A simple aptamer-dye fluorescence sensor for detecting Δ9-tetrahydrocannabinol and its metabolite in urban sewage.

This work developed an aptamer-dye complex as a label-free ratiometric fluorescence sensor for rapid analysis of THC and its metabolite in sewage samples. Integrated with a portable fluorescence capture device, this sensor exhibited excellent sensitivity with visualization of as low as 0.6 µM THC via naked-eye observation, and THC analysis can be accomplished within 4 min, which would be a complementary tool for quantifying THC in sewage samples to estimate cannabis consumption.

Proteomic Characteristics of the Prefrontal Cortex and Hippocampus in Mice with Chronic Ketamine-Induced Anxiety and Cognitive Impairment.

Schizophrenia, a complex psychiatric disorder with diverse symptoms, has been linked to ketamine, known for its N-methyl-D-aspartate (NMDA) receptor antagonistic properties. Understanding the distinct roles and mechanisms of ketamine is crucial, especially regarding its induction of schizophrenia-like symptoms. Recent research highlights the impact of ketamine on key brain regions associated with schizophrenia, specifically the prefrontal cortex (PFC) and hippocampus (Hip). This study focused on these regions to explore proteomic changes related to anxiety and cognitive impairment in a chronic ketamine-induced mouse model of schizophrenia. After twelve consecutive days of ketamine administration, brain tissues from these regions were dissected and analyzed. Using tandem mass tag (TMT) labeling quantitative proteomics techniques, 34,797 and 46,740 peptides were identified in PFC and Hip, corresponding to 5,668 and 6,463 proteins, respectively. In the PFC, a total of 113 proteins showed differential expression, primarily associated with the immuno-inflammatory process, calmodulin, postsynaptic density protein, and mitochondrial function. In the Hip, 129 differentially expressed proteins were screened, mainly related to synaptic plasticity proteins and mitochondrial respiratory chain complex-associated proteins. Additionally, we investigated key proteins within the glutamatergic synapse pathway and observed decreased expression levels of phosphorylated CaMKII and CREB. Overall, the study unveiled a significant proteomic signature in the chronic ketamine-induced schizophrenia mouse model, characterized by anxiety and cognitive impairment in both the PFC and Hip, and this comprehensive proteomic dataset may not only enhance our understanding of the molecular mechanisms underlying ketamine-related mental disorders but also offer valuable insights for future disease treatments.

Separation of bile acid isomer plays a pivotal role in bioequivalence evaluation of ursodeoxycholic acid.

Based on our experiences in bile acid profiling, this work developed and validated a liquid chromatography electrospray ionization tandem mass spectrometry method to separate endogenous bile acid isomers and quantitatively determine ursodeoxycholic acid (UDCA), glycoursodeoxycholic acid (GUDCA) and tauroursodeoxycholic acid (TUDCA) in human plasma. The separation was performed on a CORTECS C18 column with the mobile phase consisting of 1.0 mM ammonium acetate and acetonitrile-methanol (80:20, v/v). UDCA, GUDCA and TUDCA were detected in the negative mode on a triple-quadrupole mass spectrometer at the ion transitions of m/z 391 > 391, m/z 448 > 74, m/z 498 > 80, respectively. Phosphate buffer was employed as the surrogate matrix to establish the isotope internal standard corrected calibration curves of analytes. The background-method with a linearity range of 10-200 ng/mL was partially validated to determine the endogenous levels of analytes in blank human plasma, which was incorporated into the validation of bioequivalence-method with a linearity range of 50-10000 ng/mL. The bioequivalence (BE)-method was fully validated with special focus on matrix effects, which have been critically evaluated using the precision and accuracy of quality control samples prepared from the blank human plasma of 12 individuals. It is disclosed for the first time that the BE results of UDCA formulation may yield false results when the method is insufficient to separate UDCA from isoursodeoxycholic acid, a microbial metabolite of both endogenous and exogenous UDCA. The present method has established a milestone for the evaluation of UDCA formulations and is expected to provide a valuable reference for the bioanalytical development of endogenous medicinal products.

A pilot study investigating early postmortem interval of rats based on ambient temperature and postmortem interval-related metabolites in blood.

