Objective: To fabricate a hydrogel loaded with inositol hexaphosphate-zinc and preliminarily evaluate its performance in self-mineralization and osteoinduction, thereby providing a theoretical basis for the development of bone regeneration materials. Methods: The hydrogel framework (designated DF0) was formed by copolymerizing methacryloyloxyethyltrimethylammonium chloride and four-armed poly(ethylene glycol) acrylate, followed by sequentially loading inositol hexaphosphate anions via electrostatic interaction and zinc ions via chelation. The hydrogel loaded only with inositol hexaphosphate anions was named DF1, while the co-loaded hydrogel was named DF2. The self-mineralization efficacy of the DF0 , DF1 and DF2 hydrogels was characterized using scanning electron microscopy, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The biocompatibility was assessed via live/dead cell staining and a CCK-8 assay. The osteoinductive capacity of the DF0 , DF1 and DF2 hydrogels on MC3T3-E1 cells was assessed via alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. In the aforementioned cell experiments, cells cultured in standard medium served as the control group Results: The DF0, DF1, and DF2 hydrogels were successfully synthesized. Notably, DF1 and DF2 exhibited distinct self-mineralization within 6 days. Results from TEM, EDS, and SAED confirmed that the mineralization products were amorphous calcium phosphate in group DF1, and amorphous calciumzinc phosphate in group DF2. Biocompatibility tests revealed that none of the hydrogels (DF0, DF1, and DF2) adversely affected cell viability or proliferation. In osteogenic induction experiments, both ALP and ARS staining were intensified in the DF1 and DF2 groups, with the most profound staining observed in the DF2 group. Conclusion The developed inositol hexaphosphate-zinc hydrogel (DF2) demonstrates the dual capacity to generate calcium-phosphate compounds through self-mineralization while exhibiting excellent osteoinductive properties. This biocompatible, dual-promoting osteogenic hydrogel presents a novel strategy for bone regeneration.

ObjectiveTo investigate vitamin D level in children with cholestatic liver disease， and to provide a theoretical basis for vitamin D supplementation therapy in children with this disease. MethodsA total of 116 children with cholestatic liver disease who attended Department of Traditional Chinese Medicine， Beijing Children’s Hospital， Capital Medical University， for the first time from January 2022 to January 2024 were enrolled and divided into groups for comparison based on sex， age， vitamin D supplementation dose， course of the disease， and etiology. The data on the serum level of 25-hydroxyvitamin D （25-OH-D） and related biochemical parameters were collected to assess the correlation between vitamin D level and biochemical parameters. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups， and the Spearman rank correlation test was used for correlation analysis. ResultsAmong the 116 children， 76 （65.5%） had vitamin D deficiency or insufficiency. The children with vitamin D deficiency or insufficiency accounted for 65.7% （46/70） among boys and 65.2% （30/46） among girls， with no significant difference between boys and girls （χ²=0.003， P=0.956）. The children with vitamin D deficiency or insufficiency accounted for 83.3% （25/30） among the children who had never received vitamin D supplementation， 58.7% （27/46） among the children with a daily supplementation dose of 500 IU， 64.3% （18/28） among the children with a daily supplementation dose of 700 IU， and 50.0% （6/12） among the children with a daily supplementation dose of>700 IU， and there was no significant difference between these groups （χ²=6.460， P=0.091）. Comparison between the groups with different etiologies showed that the children with vitamin D deficiency or insufficiency accounted for 57.7% （15/26） in the infectious disease group， 66.7% （10/15） in the inherited metabolic disease group， 66.7% （6/9） in the drug-induced liver injury group， 100.0% （8/8） in the group with abnormal structure of the biliary system， and 63.8% （37/58） in the group with unknown etiology， and there was no significant difference between these groups （χ²=5.304， P=0.252）. Comparison between the groups with different courses of the disease showed that the children with vitamin D deficiency or insufficiency accounted for 78.4% （29/37） in the<1 month group， 54.3% （25/46） in the 1‍ — ‍3 months group， 53.3% （8/15） in the 3‍ — ‍6 months group， and 77.8% （14/18） in the>6 months group， with no significant difference between these groups （χ²=7.432， P=0.059）. Comparison between different age groups showed that compared with the infant group， the children group had a significantly higher proportion of children with vitamin D deficiency or insufficiency （χ²=9.504， P=0.018）. The correlation analysis showed that serum aspartate aminotransferase and alanine aminotransferase had no significant correlation with 25-OH-D （P>0.05）； serum alkaline phosphatase （ALP） （r=-0.286， P=0.002）， gamma-glutamyl transpeptidase （GGT） （r=-0.248， P=0.007）， total bilirubin （TBil） （r=-0.353， P<0.001）， direct bilirubin （DBil） （r=-0.299， P=0.001）， and total bile acid （r=-0.236， P=0.011） were negatively correlated with 25-OH-D， while serum calcium （r=0.263， P=0.004） and phosphorus （r=0.385， P<0.001） were positively correlated with 25-OH-D. ConclusionMost children with cholestatic liver disease have vitamin D deficiency or insufficiency， and the increase in serum ALP， GGT， TBil， DBil or total bile acid and the reduction in calcium or phosphorus may suggest vitamin D deficiency or insufficiency.

