Objective To understand the antibody levels of diphtheria and tetanus among healthy population in Shanghai Pudong New Area, and to provide a scientific basis for improving the vaccine immunization strategy. Methods Random sampling was used to select healthy people of all ages in 16 communities in Shanghai Pudong New Area from 2018 to 2024, and serum samples were collected and tested for serum anti-diphtheria and tetanus toxin IgG antibodies by enzyme-linked immunosorbent assay (ELISA) method to analyze the antibody positivity rate (≥0.1 IU/ml) and the geometric mean concentration (GMC) of antibodies. Results A total of 3 312 serum samples were included, with a male-to-female ratio of 0.76:1, and 53.77% were local residents. The seropositivity rates and geometric mean concentrations (GMC) of both diphtheria and tetanus antibodies generally declined with increasing age, but exhibited a transient rebound in the 7y-. A total of 1 175 individuals (35.48%) were seropositive for diphtheria, with a GMC of 0.054 IU/mL. For tetanus, 988 individuals (29.83%) were seropositive, with a GMC of 0.033 IU/mL. Significant differences in seropositivity rates (χ²_diphtheria=950.005,χ²_tetanus=1 324.393) and GMC (H_diphtheria=1027.160,H_tetanus=1 142.007) were observed among different age groups (P<0.001). Significant differences in seropositivity rates (χ²_diphtheria=950.005,χ²_tetanus=1324.393) and GMC (H_diphtheria=1027.160,H_tetanus=1142.007) were also found across different years (P<0.001). Conclusion The prevalence of diphtheria and tetanus antibodies in the healthy population of Pudong New Area is relatively low, particularly among adults over 20 years of age with inadequate immunization. This underscores the need to reinforce the National Immunization Program (NIP) vaccine specifications for children under 6 years of age and implement an immunization strategy for adolescents or adults against diphtheria and tetanus.

Arsenic is a semi-metal,and lipid-soluble arsenic compounds are one of the widespread forms in the environment and food chain,but there is a lack of standards for lipid-soluble arsenic compounds,which is one of the bottlenecks in the current analytical detection and toxicological studies of organic arsenic.In this study,four saturated arsenic-containing hydrocarbons,AsHC 318,AsHC 332,AsHC 346,and AsHC 374(The number is relative molecular mass),were successfully synthesized in three steps by using dimethylarsinic acid,potassium iodide,sodium hydroxide,and four brominated alkanes(1-Bromotetradecane,1-bromopentadecane,1-bromohexadecane,and 1-bromooctadecane)as raw materials.The structures of these four saturated arsenic-containing hydrocarbons were characterized by proton nuclear magnetic resonance(1H NMR)spectroscopy,13C nuclear magnetic resonance(13C NMR)spectroscopy,and high-resolution mass spectrometry(HR-MS).The yields of the method were 8%-10%,and the synthesized compounds could be used in subsequent toxicity evaluation experiments to assess the toxic effects and mechanisms of action of arsenic-containing hydrocarbons.This study provided an effective method for synthesis of arsenic-containing hydrocarbons,enriching the synthesis methods of arsenic-containing hydrocarbons,and provided raw materials for the subsequent toxicological studies of arsenic-containing hydrocarbons.