Estimation of the postmortem interval (PMI), especially the early PMI, plays a key role in forensic practice. Although several studies based on metabolomics approaches have presented significant findings for PMI estimation, most did not examine the effects of ambient temperature. In this study, gas chromatography-mass spectrometry (GC‒MS)‒based metabolomics was adopted to explore the changes in metabolites in the cardiac blood of suffocated rats at various ambient temperatures (5 °C, 15 °C, 25 °C, and 35 °C) from 0 to 24 h after death. Isoleucine, alanine, proline, valine, glycerol, glycerol phosphate, xanthine, and hypoxanthine were found to contribute to PMI in all temperature groups. Hypoxanthine and isoleucine were chosen to establish estimation models (equations) with an interpolation function using PMI as the dependent variable (f(x, y)), relative intensity as the independent variable x, and temperature as the independent variable y. Thereafter, these two models were validated with predictive samples and shown to have potential predictive ability. The findings indicate that isoleucine, alanine, proline, valine, glycerol, glycerol phosphate, xanthine, and hypoxanthine may be significant for PMI estimation at various ambient temperatures. Furthermore, a method to determine PMI based on ambient temperature and PMI-related metabolites was explored, which may provide a basis for future studies and practical applications.

Rapid Testing of Δ9-Tetrahydrocannabinol and Its Metabolite On-Site Using a Label-Free Ratiometric Fluorescence Assay on a Smartphone.

Excessive consumption of Δ9-tetrahydrocannabinol (THC) severely endangers human health and has raised public safety concerns. However, its quantification by readily rapid tools with simplicity and low cost is still challenging. Herein, we found that a G-rich THC aptamer (THC1.2) can tightly bind to thioflavin T (ThT) with strong fluorescence, which would be specifically quenched in the presence of THC. Based on that, a label-free ratiometric fluorescent sensor for the sensing of THC and its metabolite (THC-COOH) based on THC1.2/ThT as a color emitter and red CdTe quantum dots as reference fluorescence was constructed. Notably, a transition of the fluorescent color of the ratiometric probe from green to red can be instantly observed upon the increased concentration of THC and THC-COOH. Furthermore, a portable smartphone-based fluorescence device integrated with a self-programmed Python program was fabricated and used to accomplish on-site monitoring of THC and THC-COOH within 5 min. Under optimized conditions, this ratiometric fluorescent sensor allowed for an instant response toward THC and its metabolite with considerable limits of detection of 97 and 254 nM, respectively. The established sensor has been successfully applied to urine and saliva samples and exhibited satisfactory recoveries (88-116%). This ratiometric fluorescent sensor can be used for the simultaneous detection of THC and THC-COOH with the advantages of rapidness, low cost, ease of operation, and portability, providing a promising strategy for on-site detection and facilitating law enforcement regulation and roadside control of THC.

Forensic biogeographical ancestry inference: recent insights and current trends.

BACKGROUND: As a powerful complement to the paradigmatic DNA profiling strategy, biogeographical ancestry inference (BGAI) plays a significant part in human forensic investigation especially when a database hit or eyewitness testimony are not available. It indicates one's biogeographical profile based on known population-specific genetic variations, and thus is crucial for guiding authority investigations to find unknown individuals. Forensic biogeographical ancestry testing exploits much of the recent advances in the understanding of human genomic variation and improving of molecular biology. OBJECTIVE: In this review, recent development of prospective ancestry informative markers (AIMs) and the statistical approaches of inferring biogeographic ancestry from AIMs are elucidated and discussed. METHODS: We highlight the research progress of three potential AIMs (i.e., single nucleotide polymorphisms, microhaplotypes, and Y or mtDNA uniparental markers) and discuss the prospects and challenges of two methods that are commonly used in BGAI. CONCLUSION: While BGAI for forensic purposes has been thriving in recent years, important challenges, such as ethics and responsibilities, data completeness, and ununified standards for evaluation, remain for the use of biogeographical ancestry information in human forensic investigations. To address these issues and fully realize the value of BGAI in forensic investigation, efforts should be made not only by labs/institutions around the world independently, but also by inter-lab/institution collaborations.