Metastatic lung cancer continues to cause a high number of deaths due to high malignancy and poor prognosis, and the efficacy of typical chemotherapy or immunotherapy is less than ideal due to the low pulmonary accumulation and targeting of therapeutics. Here, a submicron-sized biomimetic liposome was formulated for the lung-targeted co-delivery of bacterial superantigen and paclitaxel. Recombinant staphylococcal enterotoxin C2 (rSEC2), a bacterial superantigen, was expressed with the Escherichia coli system and showed potent immunostimulatory activities to mediate tumor cell death. The submicron-sized (∼800 nm) biomimetic liposomes, namely 4T1 cell membrane-hybrid rSEC2 paclitaxel liposomes (TSPLs), exhibited high lung-accumulation efficiency and tumor homologous effect due to the suitable particle size and membrane hybridization of cancer cell membranes with phospholipids. Intravenous TSPLs remarkably inhibited metastatic lung cancer with limited systemic immune responses. TSPLs reversed the immunosuppressive state and increased the proportion of local CD4⁺ and CD8⁺ T cells in the lung; moreover, paclitaxel increased tumor cell apoptosis and reduced tumor burden. In summary, the high lung cancer targeting was achieved by particle size control and cell membrane hybridization, and the highly efficient anticancer effect was achieved by the co-delivery of superantigens and chemotherapeutic drugs.

OBJECTIVES: To explore the mechanism of Lacticaseibacillus paracasei E6 for improving vinorelbine-induced immunosuppression in zebrafish. METHODS: The intestinal colonization of L. paracasei E6 labeled by fluorescein isothiocyanate (FITC) in zebrafish was observed under fluorescence microscope. In a zebrafish model of vinorelbine-induced immunosuppression, the immunomodulatory activity of L. paracasei E6 was assessed by analyzing macrophage and neutrophil counts in the caudal hematopoietic tissue (CHT), the number of T-lymphocyte, and the expressions of interleukin-12 (IL-12) and interferon-γ (IFN-γ). The contents of short-chain fatty acids (SCFAs) in L. paracasei E6 fermentation supernatant and the metabolites of L. paracasei E6 in zebrafish were detected by LC-MS/MS-based targeted metabolomics. The immunomodulatory effects of the SCFAs including sodium acetate, sodium propionate and sodium butyrate were evaluated in the zebrafish model of immunosuppression. RESULTS: After inoculation, green fluorescence of FITC-labeled L. paracasei E6 was clearly observed in the intestinal ball, midgut and posterior gut regions of zebrafish. In the immunocompromised zebrafish model, L. paracasei E6 significantly alleviated the reduction of macrophage and neutrophil counts in the CHT, increased the fluorescence intensity of T-lymphocytes, and promoted the expressions of IL-12 and IFN-γ. Compared with MRS medium, L. paracasei E6 fermentation supernatant showed significantly higher levels of acetic acid, propionic acid and butyric acid, which were also detected in immunocompromised zebrafish following treatment with L. paracasei E6. Treatment of the zebrafish model with sodium acetate and sodium propionate significantly increased macrophage and neutrophil counts in the CHT and effectively inhibited vinorelbine-induced reduction of thymus T cells. CONCLUSIONS L. paracasei E6 can improve vinorelbine-induced immunosuppression in zebrafish through its SCFA metabolites acetic acid and propionic acid.
Animals ; Zebrafish/immunology* ; Acetic Acid/metabolism* ; Propionates/metabolism* ; Fatty Acids, Volatile/metabolism*