Objective To explore the mechanism of myocardial toxicity caused by N-methyl-3,4-methyle-nedioxyamphetamine(MDMA),the changes of intracellular calcium oscillation mode and calcium han-dling proteins during acute exposure to different concentrations of MDMA were detected,and the in-volvement of nuclear factor κB(NF-κB)and its effect on calcium handling proteins were investigated.Methods Primary rat cardiomyocytes were cultured to establish MDMA acute exposure model,and a control group was set up.The MDMA poisoning model was divided into three concentration groups of 10,100 and 1 000 μmol/L.After 1 h of exposure,the morphological changes of cardiomyocytes were ob-served,the cytotoxicity and changes in calcium signals were measured,and the changes in calcium handling proteins RyR2,SERCA2a,PLN,NCX1 and Cav1.2 were detected.The changes of NF-κB activity and the expression of nucleoprotein p-p65(Ser311)and PKCζ after MDMA exposure,and the intervention of NF-κB inhibitors pyrrolidine dithiocarbamate ammonium(PDTC)and protein kinase C(PKC)inhibitor chelerythrine(CHE)were detected by electrophoretic mobility shift assay(EMSA)and Western blotting.The effects of PDTC intervention on calcium signals,and the expressions of RyR2,SERCA2a,PLN,NCX1 and Cav1.2 after acute MDMA exposure were also observed.Results No obvious changes were observed in the morphology of cardiomyocytes after acute exposure to MDMA,whereas the oscillation waveform of intracytoplasmic calcium ion showed irregular changes with increased oscillation amplitude,intense fluctuations,irregular frequency,and increased fluctuation range of relative optical density values.The expression of RyR2,SERCA2a and NCX1 increased,while the expression of Cav1.2 and PLN de-creased.Acute MDMA exposure could increase NF-κB activity,while PDTC and CHE intervention could inhibit NF-κB activity.In MDMA exposed group,the expression of PKCζ and nucleoprotein p-p65(Ser311)both increased and could be inhibited by CHE.After the intervention of PDTC to block NF-κB,the amplitude of calcium oscillation was lower than that of the MDMA exposed group,and the expres-sion of RyR2,SERCA2a and NCX1 decreased.There was no significant change in PLN,while the ex-pression of Cav1.2 increased.Conclusion MDMA can lead to an increase of calcium ion concentration in cardiomyocytes.Calcium ions are involved in myocardial toxicity of MDMA.The mechanism is re-lated to changes in calcium handling proteins,mainly associated with the increased expression of RyR2.MDMA can up-regulate the intracellular activity of NF-κB through the PKCζ-NF-κB pathway and affect calcium handling proteins,which aggravate intracellular calcium overload during acute MDMA exposure.

Tonifying herbs described in the Shen Nong Ben Cao Jing frequently possess well-defined efficacy in dispelling pathogenic factors, including eliminating pathogenic factors, eliminating severe wind-disorders, dispelling Bi syndrome, removing blood stasis and resolving hard masses, facilitating urination and defecation, relieving chills and fever, promoting digestion, regulating and smoothing qi movement, treating carbuncles and deep-rooted ulcers, killing the :three worms: (parasites), draining pus and alleviating pain, and treating bone fractures and traumatic injuries. These effects correspond to a broad spectrum of conditions, encompassing immune, digestive, and respiratory system disorders, as well as tumors. These effects are closely related to the taste and compatibility of drugs, and are supported by modern pharmacological studies (such as anti-inflammatory, anti-tumor, immune regulation, etc.). This study could provide a novel perspective for the rational clinical application of tonifying herbs and establish a foundation for in-depth research into the multi-efficacy mechanisms of Chinese materia medica.

ObjectiveTo explore the current situation of forensic ethics practice and education by designing a questionnaire on forensic ethics， with a view to exploring the path of forensic ethics education construction. MethodsA total of 667 valid questionnaires were collected using the online survey method， basically covering various regions across the country and all sub-specialties of forensic medicine. Descriptive analysis was used to analyze the relevant data. ResultsMost practitioners had relevant ethical reflections in the process of forensic practice. 69.12% of the respondents indicated that they had studied the relevant rules， but approximately half stated that there were no corresponding ethical norms or standard operating manuals. The specific behaviors violating ethics in different units were diverse. 23.04% of the respondents reported that they had encountered unethical behaviors， but only 4.9% of them reported such violations. In terms of forensic ethics education， 87.75% of the respondents believed that there were issues with the current model of forensic ethics education. Meanwhile， the respondents showed a high degree of recognition for receiving forensic ethics education， with 84.15% of respondents expressing willingness to participate in relevant courses. More than half of respondents were willing to participate in forensic ethics education during undergraduate studies， new employee training， and regular post-employment training. ConclusionCurrently， there is a problem of ethical neglect in forensic work in China. Combining ethics courses with professional courses at the practitioner training stage and providing regular training at the practice stage are effective measures to popularize forensic ethics knowledge， enhance ethical awareness， and improve the quality of practice.