[Determination of Dichloromethane in Blood with Headspace Gas Chromatography and Gas Chromatography-Mass Spectrometry].

Objective: To establish a method for qualitative determination of dichloromethane (DCM) in blood by gas chromatography-mass spectrometry (GC-MS) and quantitative determination of DCM in blood by headspace gas chromatography (HS-GC), and to provide reliable support for forensic examination and analysis of poisoning or deaths caused by DCM. Methods: 0.5 mL blood sample was collected, added into headspace vial with chloroform as the internal standard, and processed by heating at 65 °C and evacuation treatment. The intermediate gas in the headspace vial was analyzed by GC-MS for qualitative validation of the method and by HS-GC for quantitative validation of the method. The method was then applied in forensic case analysis. Results: Qualitative validation of the examination method by GC-MS found that the chromatographic peak and mass spectral characteristic ions were specific in samples added with DCM, and that no interference was observed in the blank negative samples. The limit of detection (LOD) was 5 µg/mL. Quantitative method validation by HS-GC found that the chromatographic peak of DCM was well separated from those of eight other volatile compounds, with the resolution>1.5 in all cases; the lower limit of quantification (LOQ) was 20 µg/mL and good linearity was shown within the range of 20 and 1000 µg/mL, R>0.999; the intra-day test precision and inter-day test precision were good (relative standard deviation, or RSD<15% for both) and test accuracy was high (relative error, or δ<15%). With the method established in the study, DCM was detected successfully in the blood of two fatal cases caused by DCM poisoning, with the blood concentration being 470 µg/mL and 915 µg/mL, respectively. Conclusion: This method is shown to be a rapid, stable and accurate approach to the qualitative and quantitative forensic and toxicological analysis of DCM in blood in DCM poisoning cases or deaths caused by DCM.

Aldehyde dehydrogenase 2-associated changes in pharmacokinetics, locomotor function and peripheral glutamic acid and gamma-aminobutyric acid levels during acute alcohol intoxication in male mice.

The insufficiency of human aldehyde dehydrogenase 2 (ALDH2) has been consistently associated with high blood acetaldehyde levels and impaired locomotor function during acute alcohol intoxication. The ALDH2-associated change in peripheral glutamic acid (Glu) and gamma-aminobutyric acid (GABA) levels and its correlation with pharmacokinetics and psychomotor function remain unclear. In this study, ALDH2*2 mice were used to build an acute alcohol intoxication model after intraperitoneal administration. The blood ethanol and acetaldehyde concentrations were analyzed to generate concentration-time curves at two doses of alcohol (2.0 and 4.0 g/kg). The dose of 4.0 g/kg was selected in accordance with the preliminary behavioral evaluation result to perform the following behavioral tests (e.g. the rotarod test, the open field test, and the Y-maze test), so as to assess locomotor activity, anxiety and cognitive ability. Plasma Glu and GABA levels were determined through enzyme-linked immunosorbent assays. The results suggested that the ALDH2*2 mice had highly accumulated acetaldehyde levels, impaired locomotor activity and anxiety-like emotion but unimpaired cognitive function, compared to the wild type (WT) mice. The plasma Glu level and the ratio of Glu/GABA in the alcohol-treated WT and ALDH2*2 groups decreased from 2 to 5 h after intraperitoneal administration, whereas the GABA level did not change significantly. The blood alcohol concentration in the WT and ALDH2*2 mice was positively correlated with plasma Glu level, whereas the blood acetaldehyde level was found as the opposite. We speculate that the decline degree of Glu/GABA ratio could be associated with psychomotor retardation and needs to be further investigated.

Comprehensive metabolomic characterization of the hippocampus in a ketamine mouse model of schizophrenia.

