ObjectiveTo address the challenges of unstructured classical Chinese expressions， nested entity relationships， and limited annotated data in famous traditional Chinese medicine（TCM） case records， this study proposes a joint relation extraction framework that integrates data augmentation and entity mapping， aiming to support the construction of TCM diagnostic knowledge graphs and clinical pattern mining. MethodsWe developed an annotation structure for entities and their relationships in TCM case texts and applied a data augmentation strategy by incorporating multiple ancient texts to expand the relation extraction dataset. A cascade binary tagging framework for relation triple extraction（CasRel） model for TCM semantics was designed， integrating a pre-trained bidirectional encoder representations from transformers（BERT） layer for classical TCM texts to enhance semantic representation， and using a head entity-relation-tail entity mapping mechanism to address entity nesting and relation overlapping issues. ResultsExperimental results showed that the CasRel model， combining data augmentation and entity mapping， outperformed the pipeline-based Bert-Radical-Lexicon（BRL）-bidirectional long short-term memory（BiLSTM）-Attention model. The overall precision， recall， and F₁-score across 12 relation types reached 65.73%， 64.03%， and 64.87%， which represent improvements of 14.26%， 7.98%， and 11.21% compared to the BRL-BiLSTM-Attention model， respectively. Notably， the F₁-score for tongue syndrome relations increased by 22.68%（69.32%）， and the prescription-syndrome relations performed the best with the F₁-score of 70.10%. ConclusionThe proposed framework significantly improves the semantic representation and complex dependencies in TCM texts， offering a reusable technical framework for structured mining of TCM case records. The constructed knowledge graph can support clinical syndrome differentiation， prescription optimization， and drug compatibility， providing a methodological reference for TCM artificial intelligence research.

OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

Objective: To explore the developmental trajectories of depression in children and adolescents and their association with family types, and to analyze the role of being an only child in the context, so as to provide a basis for early identification of mental health issues in children and adolescents. Methods: The study was a secondary analysis based on the existing database of the Jiangsu Provincial Student Common Diseases and Health Influencing Factors Monitoring and Intervention Project. A total of 11 502 students who had completed at least two measurements using the Chinese version of the Center for Epidemiologic Studies Depression Scale (CES-D) between 2022 and 2024, and had complete information on family type, gender, and age, were selected as the study subjects. Latent class trajectory modeling was used to identify depression developmental trajectories. Multinomial Logistic regression was applied to analyze the association between family type and depression developmental trajectories, and the interaction effect of family type and being an only child was tested. Results: Three types of depression developmental trajectories were identified among children and adolescents: low stable type (91.3%, 10 504 students), moderate rising type (4.3%, 500 students), and high declining type (4.3%, 498 students). Significant differences were observed among the different trajectory groups in terms of gender, age, parental education level, family type, baseline CES-D score, and baseline school type ( χ 2/H=17.48, 139.97, 19.72 , 30.77, 1 081.35, 220.81, all P <0.05). Multinomial Logistic regression analysis showed that, using the low stable type as the reference trajectory group and the nuclear family as the reference family type, after adjusting for confounding factors such as gender, age, and parental education level, single parent families ( OR=1.87, 95%CI= 1.16-3.03) and grandparent headed families ( OR=1.83, 95%CI =1.04-3.21) were significantly associated with the high declining type trajectory (both P <0.05). No significant association was found between family type and the moderate rising type trajectory (all P >0.05). The interaction effect between family type and being an only child was not statistically significant ( LRT=7.71, df=8, P =0.46). Conclusions Depressive symptoms in children and adolescents show heterogeneous developmental patterns during school age. Children and adolescents from single parent and intergenerational families are more likely to follow the high decreasing trajectory.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Objective:To establish a core competence evaluation index system for pediatric internal medicine nurses.Methods:On the basis of literature review, theoretical analysis, and clinical practice of the research group, the evaluation index system of the core competence of nurses in pediatric internal medicine was preliminarily formulated after the discussion of the research group. The Delphi method was employed for two rounds of expert consultation, involving a total of 18 experts. Finally, the evaluation index system of the core competence of nurses in pediatric internal medicine was established, and the weights of indicators at all levels were calculated.Results:The effective recovery rates of the first and second rounds of expert consultation were 100.00%. In the first and second rounds of expert consultation, the authority coefficients were 0.896 and 0.890, the judgment coefficients were 0.901 and 0.889, and the familiarity coefficients were 0.847 and 0.891, with authority coefficients >0.70 in both rounds. The coefficients of variation of the two rounds of expert correspondence were 0.041-0.227 and 0.002-0.126, respectively, and the coefficients of variation of indicators at all levels were <0.25. In the first round of expert consultation, Kendall's coordination coefficients of primary, secondary, and tertiary indicators were 0.305, 0.362, and 0.364, respectively, with P values <0.001. In the second round of expert consultation, Kendall's coordination coefficients of primary, secondary, and tertiary indicators were 0.371, 0.352, and 0.380, respectively, with P values <0.001. Finally, the core competence evaluation index system of pediatric internal medicine nurses was established, including 3 first-level indicators, 14 second-level indicators, and 57 third-level indicators. Conclusions:The evaluation index system of the core competence of pediatric internal medicine nurses has scientificity, reliability, specialty-specific characteristics, and reference value, which can provide a reference for the training and evaluation of pediatric internal medicine nurses in China.

