Following the publication of the above article, an interested reader drew to the authors' attention that, in Fig. 2D on p. 834 showing the results of Transwell cell migration assay experiments for the U‑2OS cell line, the 'U‑2OS 24 h/Control' and 'U‑2OS 24 h/AST‑IV' data panels contained an overlapping section, such that these data panels were apparently derived from the same original source, where the results of differently performed experiments were intended to have been portrayed. Upon performing an independent analysis of the data in this paper in the Editorial Office, it also came to light that two pairs of data panels comparing Figs. 2C and 4C, and 2D and 4D, also contained overlapping sections. After having consulted their original data, the authors realized that Fig. 2 had inadvertently been assembled incorrectly. The revised version of Fig. 2, now showing the correct data for the 'MG‑64 48 h/AST‑IV', U‑2OS 24 h/AST‑IV' and 'U‑2OS 48 h/AST‑IV' panels in Fig. 2C and D, is shown on the next page. The authors can confirm that the errors associated with this figure did not have any significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 43: 830‑838, 2019; DOI: 10.3892/ijmm.2018.4013].

Introduction Osseointegration in patients with type 2 diabetes mellitus (T2DM) is poor, and overcoming osseointegration impairment safely and efficiently remains challenging. Objectives To investigate the effect and process of GLUL on the osteogenic differentiation and osseointegration in T2DM by using BMSCs. Methods Human BMSCs were used for osteogenic differentiation in vitro and vivo, while C57BL/6 mice and GK male rats were used for in vivo osseointegration study. Cell transfection, western blotting, coimmunoprecipitation test, microscopic thermography, transcriptome sequencing and bioinformatic analysis favored in discovery of potential target protein and specific sites. Results The expression of glutamine synthetase (GLUL) is downregulated in the jawbone-derived BMSCs of T2DM patients. In this study, we found that GLUL protein homeostasis is important for the osteogenic differentiation of BMSCs and implant osseointegration. Synovial cell apoptosis inhibitor 1 (SYVN1) mediates the ubiquitination of GLUL protein at K259/334A, reducing GLUL protein expression and affecting the osteogenic differentiation of BMSCs. On this basis, we developed a GLUL-DUBTAC called HY-X3369, which is linked by the GLUL ligand HY-126351 and the covalent ligand of the deubiquitinase OTUB1 to target the GLUL ubiquitination site and reduce GLUL ubiquitination. Through pathway degradation, HY-X3369 maintains the protein homeostasis of GLUL in T2DM. HY-X3369 promotes the osteogenic differentiation of jawbone BMSCs from T2DM patients and inhibits GLUL degradation. In vivo evaluation further confirmed that HY-X3369 promotes osseointegration in GK rats. Conclusions This study reveals a promising strategy involving HY-X3369 to promote the function of BMSCs and osseointegration in T2DM, providing a theoretical basis and candidate methods for improving osseointegration in T2DM patients.

The aim of the present study was to systematically evaluate the efficacy of narrow-diameter implants (NDIs) for restoring dentition defects in patients with diabetes and compare their clinical/radiographic outcomes with patients without diabetes (controls). Databases (PubMed, Embase, Web of Science, Cochrane Library and Google Scholar) were searched (January 1, 2000-July 15, 2025) for studies comparing NDI outcomes between patients with and without diabetes. The methodological quality and risk of bias of the included studies were assessed using the Newcastle-Ottawa Scale and the Joanna Briggs Institute Critical Appraisal Checklist. Meta-analysis was performed using RevMan v5.4 software. The nine included studies (410 patients; 688 implants) demonstrated high overall methodological quality. There was no significant intergroup difference in the survival rate [risk ratio (RR)=1.00; 95% confidence interval (CI) 0.93, 1.07; P=1.00]. Regarding radiographic outcomes, the diabetic group exhibited greater distal bone loss [mean difference (MD)=0.28 mm, 95% CI 0.02, 0.5; P=0.03), whereas the mesial bone level (MD=0.31 mm; P=0.08] and overall marginal bone level (MD=-0.02 mm; P=0.83) showed no significant differences. Furthermore, the diabetic group had markedly higher long-term (≥3 years) probing depth (MD=0.31 mm; P<0.0001), bleeding on probing (MD=14.41%; P=0.02), and plaque index (MD=13.77%; P=0.04). There was notable heterogeneity among the studies included in the meta-analysis, suggesting that individual studies may have influenced the overall findings. NDIs demonstrated satisfactory short-term survival in patients with diabetes. However, diabetes markedly increased long-term peri-implant inflammation risk and distal bone resorption, necessitating enhanced postoperative monitoring and personalized maintenance.

