BACKGROUND:Hepatitis B and C continue to pose significant challenges to global public health, and this study is aimed at evaluating their burden. METHODS:Leveraging data from the Global Burden of Disease 2021, we analyzed age-standardized mortality rates (ASMRs) and age-standardized disability-adjusted life year rates (ASDRs) for hepatitis B and C from 1990 to 2021 using Joinpoint regression, age-period-cohort models, and decomposition analysis. Bayesian age-period-cohort models were applied to project future trends up to 2036. Additionally, we assessed the burden attributable to modifiable risk factors and its association with socioeconomic indicators. RESULTS:From 1990 to 2021, the global ASMR for hepatitis B declined from 12.19 to 7.57 per 100,000, and the ASMR for hepatitis C decreased from 8.18 to 6.10 per 100,000. Despite these decreases, the absolute numbers of deaths and DALYs continued to increase, mainly driven by population growth and aging. In 2021, males carried a disproportionately higher burden of hepatitis B and C compared to females. Moreover, countries with low socioeconomic development faced a greater burden. Notably, high alcohol consumption accounted for 16.20% of hepatitis B DALYs, while drug use was responsible for 49.49% of hepatitis C DALYs. By 2036, ASMRs are projected to decline further to 5.90 per 100,000 for hepatitis B and 5.23 per 100,000 for hepatitis C. CONCLUSIONS:Although ASMRs and ASDRs have declined, the global burden of hepatitis B and C remains considerable. Continued efforts in vaccination, antiviral treatment, and control of key risk factors are crucial, especially in populations with a high burden.

Praziquantel (PZQ) is currently the only agent for treating schistosomiasis, but it is plagued by suboptimal efficacy to juvenile parasites, looming drug resistance, and inability to prevent reinfection. Thioredoxin glutathione reductase (TGR) is regarded as a promising therapeutic target due to its essential role in maintaining schistosome redox homeostasis. Herein, the crystal structures of Schistosoma japonicum TGR (SjTGR) in multiple redox states and in complex with NADPH, GSH, and the anti-helminthic agent Auranofin were elucidated. Structural analyses identified the hook-shaped conformation at the C-terminal redox center, which DTNB assays further confirmed enhances electron transfer efficiency. Structural and ITC data indicated that R317 was critical for NADPH binding via hydrogen-bond interactions. The analysis also indicated that the structure basis of Auranofin's potency was its tripartite interaction at the redox-active sites. In addition, we investigated the substrate specificity of SjTrx1i and SjTRP14, downstream proteins regulated by SjTGR, and elucidated the structural basis for this specificity by determining their oxidized/reduced structures. Furthermore, in vivo RNAi indicated knockdown of SjTGR or SjTRP14 blocked the survival and oviposition of schistosomes, thus ameliorating egg-induced granulomatous pathology in mice. This work provided a framework for knowledge-based design of novel anti-schistosomals targeting parasite-specific redox vulnerabilities.

TRIM25, an E3 ligase, is an important regulator to modulate the functions of retinoic acid inducible gene-I (RIG-I) and other factors in innate immunity. Herein the structural interaction between the 2CARD domain of RIG-I and the PRYSPRY domain of TRIM25 was investigated by NMR, X-ray crystallography, computer-assisted modeling, and cell-based assays to elucidate the complex structure of PRYSPRY/2CARD. The interacting model indicated that docking of 2CARD onto PRYSPRY brought two RIG-I molecules into a close proximity to form a dimer. The attachment of a short ubiquitin chain covalently by the TRIM25's E3 ligase activity was favorable for tethering a neighboring RIG-I dimer to form the tetrameric RIG-I by noncovalent interactions. The data supported the notion that the TRIM25-RIG-I interaction was important to activate the RIG-I pathway to suppress the replication of RNA viruses, such as vesicular stomatitis virus. This work provides a structural rationale to delineate the underlying mechanism of TRIM25 regulation of RIG-I.