Objective:Investigating the association of the systemic immune-inflammation index and the pan-inflammation index with incident non-alcoholic fatty liver disease (NAFLD).Methods:This retrospective cohort study included 42 891 participants who underwent at least two health examinations at the Second Affiliated Hospital of Dalian Medical University between 2014 and 2023. Based on their levels of the systemic immune inflammation index (SII) and the pan immune inflammation value (PIV), participants were respectively divided into four quartile groups (Q1 to Q4). Cox proportional hazards models were employed to analyze the association of different SII and PIV levels, as well as their quartile groups, with new onset NAFLD in the total population and across various subgroups. Restricted cubic splines were used to examine the dose response relationship between these inflammatory indices and incident NAFLD. Additionally, sensitivity analyses were conducted to confirm the robustness of the findings.Results:After adjusting for confounding factors, the natural logarithm-transformed lnSII ( HR=1.247, 95% CI: 1.184-1.314, P<0.001) and lnPIV ( HR=1.192, 95% CI: 1.148-1.238, P<0.001) were significantly positively associated with the risk of NAFLD. When the subjects were grouped by SII quartiles (Q1-Q4), compared with those in Q1, participants in Q2, Q3, and Q4 exhibited progressively higher risks of incident NAFLD:11.9% ( HR=1.119, 95% CI: 1.051-1.192, P<0.001), 17.1% ( HR=1.171, 95% CI: 1.100-1.248, P<0.001), and 29.1% ( HR=1.291, 95% CI: 1.211-1.377, P<0.001), respectively. Quartile analysis of PIV yielded similar trends: the risk of incident NAFLD increased for 10.4% ( HR=1.104, 95% CI: 1.034-1.179, P=0.003), 18.7% ( HR=1.187, 95% CI: 1.112-1.266, P<0.001), and 30.5% ( HR=1.305, 95% CI: 1.223-1.393, P<0.001) in Q2, Q3, and Q4 group respectively when compared to that in Q1 group. Subgroup analysis confirmed consistent associations of SII and PIV with elevated NAFLD risk across all subgroups. Conclusion:Elevated levels of SII and PIV are significantly associated with increased risk of NAFLD.

Objective:To investigate transition pattern of health status among middle-aged and elderly population in China based on frailty index.Methods:In this retrospective cohort study, middle-aged and elderly people were selected from the China Health and Retirement Longitudinal Study (CHARLS) in 2011; and 1 434 subjects were followed up to 2015. The frailty index was calculated from the prevalence of chronic diseases, daily activity ability and blood biomarkers, and the frailty state was divided by quartiles of the frailty index. Markov models were constructed to determine the transition probabilities of different frailty states.Results:The mean age of the 1 434 subjects was (59.0±9.4) years and the mean frailty index was 0.11±0.05. In the healthy individuals, 63.0% remained healthy after a four-year follow-up; during the same follow-up period, 40.9% of the mildly frail individuals and 23.0% of the moderately frail individuals remained in their baseline frailty status. Increasing age leaded to a gradual increase in the probability of the population shifting to a severely frailty state. Women were more likely to shift to severe frailty status than men (0.029 vs 0.019, Z=3.03, P=0.002). Conclusion:Among middle-aged and elderly population in China, the transition of health states follows a pattern where higher frailty levels are associated with lower stability. Advanced age and female gender are identified as risk factors for progression to severe frailty.

OBJECTIVES: To explore the underlying pharmacological mechanisms and its potential effects of Chinese medicine herbal formula Sini Powder (SNP) on hepatocellular carcinoma (HCC). METHODS: The active components of SNP and their in vivo distribution were identified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Construction of component-target-disease networks, protein-protein interaction network, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking were employed to analyze the active components and anti-HCC mechanisms of SNP. Cell viability assay and wound healing assay were utilized to confirm the effect of SNP-containing serum (2.5%, 5.0%, 10%, 20%, and 40%), isoprenaline or propranolol (both 10, 100, and 1,000 µ mol/L) on proliferation and migration of HepG 2 or Huh7 cells. Meanwhile, the effect of isoprenaline or propranolol on the β 2 adrenergic receptor (ADRB2) mRNA expression on HepG2 cells were measured by real-time quantitative reverse transcription (RT-qPCR). Mice with subcutaneous tumors were either subjected to chronic restraint stress (CRS) followed by SNP administration (364 mg/mL) or directly treated with SNP (364 mg/mL). These two parallel experiments were performed to validate the effects of SNP on stress responses. Stress-related proteins and hormones were quantified using RT-qPCR, enzyme-linked immunosorbent assay, and immunohistochemistry. Metagenomic sequencing was performed to confirm the influence of SNP on the gut microbiota in the tumor-bearing CRS mice. RESULTS: The distribution of the 12 active components of SNP was confirmed in various tissues and feces. Network pharmacology analysis confirmed the anti-HCC effects of the 5 active components. The potential anti-HCC mechanisms of SNP may involve the epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC) and signal transducer and activator of transcription 3 (STAT3) pathways. SNP-containing serum inhibited the proliferation of HepG2 and Huh7 cells at concentrations of 2.5% and 5.0%, respectively, after 24 h of treatment. Furthermore, SNP suppressed tumor progression in tumor-bearing mice exposed to CRS. SNP treatment also downregulated the expressions of stress-related proteins and pro-inflammatory cytokines, primarily by modulating the gut microbiota. Specifically, the abundance of Alistipes and Prevotella, which belong to the phylum Bacteroidetes, increased in the SNP-treated group, whereas Lachnospira, in the phylum Firmicutes, decreased. CONCLUSION SNP can combat HCC by alleviating stress responses through the regulation of gut microbiota.
Animals ; Gastrointestinal Microbiome/drug effects* ; Liver Neoplasms/microbiology* ; Carcinoma, Hepatocellular/microbiology* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Powders ; Cell Proliferation/drug effects* ; Mice ; Molecular Docking Simulation ; Cell Line, Tumor ; Hep G2 Cells ; Receptors, Adrenergic, beta-2/genetics* ; Stress, Physiological/drug effects* ; Cell Movement/drug effects* ; Male ; Protein Interaction Maps/drug effects* ; Cell Survival/drug effects* ; Proto-Oncogene Mas