INTRODUCTION:Retroperitoneal duodenal perforation is a rare but severe complication of endoscopic procedures such as ERCP and ESD, often leading to significant morbidity and mortality when diagnosed late. Previous studies have focused on early diagnosis, but data on delayed diagnosis cases are limited. This study presents four cases of delayed-diagnosis retroperitoneal duodenal perforation and introduces a novel surgical management strategy. PRESENTATION OF CASE:We report four cases diagnosed more than one month after the initial endoscopic procedure, with CT scans revealing extensive retroperitoneal fluid collections and secondary colonic perforation in some cases. Surgical interventions included right hemicolectomy and proximal jejunostomy to facilitate duodenal exposure and clearance of infectious debris. Outcomes varied, with some patients achieving full recovery while others succumbed to complications. DISCUSSION:The symptoms of retroperitoneal duodenal perforation are often subtle, leading to delayed diagnosis. Early surgical intervention is crucial if CT shows retroperitoneal fluid collections. Right hemicolectomy provides better duodenal exposure and facilitates effective debridement, improving outcomes. CONCLUSION:Early diagnosis and prompt surgical intervention, including right hemicolectomy, are essential for managing delayed retroperitoneal duodenal perforation. Further studies are needed to establish optimal management protocols for these complex cases.

BACKGROUND:Mandibular bone marrow stem cells (BMSCs) from patients with type 2 diabetes mellitus (T2DM) have poor osteogenic differentiation capacity. Elucidating the molecular mechanisms by which circular RNAs (circRNAs) play specific roles in T2DM will reveal new diagnostic biomarkers and therapeutic targets. METHODS:BMSCs with different circ_0054633 expression levels were generated. Furthermore, alkaline phosphatase (ALP) activity, alizarin red staining (ARS), and transplantation of HA/tricalcium phosphate into BMSCs were performed to detect the osteogenic effects of different levels of circ_0054633 expression in BMSCs in vivo and in vitro. RESULTS:In this study, we identified 80 differentially expressed circRNAs in jawbone-derived BMSCs from patients with T2DM. Notably, significant downregulation of circ_0054633 promoted the osteogenic differentiation of these cells in vitro and in vivo. Mechanistically, circ_0054633 acts as a miRNA sponge; specifically, it actively regulates the expression of RUNX2 by sponging miR-590-3p and thus promoting the osteogenic differentiation of the BMSCs. In addition, we found that circ_0054633 was a direct transcriptional target of RUNX2. RUNX2 overexpression activated the circ_0054633 promoter and promoted the generation of nuclear circ_0054633, whereas RUNX2 knockdown abrogated the osteogenic role of circ_0054633 and formed a circ_005463/miR-590-3p/RUNX2 positive feedback loop. CONCLUSIONS:Our results suggest that the circ_0054633/miR-590-3p/RUNX2 positive feedback loop promotes the osteogenic differentiation of BMSCs and is expected to be a potential biomarker and therapeutic target for bone regeneration in T2DM.