The abnormal expansion of GGGGCC (G4C2) repeats in the noncoding region of the C9orf72 gene is a major genetic cause of two devastating neurodegenerative disorders, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These G4C2 repeats are known to form G-quadruplex (G4) structures, which are hypothesized to contribute to disease pathogenesis. Here, we demonstrated that four DNA G4C2 repeats can fold into two structurally distinct G4 conformations: a parallel and an antiparallel topology. The high-resolution crystal structure of the parallel G4 reveals an eight-layered dimeric assembly, formed by two identical monomeric units. Each unit contains four stacked G-tetrads connected by three propeller CC loops and is stabilized through 5'-to-5' π-π interactions and coordination with a central K+ ion. Notably, the 3'-ending cytosines form a C·C+·C·C+ quadruple base pair stacking onto the adjacent G-tetrad layer. In contrast, the antiparallel G4 adopts a four-layered monomeric structure with three edgewise loops, where the C6 and C18 bases engage in stacking interaction with neighboring G-tetrad via a K+ ion. These structurally distinct G-quadruplexes provide mechanistic insights into C9orf72-associated neurodegeneration and offer potential targets for the development of structure-based therapeutic strategies for ALS and FTD.

Patients of type 2 diabetes mellitus (T2DM) were grouped into subtypes by a symptom-based diagnostic system of the traditional Chinese medicine for detecting metabolomic information that would otherwise be lost due to the high degree of variations in clinical samples. LC/MS-based metabolomic tools were employed to identify distinct metabolomic features in T2DM patients in one of the subtypes in the symptom-based diagnostic system. Several of the affected metabolic pathways could be ameliorated by the combined treatment of metformin and DPP4 inhibitor, except the taurine/hypotaurine metabolic pathway. It was possible that modulating the taurine/hypotaurine metabolism in the combined treatment with metformin and DPP4 inhibitor would enhance the therapeutic effects. To this end, a mouse diabetic model was treated with taurine in addition to metformin and DPP4 inhibitor. Indeed supplementing taurine during the combined treatment led to improvements in various indicators of the disorder such as those for the fatty acid and glucose metabolisms. It could be concluded that taurine was a useful supplement for treating T2DM with metformin and DPP4 inhibitor.

Pyroptosis plays a crucial role in physiological and pathological processes. As melanoma cells are resistant to apoptosis but express gasdermin proteins, it is appealing to counter melanoma with the induction of gasdermin-executed pyroptosis. GSDMC, initially cloned from metastatic melanoma cells, has been demonstrated as a potential executioner of pyroptosis. However, no lead compounds that trigger GSDMC-mediated pyroptosis have been reported, which limits the in-depth investigation of GSDMC functions. Here, we discovered a chemical compound, dodecyl 1H-benzo[d]imidazole-5-carboxylate (DdBIC), that targeted the nuclear receptor Nur77 to induce pyroptosis through cleaving GSDMC by granzyme B in melanoma cells. Upon DdBIC binding, Nur77 was translocated to the mitochondria to activate the hemoprotein SDHA to overconsume succinyl-CoA, subsequently disrupting the homeostasis of heme in the SDH complex and resulting in electron leakage to induce mito-ROS production. This mito-ROS signal was sensed by the mitochondrial protease OMA1 via oxidation, which led to downstream OPA1 cleavage and subsequent released into the cytoplasm. Cytosolic OPA1 activated PERK to induce the integrated stress response (ISR), which further activated granzyme B to cleave GSDMC, culminating in the induction of pyroptosis. Together, this study elucidates a signal cascade from Nur77-impaired homeostasis of heme metabolism to PERK-mediated ISR activation, and reveals a novel paradigm, by which granzyme B, rather than caspases, cleaves GSDMC for pyroptotic induction and provides a new strategy for the therapeutic treatment of melanoma by lead compound DdBIC.

Nur77, a member of the NR4A nuclear receptor family, plays a critical role in tumorigenesis and cancer progression. Ligands activating its nongenomic functions hold therapeutic promise in oncology. Our previous work identified NB1, a 4,4'-bipyridyl cinnamamide derivative, as a novel Nur77 B-site ligand that induces mitochondrial translocation of Nur77 and triggers Nur77/Bcl-2-mediated apoptosis. Through structure-based optimization, we developed NF1 by replacing the 4-hydroxypiperidine group with an N-methylpentane moiety. This modification enhanced the compound's Nur77-binding affinity and stability. NF1 maintains a similar binding mode to NB1, effectively induced apoptosis via the Nur77-Bcl-2 pathway, and demonstrates significant in vivo antitumor efficacy, acceptable pharmacokinetics, and a high safety profile (LD50 > 500 mg/kg). Collectively, these results establish NF1 as a promising candidate for further development in cancer therapy.

