Objective: To investigate the barrier membrane fixation performance and enhanced guided bone regeneration (GBR) capability of a thermosensitive adhesive containing bioactive glass nanoparticles in order to provide a novel solution for membrane fixation during GBR procedures. Methods: M2NP@BGN (methoxyethyl acrylate-co-N-isopropylacrylamide-co-protocatechuic acid@Bioactive glass nanoparticle), a thermosensitive adhesive, was synthesized via free radical polymerization by compositing methoxyethyl acrylate, N-isopropylacrylamide, and protocatechuic acid into a basic adhesive that was modified with bioactive glass nanoparticle (BGN). The successful fabrication of basic adhesive M2NP was characterized by attenuated total reflection-Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The thermosensitive adhesive M2NP@BGN (BGN concentration of 1 mg/mL) was characterized by scanning electron microscopy and a rheometer. By adjusting the BGN concentration (0.1 mg/mL, 0.5 mg/mL, 1 mg/mL, and 2 mg/mL), the adhesive and mechanical strengths were investigated with a universal testing machine. Biocompatibility was evaluated with a cell counting kit-8 assay and hemolysis test to identify the optimal formulation. The optimal material’s extract was co-cultured with mouse bone marrow mesenchymal stem cells, and its osteogenic activity was examined in vitro by quantitative real-time PCR, alkaline phosphatase, and alizarin red S staining. The rat mandibular defect model was established, filled with bone graft, and divided into 3 groups based on membrane fixation method: M2NP@BGN (BGN concentration of 1 mg/mL) fixation group (M2NP@BGN), titanium nail fixation group (Nail), and unfixed control group (Negative). Bone regeneration was analyzed after 8 weeks by micro computed tomography and histological staining. Results: M2NP@BGN (BGN concentration of 1 mg/mL) was successfully synthesized and demonstrated rapid gelation under warm, humid conditions. The adhesive with a BGN concentration of 1 mg/mL exhibited the highest adhesive strength (P < 0.001) and significantly enhanced mechanical strength (P < 0.001) under 37℃ wet conditions. All formulations showed excellent biocompatibility, with cell viability > 80% and hemolysis ratio < 5%. M2NP@BGN (BGN concentration of 1 mg/mL) significantly upregulated the expression of Runx2 and Col I (P < 0.001) and enhanced the activity of osteogenic differentiation markers (P < 0.05). In the animal model, the M2NP@BGN group (BGN concentration of 1 mg/mL) achieved significantly higher bone volume fraction and better bone maturity compared to the negative and nail groups (P < 0.05). Conclusion M2NP@BGN (BGN concentration of 1 mg/mL) combines excellent wet adhesion with potent osteogenic activity, enhances the bone augmentation efficacy of membranes, and presents a novel fixation strategy with significant clinical translation potential for GBR therapy.

ObjectiveTo investigate the protective effect of liver-targeted fibroblast growth factor 21 （FGF21） overexpression against CCl₄-induced acute liver injury （ALI） and its association with silent information regulator 1/glutathione peroxidase 4 （SIRT1/GPX4） expression and ferroptosis-related markers. MethodsFemale ICR mice （8 weeks old） were randomly divided into Control， CCl₄， adeno-associated virus （AAV）-FGF21， and AAV-FGF21 + CCl₄ groups. Liver-targeted FGF21 overexpression was achieved via tail vein injection of AAV8-FGF21 virus with green fluorescent protein （GFP） labeling. ALI was induced by intraperitoneal injection of CCl₄ （0.3 mL/kg）， with sample collection at 12 hours. Body weight and liver weight were recorded to calculate the liver weight/body weight. Alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using a biochemical analyzer. FGF21 expression in liver tissues was detected by immunofluorescence. Hepatic histopathology was evaluated by HE staining. RT-qPCR was performed to assess mRNA expression of ferroptosis and iron metabolism-related genes （ACSL4， PTGS2， HJV， FPN， GPX4）， FGF21， and SIRT1. Protein expression of FGF21， SIRT1， and GPX4 were determined by Western blot. Iron content， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD） activity in liver homogenate were quantified using assay kits. ResultsCompared with the Control group， the FGF21 mRNA and protein expression elevated in CCl₄ group； serum ALT/AST levels and liver weight/body weigh increased. The HE staining results showed that the liver cell membranes were ruptured. The mRNA levels of ACSL4 and PTGS2， the iron content and MDA levels all increased （P<0.01）. The mRNA levels of SIRT1， GPX4， HJV， and FPN， the GSH level and SOD activity all decreased （P<0.05）， and the protein levels of SIRT1 and GPX4 both decreased （P<0.05）. Compared with the CCl₄ group， the serum levels of ALT and AST in the AAV-FGF21 + CCl4 group were decreased （P<0.01）， and the liver/body ratio of mice decreased （P<0.01）. The results of HE staining showed that the degree of liver injury was alleviated. The mRNA levels of ACSL4 and PTGS2， iron content and MDA level all decreased （P<0.01）， while the mRNA levels of SIRT1， GPX4， HJV， FPN， GSH level and SOD activity all increased （P<0.05）. The protein levels of SIRT1 and GPX4 both increased （P<0.05）. ConclusionFGF21 overexpression is associated with enhanced SIRT1/GPX4 expression and suppression of ferroptosis features， thereby contributing to the alleviation of CCl₄-induced ALI.

