OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.

OBJECTIVE: To develop a user-friendly visualization application for the automatic annotation of Human Phenotype Ontology (HPO) terms based on large language models and retrieval-augmented generation (RAG) technology, and to validate its performance in an authoritative case dataset. METHODS: By integrating the domestic open-source large language model DeepSeek-V3 with RAG technology, an interactive web application was deployed on the Streamlit cloud platform. Using only the latest official HPO dataset as the data source, the lightweight sentence-embedding model BAAI/bge-small-en-v1.5 was employed to construct a FAISS vector index. During the online phase, a four-step closed-loop process is automatically completed: multilingual translation, phenotype phrase extraction, RAG candidate retrieval, term mapping, and official database validation. 121 English case reports publicly released by BMJ Case Reports and Oxford Medical Case Reports (with a gold-standard HPO set of 1 794 terms) were selected for application validation. Precision, recall, and F1 score were calculated and compared horizontally with traditional dictionary tools, standalone large language models, and the similar application "RAG-HPO". Finally, replace the model with the more advanced ChatGPT-5 and evaluate its performance on the newly extracted dataset. RESULTS: An HPO term automatic annotation visualization application named PhenoRAG, based on large language models and RAG technology, was successfully developed. Users can access it directly via a web link. Across the 112 cases, a total of 2 150 HPO terms were generated; 2,064 (96.0%) were fully validated by the official database, with a hallucination rate of 1.3% and an HPO ID-name mismatch rate of 2.7%. After deduplication, 1,906 terms remained for testing. The overall precision was 63.65%, recall was 67.34%, and F1 was 65.44%, significantly outperforming traditional annotation tools (F1: 0.45-0.49, P < 0.001). Although PhenoRAG's F1 was lower than that of RAG-HPO (F1 = 0.78, P < 0.001), which relies on a manually constructed synonym database of 54 000 entries plus the HPO dataset, it requires no additional dictionary maintenance and can be used without any background in computer programming. Moreover, after switching to the GPT-5 model, PhenoRAG exhibited no hallucination rate on the new dataset, and its F1 score significantly increased (P = 0.038). CONCLUSION Without constructing a synonym database, the PhenoRAG achieved high-accuracy automatic mapping from clinical text to standard HPO terms. It features a low usage threshold, free access, and a Chinese-language interface, and can directly serve rare disease diagnosis, genetic counseling, and research scenarios in China and worldwide, warranting further clinical promotion and multicenter validation.
Humans ; Phenotype ; Biological Ontologies ; Language ; Software ; Large Language Models

Background Neck-related work-related musculoskeletal disorders (WMSDs) are a major type of musculoskeletal disorders with a relatively high proportion. Shanghai has a large number of occupational populations; however, the occurrence of WMSDs at neck among the occupational populations across industries in this city has not been reported, and needs to be addressed. Objective To understand the occurrence of neck-related WMSDs and their influencing factors among occupational populations in 8 industries in Shanghai, and to provide a scientific basis for the prevention and control of WMSDs in this population. Methods From February 2024 to February 2025, a cross-sectional survey employed stratified cluster sampling to select 7829 employed workers from 48 enterprises across 8 industries in Shanghai. The study investigated the occurrence of neck-related WMSDs among the participants over the preceding 12 months. Logistic regression analysis was employed to examine the relationships between WMSDs and various occupational factors. Results A total of 7770 questionnaires were collected, yielding an effective response rate of 99.2%. Overall, the positive rate of neck-related WMSDs among the participants was 11.89% (924/7770). Among different industries, the environmental sanitation industry (19.48%), pharmaceutical manufacturing industry (14.57%), and cigarette manufacturing industry (13.66%) had higher prevalence of neck-related WMSDs. Univariate analysis showed that the risk of neck-related WMSDs was higher in the following groups: those with a job tenure ≥5 years in the current position (OR=1.50–1.70), females (OR=1.77), those with higher education levels (master’s degree or above, OR=2.27), and those with worse self-rated health (very poor health, OR=4.38) (P＜0.05). Multivariate logistic regression analysis identified the following independent risk factors for neck WMSDs: environmental sanitation industry (OR=7.30, 95%CI: 4.72, 11.87), higher educational attainment (master’s degree or above: OR=2.16, 95%CI: 1.36, 3.35), worse self-rated health status (very poor: OR=1.95, 95%CI: 1.31, 2.85), work performed in a single workshop (OR=1.36, 95%CI: 1.13, 1.64), understaffing (OR=1.46, 95%CI: 1.25, 1.70), slight neck forward flexion (OR=1.64, 95%CI: 1.32, 2.06), severe neck forward flexion (OR=2.55, 95%CI: 1.97, 3.30), and maintaining a fixed neck posture for a prolonged period (OR=2.28, 95%CI: 1.93, 2.70). Conversely, work rotation (OR=0.75, 95%CI: 0.65, 0.87), adequate rest (OR=0.70, 95%CI: 0.60, 0.82), and severe back flexion (OR=0.63, 95%CI: 0.46, 0.85) were protective factors against neck-related WMSDs. For the nomogram, the area under the curve (AUC)=0.75 (95%CI: 0.74, 0.77), Hosmer-Lemeshow test P=0.764, and Brier score=0.094, indicating that the model had good discrimination and calibration. Conclusion Among the occupational populations in Shanghai, the environmental sanitation industry, pharmaceutical manufacturing industry, and cigarette manufacturing industry are identified as high-risk industries for neck-related WMSDs. Industry affiliation, educational level, work organization patterns, and awkward neck working postures are confirmed as the core influencing factors for the development of neck-related WMSDs. Targeted and comprehensive intervention measures should be formulated focusing on the aforementioned high-risk industries and key influencing factors. Multi-dimensional collaborative efforts, including ergonomic optimization, improvement of labor management systems, and strengthened health education and promotion, should be implemented to effectively control the risk of neck-related WMSDs in the occupational population, and to provide robust statistical evidence for the advancement of regional occupational health prevention and control strategies.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

