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 compare six existing Chinese standards related to visual disability,including Disability Assessment and Code for Life Insurance(Insurance Standard),Specification for Ability Assessment of Older Adults(Elderly Stan-dard),Grading of Disability due to Human Body Injury(Judicial Standard),Standard for Identify Work Ability—Gradation of Disability Caused by Work-related Injuries and Occupational Diseases(Work Injury Standard),Standard for Assessment of Disability Grades of Military Personnel(Military Standard),and Classification and Grading Criteria of Disability(Disability Classification Standard).Methods Based on the theoretical framework of International Classification of Functioning,Disability and Health(ICF)and International Classification of Diseases,the 11th Revision(ICD-11),and with reference to World Report on Vision(WRV),this study analyzed and compared five key dimensions of visual disability across the six stan-dards:definition,classification,grading,assessment methods and coding systems.Results In terms of definition,the insurance,work injury,military,and disability classification standards emphasized vi-sual structure and function,focusing on visual acuity and visual field;the insurance and elderly standards incor-porated activities and participation,reflecting the concept of functional vision;the judicial standard lacked a dedi-cated definition of visual disability.In terms of grading,each standard graded visual disability into different lev-els acoording to different functional indicators.In terms of coding,only the insurance standard adopted the ICF framework,while others used non-ICF numeric codes or lacked standardized coding.In terms of assessment tools,the elderly standard employed a customized perceptual and participation scoring system,while others re-lied primarily on vision charts.Conclusion Most current Chinese standards focus on impairments in visual function,with limited attention to activity limitations and participation restrictions.It is needed for incorporating the concept of functional vision,aligned with ICF and WRV,to establish a unified conceptual framework,terminology,coding system for visual disability,and comprehensive assessments that reflect not only impairments but also the impact on daily functioning and en-vironmental interaction.

BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.

Objective To comprehensively understand the map of transcripts during mitosis and their regulatory mechanisms of HAP 1 cells by conducting transcriptome sequencing analysis after being released by mitotic synchro-nization arrest.Methods HAP1 cells were subjected to mitotic synchronous arrest with nocodazole and samples were collected after 0,20,80 min release,and RNA sequencing(RNA-seq)were performed.The transcriptome data was cleaned and the differentially expressed genes,expression trend clustering and functional enrichment com-bined with the protein interaction network were analyzed to explore the changes of signaling pathways in HAP 1 cells during mitosis.Results The transcriptome of HAP1 cells after synchronous release from mitosis underwent significant changes in time series,and differential gene cluster analysis revealed four gene clusters were enriched in important biological processes such as p53 signaling and cytoplasmic translation.Conclusions The transcriptome time-dependent dynamic changes during mitosis in HAP1 cells are coordinated regulation of key signaling pathways including cellular stress response,translational control and chromatin remodeling,ensuring a balance between growth and stress response upon mitotic exit.

ObjectiveTo explore the effect of different drying conditions on the appearance and intrinsic quality indicators of Pinelliae Rhizoma for screening suitable drying conditions， so as to provide reference for its standardized production and quality evaluation. MethodsDifferent dried samples of Pinelliae Rhizoma were prepared by lime-assisted sweating method and intermittent drying method. Visual analysis was employed to measure the color brightness values（L^*） of the surface， cross-section and powder of the samples， texture analyzer was used to determine the hardness of the samples under different drying conditions. The total starch content was calculated by measuring the contents of amylose and amylopectin in the samples with ultraviolet-visible spectroscopy. High performance liquid chromatography（HPLC） was used to determine the contents of seven nucleoside components（uracil， hypoxanthine， uridine， inosine， guanosine， β-thymidine and adenosine） in the samples. Pearson correlation analysis was conducted to explore the correlation between the external characteristics and intrinsic indicators of the different dried samples. Principal component analysis（PCA） was used to comprehensively rank the data of various indicators， and partial least squares-discriminant analysis（PLS-DA） was used to screen differential components with variable importance in the projection（VIP） value>1. Furthermore， the difference between the optimal drying condition for Pinelliae Rhizoma and the traditional sun-drying method was explored by independent samples t-test. ResultsWith the increase of temperature， the color of the intermittently dried samples gradually deepened， while their hardness gradually decreased. Concurrently， the contents of extract， total starch， uridine and adenosine exhibited an upward trend， whereas the contents of uracil， hypoxanthine and inosine displayed a downward trajectory. Compared with the intermittent drying group， the content of extract in the samples subjected to lime-assisted sweating increased. With the increase of lime dose， the hardness and the total content of nucleoside components in the samples showed a downward trend， while the total starch content showed an upward trend. Correlation analysis showed that the comprehensive score of L^* was negatively correlated with the contents of uracil， hypoxanthine and inosine， and positively correlated with the contents of uridine， guanosine and adenosine. Hardness was negatively correlated with adenosine content， and positively correlated with the contents of inosine， uracil and hypoxanthine. Through comprehensive consideration and comprehensive score of principal components， the method of 5% lime-mixed sweating for 6 days emerged as the top-ranking approach. Except for the extract， the results of independent samples t-test showed that there was no significant difference between the 5% lime-mixed sweating for 6 days and the traditional sun-drying in terms of other content indicators. ConclusionThe whiteness and firmness of Pinelliae Rhizoma exhibit significant correlations with its chemical composition， while uridine， uracil， guanosine， adenosine and inosine are the key constituents responsible for the quality difference of Pinelliae Rhizoma under different drying conditions. The lime-assisted sweating method optimized in this study can be proposed as a viable alternative to the traditional sun-drying method. This method not only ensures the quality of the medicinal material but also effectively reduces the drying time and prevents mold contamination， which provides a valuable reference for the standardization of drying conditions and the establishment of quality evaluation criteria for Pinelliae Rhizoma.