Background/Aims : Early-onset inflammatory bowel disease (EO-IBD) poses a global health challenge with its distinct clinical manifestations and complex progression. Methods : In this study, IBD cases occurring before age 20 were defined as EO-IBD. Data were extracted from the Global Burden of Disease 2021 database. Temporal trends were assessed using Joinpoint regression analysis, and future epidemiological trends were projected using the Bayesian age-period-cohort (BAPC) model. Health disparities across various sociodemographic index (SDI) regions were quantified using the slope index of inequality and concentration index. Results : From 1990 to 2021, the global number of EO-IBD cases increased, while the incidence rates showed minimal change. Mortality and disability-adjusted life years (DALYs) rates briefly increased before a rapid decline after 1992. In 2021, males had higher mortality and DALYs rates due to EO-IBD than females. The highest mortality and DALYs rates were observed in the <5 years and 15 to 19 years age groups. Geographically, high SDI regions had the highest incidence, prevalence, and DALYs rates, while low SDI regions had the highest mortality rates. BAPC projections indicate that by 2036, the age-standardized incidence rate and prevalence rate will increase, whereas the age-standardized mortality rate and DALYs rates will continue to decline. Conclusions : The incidence of EO-IBD is projected to exhibit an increasing trend in the future. Although the global mortality and DALYs rates of EO-IBD have decreased, significant disparities persist across age groups and regions. Targeted prevention and control strategies are needed to address the needs of high-risk populations and regions.

ETHNOPHARMACOLOGICAL RELEVANCE:Lianhua Qingwen (LHQW), a traditional Chinese medicine, combines three classical formulas-Maxing Shigan decoction (MXSGD), Yinqiao powder (YQP), and Rhei Radix et Rhizoma (Dahuang)-demonstrating adaptive optimization of classical prescriptions. Despite its well-documented pharmacological effects, the scientific rationale for its compatibility remains underexplored. AIM OF THE STUDY:To elucidate the functional roles and synergistic mechanisms of LHQW through a formula-disassembled strategy combined pharmacodynamic (PD) and pharmacokinetic (PK) analysis. MATERIALS AND METHODS:LHQW's components were identified using UPLC-HRMS. Three disassembled prescriptions (DPs): LHQW-M (excluding MXSGD-related herbs), LHQW-Y (excluding YQP-related herbs), and LHQW-D (excluding Dahuang) were created based on LHQW's compatibility theory. Multidimensional PD models were established to assess antiviral, anti-inflammatory, gut-lung axis regulation, antitussive, and antipyretic effects. Systemic exposure of key components in rat plasma was quantified using HPLC-MS/MS, followed by PK-PD integrated analysis. RESULTS:The botanical origins of 211 compounds identified in LHQW were clarified. PD evaluations revealed that YQP-derived components drove antiviral and anti-mucus effects, MXSGD mediated antitussive and antipyretic actions, and Dahuang enhanced gut-lung axis protection. Synergistic anti-inflammatory effects emerged from multi-components. PK analysis showed higher systemic exposure of certain components in LHQW than its DPs, correlating with PD efficacy. CONCLUSIONS:Using an integrated formula-disassembled strategy and PK-PD analysis, we systematically deciphered LHQW's compatibility principle: YQP, MXSGD, and Dahuang exert distinct therapeutic effects and synergistic mechanisms; intact LHQW's optimized component exposure underpins its holistic efficacy. These findings provide mechanistic evidence for LHQW's formula design, highlighting the scientific intelligence of integrating classical and modern medical principles.

