Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

ObjectiveTo investigate the effects of jatrorrhizine on endogenous metabolites and metabolic pathways in the mouse model of ulcerative colitis. MethodsThirty male C57BL/6J mice were randomly divided into the normal group， the model group， the low-dose and high-dose jatrorrhizine groups （0.04， 0.16 g·kg^-1）， and the mesalazine group （0.52 g·kg^-1）The mouse model of ulcerative colitis was established with 3% dextran sulfate sodium （DSS） and treated with different doses of jatrorrhizine by gavage. The changes in body weight， colon length， disease activity index （DAI）， and colonic histopathology were analyzed to evaluate the therapeutic effects of jatrorrhizine. UPLC-Q-TOF/MS was employed to determine the serum and fecal levels of metabolites in mice. Metabolomics methods were used to screen the differential metabolites， on the basis of which the potential therapeutic mechanism of jatrorrhizine on DSS-induced ulcerative colitis in mice was investigated. ResultsAfter intervention with jatrorrhizine， the model mice showed significantly decreased DAI（P<0.05，P<0.01）， recovered colon length，（P<0.05，P<0.01） and alleviated histopathology of the colon. The metabolomics study screened out 13 differential metabolites in the serum and 8 differential metabolites in the feces. The pathway enrichment analysis predicted three potential metabolic pathways： Biosynthesis of unsaturated fatty acids， phenylalanine， tyrosine and tryptophan biosynthesis， and phenylalanine metabolism. ConclusionJatrorrhizine may treat ulcerative colitis by regulating the biosynthesis and metabolism of amino acids and the synthesis of unsaturated fatty acids.

Objective To evaluate the effect of LifePort combined with polymyxin B in preventing donor-derived infections caused by preservation solution contamination. Methods Clinical data of 110 kidney transplant recipients were retrospectively analyzed. According to the decontamination status of preservation solution, the recipients were divided into the decontamination group (n=62) and the non-decontamination group (n=48). The general data of the two groups were compared, and the preventive effect of polymyxin B on possible donor-derived infections (p-DDI) was analyzed, especially infections associated with multidrug-resistant Gram-negative bacteria (MDR GNB). Results There were no statistically significant differences in baseline data (gender, age, preservation solution contamination status, etc.) between the decontamination group and the non-decontamination group (all P > 0.05). The overall contamination rate of preservation solution was 80.0%, and 68 contaminated samples were with single microorganism and 20 with multiple microorganisms. Coagulase-negative staphylococci, Enterococcus and Klebsiella pneumoniae were the most common microorganisms in the positive samples. Fifteen cases of preservation solution were contaminated by MDR GNB, including 10 cases in the non-decontamination group and 5 cases in the decontamination group, with no statistically significant difference between the two groups (P = 0.053). Postoperative infection-related events occurred in 69 recipients, including 39 cases in the non-decontamination group and 30 cases in the decontamination group, with the incidence rate in the non-decontamination group significantly higher than that in the decontamination group (P < 0.001). Only 10 cases of infections were identified as p-DDI, all of which were positive for preservation solution culture, including 8 cases in the non-decontamination group and 2 cases in the decontamination group (P < 0.05). There were 5 cases of p-DDI related to MDR GNB in the non-decontamination group, while no such cases occurred in the decontamination group (P < 0.05). No adverse reactions related to polymyxin B were observed, and no recipient death or renal allograft dysfunction occurred in either group. Conclusions Adding polymyxin B to the preservation fluid during hypothermic machine perfusion with LifePort before renal transplantation may reduce p-DDI and its potential adverse consequences.

OBJECTIVE To systematically evaluate the quality of the Heat-clearing and symptom-relieving formula and screen potential marker components that influence the quality of the formula. METHODS The contents of 11 components （calycosin-7- O - β -D-glucoside， ononin， hyperoside， isoquercitrin， baicalin， baicalein， cryptotanshinone， tanshinone Ⅱ A ， tanshinone Ⅰ， senkyunolide A， ferulic acid） in the Heat-clearing and symptom-relieving formula were determined by high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）. Using the contents of the aforementioned components as variables， cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were conducted using OriginPro 2024 software and SIMCA 14.1 software； marker components affecting the quality of the Heat-clearing and symptom-relieving formula were then screened based on the criteria of variable importance in the projection （VIP） value＞1 and P ＜0.05. The comprehensive evaluation of 20 batches of samples was carried out using the entropy weight-technique for order preference by similarity to ideal solution（TOPSIS） and grey correlation analysis （GCA） methods. RESULTS The contents of the above 11 components were 7.993-72.866， 4.542-31.228， 727.666-1 901.884， 496.846-1 293.279， 1 995.501-6 779.150， 54.500-241.280， 150.302-304.339， 79.698-189.206， 257.118-682.418， 5.498-21.687， 7.524-26.935 μg/g. CA， PCA and OPLS-DA results showed that 20 batches of samples were grouped into 2 categories. Q1， Q3， Q4， Q7-Q9， Q12， Q15， Q16 were grouped into one category， and the rest were grouped into another category； VIP values of ferulic acid， tanshinone Ⅱ A ， baicalin， cryptotanshinone， calycosin-7- O - β -D-glucoside and ononin were all greater than 1 （ P ＜0.05）. Both the entropy weight-TOPSIS and GCA methods showed that the samples ranked in the top 11 according to the euclidean distance and relative correlation degree were Q2， Q5， Q6， Q10， Q11， Q13， Q14， Q17-Q20. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate and highly sens itive. Combined with chemical pattern recognition analysis， entropy weight-TOPSIS and GCA methods， this method can be used to evaluate the quality of the Heat-clearing and symptom-relieving formula. Ferulic acid， tanshinone Ⅱ A ， baicalin， cryptotanshinone， calycosin-7- O - β -D-glucoside and ononin may be the marker components that affect the quality of this formula. The overall quality of 11 batches of the Heat-clearing and symptom-relieving formula， including Q17， is relatively superior.