OBJECTIVES: To investigate the efficacy of Lactobacillus plantarum ZG03 (L. plantarum ZG03) for ameliorating oxidative stress in zebrafish. METHODS: We evaluated the growth pattern of L. plantarum ZG03, observed its morphology using field emission scanning electron microscopy, and assessed its safety and potential efficacy with whole-genome sequencing for genetic analysis. FITC-labeled ZG03 was used to observe its intestinal colonization in zebrafish. In a zebrafish model of 2% glucose-induced oxidative stress, the effect of ZG03 was evaluated by assessing the changes in neutrophils in the caudal hematopoietic tissue (CHT), superoxide dismutase (SOD) activity, reactive oxygen species (ROS) levels, and malondialdehyde (MDA) content. Liquid chromatography-mass spectrometry-based targeted metabolomics was used for analyzing short-chain fatty acids (SCFAs) in the zebrafish, and the antioxidant effects of the key metabolites (acetate, propionate, and caproate) were tested. RESULTS: On MRS agar, L. plantarum ZG03 formed circular, smooth, moist, and milky-white colonies with a rod-shaped cell morphology. Genomic analysis revealed abundant sugar metabolism gene clusters. After inoculation of FITC-labeled L. plantarum ZG03 in zebrafish, green fluorescence was clearly observed in the intestinal bulb, mid-intestine, and hind intestine. In zebrafish with glucose-induced oxidative stress, L. plantarum ZG03 significantly reduced ROS levels and the number of neutrophils in the CHT with increased SOD activity. L.plantarum ZG03 significantly increased the content of SCFAs including acetic acid, propionic acid, and caproic acid in zebrafish metabolites. In addition, sodium acetate, sodium propionate, and sodium caproate in the SCFAs significantly increased SOD activity in the zebrafish models. CONCLUSIONS L. plantarum ZG03 ameliorates oxidative stress in a glucose-induced zebrafish model through its metabolites, particularly the SCFAs including acetic acid, propionic acid and caproic acid.
Animals ; Zebrafish/metabolism* ; Oxidative Stress ; Lactobacillus plantarum/metabolism* ; Fatty Acids, Volatile/metabolism* ; Probiotics ; Reactive Oxygen Species/metabolism* ; Superoxide Dismutase/metabolism*

Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Animals ; Osteoarthritis/physiopathology* ; Mice ; Sympathetic Nervous System/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Arthralgia ; Sensory Receptor Cells ; Disease Models, Animal ; Norepinephrine ; Male ; Temporomandibular Joint/physiopathology* ; Pain Measurement

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

OBJECTIVES: To investigate the clinical application of the digital-assisted reconstruction of the mandible and tumors with free fibula transplantation and immediate implantation via the intraoral approach. METHODS: Twelve patients with benign mandibular tumors were collected. Three-dimensional mandibular reconstruction was performed digitally before surgery to simulate mandibular tumor resection, fibula resection and reconstruction, and implant implantation. The intraoperative resection of the mandibular tumor was conducted through the intraoral approach under the guidance of a guide plate, and fibula resection, molding, reconstruction, and oral fixation were immediately performed. Implant implantation was performed during the second phase of implant surgery and denture restoration was performed 1-2 months after surgery. RESULTS: The types of mandibular defects were BrownⅠ (one case), Ⅰc (four cases), Ⅱ (one case), Ⅱc(three cases), and Ⅲ (three cases). The length of the fibular bone was 12-22 cm. The number of fibular molding amputations was as follows: two cases in two segments, six cases in three segments, three cases in four segments, and one case in five segments. All of these cases underwent folding fibular reconstruction of mandibular and alveolar bone defects. A total of 44 implants were implanted, and none failed after operation. CONCLUSIONS The intraoral approach is a reliable method for the resection of mandibular benign tumors, with few postoperative complications and the ability to position and fix accurately the reconstructed folded fibula under digital design. The immediate implantation of the transplanted fibula does not affect the blood supply and has a high success rate. It is an effective and reliable method for the resection and reconstruction of mandibular benign tumors.
Humans ; Fibula/transplantation* ; Mandibular Neoplasms/surgery* ; Mandibular Reconstruction/methods* ; Bone Transplantation/methods* ; Male ; Middle Aged ; Female ; Mandible/surgery* ; Adult ; Free Tissue Flaps ; Surgery, Computer-Assisted