ETHNOPHARMACOLOGICAL RELEVANCE:Perimenopause is a transitional period in women marked by hormonal fluctuations, often resulting in symptoms such as hot flashes and mood disturbances. According to traditional Chinese medicine, these symptoms are linked to liver stagnation and kidney deficiency, and ChaiHu ShuGan San (CSS), a classical multi-herbal formulation, has been traditionally used to alleviate mood-related symptoms and modulate endocrine function in women during the perimenopausal transition, but the underlying mechanisms and active compounds remain unclear. AIM OF THE STUDY:This study aims to explore the active substances and potential mechanisms of CSS in treating PMS through steroid hormone metabolic pathways and in vivo exposure profiles. MATERIALS AND METHODS:A perimenopausal rat model was induced via ovariectomy. LC-MS/MS was employed to establish CSS metabolites profile and the TMAO (trimethylamine-N-oxide) level in rat plasma. High-exposure compounds underwent molecular docking and network pharmacology to explore interactions with steroid metabolism pathways. Biochemical markers HPA axis hormones (in plasma), IL-10 (in plasma) and FMO3 (flavin-containing monooxygenase 3, in rat liver and serum) levels were measured. The Cellular Thermal Shift Assay (CETSA) was used to provide in vitro validation of compounds binding to FMO3. RESULTS:CSS treatment was shown to regulate abnormal hormone levels, reduce triglycerides and cholesterol, and increase IL-10 levels, alleviating PMS symptoms in rats. LC-MS/MS identified liquiritigenin, isosakuranetin, and hesperetin as high-exposure components. Network pharmacology and molecular docking suggest that these three flavonoids interact with the FMO3 enzyme. CETSA results showed that these flavonoids directly bind to the FMO3 protein. CSS decreased the FMO3 level in rat liver and serum. CONCLUSIONS:CSS alleviates PMS symptoms in rats and ameliorates the abnormal changes in disease-related biochemical markers. Inhibition of FMO3 pathways is involved in the effects of CSS. This study provides further pharmacological and chemical justifications for the use of CSS in PMS management.

Liver fibrosis is an abnormal wound-healing response to liver injuries. It can lead to liver cirrhosis, and even liver cancer and liver failure. There is a lack of treatment for liver fibrosis and it is of great importance to develop anti-fibrotic drugs. A pivotal event in the process of developing liver fibrosis is the activation of hepatic stellate cells (HSCs), in which the nuclear receptor Nur77 plays a crucial role. This study aimed to develop novel anti-fibrotic agents with Nur77 as the drug target by modifying the structure of THPN, a Nur77-binding and anti-melanoma compound. Specifically, a series of para-positioned 3,4,5-trisubstituted benzene ring compounds with long-chain backbone were generated and tested for anti-fibrotic activity. Among these compounds, compound A8 was with the most potent and Nur77-dependent inhibitory activity against TGF-β1-induced activation of HSCs. In a crystal structure analysis, compound A8 bound Nur77 in a peg-in-hole mode as THPN did but adopted a different conformation that could interfere the Nur77 interaction with AKT, which was previous shown to be important for an anti-fibrotic activity. In a cell-based assay, compound A8 indeed impeded the interaction between Nur77 and AKT leading to the stabilization of Nur77 without the activation of AKT. In a mouse model, compound A8 effectively suppressed the activation of AKT signaling pathway and up-regulated the cellular level of Nur77 to attenuate the HSCs activation and ameliorate liver fibrosis with no significant toxic side effects. Collectively, this work demonstrated that Nur77-targeting compound A8 is a promising anti-fibrotic drug candidate.

The abnormal GGGGCC hexanucleotide repeat expansions (HREs) in C9orf72 cause the fatal neurodegenerative diseases including amyotrophic lateral sclerosis and frontotemporal dementia. The transcribed RNA HREs, short for r(G4C2)n, can form toxic RNA foci which sequestrate RNA binding proteins and impair RNA processing, ultimately leading to neurodegeneration. Here, we determined the crystal structure of r(G4C2)2, which folds into a parallel tetrameric G-quadruplex composed of two four-layer dimeric G-quadruplex via 5'-to-5' stacking in coordination with a K+ ion. Notably, the two C bases locate at 3'- end stack on the outer G-tetrad with the assistance of two additional K+ ions. The high-resolution structure reported here lays a foundation in understanding the mechanism of neurological toxicity of RNA HREs. Furthermore, the atomic details provide a structural basis for the development of potential therapeutic agents against the fatal neurodegenerative diseases ALS/FTD.