Low-intensity pulsed ultrasound (LIPUS) has been used as an effective noninvasive method for treating fractures and osteoarthrosis, but the application in the field of oral implantation is in its infancy. This study aimed to clarify the effect and mechanism of LIPUS on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and implant osseointegration, and to provide an experimental basis for future clinical applications. Dental implants were inserted into Wistar rat femurs, and LIPUS was performed for 4 weeks. Micro-CT and toluidine blue staining were used to assess implant osseointegration. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to identify enriched functional terms and signalling pathways for differentially expressed genes from LIPUS-treated rat BMSC RNAseq data obtained from the GEO database. The random forest method was used to identify key risk genes according to the mean decrease Gini (MDG) coefficient. Then, LIPUS was applied to treat rat BMSCs, and alkaline phosphatase (ALP) staining, alizarin red staining, RT-PCR and western blotting were used to determine whether LIPUS could promote BMSC osteogenic differentiation via integrin α11 (ITGA11) and the focal adhesion pathway. Our in vivo experimentations verified that LIPUS significantly increased new bone formation and osseointegration around the implant in rats. Bioinformatics analysis of RNA-seq data revealed that the upregulated genes in BMSCs after LIPUS treatment were significantly enriched in osteoblast differentiation-related functions and focal adhesion-related pathways. Random forest analysis revealed that ITGA11 was the most significant factor affecting BMSC osteogenic differentiation among the differentially expressed genes. In addition, LIPUS significantly increased ALP expression and mineralized nodule formation in rat BMSCs by upregulating ITGA11 and increasing the activity of FAK/PI3K/AKT/GSK3β/β-catenin pathway. LIPUS can effectively promote implant osseointegration in rats and improve rat BMSC osteogenic differentiation by upregulating ITGA11 and increasing the activity of the downstream focal adhesion pathway.

Objective:Fungiform papillae contain taste buds and play a critical role in mastication and the gustatory system. In this study, we report a series of sequential observations of organogenesis of fungiform papillae in miniature pigs, as well as changes in the expression of BMP2, BMP4, Wnt5a, Sox2, and Notch1 signaling pathway components.Design:In this study, we investigated the spatiotemporal expression patterns of BMP, Wnt, Sox2 and Notch in the fungiform papillae of miniature pigs at the bud stage (E40), cap stage (E50) and bell stage (E60). Pregnant miniature pigs were obtained, and the samples were processed for histological staining. Immunohistochemistry and real-time PCR were used to detect the mRNA and protein expression levels of BMP2, BMP4, Wnt5a, Sox2, and Notch1.Results:At E40, fungiform papillae were present on the anterior two-thirds of the tongue in a specific array and pattern. The fungiform papillae were enlarged and basically developed at E50 and were largest at the earlier stage (E60). Most of the BMP2 was concentrated in the epithelial layer and the connective tissue core of the fungal papilloma and gradually accumulated from E40-E60. BMP-4 was weakly expressed in the fungiform papillae epithelia, but BMP-4-positive cells were also observed in the developing tongue muscle at E50 and E60. Wnt5a-positive cells were observed in the fungiform papillae epithelia and developing tongue muscle at all three time points. Sox2-positive cells were observed only in fungiform papillae epithelial cells, and Notch1-positive cells could not be detected.Conclusions:This study provides primary data regarding the morphogenesis and expression of developmental signals in the fungiform papillae of miniature pigs, establishing a foundation for further research in both this model and humans.

OBJECTIVES:To investigate the effect of liraglutide on osteogenesis in human alveolar bone marrow mesenchymal stem cells (BMSCs) and the influence of liraglutide on implant-bone integration in rats with T2DM. SUBJECTS AND METHODS:Extracting BMSCs from the alveoli of diabetic patients treated with insulin. BMSCs were treated with different concentrations of liraglutide. Osteogenesis and the underlying mechanism were investigated via ALP detection, ALP staining, Alizarin Red S staining, Western blotting, and RT-PCR. Liraglutide was given to Wistar and GK rats after implantation, and new bone formation around the implants was analyzed via micro-CT. Implant-bone integration in rats was investigated via toluidine blue staining. RESULTS:Liraglutide enhanced osteogenesis in BMSCs via the BMP2/Smad/Runx2 signaling pathway. The optimal concentration of liraglutide that promoted osteogenesis was 10-8 mol/L. At concentrations higher than 10-7 mol/L, liraglutide had a negative effect on BMSCs. At a concentration of 10-8 mol/L liraglutide, BMSCs and diabetes mellitus-bone marrow stromal cells (DM-BMSCs) showed optimal osteogenesis. Liraglutide promoted implant-bone integration and new bone formation in Wistar and GK rats. CONCLUSIONS:Liraglutide not only promotes osteogenesis of BMSCs in normoglycemic individuals but also enhances osteogenesis of BMSCs in diabetic patients treated with insulin and enhances osseointegration in rats.