Ketamine is a noncompetitive antagonist of N-methyl-D-aspartate receptors (NMDARs). We have shown that ketamine can induce cognitive impairments and schizophrenia-like symptoms in mice. However, the detailed metabolic profile changes in the progression of ketamine-induced schizophrenia-like symptoms are still not fully elucidated. In this study, an ultra-performance liquid chromatography-Q-Exactive hybrid quadrupole-Orbitrap mass spectrometry-based untargeted hippocampus high-throughput metabolomics method was first performed to screen for potential biomarkers in a schizophrenia-like state in a chronically administered ketamine-induced mouse model. Our results identified that the amino acid and energy metabolism pathways were significantly affected in mouse models of ketamine-induced schizophrenia. The detailed amino acid profiles were subsequently quantified in the hippocampus. The results showed that ketamine dramatically decreased the Lys, Gly, and Ser levels while significantly increasing the Gln level and relative Glu-to-GABA ratio. Our study suggested that Gln, Gly and Ser metabolism disturbances might be involved in ketamine-induced schizophrenia-like phenotypes. This research offers a fresh viewpoint for creating new neuroleptic medications and contributes to understanding the mechanisms underlying ketamine-induced schizophrenia.

Evaluation of the effects of four types of tea on the activity of cytochrome P450 enzymes with a probe cocktail and HPLC-MS/MS.

Background: Tea, the world's second most popular drink, is an essential part of some people's lives. Thus, this study aimed to explore potential tea-drug interactions with a view to promoting the rational administration of drugs. Methods: A specific and sensitive approach involving high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and a probe cocktail was established and validated to evaluate the inhibitory effects of four teas on five cytochrome P450 (CYP450) enzymes in rats. Metoprolol tartrate (MT), omeprazole (OMP), phenacetin (PNT), tolbutamide (TOL), and testosterone (T) were selected as the probe drugs for CYP2D6, CYP2C19, CYP1A2, CYP2C6, and CYP3A1/2, respectively, and were simultaneously quantified in the multiple reaction monitoring (MRM) mode with positive electrospray ionization (ESI+) in a single 12-min run. Results: The extraction recoveries, matrix effect values, as well as intra/interday accuracy and precision met the determination standards. CYP1A2 and CYP2C6 were strongly inhibited by green tea, and CYP2C6 was also strongly inhibited by Pu'er tea. Ti Kuan Yin tea had a weak inhibitory effect, and black tea had only a slight inhibitory effect, on CYP1A2. Furthermore, the four types of tea did not have significantly altered the activity of CYP2D6, CYP2C19, and CYP3A1/2 in vitro. Conclusions: The method used in the present study was successfully applied to assess the inhibitory effects of aqueous extracts of four types of tea on CYP450 isoforms in vitro. The results suggest that different types of tea have different effects on drug metabolism.

Analytical method for detection and quantification of new emerging drug etaqualone in human blood and urine by gas chromatography tandem mass spectrometry.

Analytical procedure for detection and quantification of etaqualone in human blood and urine using GC-MS/MS was established and applied to authentic human samples obtained from volunteers. A liquid-liquid extraction method was employed. Each 1.0 mL of blood or urine was alkalized and extracted with diethyl ether. The solvent layer was evaporated to dryness and reconstituted with methanol then analyzed by GC-MS/MS. linear relationships within the concentration range of 1-100 ng/mL were obtained in calibrators for both blood and urine, demonstrating correlation coefficients values being>0.999. For blood and urine samples, the intra-day assay precision and accuracy values are each less than 3.65%, 7.13%, and 6.02%, 9.12%; those values of the inter-day assay are each less than 1.82%, 6.74%, and 3.99%, 7.41%. The extraction recovery rates for etaqualone ranged from 98.7% to 106%. The lower limit of quantifications was 1.0 ng/mL in both blood and urine. Stabilities of etaqualone in blood and urine were satisfactory under various temperatures within 15 days. 8.51 and 2.06 ng/mL of etaqualone in blood and urine were detected at 4 h later oral ingestion; 6.91 and 3.94 ng/mL of etaqualone were also detected 30 min and 2 h later smoking from blood and urine.

High-Throughput mRNA Sequencing Reveals Potential Therapeutic Targets of Febuxostat in Secondary Injury After Intracerebral Hemorrhage.