Objective:To evaluate the treatment strategies and outcomes for contracted nasal deformity.Methods:A retrospective review was conducted of the patients with contracted noses who underwent surgery at the Department of Plastic and Aesthetic Surgery, the Second Xiangya Hospital of Central South University, between January 2021 and January 2024. Based on the pathologic-anatomic features and severity of the deformity, patients were categorized as having mild, moderate or severe contraction. Mild cases received extensive subcutaneous dissection and framework reconstruction with various grafts. Moderate cases underwent preoperative nasal-skin distraction and intra-operative reconstruction with lower lateral or septal cartilage. Severe cases, in addition to reconstruction of the lower lateral cartilage and nasal septum, underwent individualized repair, including mucosal or cutaneous defect resurfacing. Postoperative follow-up assessed nasal appearance, complications and recurrence of contraction. Nasal aesthetics were quantified with visual analogue scale (VAS, 0-10 points; higher scores = less deformity), and patient satisfaction with the rhinoplasty outcome evaluation (ROE) questionnaire (0 = very dissatisfied, 100 = very satisfied) before surgery and at final follow-up. Paired t-test was used for VAS and ROE comparisons; categorical variables were analyzed with the χ2 test. A P-value < 0.05 denoted statistical significance. Results:A total of 96 patients were included, comprising 7 males and 89 females, aged (27.4 ± 8.0) years (19-58 years). There were 64 cases of mild, 19 cases of moderate, and 13 cases of severe contracted nose deformities. Postoperative follow-up(14.0 ± 4.6) months (6-19 months). No cases of abnormal nasal appearance, infection, necrosis, scar hyperplasia, or recurrence of contracted nose were observed during follow-up. Significant improvements in nasal aesthetic outcomes were observed. The VAS scores for mild, moderate, and severe contracted noses increased significantly from preoperative values of 4.7 ± 1.0, 3.0 ± 1.2, and 2.2± 1.1 to postoperative values of 8.6 ± 0.7, 8.9 ± 0.7, and 8.2 ± 0.9, respectively (all P < 0.01). Similarly, the ROE scores improved significantly from 59.1 ± 10.0, 34.2 ± 12.1, and 28.5± 6.3 preoperatively to 90.2 ± 9.5, 91.5 ± 7.5, and 93.3 ± 5.8 postoperatively (all P < 0.01). Conclusion:Selecting appropriate surgical methods based on the pathological and anatomical characteristics and severity of contracted nose deformities can achieve favorable outcomes. Postoperative nasal aesthetic appearance is significantly improved, and patient satisfaction is high.