STUDY DESIGN:A retrospective study.OBJECTIVE:To compare the mini nutritional assessment-short form (MNA-SF), geriatric nutritional risk index, prognostic nutritional index (PNI), and preoperative serum albumin level as predictors of postoperative adverse events (AEs) in degenerative spine deformity (DSD) patients.SUMMARY OF BACKGROUND DATA:Although various nutritional screening tools have been well evaluated in patients undergoing spinal fusion surgery, the most suitable tool for the DSD population remains uncertain at present.PATIENTS AND METHODS:The authors reviewed consecutive patients who underwent thoracolumbar fusion surgery for DSD between August 2016 and May 2023. Four screening tools were used to assess preoperative nutritional status. Patients were divided into two categories according to each screening tool, and the four screening tools were compared regarding their predictive power for postoperative AEs, including the rates of extended length of hospital stays (LOS), complications, and readmission within three months. Physical functional indicators such as time to first ambulation, nonhome discharge, and postoperative LOS were assessed as secondary outcome measures. A multivariable logistic regression analysis was used to identify factors associated with postoperative AEs.RESULTS:A total of 228 patients were included. The demographic characteristics, underlying disease, and magnitude of correction were not significantly different between well-nourished and malnourished groups. The nutritional risks shown by MNA-SF and albumin level were significantly associated with infectious complications ( P <0.05). The nutritional risk shown by MNA-SF was significantly associated with nonhome discharge, prolonged postoperative LOS (12.5±8.2 vs. 10.3±6.1, P =0.039), and delayed ambulation (3.7±2.1 vs. 2.2±1.8, P =0.001). Multivariable logistic regression revealed that PNI <50 was significantly associated with total AEs and minor AEs after DSD surgery.CONCLUSIONS:PNI was significantly associated with the incidence of total AEs and minor AEs, while preoperative albumin level and MNA-SF were more effective in predicting postoperative infectious complications and delayed recovery of physical function, respectively.LEVEL OF EVIDENCE:Level III.

Blood glucose fluctuation leads to poor bone defect repair in patients with type 2 diabetes (T2DM). Strategies to safely and efficiently improve the bone regeneration disorder caused by blood glucose fluctuation are still a challenge. Neutral sphingophospholipase 2 (Smpd3) is downregulated in jawbone-derived bone marrow mesenchymal stem cells (BMSCs) from T2DM patients. Here, we investigated the effect of Smpd3 on the osteogenic differentiation of BMSCs and utilized exosomes from stem cells overexpressing Smpd3 as the main treatment based on the glucose responsiveness of phenylboronic acid-based polyvinyl alcohol crosslinkers and the protease degradability of gelatin nanoparticles. The combined loading of Smpd3-overexpressing stem cell-derived exosomes (Exos-Smpd3) and nanosilver ions (Ns) to construct a hydrogel delivery system (Exos-Smpd3@Ns) promoted osteogenesis and differentiation of BMSCs in a glucose-fluctuating environment, ectopic osteogenesis of BMSCs in a glucose-fluctuating environment and jawbone regeneration of diabetic dogs in vitro. Mechanistically, Smpd3 promoted the osteogenesis and differentiation of jawbone-derived BMSCs by activating autophagy in the jawbone and inhibiting macrophage polarization and oxidative stress caused by blood glucose fluctuations. These results reveal the role and mechanism of Smpd3 and the Smpd3 overexpression exosome delivery system in promoting BMSC function and bone regeneration under blood glucose fluctuations, providing a theoretical basis and candidate methods for the treatment of bone defects in T2DM patients.