Guanine (G)-rich nucleic acid sequences can form diverse G-quadruplex structures located in functionally significant genome regions, exerting regulatory control over essential biological processes, including DNA replication in vivo. During the initiation of DNA replication, Cdc6 is recruited by the origin recognition complex (ORC) to target specific chromosomal DNA sequences. This study reveals that human Cdc6 interacts with G-quadruplex structure through a distinct region within the N-terminal intrinsically disordered region (IDR), encompassing residues 7-20. The binding region assumes a hook -type conformation, as elucidated by the NMR solution structure in complex with htel21T18. Significantly, mutagenesis and in vivo investigations confirm the highly specific nature of Cdc6's recognition of G-quadruplex. This research enhances our understanding of the fundamental mechanism governing the interaction between G-quadruplex and the N-terminal IDR region of Cdc6, shedding light on the intricate regulation of DNA replication processes.

BackgroundIs de novo metastatic breast cancer (dnMBC) the same disease in the elderly as in younger breast cancer remains unclear. This study aimed to determine the metastatic patterns and survival outcomes in dnMBC according to age groups.MethodsWe included patients from the Surveillance Epidemiology and End Results program. Chi-square test, multivariate logistic regression analyses, and multivariate Cox regression models were used for statistical analyses.ResultsA total of 17719 patients were included. There were 3.6% (n=638), 18.6% (n=3290), 38.0% (n=6725), and 39.9% (n=7066) of patients aged <35, 35-49, 50-64, and ≥65 years, respectively. Older patients had a significantly higher risk of lung metastasis and a significantly lower risk of liver metastasis. There were 19.1%, 25.6%, 30.9%, and 35.7% of patients with lung metastasis in those aged <35, 35-49, 50-64, and ≥65 years, respectively. Moreover, the proportion of liver metastasis was 37.6%, 29.5%, 26.3%, and 19.2%, respectively. Age was the independent prognostic factor associated with breast cancer-specific survival (BCSS) and overall survival (OS). Those aged 50-64 years had significantly inferior BCSS (P<0.001) and OS (P<0.001) than those aged <35 years. Patients aged ≥65 years also had significantly lower BCSS (P<0.001) and OS (P<0.001) than those aged <35 years. However, similar outcomes were found between those aged 35-49 and <35 years.ConclusionOur study suggests that different age groups may affect the metastatic patterns among patients with dnMBC and the survival of younger patients is more favorable than those of older patients.

Background Not all eligible breast cancer (BC) patients could afford the expensive test of 21-gene recurrence score (RS) assay. This study aimed to identify clinicopathological factors associated with high-risk RS and examine whether these factors correlate with the benefit of chemotherapy. Research design and methods Patients diagnosed with early-stage BC, node-negative, and estrogen receptor-positive disease were identified from the Surveillance, Epidemiology, and End Results Oncotype DX database. Result We included 74,605 patients. Those with higher grade (p < 0.001) and progesterone receptor-negative (PR Neg) (p < 0.001) had the highest odds of a high-risk RS. Among them, 3.2%, 10.1%, 39.1%, 18.6%, 41.6%, and 80.1% had high-risk RS tumors in PR-positive (PR Pos)/well-differentiated (G1), PR Pos/moderately differentiated (G2), PR Pos/poorly and/or undifferentiated (G3), PR Neg/G1, PR Neg/G2, and PR Neg/G3 groups, respectively. Receipt of chemotherapy was associated with improved breast cancer-specific survival (p = 0.010) and overall survival (p < 0.001) in high-risk RS cohort. However, there were no survival benefits from chemotherapy in patients with PR Neg/G3 disease and other groups after stratification by grade and PR status (all p >= 0.05). Conclusion Our study aids in refining patient selection for the RS testing, which is crucial given its economic implications. However, 21-gene RS remains pivotal for treatment decision-making.