Objective To investigate the expression levels of microRNA-34a(miR-34a),β-catenin and pro-grammed death receptor-1(PD-L1)in cancer tissues of patients with cervical cancer(CC)and their correla-tion with patients' prognosis.Methods A total of 83 patients with CC admitted to Yuncheng Central Hospital Affiliated to Shanxi Medical University from June 2021 to January 2024 were selected as the research objects.General data,CC tissue and adjacent normal tissue samples of all patients were collected.The mRNA expres-sion levels of miR-34a,β-catenin and PD-L1 in CC tissues and adjacent normal tissues were detected by fluo-rescence quantitative PCR and compared.The expression levels of β-catenin and PD-L1 in CC tissues and adja-cent normal tissues were detected by immunohistochemistry.Multivariate Logistic regression analysis was used to analyze the influencing factors of prognosis in CC patients.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of miR-34a,β-catenin and PD-L1 expression levels in CC pa-tients with poor prognosis.Results Compared with adjacent normal tissues,the expression level of miR-34a of the CC tissues was lower,while the expression levels of β-catenin and PD-L1 were higher(P＜0.05).The positive expression rates of β-catenin and PD-L1 protein in CC tissues were higher than those of adjacent nor-mal tissues(89.16％vs.10.84％,78.31％vs.20.48％,x2=101.807,55.526,P＜0.05).There were no sig-nificant differences in age and body mass index(BMI)between the good prognosis group and the poor progno-sis group(t=1.508,1.820,both P＞0.05),while there were significant differences in International Federa-tion of Gynecology and Obstetrics(FIGO)stage and differentiation degree between the two groups(x2=8.451,9.115,both P＜0.05).Compared with the good prognosis group,the expression level of miR-34a of the poor prognosis group was lower,while the expression levels of β-catenin and PD-L1 were higher(P＜0.05).Multivariate Logistic regression analysis showed that increased expression of miR-34a was an protective factor for poor prognosis in CC patients,while the increased expression levels of β-catenin and PD-L1,Ⅱ a and Ⅱ b FIGO staging and low differentiation were independent risk factors for poor prognosis in CC patients(P＜0.05).ROC curve analysis showed that miR-34a,β-catenin and PD-L1 all had certain predictive value for the poor prognosis of CC patient,and the area under the curve(AUC)of the single detection was 0.765,0.836 and 0.797,respectively.The AUC of the combined detection was 0.914(Z=2.631,2.331,2.571,P=0.009,0.020,0.010).Conclusion The expression levels of miR-34a,β-catenin and PD-L1 mRNA affect the prognosis of CC patients.Increased expression of miR-34a is an protective factor for poor prognosis in CC patients,in-creased β-catenin and PD-L1 expressions are independent risk factors for poor prognosis in CC patients,and all three factors can be used as biomarkers to predict poor prognosis in CC patients,and the combined detection of the three has the highest prognostic value.

Objective To evaluate the outcomes of continuing education program by a survey among 73 participa-ting physicians before and after the course training with 73 and 65 valid responses before and after the workshop col-lected respectively.Methods The questionnaire covered physicians' basic information,their understanding of pre-cision treatment,feedback on the course content and suggestions about the workshop.Data analysis was performed using SPSS 22.0 software,primarily employing descriptive statistics and x2 tests.Results The overall satisfaction rate among participants was 90.77％,with the lung cancer session(90.77％)and practical case analysis(86.15％)being the most popular.The course significantly improved physicians' understanding of proteomics analysis(P＜0.05)and the importance of adjusting treatment plan in precision treatment of tumors(P＜0.05).Ad-ditionally,81.54％of physicians agreed that precision treatment of tumors significantly enhanced patients'quality of life(P＜0.05).Physicians also showed increased attention to multidisciplinary team(MDT)and patient mental health.Suggestions for future courses included optimizing resource provision and increasing interactive sessions.Conclusions This continuing education program has achieved remarkable results in enhancing physicians' knowl-edge and capacity building of precision treatment for cancer.The evaluation of the course suggests that future educa-tion should further focus on the actual needs of physicians and to optimize the content design to support the applica-tion of precision treatment in clinical practice.