ObjectiveTo investigate the application of central auditory testing combined with electroencephalographic features in the early screening of mild cognitive impairment due to Alzheimer's disease. MethodsA convenience sampling method was used to conduct a field survey in the Qixia District of Nanjing City, Jiangsu Province, from July to September, 2025. A total of 40 older adults diagnosed as mild cognitive impairment due to Alzheimer's disease and 23 cognitively normal older adults were recruited. Auditory N-back and dichotic listening paradigms were employed for assessment, while the scores of Montreal Cognitive Assessment Beijing Version (MoCA-BJ) and 32-channel electroencephalogram (EEG) data were simultaneously collected. Binary logistic regression analysis was applied to identify predictive indicators, receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated. ResultsThe total score of dichotic listening was positively correlated with overall cognitive function (r = 0.475, P < 0.01), while right-ear advantage showed negative correlations with overall cognition, visuospatial ability, abstract reasoning, and delayed recall (r < -0.276, P < 0.05). Task performance across all conditions of the N-back task was positively correlated with overall cognitive function (r > 0.249, P < 0.05). Regarding EEG features, δ and θ band power and power peaks were positively correlated with delayed recall (r > 0.258, P < 0.05), whereas (α+θ)/(α+β) and θ/(α+β) were positively correlated with naming ability and visuospatial executive function, respectively (r > 0.261, P < 0.05). The results of the binary logistic regression analysis showed that the total score of binaural dichotic listening, the accuracy of 1-back task, the average power of δ waves, and the ratio of θ/(α+β) were independent influencing factors for mild cognitive impairment due to Alzheimer's disease (P < 0.05). The ROC analysis indicated that the AUC for auditory task performance and EEG features were 0.845 and 0.735 respectively, and when combined, the AUC increased to 0.862. ConclusionThe screening model based on the integration of auditory task performance and EEG features can be used in the early identification of mild cognitive impairment due to Alzheimer's disease.

Objective We reviewed and analyzed the epidemiological data of 83 imported dengue fever cases reported in Fengtai District, Beijing, from 2007 to 2025, to delineate their epidemiological characteristics and guide the dengue fever prevention and control strategy in the future. Methods Data on dengue fever cases in Fengtai District from 2007 to 2025 were collected to identify the epidemic factors and characteristics using descriptive epidemiological method. Results All 83 dengue fever cases reported in this region over the past two decades have been imported from abroad or other domestic areas, with Southeast Asian countries being identified as the primary source of imported infections, accounting for 42 cases (50.60%), followed by 15 cases (18.07%) from Chinese provinces other than Beijing. The remaining import sources included 13 cases from South Asia,8 from African countries, and each from Oceania, South America, and Europe. Disease onset was found concentrated between May and November. The sex ratio (male-to-female) is 1.59:1. The age of onset ranged from 14 to 61 years old, with a median age of 36. The largest proportion of cases was observed among cadres and office workers (31 cases, 37.35%), followed by businessmen (13 cases, 15.67%), and householders or the unemployed (10 cases,12.05%). Travel visit was identified as the primary reason for their exposure history. Conclusions All dengue fever cases reported in Fengtai from 2007 to 2025 were imported, with an increasing trend of imported cases in Beijing originating from other Chinese provinces. It is essential to strengthen health education for foreign travelers and returning residents, enhance clinical diagnosis and treatment training for medical personnel, eliminate mosquito breeding sites, and reduce mosquito density through active patriotic health campaigns.

