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.

To investigate the pharmacological substances basis and anti-vitiligo mechanism of Carum carvi L. (caraway) fruits, chemical and blood-absorbed components were identified using mass spectrometry combined with literature study and database analysis. A “blood-absorbed components–target genes–pathways” network was constructed through network pharmacology. The pharmacological effects of Carum carvi L. extract and its key blood-absorbed component, acacetin, were validated in vitro. 72 chemical components were identified in the extract, with 11 prototype blood-absorbed components and 26 metabolites being detected in the plasma of SD rats. 14 key active components and 24 key targets were predicted. In vitro experiments demonstrated that acacetin at 10 μmol/L exhibited melanogenesis-promoting and tyrosinase-activating effects compared with the positive control, significantly upregulating the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase (tyrosinase, TYR). This study comprehensively analyzes the chemical and blood-absorbed components of Carum carvi L. and elucidates its pharmacological substances basis, which provides a theoretical foundation for the anti-vitiligo effects of acacetin.

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.

OBJECTIVE T o carry out the health economics evaluation and cost-benefit analysis of the type b Hae-mophilus influenzae(Hib)vaccination for the children who were hospitalized due to Hib infection so as to provide evidence for public health policies.METHODS The children who were diagnosed with Hib-related respiratory tract infections or meningitis and were hospitalized in respiratory medicine department,infection management depart-ment,emergency rooms and neurology department of Jiangxi Provincial Children's Hospital from Jan.1,2021 to Dec.31,2023 were recruited as the research subjects.Based on a 1∶1 matching condition,the matching variables included four items such as the same age for the admission to the hospital,same gender,same department and same grade of disease severity.The children for whom the primary immunization of Hib vaccination(including Hib monovalent vaccine and Hib-containing combination vaccine)were completed and the integrity of vaccination infor-mation could be checked out were assigned as the intervention group,while the children for whom the primary im-munization of Hib vaccination was not completed were chosen as the control group.The clinical data,vaccination data and the data such as length of hospital stay and hospitalization cost were collected from the children.The cost-benefit of the Hib vaccination among the children with Hib infection was observed.RESULTS A total of 622 hospi-talized children who were detected with Hib-positive respiratory tract infections or meningitis were enrolled in the study,and 73 children(20 children from infection management department,27 children from respiratory medi-cine department,26 children from emergency rooms)were finally included in the intervention group after matc-hing and multiple rounds of screening,73 children were chosen as the control group based on a 1∶1 matching con-dition.The male children accounted for 57.53％(42 cases)in both groups,and the female children accounted for 42.47％(31 cases)in both groups.With the respect to the length of hospital stay,it was 7.00(5.00,8.00)days in the intervention group,7.00(6.00,8.00)days in the control group(Z=-0.341,P=0.733).In terms of the hospitalization cost,it was 7 756.17(6 617.92,10 617.69)yuan in the intervention group,9 040.65(8 033.76,10 935.84)yuan in the control group(Z=-2.795,P=0.005).The cost of Hib vaccination was 343.03 yuan per capita in the intervention group,and the benefit-cost ratio(BCR)was 1∶3.74(343.03 yuan/1 284.48 yuan).CONCLUSIONS The Hib vaccination can save the hospitalization cost and has high cost effectiveness.It is sugges-ted that the Hib vaccination should be promoted and the coverage rate of Hib vaccination should be raised among the age-eligible children.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer's disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.

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.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.