Neuropathic pain is frequently comorbidity with cognitive deficits. Neuralized1 (Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory. However, the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive. Herein, we found that lumbar 5 spinal nerve ligation (SNL) in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus. The Neurl1 expression in the hippocampal CA1 was decreased after SNL. And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2. Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment, and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL. Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity. The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1. Collectively, the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and, in turn, repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.
Animals ; Male ; Neuralgia/metabolism* ; Rats ; Down-Regulation/physiology* ; Ubiquitination/physiology* ; Neuronal Plasticity/physiology* ; Rats, Sprague-Dawley ; CA1 Region, Hippocampal/metabolism* ; Cognitive Dysfunction/metabolism* ; RNA-Binding Proteins/metabolism* ; Receptors, AMPA/metabolism*

Objective To investigate the effect of ankle pump exercises,based on hemodynamic mechanisms,on the prevention of venous thrombosis in stroke patients.Methods A total of 110 stroke patients,admitted to a tertiary A hospital in Jiangsu Province between June 2023 and June 2024,were selected using a convenience sampling method.The patients were divided into an experimental group and a control group,with 55 patients in each group.The experimental group received ankle pump exercise nursing interventions based on hemodynamic mechanisms,while the control group received routine nursing interventions.The incidence of lower extremity deep vein thrombosis,Pittsburgh Rehabilitation Participation Scale scores,subjective perceived fatigue,and exercise self-efficacy scores were compared between 2 groups on the 7th day of hospitalization.Results No dropouts occurred in either group.The incidence of deep vein thrombosis was significantly lower in the experimental group than it in the control group(P=0.004).The Pittsburgh Rehabilitation Participation scores on day 1,3,5,and 7 were higher in the experimental group compared to them in the control group(P＜0.001).A significant time-dependent trend was observed in Pittsburgh Rehabilitation Participation scores(P=0.034).Subjective fatigue was significantly lower in the experimental group at various time points(P＜0.001).Both groups showed an increase in exercise self-efficacy over time(P=0.016),with the experimental group demonstrating higher exercise self-efficacy than the control group on the day before discharge(P=0.003).Conclusion Ankle pump exercises,based on hemodynamic mechanisms,can effectively reduce the incidence of deep vein thrombosis in stroke patients,enhance rehabilitation participation and exercise self-efficacy,without increasing subjective fatigue.

Objective·To establish a research framework for serotonylation of proteins and to provide a methodological basis for the identification of serotonylated proteins.Methods·The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression of the transglutaminase 2(TGM2)gene,which encodes the key enzyme for serotonylation,and the solute carrier family 6(SLC6A4)gene,which encodes the serotonin transporter(SERT),in normal and pan-cancer tissues.5-Propargyltryptamide(5-PT),a serotonin derivative,was synthesized stepwise from serotonin hydrochloride,and its structure was characterized by the Fourier transform infrared spectroscopy(FT-IR),proton nuclear magnetic resonance(1H-NMR),carbon nuclear magnetic resonance(13C-NMR),and time-of-flight mass spectrometry(TOF-MS).The intracellular uptake of 5-PT in the human pancreatic cancer cell line AsPC-1 and mouse immune cells,including CD4+T cells,CD8+T cells,and bone marrow-derived macrophages(BMDMs),was detected by using flow cytometry.Click chemistry,co-immunoprecipitation,and mass spectrometry analysis techniques were employed to identify serotonylated proteins,and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was performed.Results·Bioinformatics analysis indicated that TGM2 and SLC6A4 were widely expressed in various normal tissues and across pan-cancer tissues.The flow cytometry results showed that the synthesized 5-PT can be taken up into the human pancreatic cancer cell line AsPC-1 and mouse immune cells,including CD4+T cells,CD8+T cells,and BMDMs,via the SERT.Mass spectrometry analysis data showed that a significant amount of serotonylated proteins were enriched in various cells treated with 5-PT.KEGG enrichment analysis revealed that these proteins were involved in important pathways related to glycolysis and amino acid synthesis.Conclusion·By using the synthesized 5-PT,multiple serotonylated proteins are enriched in various cell types.A research system for identifying serotonylated proteins has been successfully established,providing a relatively simple and efficient method for studying protein serotonylation.