Objective To explore the association and diagnostic performance of liver imaging reporting and data system(LI-RADS)CT signs with hepatocellular carcinoma(HCC)both in the LI-RADS target population and patients without LI-RADS-defined HCC risk factors.Methods A retrospective analysis was conducted on the data of 435 patients with 482 hepatic lesions confirmed by pathology.Of these,306 cases were assigned to the HCC group(327 HCC lesions),and other 129 cases were assigned to the non-HCC group(77 malignancies and 78 benign lesions).Receiver operating characteristic(ROC)curve analysis assessed the diagnostic performance of LI-RADS v2018 CT signs for HCC,and logistic regression analyses determined the association of CT signs with HCC.Results The asso-ciation of CT signs with all HCC lesions was statistically significant for non-peripheral washout[odds ratio(OR)15.1;95％ confi-dence interval(CI)5.6-40.4;P＜0.01]and non-rim arterial phase hyperenhancement(APHE)(OR 12.4;95％ CI 7.5-20.5;P＜0.01)higher than enhanced capsule(OR 9.9;95％ CI 2.8-34.8;P＜0.01;OR 2.4;95％ CI 1.4-3.8;P=0.01).The sensitivity,specificity,positive predictive value(PPV),and area under the curve(AUC)for diagnosing HCC were 85％,83％,91％,and 0.84,respectively for non-peripheral washout;82％,77％,88％ and 0.79,respectively for non-rim APHE;and 31％,98％,97％ and 0.65,respectively for enhanced capsule.Sensitivity(88％ vs 87％),specificity(83％ vs 82％),PPV(92％ vs 91％)and AUC(0.90 vs 0.87)were all slightly higher when non-peripheral washout,non-rim APHE,enhanced capsule,and ancillary features were combined for the diagnosis of HCC compared to combining the three major features.Enhanced capsule(OR 13.3;95％ CI 3.6-48.9;P＜0.01),blood products in mass(OR 20.3;95％ CI 2.4-171.4;P＜0.01),and mosaic appearance(OR 37.7;95％ CI 4.2-340.0;P＜0.01)were associations with HCC presenting with atypical imaging features and provided high specificity from 98％ to 99％.Conclusion In theLI-RADS target population and patients without LI-RADS-defined HCC risk factors,LI-RADS v2018 CT signs show excellent diag-nostic performance for HCC.Two ancillary features,blood products in mass and mosaic appearance,show good specificity for HCC with atypical imaging features.

Objective To explore the effectiveness of the peripheral arterial calcification scoring system(PACSS)based on computed tomography angiography(CTA)in assessing renal function in patients with peripheral arterial disease(PAD).Methods The clinical data,CTA imaging data,and laboratory results from PAD patients who underwent lower limb artery CTA examination were retrospectively collected.The PACSS was utilized to score the calcification in both lower limb arteries.Participants were categorized into three groups based on their estimated glomerular filtration rate(eGFR)(normal group:eGFR≥90 mL/min;mild renal dysfunction group:eGFR 60-89 mL/min,and moderate to severe renal dysfunction group:eGFR＜60 mL/min).The demographic data,clinical symptoms,and comorbidities among the three groups were compared by analysis of variance(ANOVA).The Spearman correlation coefficient was employed to evaluate the relationship between eGFR,cystatin C,and PACSS score.Results The age(P＜0.001)and PACSS score(P＜0.05)of patients with renal dysfunction were significantly higher than those of patients with normal renal function.However,there were no significant differences in gender,prevalence of diabetes,hypertension,or severe limb ischemia.Spearman correlation analysis showed that eGFR was negatively correlated with PACSS score(r=-0.18 in the right lower limb,P=0.037,r=-0.24 in the left lower limb,P=0.006).In contrast,cystatin C was positively correlated with PACSS score(r=0.26 in the right lower limb,P＜0.001,r=0.22 in the left lower limb,P=0.002).Conclusion The PACSS score of lower limb artery in PAD patients is corre-lated with the severity of renal dysfunction.This finding may facilitate early warning and clinical intervention for PAD patients with renal dysfunction.

eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.