Objectives:To compare the intraoperative neurophysiological monitoring(IONM)results during 3-column osteotomy surgery in severe congenital scoliosis(CS)patients with or without intraspinal anomalies,and to explore the effect of intraspinal anomaly on the incidence of IONM alarm events and postoperative out-comes in CS patients.Methods:Clinical data of patients with severe CS who underwent 3-column osteotomy surgery in our hospital from September 2020 to May 2023 were retrospectively analyzed.The patients were divided into two groups according to whether combined with intraspinal anomalies.The basic information,the latency and amplitude of somatosensory evoked potentials(SSEPs)of both lower extremities,amplitude of tran-scranial electric motor evoked potentials(TCeMEPs),as well as the sensitivity and specificity of multimodal IONM were compared between the two groups.The incidence of IONM alarm events and postoperative out-comes were analyzed.Results:A total of 37 patients who met the criteria were included in the study,of which 14 patients combined with intraspinal anomalies,including 8 cases of syringomyelia,2 case of tethered cord,1 case of diastematomyelia,1 case of diastematomyelia combined with tethered cord,and 2 cases of sy-ringomyelia combined with tethered cord.The latency of SSEPs-P3 7 in the concave side lower extremity of CS patients with intraspinal anomalies was significantly longer than that of CS patients without intraspinal anomalies(40.9±3.3ms vs 38.0±3.7ms,P=0.03).In addition,the sensitivity and specificity of multimodal IONM were comparable between the two groups.There was no significant difference in the incidence of abnormal SSEPs,the incidence of IONM alarm events and the incidence of postoperative neurological symptoms between the two groups(P＞0.05).Conclusions:Multimodal IONM provides excellent monitoring effects in severe CS paitents undergoing 3-column osteotomy surgery.The latency of SSEPs-P37 in the concave side lower ex-tremity of CS patients with intraspinal anomalies was significantly longer than that of CS patients without in-traspinal anomalies.Intraspinal anomalies don't increase the incidence of intraoperative IONM alarm events or the incidence of postoperative neurological complications.

Encephalomyocarditis virus(EMCV)is a zoonotic pathogen that causes encephalitis and myocarditis as its primary clinical manifestations.To explore effective preventive measures,this study utilized a Bac-to-Bac expression system to insert the EMCV P12A and 3C genes into the pFastBacDual shuttle vector,resulting in the generation of the recombinant baculovirus Ac-P12A-3C.This facilitated the large-scale expression and purification of EMCV virus-like particles(VLPs),which were correctly assembled into particles of approximately 30 nm in diameter,as ob-served by electron microscopy.Immunization and challenge experiments in mice demonstrated that these VLPs could effectively protect against EMCV infection,achieving a protection rate of 100％.Histopathological sections indicated that,compared to the PBS control group,the VLP immuniza-tion group exhibited significantly reduced tissue damage,along with a marked decrease in viral load within the tissues.In piglets,immunization with the VLPs elicited a robust humoral response,with neutralizing antibody titers reaching 1∶320 to 1∶640 after a second immunization,and no signifi-cant adverse reactions were observed throughout the immunization process.This study preliminarily explores the immunogenicity and safety of the VLP vaccine,laying the foundation for the development of a subunit vaccine based on EMCV VLPs and offering a new strategy for the prevention and control of encephalomyocarditis.