Objective To analyze the reasons and influencing factors of ambiguous medical records,and propose targe-ted intervention strategies.Methods The medical records discharged from the Department of Otolaryngology,Head and Neck Surgery of a large Class Ⅲ hospital in Xi'an from January 2023 to December 2023 were retrospectively collected,and the medical records groups and ambiguous medical records were screened through the DRG information platform.The clinical features,defect causes and risk factors of ambiguous cases were analyzed statistically.Results There were 4 124 discharged cases in the year,of which 77 were ambiguous cases,accounting for 1.87％.Compared with the non-ambiguous group,more patients in the ambig-uous group adopted a self-funded approach,experienced a transfer and a longer hospital stay.The proportion of surgery and trau-ma in ambiguous group was higher,but the proportion of tumor patients was lower.Due to DRG grouping rules,64 cases(83.1％)were divided into ambiguous groups,which was the primary direct cause.Binary Logistic regression indicated that self-paid medical treatment(OR=2.2),transfer(OR=4.8),hospitalization ≥7 days(OR=3.1),trauma(OR=15.0),and total cost＞20 000 yuan(OR=1.7)were the risk factors for ambiguous disease cases(P＜0.05),while tumor disease was the pro-tective factor(OR=0.6,P＜0.05).Conclusion The emergence of ambiguous medical records involves many aspects such as clinical diagnosis and treatment,hospital management,health policy and so on,which has an important impact on hospital per-formance and medical insurance fund.Only by strengthening the level of hospital management,improving the quality of informa-tion system,and promoting the coordination and communication between doctors,management and patients,can we effectively re-duce the occurrence of ambiguous medical records.

Background Medical insurance payment lists are important evidence for health insurance settlement and the basis for reasonable DRG payments.However,there are currently many quality control defects that affect the correct DRG assign-ment and the reasonable payment of medical insurance funds.Methods This paper adopts a case analysis approach,combined with clinical knowledge,coding specifications,and mapping relationships,to analyze the quality defects of the current medical insurance payment lists in the hospital.Results This paper proposes refined management strategies and suggestions,including strengthening information construction,improving the professional level of quality control personnel,improving the data quality of the front-end medical record homepage,optimizing the mapping relationship of the dictionary library,carrying out clinical com-munication and training,and establishing a closed-loop quality control system for medical insurance payment lists.These strate-gies effectively improve the data quality of medical insurance payment lists and the accuracy of DRG assignment.Conclusion The management of medical insurance payment lists involves multiple links,departments,and technologies and needs continuous improvement to support hospital refined management.

In order to establish a competitive chemiluminescent enzyme-linked immunoassay for rapid and quantitative detection of Senecavirus A antibodies,the polystyrene plate was coated with inactivated Senecavirus A antigen,and the monoclonal antibodies against Senecavirus A VP2 and VP3 proteins labeled by horseradish peroxidase(HRP)were used as the competitive enzymic anti-bodies of the antibodies in the serum samples.The standard curve of the calibrator prepared by di-lution of positive serum was drawn to achieve quantitative detection.The successfully established SVA competitive CLEIA reported the result within 45 minutes.The maximum dilution of 1∶2 048 for calibrator serum was still detectable with no cross-reaction with the standard positive serum of other five kinds of virus antigens such as foot-and-mouth disease.The coefficient of variation within batches was less than 10％,and the coefficient of variation between batches was less than 15％,which showed good repeatability and stability.The positive and negative coincidence rates were 95.30％and 97.57％,respectively,and the total coincidence rate was 96.88％,showing high consistency.The SVA competitive CLEIA assay established in this study can be used for the rapid quantitative detection of Senecavirus A antibodies,filling the gap in the domestic rapid quantitative detection of SVA antibodies.

Objective To establish a reversed-phase HPLC method for determining three stereoisomers in baloxavir marboxil and provide a basis for the quality specification of baloxavir marboxil.Methods The chromatographic column was CHIRALPAK IC-3(4.6 mm × 150 mm,3 μm),The mobile phase was acetonitrile-0.1％formic acid aqueous solution-isopropanol(35:50:15).The column temperature was 40 ℃.The flow rate was 0.5 mL·min-1.The injection volume was 10 μL.The detection wavelength was 259 nm.Result The isomer peaks were completely separated from the principal component peak.The detection limits for stereoisomers 1,2 and 3 were 0.024 7,0.038 7,0.038 1 μg·mL-1 respectively.The quantitation limits for stereoisomers 1,2 and 3 were 0.049 4,0.077 3,0.076 1 μg·mL-1 respectively.There were good linear relationships between the concentrations and peak area within the ranges of the study,and the linearity concentration ranges of stereoisomers 1,2 and 3 were 0.049 5-0.989 0 μg·mL-1,0.051 6-1.031 0 μg·mL-1,0.050 8-1.015 0 μg·mL-1 respectively.The linear correlation coefficients were 0.999 4.The recovery was 92.28％-103.90％.The sample solution was stable in 48 h at room temperature.Conclusion The method is accurate and reliable for determining stereoisomers in baloxavir marboxil,and provide a guideline of quality standards of baloxavir marboxil and safety evalution.