Objective To compare six existing Chinese standards related to visual disability,including Disability Assessment and Code for Life Insurance(Insurance Standard),Specification for Ability Assessment of Older Adults(Elderly Stan-dard),Grading of Disability due to Human Body Injury(Judicial Standard),Standard for Identify Work Ability—Gradation of Disability Caused by Work-related Injuries and Occupational Diseases(Work Injury Standard),Standard for Assessment of Disability Grades of Military Personnel(Military Standard),and Classification and Grading Criteria of Disability(Disability Classification Standard).Methods Based on the theoretical framework of International Classification of Functioning,Disability and Health(ICF)and International Classification of Diseases,the 11th Revision(ICD-11),and with reference to World Report on Vision(WRV),this study analyzed and compared five key dimensions of visual disability across the six stan-dards:definition,classification,grading,assessment methods and coding systems.Results In terms of definition,the insurance,work injury,military,and disability classification standards emphasized vi-sual structure and function,focusing on visual acuity and visual field;the insurance and elderly standards incor-porated activities and participation,reflecting the concept of functional vision;the judicial standard lacked a dedi-cated definition of visual disability.In terms of grading,each standard graded visual disability into different lev-els acoording to different functional indicators.In terms of coding,only the insurance standard adopted the ICF framework,while others used non-ICF numeric codes or lacked standardized coding.In terms of assessment tools,the elderly standard employed a customized perceptual and participation scoring system,while others re-lied primarily on vision charts.Conclusion Most current Chinese standards focus on impairments in visual function,with limited attention to activity limitations and participation restrictions.It is needed for incorporating the concept of functional vision,aligned with ICF and WRV,to establish a unified conceptual framework,terminology,coding system for visual disability,and comprehensive assessments that reflect not only impairments but also the impact on daily functioning and en-vironmental interaction.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

Objective:To analyze the incidence and perinatal factors of death or severe intraventricular hemorrhage (sIVH) within the first week of life in preterm infants with gestational age <32 weeks.Methods:Based on the online data platform of Sina-northern Neonatal Network, a case-control study was conducted using clinical data from 8 903 preterm infants with gestational age <32 weeks admitted to 35 neonatal intensive care unit (NICU) between 2019 and 2023. Infants were classified by gestational age at birth into very preterm infants and extremely preterm infants. Infants who died or developed sIVH within the first week of life were defined as the case group, while those who survived and did not develop sIVH were defined as the control group. The general information of the infants, maternal perinatal factors, the 5 th minute Apgar score, incidence of hypothermia or early-onset sepsis, and the first arterial blood pH value were compared between the case and control groups of very preterm infants and extremely preterm infants. The χ2 test and Wilcoxon rank-sum test were used for intergroup comparisons. A multivariable logistic regression model was used to analyze the factors for death or sIVH within the first week of life in very preterm and extremely preterm infants. Results:Among the 8 903 preterm infants with gestational age <32 weeks, 4 993 (56.1%) were male, with a gestational age at birth of 30.0 (28.4, 31.0) weeks. A total of 865 cases (9.7%) were death or sIVH within the first week of life. The case group took up 5.8% (426/7 316) and 27.7% (439/1 587) of very preterm infants and extremely preterm infants, respectively. Compared to the control group, the case group of very preterm and extremely preterm infants both had higher incidences of low gestational age, low birth weight, small for gestational age, the 5 th minute Apgar score ≤7, early-onset sepsis, hypothermia at admission, and first arterial blood pH <7.20 (all P<0.001). The proportion of mother′s full course antenatal corticosteroids use were both lower in both case group (both P<0.001). Multivariate Logistic regression analysis revealed several risk factors for death or sIVH within the first week of life in very preterm and extremely preterm infants, including: low gestational age ( OR=0.70 and 0.74, 95% CI 0.60-0.82 and 0.66-0.83, both P<0.001), low birth weight ( OR=0.99 and 0.99, 95% CI 0.99-1.00 and 0.99-1.00, both P<0.05), early-onset sepsis ( OR=1.82 and 2.20, 95% CI 1.42-2.34 and 1.74-2.79, both P<0.001), the 5 th minute Apgar score ≤7 ( OR=1.41 and 2.69, 95% CI 1.10-1.81 and 2.17-3.34, both P<0.01), hypothermia at admission ( OR=1.55 and 1.38,95% CI 1.17-2.07 and 1.08-1.76,both P<0.05) and the first arterial blood pH <7.20 ( OR=2.20 and 2.57, 95% CI 1.70-2.84 and 2.05-3.21, both P<0.001). Multiple births were an independent risk factor only for extremely preterm infants ( OR=1.32, 95% CI 1.02-1.71, P<0.05). Prenatal administration of a full course of antenatal corticosteroids was identified as a protective factor in very preterm and extremely preterm infants ( OR=0.74 and 0.62, 95% CI 0.58-0.95 and 0.51-0.76, both P<0.05). Conclusions:The incidence of death or sIVH within the first week of life remains high in preterm infants with gestational age <32 weeks. The smaller gestational age and lower birth weight, early-onset sepsis, birth asphyxia, hypothermia at admission, and a first arterial blood pH <7.20 were independent risk factors for death or sIVH within the first week of life in preterm infants with gestational age <32 weeks. A full course of antenatal corticosteroids significantly reduced the risk of these adverse outcomes.

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 compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.