OBJECTIVE To evaluate the quality of Zhachong-13 pills.METHODS The contents of agarotetrol， costunolide， hypaconitine， dehydrocostus lactone， mesaconitine， aconitine， liquiritigenin， glycyrrhizic acid， ellagic acid， liquiritin， corilagin， and gallic acid in 18 batches of samples were determined by high-performance liquid chromatography-tandem triple quadrupole mass spectrometry （HPLC-MS/MS） method. Cluster analysis （CA） was performed using the Microbioinformatics online analysis platform. Principal component analysis （PCA） and orthogonal partial least squares discriminant analysis （OPLS-DA） were performed using SIMCA 14.1 software. Random forest， extremely randomized trees， and extreme gradient boosting machine learning models were constructed using the SPSSAU online analysis platform. The comprehensive quality of the samples was evaluated by the entropy weight-technique for order preference by similarity to ideal solution （TOPSIS） method.RESULTS The contents of the above 12 components were 104.331-694.382， 652.217-1 085.075， 6.051-130.980， 612.174-1 417.179， 1.018-32.239， 0.953-24.967， 65.552-652.239， 2 019.412-5 385.807， 52.867-4 990.450， 156.307-883.180， 10.142-475.722， and 1 102.863-4 826.396 μg/g， respectively. The results of CA and PCA showed that the 18 batches of samples were divided into two categories： S1-S6， S10-S15 were grouped into one category， while S7-S9 and S16-S18 were grouped into another category. The OPLS-DA results showed that the variable importance in projection values of mesaconitine， glycyrrhizic acid， liquiritin， ellagic acid， hypaconitine， liquiritigenin， agarotetrol， gallic acid， and dehydrocostus lactone were greater than 1. The results of the three machine learning models showed that ellagic acid and hypaconitine had relatively large differential contributions. The entropy weight-TOPSIS results showed that the overall quality of samples from manufacturer B was superior to that of the other four manufacturers.CONCLUSIONS The established method is stable and feasible， and can be used to evaluate the quality of Zhachong-13 pills， in combination with multivariate statistical analysis. Ellagic acid and hypaconitine are differential markers that affect its quality.

[摘 要] 目的：探讨lncRNA DLEU2通过EZH2/H3K27me3途径调控IKKα介导甲状腺癌（TC）放射性碘抵抗的作用机制。方法：利用TCGA数据库分析TC中DLEU2的表达及其与EZH2的相关性。构建放射性碘抵抗的TPC-1细胞（RR-TPC-1细胞）模型及裸鼠移植瘤模型，通过敲低或过表达DLEU2（si-DLEU2/OE-DLEU2）、抑制EZH2（UNC1999）、过表达IKKα（OE-IKKα）进行干预，采用qPCR、WB、RIP、ChIP、CCK-8、流式细胞术、TUNEL染色及体内成瘤实验检测基因与蛋白表达、表观修饰、细胞增殖、凋亡及肿瘤生长。结果：TCGA分析显示，DLEU2在TC组织中显著上调（P < 0.001），与患者不良预后相关（P = 0.008 4），且与EZH2表达呈正相关（r = 0.390, P < 0.001）；RIP证实EZH2与DLEU2存在相互作用/结合（P < 0.05）。体外实验表明，敲低DLEU2可显著下调RR-TPC-1细胞中EZH2、IKKα表达及H3K27me3修饰水平，抑制NF-κB通路活化（P < 0.05或P < 0.01），抑制细胞增殖、促进凋亡（均P < 0.05）。联合敲低DLEU2与抑制EZH2进一步增强上述效应，而过表达IKKα则可部分逆转上述效应（P < 0.05或P < 0.01）。体内实验进一步证实，敲低DLEU2联合抑制EZH2可显著抑制移植瘤生长，增加肿瘤细胞凋亡（均P < 0.01）；IKKα过表达则部分逆转上述抗肿瘤效应（P < 0.05或P < 0.01）。结论：lncRNA DLEU2通过招募EZH2催化H3K27me3修饰，间接激活IKKα/NF-κB信号并形成正反馈环路，介导TPC-1细胞131I抵抗。