OBJECTIVES:Osseointegration of oral implants has a low success rate in patients with type 2 diabetes. This is because of the inhibition of osteogenic differentiation in the jawbone marrow mesenchymal stem cells, in which the expression of microRNA(miR)-491-5p is significantly downregulated, as ascertained through gene chip screening. However, the underlying mechanisms are unclear. Here, we aimed to clarify the mechanisms involved in the influence of miR-491-5p on osteogenic differentiation.SUBJECTS AND METHODS:Jawbone marrow mesenchymal stem cells were isolated from jawbones of patients with type 2 diabetes and subjected to bioinformatics and functional analyses. Osteogenesis experiments were conducted using the isolated cells and an in vivo model.RESULTS:Knockdown and overexpression experiments revealed the positive effects of miR-491-5p expression on osteogenic differentiation in vivo and in vitro. Additionally, a dual-luciferase assay revealed that miR-491-5p targeted the SMAD/RUNX2 pathway by inhibiting the expression of epidermal growth factor receptor.CONCLUSIONS:miR-491-5p is vital in osteogenic differentiation of jawbone mesenchymal stem cells; its downregulation in type 2 diabetes could be a major cause of decreased osteogenic differentiation. Regulation of miR-491-5p expression could improve osteogenic differentiation of jawbone mesenchymal stem cells in patients with type 2 diabetes.

PurposeSmall bowel carcinoma (SBA) is a rare gastrointestinal cancer with a poor prognosis. Recent genomic profiling studies revealed that the landscape of molecular alterations in SBA was distinct from colorectal cancer (CRC) and gastric cancer (GC). To explore driver and targetable alterations in SBA, we performed next-generation sequencing in 107 Chinese SBA patients.MethodsDNA from paraffin-embedded SBA samples and the corresponding peripheral blood control samples were analyzed through a next-generation sequencing panel. Somatic alterations including point mutations, indels, copy number alterations, gene fusions as well as pathogenic germline variants were characterized.ResultsMore than half of SBA cases carried KRAS mutations, including canonical (G12, G12, Q61) and atypical mutations (A146, L19, and K117). To our best knowledge, this was the first report of rare driver alterations including KRAS A146V/L19F, PIK3CA N345K/G364R/Q546E, and ZKSCAN1-MET fusion in SBA. Compared to KRAS-mutant patients, alternative activating alterations were enriched in KRAS wild-type patients, and some of them are targetable. Among BRAF-mutated SBA patients, class 1/2 BRAF mutants were mutually exclusive with RAS mutations, but class 3 BRAF mutants were not. Activating ERBB2 alternations, including amplification and activating mutations, represent the most common targetable alternation in this SBA cohort. Of note, the spectrums of BRAF and PIK3CA mutations in this Chinese SBA cohort were distinct from those of a European SBA cohort. Patients with three druggable mutations (PIK3CA, MAP2K1, KRAS G12C) had a high prevalence of concurring drivers, which may interfere with the clinical efficacy of single-target therapy.ConclusionTaken together, our work provided a comprehensive analysis of driver and targetable alterations in SBA, which can facilitate the practice of precision oncology in this challenging disease.

Background Bispecific antibodies (BsAb) that target dual tumor-associated antigens can invoke synergistic effects between two signaling pathways, increase target tissue specificity, and reduce systemic toxicity. Combining antibody-mediated specific targeting with potent killing from a cytotoxic payload, antibody-drug conjugates (ADC), especially bispecific ADCs (BsADC), have become powerful therapeutic strategies. EGFR and MET are oncogenic proteins that are co-expressed in a wide range of tumors. Moreover, MET amplification is largely associated with drug resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI) in non-small cell lung cancer (NSCLC) patients. Methods Biocytogen developed a fully human EGFR × MET BsADC using our proprietary common light chain RenLite® mouse platform and knobs-into-holes technology, evaluated internalization by flow cytometry and IncuCyte, and binding affinity potential by flow cytometry. In vivo drug efficacies were screened in severely combined immunodeficient B-NDG mice inoculated with NCI-H1975 and NCI-H292 cell-derived xenografts, as well as patient-derived NSCLC and pancreatic ductal adenocarcinoma (PDAC) xenograft models. Results The BsAb showed enhanced internalization and binding affinity compared to parental monoclonal and monovalent antibodies in the EGFR/MET co-expressing NCI-H1975 cell lines. After conjugating the BsAb with monomethyl auristatin E (MMAE) via a protease-cleavable linker, the resulting BsADC, DM005, exhibited a remarkable and dose-dependent anti-tumor efficacy in NCI-H1975 and NCI-H292 cell line-derived xenograft models. Moreover, in multiple patient-derived xenografts of NSCLC and pancreatic ductal adenocarcinoma (PDAC), which co-express EGFR and MET, DM005 demonstrated superior and durable efficacy that outperformed benchmark antibodies at a lower dose (3 mg/kg). Conclusions Collectively, these results suggest that DM005 can be an effective treatment option for EGFR and MET co-expressing tumors and overcome MET-driven EGFR-TKI resistance to improve patient outcomes. Ethics Approval All animal studies were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of Biocytogen Beijing Co., Ltd.