Febuxostat is a urate-lowering medication for the treatment of patients with gout. This study was performed to elucidate the effects and underlying mechanisms of febuxostat on neuronal injury induced by intracerebral hemorrhage (ICH) in mice. The results showed that the administration of febuxostat improved neurological severity scores and blood-brain barrier (BBB) permeability. Moreover, febuxostat attenuated neuronal cell death and cytokine levels compared with the ICH group. Next, we conducted a transcriptome analysis of the neuroprotective effects of febuxostat. The overlapping significant differentially expressed genes (DEGs) were identified. Gene ontology (GO) analysis revealed that the overlapping significant DEGs were most enriched in five items. The intersecting DEGs of the aforementioned five pathways were Wisp1, Wnt7b, Frzb, and Pitx2. In addition, GO terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed that DEGs were mainly involved in the wnt signaling pathway. Furthermore, the expression of Wisp1 and Wnt7b in the perihematomal region at 72 h post-ICH was observed. The results showed that both Wisp1 and Wnt7b were increased in the ICH group and were decreased by the administration of febuxostat. Taken together, the study showed that febuxostat protected against secondary brain injury after ICH and the Wnt7b-Wisp1 pathway was closely related to neuroprotective effects.

Assessment of the forensic application of 50 Y-STR markers in a large pedigree.

Short tandem repeats on the Y chromosome (Y-STRs), characterized by paternal inheritance, are valuable in forensic practice. Notably, the potential application of Y-STRs in pedigrees should be drawn upon, especially in China's surname-concentrated natural villages. The study focused on 50 Y-STRs, including 13 rapidly mutating (RM) Y-STRs that largely constitute the current Y-STR commercial kits, and determined the differences in these Y-STRs between branches in a large pedigree and the discriminatory power of these haplotypes in different units for male relatives. As indicated in the results, 14 inconsistencies were observed at 9 Y-STRs between 10 father-son pairs. In addition, these 50 Y-STR haplotypes discriminated 10 out of 47 father-son pairs, 106 of 148 cousin pairs, 70 of 119 uncle-nephew pairs, 17 of 39 brother pairs, and 14 out of 33 grandfather-grandson pairs in a large pedigree. The RM Y-STR set is able to differentiate close male relatives in a large pedigree.

Astrocyte Activation, but not Microglia, Is Associated with the Experimental Mouse Model of Schizophrenia Induced by Chronic Ketamine.

Ketamine is a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors. Many experimental studies have shown that ketamine can induce cognitive impairments and schizophrenia-like symptoms. While much data have demonstrated that glial cells are associated with the pathophysiology of psychiatric disorders, including schizophrenia, the response of glial cells to ketamine and its significance to schizophrenia are not clear. The present study was intended to explore whether chronic ketamine treatment would induce behavioral and glial changes in mice. First, ketamine was used to stimulate behavioral abnormalities similar to schizophrenia evaluated by the open field test, elevated plus-maze test, Y maze test, novel object recognition test, and tail suspension test. Secondly, histopathology and Nissl staining were performed. Meanwhile, immunofluorescence was used to evaluate the expression levels of IBA-1 (a microglial marker) and GFAP (an astrocyte marker) in the mouse hippocampus for any change. Then, ELISA was used to analyze proinflammatory cytokine levels for any change. Our results showed that ketamine (25 mg/kg, i.p., qid, 12 days) induced anxiety, recognition deficits, and neuronal injury in the hippocampus. Moreover, chronic ketamine treatment enhanced GFAP expression in CA1 and DG regions of the hippocampus but did not influence the expression of IBA-1. Ketamine also increased the levels of IL-1ß, IL-6, and TNF-α in the mouse hippocampus. Our study created a new procedure for ketamine administration, which successfully induce negative symptoms and cognitive-behavioral defects in schizophrenia by chronic ketamine. This study further revealed that an increase in astrocytosis, but not microglia, is associated with the mouse model of schizophrenia caused by ketamine. In summary, hippocampal astrocytes may be involved in the pathophysiology of ketamine-induced schizophrenia-like phenotypes through reactive transformation and regulation of neuroinflammation.

Consistency and synchronization of AMPK-glycogen in endometrial epithelial cells are critical to the embryo implantation.