Background and Aims:In recent years,with the continuous progress of systemic therapy,hepatic arterial infusion chemotherapy(HAIC)combined with immune checkpoint inhibitors and anti-angiogenic agents has demonstrated significant efficacy in the treatment of advanced hepatocellular carcinoma(HCC).However,direct comparisons between different immunotherapeutic targets,such as PD-1 and PD-L1 inhibitors,in terms of clinical benefit and safety remain limited.This study aimed to compare the efficacy and safety of HAIC plus bevacizumab and sintilimab(HAIC-BP1)versus HAIC plus bevacizumab and atezolizumab(HAIC-BPL)in advanced HCC.Methods:A retrospective analysis was conducted on 88 patients with advanced HCC who received first-line HAIC-BP1or HAIC-BPL at Sun Yat-sen University Cancer Center between January 2020 and December 2022.Progression-free survival(PFS),overall survival(OS),objective response rate(ORR),disease control rate(DCR),and adverse events(AEs)were compared between the two groups.Cox regression analysis was performed to identify prognostic factors affecting PFS.Results:A total of 47 patients were included in the HAIC-BP1 group and 41 patients in the HAIC-BPL group,with no statistically significant differences in baseline characteristics between the two groups(all P>0.05).The ORR(59.6%vs.65.9%)and DCR(72.3%vs.80.5%)did not significantly differ between the HAIC-BP1 group and the HAIC-BPL group(both P>0.05).After a median follow-up of 16.3 months,there were no significant differences in median OS(21.3 months vs.22.4 months)or median PFS(6.7 months vs.6.2 months)between the HAIC-BP1 group and the HAIC-BPL group(both P>0.05).The incidence of AEs was similar,and no treatment-related deaths occurred.Multivariate Cox regression analysis identified tumor diameter>10 cm as an independent adverse prognostic factor for PFS(HR=0.48,95%CI=0.27-0.83,P=0.009).Conclusion:Both HAIC-BP1 and HAIC-BPL demonstrated comparable efficacy and favorable safety profiles as first-line treatment options for advanced HCC.Tumor diameter>10 cm was an independent unfavorable prognostic factor for PFS,underscoring the importance of patient stratification in clinical decision-making.

Aim To explore the influence of demethy-lase fat mass and obesity-related genes(FTO)on the abnormal contractile function of diabetic coronary smooth muscle.Methods Smooth muscle specific FTO knockout mice(FTOSMKO)were prepared by Cre-loxP recombinant technology.They were divided into four groups:control(WT)group,diabetes model group(DM),FTO knockout group(FTOSMKO),and FTOSMKO diabetic group(FTOSMKO-DM),with 15 mice in each group.Diabetic mice were prepared by intraperitoneal injection of streptozotocin(STZ);the remaining mice were injected with an equal amount of citric acid-sodi-um citrate buffer.The effects of 5-HTon the contractile response of coronary artery smooth muscle in the four groups of mice were observed by the technique of small-vessel ring tensiometry.Western blot and Dot blot were used to detect the changes of FTO protein and N6-methyladenine(m6A)methylation modification levels in mouse vascular tissues.Results Compared with the WT group,the DM group had significantly higher blood glucose(P＜0.01)and lower body weight(P＜0.05);the level of FTO protein in aorta of DM group increased(P＜0.01),and the level of m6A methylation modification decreased(P＜0.01).The 5-HT-induced contractile response significantly de-creased in the DM group compared with the WT group(P＜0.01),whereas the contractile response signifi-cantly increased in the FTOSMKO-DM group compared with the DM group(P＜0.01);the non-L-type calci-um channel-mediated vascular smooth muscle contrac-tile response was enhanced in the FTOSMKO-DM group,among which,the contractions induced by 1,4,5-triphosphate inositol receptor(IP3R)and caffeine-ac-tivated ranine receptor(RyR)mediated by sarcoplas-mic reticulum calcium release both significantly in-creased(P＜0.05).Conclusions Specific knock-down of smooth muscle FTO improves coronary artery responsiveness to the vasoconstrictor 5-HT in diabetic mice,which may be related to abnormalities in the FTO-mediated 5-HT receptor signaling pathway.

Sennoside A(SA),a typical prodrug,exerts its laxative effect only after its transformation into rhei-nanthrone catalyzed by gut microbial hydrolases and reductases.Hydrolases have been identified,but reductases remain unknown.By linking a photoreactive group to the SA scaffold,we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling(ABPP).From lysates of an active strain,Bifidobacterium pseudocatenulatum(B.pseu-docatenulatum),397 proteins were enriched and subsequently identified using mass spectrometry(MS).Among these proteins,chromate reductase/nicotinamide adenine dinucleotide(NADH)phosphate(NADPH)-dependent flavin mononucleotide(FMN)reductase/oxygen-insensitive NADPH nitroreductase(nfrA)was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource(UniProt)database screening.We also determined that recombinant nfrA could reduce SA.Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.