Objective: To analyze the issuance of Chinese adolescents mental health promotion policies and policy objects, and to explore the use of different object policy tools and the effectiveness of the policy, so as to provide reference for the improvement of the subsequent policy. Methods: Adolescents mental health promotion policies published and policy documents that included adolescents in mental health promotion policies and regulations in China from 2014 to the present were obtained, with the search period of July to August 2024. Policy content and effectiveness were analyzed by using content cross tabulation analysis and Policy Modeling Consistency Index Model (PMC index model). It coded with Nvivo 20 software to understand the types of tools that policy depends on. Results: A total of 41 documents were included. The number of adolescent mental health promotion policy texts rose by year, most of which were issued independently, accounting for 70% of the total number of texts issued; 30% were jointly issued, with the Ministry of Education and the National Health Commission as the core subjects. Supply type policy tools accounted for 47.45 % of the total, while environment type and demand type policy tools accounted for 29.68% and 22.87% respectively; the use of policy tools by different policy targets varies, with families and social organizations using more supply type and demand type policy tools, while the education system and healthcare institutions were more inclined to supply type policy tools, and the government departments were more inclined to supply type policy tools and environment type policy tools. In terms of policy effectiveness, there was a common problem of a lack of incentives and constraints, and the PMC values of two long term planning mental health policies were high (7.76, 7.56), and both reached the excellent level. Conclusions China has paid more attention to adolescents mental health, and the basic guarantees have been established and overall policy effectiveness is good, but the use of policy tools is uneven. There is a need to improve the operational content of medium and long term policies and to strengthen synergies between implementing departments.

Psoraleae Fructus is derived from the dried fruit of the Psoralea corylifolia L. It has the effects of tonifying the kidney, strengthening the Yang, warming the spleen and stopping diarrhea, and is used for the treatment of kidney deficiency and impotence, lumbar soreness and cold pain, osteoporosis and other diseases, and it is a commonly used tonic traditional Chinese medicine in Chinese medicine clinics in China. However, in recent years, the clinical adverse reactions of Psoraleae Fructus (PF) and related preparations have been increasingly reported, especially hepatotoxicity, which has become a bottleneck in the clinical application of PF and associated preparations. The safety of PF was rarely recorded in ancient texts, but modern clinical and experimental research has shown that PF not only has direct toxicity but also has immune-idiosyncratic toxicity. For this reason, this study comprehensively analyzes the evolution of PF effect/toxicity records in ancient and modern canonical literature, and combines with the progress of modern pharmacology and toxicology research, to conduct an in-depth discussion on the clinical characteristics, causative mechanisms and risk factors of PF hepatotoxicity. On this basis, based on the three-dimensional "human-medicine-use" precise prevention and control strategy for the safety risk of traditional Chinese medicine proposed by the author's team, safety risk prevention and control measures for PF and related preparations were developed, aiming at guiding the safe and rational use of PF and related preparations in the clinic and promoting the healthy and sustainable development of PF-related industries.

POEMS syndrome is a rare condition associated with plasma cell disorders， and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease， the patients presented with lower limb weakness， hepatosplenomegaly， lymph node enlargement， ascites， hypothyroidism， positive M protein， and skin hyperpigmentation， and ¹⁸F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome， and the symptoms were relieved after immunomodulatory treatment.