Uterine receptivity to the embryo is crucial for successful implantation. The establishment of uterine receptivity requires a large amount of energy, and abnormal energy regulation causes implantation failure. Glucose metabolism in the endometrium is tissue specific. Glucose is largely stored in the form of glycogen, which is the main energy source for the endometrium. AMP-activated protein kinase (AMPK), an important energy-sensing molecule, is a key player in the regulation of glucose metabolism and its regulation is also tissue specific. However, the mechanism of energy regulation in the endometrium for the establishment of uterine receptivity remains to be elucidated. In this study, we aimed to investigate the energy regulation mechanism of mouse uterine receptivity and its significance in embryo implantation. The results showed that the AMPK, p-AMPK, glycogen synthase 1, and glycogen phosphorylase M levels and the glycogen content in mouse endometrial epithelium varied in a periodic manner under regulation by the ovarian hormone. Specifically, progesterone significantly activated AMPK, promoted glycogenolysis, and upregulated glycogen phosphorylase M expression. AMPK regulated glycogen phosphorylase M expression and promoted glycogenolysis. AMPK was also found to be activated by changes in the energy or glycogen of the endometrial epithelial cells. The inhibition of AMPK activity or glycogenolysis altered the uterine receptivity markers during the window of implantation and ultimately interfered with implantation. In summary, consistency and synchronization of AMPK and glycogen metabolism constitute the core regulatory mechanism in mouse endometrial epithelial cells involved in the establishment of uterine receptivity.

GLUT4 in Mouse Endometrial Epithelium: Roles in Embryonic Development and Implantation.

GLUT4 is involved in rapid glucose uptake among various kinds of cells to contribute to glucose homeostasis. Prior data have reported that aberrant glucose metabolism by GLUT4 dysfunction in the uterus could be responsible for infertility and increased miscarriage. However, the expression and precise functions of GLUT4 in the endometrium under physiological conditions remain unknown or controversial. In this study, we observed that GLUT4 exhibits a spatiotemporal expression in mouse uterus on pregnant days 1-4; its expression especially increased on pregnant day 4 during the window of implantation. We also determined that estrogen, in conjunction with progesterone, promotes the expression of GLUT4 in the endometrial epithelium in vivo or in vitro. GLUT4 is an important transporter that mediates glucose transport in endometrial epithelial cells (EECs) in vitro or in vivo. In vitro, glucose uptake decreased in mouse EECs when the cells were treated with GLUT4 small interfering RNA (siRNA). In vivo, the injection of GLUT4-siRNA into one side of the mouse uterine horns resulted in an increased glucose concentration in the uterine fluid on pregnant day 4, although it was still lower than in blood, and impaired endometrial receptivity by inhibiting pinopode formation and the expressions of leukemia inhibitory factor (LIF) and integrin ανß3, finally affecting embryonic development and implantation. Overall, the obtained results indicate that GLUT4 in the endometrial epithelium affects embryo development by altering glucose concentration in the uterine fluid. It can also affect implantation by impairing endometrial receptivity due to dysfunction of GLUT4.

Bioequivalence of 2 Aripiprazole Orally Disintegrating Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions.

To assess the bioequivalence of 2 formulations of aripiprazole orally disintegrating tablets and to monitor their safety and tolerability in Chinese subjects, a single-site, open-label, randomized, 2-preparation, single-dose, 2-period crossover design was conducted. All 60 subjects were randomly divided into the fasting group and the fed group. Blood samples were collected at scheduled times after a single oral dose of orodispersible tablets containing 10 mg of aripiprazole. In the fasting state, the geometric mean ratios (90% confidence intervals [CIs]) of the test/reference formulation were 92.22%-100.20% for the area under the concentration-time curve (AUC) from time zero to the last measured concentration (AUC0-t ), 91.73%-100.14% for the AUC from administration to infinite time (AUC0-∞ ), and 98.52%-112.52% for the maximum plasma concentration (Cmax ). In the fed state, AUC0-t , AUC0-∞ , and Cmax were 92.23%-100.20%, 91.73%-100.14%, and 95.91%-105.13%, respectively. The 90%CIs of the test/reference AUC ratio and Cmax ratio were within the acceptance range of 80.00%-125.00% for bioequivalence. Neither the maximum peak plasma concentration (tmax ) nor the terminal elimination half-life (t1/2 ) showed any significant difference. No serious adverse events) were encountered during the study. The test and reference formulations were bioequivalent under both fasting and fed conditions and were found to be safe and tolerated.