Objective To establish a reversed-phase HPLC method for determining three stereoisomers in baloxavir marboxil and provide a basis for the quality specification of baloxavir marboxil.Methods The chromatographic column was CHIRALPAK IC-3(4.6 mm × 150 mm,3 μm),The mobile phase was acetonitrile-0.1％formic acid aqueous solution-isopropanol(35:50:15).The column temperature was 40 ℃.The flow rate was 0.5 mL·min-1.The injection volume was 10 μL.The detection wavelength was 259 nm.Result The isomer peaks were completely separated from the principal component peak.The detection limits for stereoisomers 1,2 and 3 were 0.024 7,0.038 7,0.038 1 μg·mL-1 respectively.The quantitation limits for stereoisomers 1,2 and 3 were 0.049 4,0.077 3,0.076 1 μg·mL-1 respectively.There were good linear relationships between the concentrations and peak area within the ranges of the study,and the linearity concentration ranges of stereoisomers 1,2 and 3 were 0.049 5-0.989 0 μg·mL-1,0.051 6-1.031 0 μg·mL-1,0.050 8-1.015 0 μg·mL-1 respectively.The linear correlation coefficients were 0.999 4.The recovery was 92.28％-103.90％.The sample solution was stable in 48 h at room temperature.Conclusion The method is accurate and reliable for determining stereoisomers in baloxavir marboxil,and provide a guideline of quality standards of baloxavir marboxil and safety evalution.

Objective To analyze the reasons and influencing factors of ambiguous medical records,and propose targe-ted intervention strategies.Methods The medical records discharged from the Department of Otolaryngology,Head and Neck Surgery of a large Class Ⅲ hospital in Xi'an from January 2023 to December 2023 were retrospectively collected,and the medical records groups and ambiguous medical records were screened through the DRG information platform.The clinical features,defect causes and risk factors of ambiguous cases were analyzed statistically.Results There were 4 124 discharged cases in the year,of which 77 were ambiguous cases,accounting for 1.87％.Compared with the non-ambiguous group,more patients in the ambig-uous group adopted a self-funded approach,experienced a transfer and a longer hospital stay.The proportion of surgery and trau-ma in ambiguous group was higher,but the proportion of tumor patients was lower.Due to DRG grouping rules,64 cases(83.1％)were divided into ambiguous groups,which was the primary direct cause.Binary Logistic regression indicated that self-paid medical treatment(OR=2.2),transfer(OR=4.8),hospitalization ≥7 days(OR=3.1),trauma(OR=15.0),and total cost＞20 000 yuan(OR=1.7)were the risk factors for ambiguous disease cases(P＜0.05),while tumor disease was the pro-tective factor(OR=0.6,P＜0.05).Conclusion The emergence of ambiguous medical records involves many aspects such as clinical diagnosis and treatment,hospital management,health policy and so on,which has an important impact on hospital per-formance and medical insurance fund.Only by strengthening the level of hospital management,improving the quality of informa-tion system,and promoting the coordination and communication between doctors,management and patients,can we effectively re-duce the occurrence of ambiguous medical records.

Objective·To establish a research framework for serotonylation of proteins and to provide a methodological basis for the identification of serotonylated proteins.Methods·The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression of the transglutaminase 2(TGM2)gene,which encodes the key enzyme for serotonylation,and the solute carrier family 6(SLC6A4)gene,which encodes the serotonin transporter(SERT),in normal and pan-cancer tissues.5-Propargyltryptamide(5-PT),a serotonin derivative,was synthesized stepwise from serotonin hydrochloride,and its structure was characterized by the Fourier transform infrared spectroscopy(FT-IR),proton nuclear magnetic resonance(1H-NMR),carbon nuclear magnetic resonance(13C-NMR),and time-of-flight mass spectrometry(TOF-MS).The intracellular uptake of 5-PT in the human pancreatic cancer cell line AsPC-1 and mouse immune cells,including CD4+T cells,CD8+T cells,and bone marrow-derived macrophages(BMDMs),was detected by using flow cytometry.Click chemistry,co-immunoprecipitation,and mass spectrometry analysis techniques were employed to identify serotonylated proteins,and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was performed.Results·Bioinformatics analysis indicated that TGM2 and SLC6A4 were widely expressed in various normal tissues and across pan-cancer tissues.The flow cytometry results showed that the synthesized 5-PT can be taken up into the human pancreatic cancer cell line AsPC-1 and mouse immune cells,including CD4+T cells,CD8+T cells,and BMDMs,via the SERT.Mass spectrometry analysis data showed that a significant amount of serotonylated proteins were enriched in various cells treated with 5-PT.KEGG enrichment analysis revealed that these proteins were involved in important pathways related to glycolysis and amino acid synthesis.Conclusion·By using the synthesized 5-PT,multiple serotonylated proteins are enriched in various cell types.A research system for identifying serotonylated proteins has been successfully established,providing a relatively simple and efficient method for studying protein serotonylation.