ObjectiveTo investigate the correlation between sleep patterns and myopia progression among younger school-age children at a primary school in Changning District of Shanghai, based on the data from the Shanghai Students’ Common Diseases and Health Influencing Factors Monitoring System and a sleep-specific survey, so as to provide data support for myopia prevention and control in this age group. MethodsOne primary school was selected from the common diseases and health influencing factors monitoring system for students in Changning District, Shanghai. A total of 230 first-grade students were included in the study. Myopia and refractive parameters were examined, and sleep patterns were investigated. General demographic characteristics and myopia-related behavior data of the students were also collected. Sleep patterns were evaluated in terms of sleep duration, sleep efficiency, and sleep quality, with the latter assessed using the Chinese version of the Children’s Sleep Habits Questionnaire (CSHQ). Multiple linear regression and binary logistic regression models were used to analyze the association between sleep patterns and myopia progression among these students. ResultsThe results of the regression analyses revealed that the total CSHQ score of the students at baseline survey was (48.85±7.15) points. Their sleep efficiency was (94.49±8.48)%, sleep duration was (9.58±0.93) hours, and the proportion of those with insufficient sleep (<10 hours) was 78.26%. At baseline survey, students’ higher daytime sleepiness scores were associated with lower spherical equivalent (SE) ( β=-0.18, 95%CI: -0.31 to -0.04) and an increased risk of axial length (AL) / corneal radius (CR) ratio >3 (OR=1.52, 95%CI: 1.00 to 2.29), whereas longer sleep duration and higher sleep efficiency were associated with higher SE (β=0.18, 95%CI: 0.05 to 0.32; β=0.17, 95%CI: 0.04 to 0.31, respectively), shorter (AL) (β=-0.15, 95%CI: -0.27 to -0.03; β=-0.13, 95%CI: -0.25 to 0, respectively) and a reduced risk of AL /CR>3 (OR=0.70, 95%CI: 0.51 to 0.96; OR=0.73, 95%CI: 0.53 to 0.99, respectively). At baseline survey, children’s higher propensity for sleep problems (OR=1.70, 95%CI: 1.04 to 2.78), sleep resistance (OR=2.26, 95%CI: 1.36 to 3.75), and sleep anxiety scores (OR=2.15, 95%CI: 1.33 to 3.48) were all associated with an increased risk of AL/CR >3 at follow-up (all P<0.05). Furthermore, higher sleep anxiety scores predicted prolonged AL at follow-up (β=0.03, 95%CI: 0 to 0.05). According to the mixed-effects model, higher daytime sleepiness scores and prolonged sleep duration were independently linked to reduced right-eye SE (β=-0.05, 95%CI: -0.10 to 0, P<0.05) and shorter right-eye AL (β=-0.05, 95%CI: -0.10 to 0, P<0.05). ConclusionIn this school in Shanghai, there are problems of insufficient and poor-quality sleep among young children. Sleep problems such as sleep resistance, delayed sleep onset, sleep anxiety, and daytime sleepiness among children may accelerate the risk of myopia progression, while longer sleep duration and higher sleep efficiency may serve as protective factors against the occurrence and development of myopia.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

Traditional Chinese medicine （TCM） has unique advantages in the management of liver diseases； however， traditional TCM efficacy evaluation is highly subjective with a lack of standardized criteria， and the evaluation criteria for modern medicine are incompatible with the characteristics of TCM interventions， leading to a marked dissociation between diseases， symptoms， and syndromes. To address the above issues， this article proposes the core principle of disease-symptom-syndrome integration and establishes a four-dimensional efficacy evaluation system including TCM syndrome efficacy， patient-reported outcomes， overall disease prognosis， and changes in biological indicators. This article systematically elaborates on the core connotation， indicator selection criteria， and quantification methods of each dimension and clarifies the implementation principles and strategies， in order to provide methodological support for high-quality clinical research and the production of high-level evidence-based data in TCM treatment of liver diseases and promote the modernization and internationalization of TCM diagnosis and treatment.

