHC affects MIRI through ACSL4-mediated ferroptosis in vivo and in vitro.

BACKGROUND: Acute lung injury (ALI) attracted attention among physicians because of its high mortality. We aimed to determine whether the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) pathway is involved in the protective effects of penehyclidine hydrochloride (PHC) against lipopolysaccharide (LPS)-induced ALI.
METHODS: H&E staining was used to observed pathological changes in the lung tissues. ELISA was used to evaluate the concentration of inflammatory mediators in the bronchoalveolar lavage fluid (BALF). White-light microscopy was performed to observe the TUNEL-positive nuclei. The viability of NR8383 alveolar macrophages was determined by using CCK-8. The levels of MPO, MDA, SOD, and GSH-Px were analyzed using ELISA kits. Western blotting was used to evaluate the ERS-associated protein levels and the phosphorylation of PI3K and Akt.
RESULTS: PHC administration defended against LPS-induced histopathological deterioration and increased pulmonary edema and lung injury scores, while all of these beneficial effects were inhibited by LY. In addition, PHC administration mitigated oxidative stress as indicated by decreases in lung myeloperoxidase (MPO) and malondialdehyde (MDA) concentrations, and increases in glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) concentrations. It also alleviated LPS-induced inflammation. PHC administration attenuated apoptosis-associated protein levels, improved cell viability, and decreased the number of TdT-mediated dUTP Nick-End Labeling (TUNEL)-positive cells. Furthermore, PHC inhibited ERS-associated protein levels. Meanwhile, the protection of PHC against inflammation, oxidative stress, apoptosis, and ERS was inhibited by LY. Moreover, PHC administration increased PI3K and Akt phosphorylation, indicating that the upregulation of the PI3K/Akt pathway, while this pathway was inhibited by LY.
CONCLUSIONS: PHC significantly activates the PI3K/Akt pathway to ameliorate the extent of damage to pulmonary tissue, inflammation, oxidative stress, apoptosis, and ERS in LPS-induced ALI.

To investigate the effects of penehyclidine hydrochloride combined with dexmedetomidine on pulmonary function in patients undergoing heart valve surgery with cardiopulmonary bypass (CPB).
A total of 180 patients undergoing elective heart valve surgery with CPB were randomly divided into four groups: 45 in group P (intravenous penehyclidine hydrochloride 0.02 mg/kg 10 min before anesthesia induction and at the beginning of CPB, total 0.04 mg/kg); 43 in group D (dexmedetomidine 0.5 μg/kg/h after induction of anesthesia until the end of anesthesia); 44 in group PD ( penehyclidine hydrochloride 0.04 mg/kg combined with dexmedetomidine 0.5 μg/kg/h intravenously during anesthesia); and 43 in group C (same amount of normal saline 10 min before and after anesthesia induction, to the end of anesthesia, and at the beginning of CPB). The main outcomes were the incidence and severity of postoperative pulmonary complications (PPCs). The secondary outcomes were: (1) extubation time, length of stay in intensive care, and postoperative hospital stay, and adverse events; and (2) pulmonary function evaluation indices (oxygenation index and respiratory index) and plasma inflammatory factor concentrations (tumor necrosis factor-α, interleukin-6, C-reactive protein and procalcitonin) during the perioperative period.
The incidence of PPCs in groups P, D and PD after CPB was lower than that in group C (P < 0.05), and the incidence in group PD was significantly lower than that in groups P and D (P < 0.05). The scores for PPCs in groups P, D and PD were lower than those in group C (P < 0.05).
Combined use of penehyclidine hydrochloride and dexmedetomidine during anesthesia reduced the occurrence of postoperative pulmonary dysfunction, and improved the prognosis of patients undergoing heart valve surgery with CPB.
The trial was registered in the Chinese Clinical Trial Registry on 3/11/2020 (Registration No.: ChiCTR2000039610).

UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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).
UNASSIGNED: PHC has several advantages over atropine as an anticholinergic drug in AOPP.

Postoperative nausea and vomiting (PONV) is a common and distressing complication of laparoscopic bariatric surgery (LBS). Penehyclidine hydrochloride has been reported to be effective in preventing PONV. Considering the potential preventive effects of penehyclidine against PONV, we hypothesized that intravenous infusion of penehyclidine may alleviate PONV within the first 48 h in patients scheduled for LBS.
Patients who underwent LBS were randomly assigned (1:2) to receive saline (Control group, n = 113) or a single intravenous dose of penehyclidine 0.5 mg (PHC group, n = 221). The primary outcome was incidence of PONV within the first 48 h postoperatively. Secondary endpoints included severity of PONV, need for rescue antiemetic therapy, volume of water intake, and time to first flatus.
PONV occurred in 159 (48%) patients within the first 48 h postoperatively, including 51% in the Control group and 46% in the PHC group. There was no significant difference in the incidence or severity of PONV between the two groups (P > 0.05). Within the first 24 h and 24-48 h, no significant difference was found in incidence or severity of PONV, postoperative nausea, postoperative vomiting, need for rescue antiemetic therapy, or volume of water intake (P > 0.05). Kaplan-Meier curves showed that penehyclidine was significantly associated with a prolonged time to first flatus (median onset time: 22 h vs. 21 h, P = 0.036).
Penehyclidine did not decrease incidence and severity of PONV in patients undergoing LBS. However, a single intravenous dose of penehyclidine (0.5 mg) was associated with a slightly prolonged time to first flatus.
Chinese Clinical Trial Registry (ChiCTR2100052418, http://www.chictr.org.cn/showprojen.aspx?proj=134893 , date of registration: 25/10/2021).

Thiamethoxam belongs to the second generation of neonicotinoid insecticides, and case of acute poisoning with thiamethoxam had never reported in China. This paper reviewed a case of oral poisoning with thiamethoxam pesticides, the patient suffered vomiting, generalized convulsions, confusion, and decreased oxygen saturation. After treated with gastric lavage, ventilator support, and the use of propofol, midazolam, sodium phenobarbital, and sodium valproate, the convulsions could not be controlled. Untill treated with penehyclidine hydrochloride and hemoperfusion combined with hemofiltration, the patient finally recovered and was discharged from the hospital. We suggest that the main treatments for acute severe thiamethoxam poisoning are decontamination and symptomatic support, pentoxifylline hydrochloride and hemoperfusion combined with hemofiltration may improve the patients\' prognosis.
噻虫嗪属于第二代新烟碱类杀虫剂，其急性中毒病例国内未见报道。本文回顾1例患者口服噻虫嗪中毒后出现呕吐、全身抽搐、神志不清、氧饱和度下降。经洗胃、呼吸机支持，并使用丙泊酚、咪达唑仑、苯巴比妥钠、丙戊酸钠仍无法控制抽搐。后予盐酸戊乙奎醚和血液灌流联合血液滤过治疗，患者最终康复出院。结合已发表的新烟碱类中毒文献，我们建议急性重度噻虫嗪中毒主要的治疗是洗消和对症支持治疗，盐酸戊乙奎醚和血液灌流联合血液滤过治疗可能改善患者预后。.