The failure rate of dental implantation in patients with well-controlled type 2 diabetes mellitus (T2DM) is higher than that in non-diabetic patients. This due, in part, to the impaired function of bone marrow mesenchymal stem cells (BMSCs) from the jawbone marrow of T2DM patients (DM-BMSCs), limiting implant osseointegration. RNA N6-methyladenine (m6A) is important for BMSC function and diabetes regulation. However, it remains unclear how to best regulate m6A modifications in DM-BMSCs to enhance function. Based on the "m6A site methylation stoichiometry" of m6A single nucleotide arrays, we identified 834 differential m6A-methylated genes in DM-BMSCs compared with normal-BMSCs (N-BMSCs), including 43 and 790 m6A hypermethylated and hypomethylated genes, respectively, and 1 gene containing hyper- and hypomethylated m6A sites. Differential m6A hypermethylated sites were primarily distributed in the coding sequence, while hypomethylated sites were mainly in the 3'-untranslated region. The largest and smallest proportions of m6A-methylated genes were on chromosome 1 and 21, respectively. MazF-PCR and real-time RT-PCR results for the validation of erythrocyte membrane protein band 4.1 like 3, activity-dependent neuroprotector homeobox (ADNP), growth differentiation factor 11 (GDF11), and regulator of G protein signalling 2 agree with m6A single nucleotide array results; ADNP and GDF11 mRNA expression decreased in DM-BMSCs. Furthermore, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that most of these genes were enriched in metabolic processes. This study reveals the differential m6A sites of DM-BMSCs compared with N-BMSCs and identifies candidate target genes to enhance BMSC function and improve implantation success in T2DM patients.

Introduction: Anastomotic leakage is the horrendous complication after the laparoscopic rectal cancer resection. The main objective of the present study is to assess the relationship between AL, tumor recurrence and overall survival in rectal cancer patients treated with laparoscopic surgery. Methods: One hundred seventy patients who were diagnosed as rectal cancer with stages 1-3 followed by laparoscopic surgery between March 2012 and February 2017 from Beijing Friendship Hospital were evaluated retrospectively. Twelve factors after laparoscopic surgery were evaluated by the univariate analysis and multivariate analysis. The disease-free survival and overall survival curves were performed by the Kaplan- Meier method and were compared with the log-rank test. Results: The incidence rate of AL was 18.82%. The multivariate analysis showed AL [Hazard Ratio (HR); 3.114, 95% Confidence Interval (CI); 1.029-9.428, P; 0.044], advanced TNM stage [HR; 12.714, 95%CI; 2.364-68.377, P; 0.003] and intraoperative blood loss [HR; 0.269, 95%CI; 0.085-0.859, P; 0.027] were associated with poor OS. In addition, AL [Hazard Ratio (HR); 3.134, 95% Confidence Interval (CI); 1.274-7.711, P; 0.013] and advanced TNM stage [HR; 88.378, 95%CI; 2.231-31.465, P; 0.002] were associated with poor DFS. The logrank test p-value for OS and DFS curve by Kaplan-Meier method were 0.382 and 0.108 respectively. Conclusion: Anastomotic leakage was associated with poorer overall survival and increased risk of tumor recurrence. Moreover, there was no difference in three-year/five-year overall survival rate and disease-frees survival rate between the leakage and non-leakage groups in the present analysis.