Objective To investigate the causal relationship between circulating metabolites and non-alcoholic fatty liver disease(NAFLD)using Mendelian randomization analysis.Methods Summary statistics from genome-wide association study provided by Nightingale Health and the FinnGen Consortium were retrospectively collected.A two-sample Mendelian randomization analysis was performed to assess the causal effects of 233 blood metabolites on NAFLD,with the inverse-variance weighting method as the primary analytical approach.Results Elevated levels of glycoprotein acetylation(OR=3.30,95％CI:1.64-6.62,P=0.0008),the ratio of free cholesterol to total lipids in very low-density lipoprotein(VLDL)(OR=3.50,95％CI:1.63-7.48,P=0.0013),serum total triglycerides(OR=2.26,95％CI:1.38-3.70,P=0.0012),saturated fatty acids(OR=2.47,95％CI:1.40-4.36,P=0.0018),total cholesterol in VLDL(OR=2.20,95％CI:1.36-3.59,P=0.0015),the ratio of triglycerides to total lipids in very large high-density lipoprote(HDL)(OR=2.91,95％CI:1.53-5.55,P=0.0011),and triglycerides in very small VLDL(OR=2.27,95％CI:1.43-3.62,P=0.0006)were positively associated with NAFLD.Conversely,total cholesterol in high-density lipoprotein 2(OR=0.44,95％CI:0.27-0.71,P=0.0007)and total cholesterol in HDL(OR=0.44,95％CI:0.28-0.72,P=0.0009)were inversely associated with NAFLD.Heterogeneity tests indicated no significant heterogeneity among instrumental variables,confirming the robustness of the findings.Conclusion This study identified seven metabolites associated with an increased risk of NAFLD and two metabolites linked to a reduced risk,highlighting their potential roles in the pathogenesis and progression of NAFLD.

Objective To observe the value of artificial intelligence ultrasound combined with serum hyaluronic acid synthase 2(HAS2)and trefoil factor-1(TFF1)for early diagnosis of breast cancer.Methods Totally 176 patients with suspected breast cancer were retrospective enrolled and divided into malignant group(n=50)and benign group(n=126)according to pathological results.Artificial intelligence ultrasound and convolutional neural network algorithms were used to automatically label suspicious breast lesions.The lesions were manually graded based on breast imaging reports and data systems,classifying 0-3 grades as benign lesions,4-5 grades as malignant lesions.Clinical data and artificial intelligence ultrasound manifestations were compared between groups.Receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to evaluate the efficacy of HAS2,TFF1,artificial intelligence ultrasound and their combination for diagnosing breast cancer.Results HAS2,TFF1,as well as the proportions of abnormal glandular thickness,low-echo lesions and abnormal blood flow morphology in malignant group were all higher than those in benign group(all P＜0.001).AUC of serum HAS2,TFF1 and artificial intelligence ultrasound for diagnosing breast cancer was 0.772,0.754 and 0.859,respectively.The combined diagnostic efficacy of the above three(AUC=0.925)was higher than single diagnostic efficacy(all P＜0.05).Conclusion Artificial intelligence ultrasound combined with serum HAS2 and TFF1 had good efficacy for early diagnosis of breast cancer.

Objective To systematically evaluate and synthesize the experience and coping process of bowel symptoms in patients after sphincter-preserving surgery for rectal cancer,and to provide the evidence for the subsequent development of bowel symptom management strategies.Methods A comprehensive search was conducted across the Pubmed,Cochrane Library,CINAHL,Embase,Web of Science,CNKI,Wanfang Database,VIP Database and CBM Database for qualitative studies on the experience of bowel symptoms in post-sphincter-preserving surgery patients with rectal cancer.The search period was from database inception to October 2024.The quality of the included literature was assessed according to the Australian Joanna Briggs Institute Center for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research,and the results were synthesized through the aggregative integration method.Results 14 studies were included,yielding 52 research findings,which were grouped into 10 subcategories and further synthesized into 4 results:the physical and psychological experiences of patients with bowel symptoms;the impact of bowel symptoms on patients'daily lives;coping styles for bowel symptoms in patients;facilitators of patients bowel symptom coping.Conclusion Bowel symptoms have significant negative impacts on the lives of patients following sphincter-preserving surgery for rectal cancer,and healthcare professionals should address these patients'needs by developing effective symptom management strategies and supporting patients in enhancing self-management abilities to improve quality of life.