Objective:To observe and analyze the ocular clinical features and pathogenic genes of horizontal gaze palsy with progressive scoliosis (HGPPS).Methods:A pedigree study was conducted.Two families with HGPPS diagnosed by ophthalmology examination at Henan Children's Hospital from November 2023 to April 2024 were included, with 3 people from two generations in each family.Medical history and family history of the subjects were inquired.Vision acuity, diopter, anterior segment, intraocular pressure, wide-angle laser scanning ophthalmoscopy, optical coherence tomography, visual evoked potential (VEP), electroretinogram (ERG), ocular B-ultrasound, full spine AP+ lateral view, orbit+ skull+ cervical spine+ thoracic spine+ lumbosacral spine MRI plain scan were performed on the subjects.Whole genomic DNA was extracted from 2 ml of peripheral venous blood collected from the subjects, and gene sequencing was performed using whole exome sequencing (WES) technology.Suspicious pathogenic variant loci were verified by Sanger sequencing, and the pathogenicity of gene variant loci was analyzed according to the ACMG standards and guidelines for the interpretation of sequence variants.This study followed the Declaration of Helsinki.The study protocol was reviewed and approved by the Ethics Committee of Henan Children's Hospital (No.2024-KY-0024).All subjects and guardians signed informed consent forms and were informed of relevant matters before genetic testing.Results:The proband from family 1 was male, 3 years and 2 months old.At the age of 6 months, he was found to have head tilted to the left with a right scoliosis of the spine centered on T11-12 and no obvious abnormalities on VEP and ERG examinations.The proband from family 2 was male, 3 years and 4 months old, with a left scoliosis of the spine centered on T12.Both probands developed horizontal fixation paralysis, unable to rotate eye outward, slightly limited inward rotation, left eye hypertropia, mild horizontal nystagmus, normal vertical eye movement, backward development of major movements, and normal vision, anterior segment and fundus.MRI examination showed that the medulla oblongata was butterfly shaped, and a brainstem fissure could be seen in the center of the medulla oblongata.The genetic testing showed that the proband from family 1 had compound heterozygous variations c. 1054delC/p.Gln352Serfs *90 (M1) in exon 7 and c. 1219G>T/p.Gly407Cys (M2) in exon 8 of ROBO3 gene.The father of the proband carried M1 and the mother of the proband carried M2.The proband from family 2 had compound heterozygous variations c. 1888C>T/p.R630X (M3) in exon 12 and c. 2684C>A/p.A895E (M4) in exon 17 of ROBO3 gene.M1 and M3 were possible pathogenic, and M2 and M4 were of unknown clinical significance, and prediction software predicted M2 and M4 were harmful variations. Conclusions:The main clinical features of two HGPPS pedigree are horizontal fixation paralysis and progressive scoliosis, accompanied by nystagmus and strabismus.MRI shows brainstem fissure in the central medullary area.Four variants are novel variants, which increases the variation spectrum of ROBO3 gene.

ObjectiveThis paper proposes a novel real-time bedside pulmonary ventilation monitoring method for the diagnosis of chronic obstructive pulmonary disease (COPD), based on electrical impedance tomography (EIT). Four indicators—center of ventilation (CoV), global inhomogeneity index (GI), regional ventilation delay inhomogeneity (RVDI), and the ratio of forced expiratory volume in one second to forced vital capacity (FEV₁/FVC)—are calculated to enable the spatiotemporal assessment of COPD. MethodsA simulation of the respiratory cycles of COPD patients was first conducted, revealing significant differences in certain indicators compared to healthy individuals. The effectiveness of these indicators was then validated through experiments. A total of 93 subjects underwent multiple pulmonary function tests (PFTs) alongside simultaneous EIT measurements. Ventilation heterogeneity under different breathing patterns—including forced exhalation, forced inhalation, and quiet tidal breathing—was compared. EIT images and related indicators were analyzed to distinguish healthy individuals across different age groups from COPD patients. ResultsSimulation results demonstrated significant differences in CoV, GI, FEV₁/FVC, and RVDI between COPD patients and healthy individuals. Experimental findings indicated that, in terms of spatial heterogeneity, the GI values of COPD patients were significantly higher than those of the other two groups, while no significant differences were observed among healthy individuals. Regarding temporal heterogeneity, COPD patients exhibited significantly higher RVDI values than the other groups during both quiet breathing and forced inhalation. Moreover, during forced exhalation, the distribution of FEV₁/FVC values further highlighted the temporal delay heterogeneity of regional lung function in COPD patients, distinguishing them from healthy individuals of various ages. ConclusionEIT technology effectively reveals the spatiotemporal heterogeneity of regional lung function, which holds great promise for the diagnosis and management of COPD.