The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77’s non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands. Moreover, the lack of pharmaceutical ligands restricts Nur77’s therapeutic proof of concept. Herein, we developed a first-in-class Nur77 site B ligand (NB1) that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria. The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode. Importantly, NB1 showed favorable pharmacokinetic profiles and safety, as evidenced by its good oral bioavailability in rats and lack of mortality, bodyweight loss, and pathological damage at the 512.0 mg/kg dose in mice. Furthermore, oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model. Together, our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.

Insulin resistance (IR) and adipose tissue amplify the metabolic and reproductive outcomes in women with polycystic ovary syndrome (PCOS). It has been widely discussed that body composition influences metabolic health. Still, limited studies were focused on the role of the fat-free mass index (FFMI) in assessing IR in PCOS women. We aimed to explore the associations between FFMI/fat mass index (FMI) and IR in women with PCOS and assess the role of FFMI in predicting IR in women with PCOS. In the current cross-sectional study, women with PCOS aged between 18 and 40 years were enrolled from October 2018 to July 2022. Baseline demographic information was obtained using standardized self-administered questionnaires. Anthropometric, biochemical, and hormonal information was measured and recorded by investigators. Pearson’s correlation and multivariable logistical regression were used to analyze the associations of FFMI/FMI and IR. In addition, receiver operating characteristic (ROC) curves were implied to measure the predictive role of FFMI/FMI for IR in women with PCOS. A total of 371 women with PCOS, reproductive age (27.58 ± 4.89) were enrolled. PCOS women with IR have higher levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), homeostatic model assessment of insulin resistance (HOMA-IR), FMI, and FFMI than that without IR. FMI (r = 0.492, p < 0.001) and FFMI (r = 0.527, p < 0.001) were positively associated with IR. After adjusting for potential confounders, FMI and FFMI were significantly associated with IR in PCOS women, and the OR was 1.385 (95

目的 研究2型糖尿病(T2DM)常见病性证素及理化指标与FTO基因表达水平的相关性,初步阐明T2DM常见病性形成的分子生物学基础.方法 收集T2DM患者共396例,应用证素辨证法统计其病性、病位分布情况,并从中筛选常见病性证素进行分组,其中痰组30例、湿组29例和阴虚组31例,并选取30例健康人为健康组.理化指标检测包括体质量指数(BMI)、腰围(WC)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、AST/ALT、谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、空腹血糖(FPG)以及尿素氮(BUN);实时荧光定量PCR法检测FTO基因表达水平.结果 ①T2DM病性证素频次由高到低依次为:痰、湿、阴虚、气虚、阳虚、热、血瘀、气滞;病位证素频次由高到低依次为:肝、肾、脾、肺、心、胆、胃.② 与健康组比较,痰组、湿组、阴虚组中BMI、WC、ALT、ALP、TG、FPG均明显提高(P<0.05,P<0.01),AST/ALT、HDL-C均明显降低(P<0.05,P<0.01);痰组、湿组GGT均明显提高(P<0.01,P<0.05).③ 与健康组比较,痰组、湿组和阴虚组FTO基因表达水平均明显提高(P<0.01);与痰组比较,湿组和阴虚组FTO基因表达水平均明显降低(P<0.01).④ 痰组、湿组和阴虚组FTO基因表达水平与理化指标之间不存在相关性(P>0.05).结论 T2DM病性证素前3位为痰、湿、阴虚;病位证素前3位是肝、肾、脾.FTO基因水平的高表达可能是影响T2DM痰证形成的生物学基础.

目的 调查福建省某地某三甲医院医学科研人员科研诚信的认知现状和存在问题,为制定相关政策提供参考依据.方法 2020 年 5 月,以某三甲医院医学科研人员为调查对象,采用便利抽样方法,开展线上问卷调查.结果 医学科研人员对于不当署名的认知情况有待提高.申请阶段得分在学历(H=8.821,P=0.012)和岗位类型(H=16.676,P=0.001)间存在差异.研究实施成果发表阶段得分在岗位类型(H=17.131,P=0.001)、是否接受科研诚信教育的经历(H=4.625,P=0.032)间存在差异.护理组认知得分均较低.结论 医院需开展多元化、内容全面的科研诚信课程.医院应对各个岗位类型、各个工作阶段的科研人员实行科研业务流程化管理,实现科研诚信教育的范围全覆盖、职业生涯全贯穿.