A 9-year retrospective study of poisoning-related deaths in Southwest China (Sichuan).

Poisoning is an increasing and significant burden that causes morbidity and mortality worldwide. In this retrospective study, poisoning-related cases that occurred in 19 cities and prefectures in Sichuan, Southwest China, between 2010 and 2018 were collected from the West China Forensic Medical Center of Sichuan and Public Security Bureaus. A total of 782 poisoning-related deaths were recorded, and their demographic characteristics, season of death, type of poison, and manner and cause of death were analysed. Of these cases, the victims were predominantly male (65.3%), and the 21∼50-year-old age group included the most victims (63.2%). The rural incidence was 71%. The most common poisoning agent was pesticide (40%), followed by toxic gases (32%), and there were cases of poisoning by poisonous animals and plants that are not common in other regions of China. The predominant manner of poisoning death was accident (50%), followed by suicide (38.3%) and homicide (5.0%). In this study, relevant information on poisoning-related cases was collected and compared with the poisoning data from other areas of China and foreign countries to provide guidance for the formulation of public health policies in Sichuan, Southwest China.

Ketamine Affects the Expression of ErbB4 in the Hippocampus and Prefrontal Cortex of Rats.

Schizophrenia is a severe chronic neuropsychiatric disorder, and its exact pathogenesis remains unclear. This study investigated the effect of ketamine on the expression of ErbB4 (considered a schizophrenia candidate gene) in the hippocampus and prefrontal cortex of rats. Rats were randomly divided into four groups: control, low-dose, medium-dose and high-dose groups. The low-dose, medium-dose and high-dose groups were intraperitoneally injected with 15 mg/kg, 30 mg/kg and 60 mg/kg ketamine, respectively, twice a day (9:00 a.m. and 9:00 p.m.); the control group was administered normal saline. The treatment lasted 7 days. After treatment, rats were euthanized, and their brain tissues were collected and then analyzed by immunohistochemistry. The results of immunohistochemistry staining demonstrated that the ErbB4 protein was expressed exclusively in the CA3 region of the hippocampus and the Cg1 region of the prefrontal cortex. Ketamine administration significantly decreased the expression of ErbB4 in a dose-dependent manner. The high-dose ketamine treatment was found to be optimal for establishing a rat model for schizophrenia. Ketamine induced symptoms similar to schizophrenia in humans. The ketamine-induced rat model for schizophrenia constructed in this study provides novel insights to better understand the pathogenic mechanisms of schizophrenia and aid in drug discovery.

mTOR Expression in Hippocampus and Prefrontal Cortex Is Downregulated in a Rat Model of Schizophrenia Induced by Chronic Administration of Ketamine.

Schizophrenia is a severe chronic neuropsychiatric disorder, and it negatively affects individuals' quality of life, but the pathogenesis of schizophrenia remains unclear. This study aimed to explore whether the administration of ketamine in rats causes changes in mTOR (mechanistic/mammalian target of rapamycin) expression in the hippocampus and prefrontal cortex. Ketamine was used to establish an animal model of schizophrenia. Rats were randomly divided into four groups: control group (normal saline), low-dose group (15 mg/kg ketamine), middle-dose group (30 mg/kg ketamine), and high-dose group (60 mg/kg ketamine). The rats were intraperitoneally injected with ketamine or normal saline twice a day (9 AM and 9 PM) for 7 consecutive days. Immunohistochemistry was used to detect mTOR protein expression in the hippocampus and prefrontal cortex from rats at 13 h after the last treatment. Using immunohistochemistry, the expression of the mTOR protein was localized exclusively in the CA3 region of the hippocampus and in the Cg1 region of the prefrontal cortexes. Ketamine at 60 mg/kg decreased the expression of mTOR protein in the brain of rats. Ketamine successfully established a rat model of schizophrenia. This study helps elucidate the mechanisms of ketamine-induced schizophrenia and provides novel insights for drug discovery and development.