The aim of this study was to assess the shear bond strength and durability between plasma-pretreated and polydopamine (PDA)-coated zirconia and titanium. Four groups were prepared according to the different surface treatments (untreated ZrO2, plasma-pretreated ZrO2, PDA-coated ZrO2, and plasma-pretreated and PDA-coated ZrO2 (PP+PDA-ZrO2). The surface topography and roughness, contact angle, and elemental analysis of the coatings of the four groups were investigated, and the bond strength and durability of the specimens were evaluated based on shear bond strength and thermocycle tests. Physical and chemical characterization results confirmed that PDA coatings can be successfully formed on zirconia substrates. The roughness and hydrophilicity were significantly higher in the PP+PDA-ZrO2 group, which demonstrated better shear bond strength and durability between zirconia and titanium. The plasma pretreatment of zirconia substrates can enhance the stability of the PDA coating layer, and hybrid surface modifications can provide several bonding advantages for clinical use.

The patients with type 2 diabetes mellitus (T2DM) have high dental implant failure frequency. This study explores the function of glimepiride local delivery on dental implant osseointegration in diabetes animal. Glimepiride loaded PLGA microspheres were loaded on the surface of the dental implant, and transplanted into ten Goto-Kakizaki (GK) rats. Blood sugar level and Implant Stability Quotient (ISQ) were measured every week after surgery. Histological, osseointegration rate and bone-implant contact (BIC) rate analysis were performed to evaluate dental osseointegration. The results showed that Glimepiride loaded Poly-lactide-co-glycolide (PLGA) microspheres have sustained-release curve. The glimepiride group exhibited greater ISQ than the control group. The BIC rate of the control and glimepiride group was 44.60%±1.95% and 59.80%±1.79%, respectively. This study demonstrated that the glimepiride group has a significantly greater osseointegration rate than that of the control group. Thus, Glimepiride could provide an alternative drug release microspheres for enhance the dental implant osseointegration in diabetes patients.

目的 探索2型糖尿病患者(Type-2 Diabetes Mellitus,T2DM)和非糖尿病患者的骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)生物学功能差异以及胰岛素样生长因子结合蛋白2(insulin-like growth factor-binding proteins-2,IGFBP2)在2型糖尿病种植患者牙槽突骨髓间充质干细胞中的表达差异.方法 原代培养2型糖尿病患者及非糖尿病人牙槽突BMSCs,采用MTT比色法检测两组细胞增殖能力的差异,碱性磷酸酶染色及活力测定检测成骨分化能力的差异,茜素红染色检测矿化能力的差异,RT-qPCR、Western blot方法研究IGFBP2在糖尿病患者BMSCs中的表达水平与非糖尿病人之间的差异.结果 两组细胞的增殖曲线显示,糖尿病组BMSCs细胞增殖速度显著低于非糖尿病人组(P<0.05);ALP染色及活力值结果显示,糖尿病组细胞成骨分化能力显著降低(P<0.05);茜素红染色可见糖尿病组的细胞染色相比于非糖尿病人组明显较浅,表明糖尿病组的BMSCs的矿化能力较弱;RT-qPCR和Western-blot结果见糖尿病组BMSCs的IGFBP2的mRNA表达和蛋白翻译水平显著高于非糖尿病人组,差异具有统计学意义(P<0.05).结论 2型糖尿病患者牙槽突骨髓间充质干细胞的增殖、成骨分化及矿化能力均低于非糖尿病人,IGFBP2的异常高表达可能在种植体愈合过程中起到负面作用.

Dental implant restoration is the preferred choice for patients with dentition defects or edentulous patients, and obtaining stable osseointegration is the determining factor for successful implant healing. The risk of implant failure during the healing stage is still an urgent problem in clinical practice due to differences in bone quality at different implant sites and the impact of some systemic diseases on bone tissue metabolism. Low-intensity pulsed ultrasound (LIPUS) is a noninvasive physical intervention method widely recognized in the treatment of bone fracture and joint damage repair. Moreover, many studies indicated that LIPUS could effectively promote the osseointegration of dental implants and improve the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). This review is aimed at investigating the research progress on the use of LIPUS in dental implant medicine from three aspects: (1) discuss the promoting effects of LIPUS on osseointegration and peri-implant bone regeneration, (2) summarize the effects and associated mechanisms of LIPUS on the biological functions of BMSCs, and (3) introduce the application and prospects of LIPUS in the clinical work of dental implantation. Although many challenges need to be overcome in the future, LIPUS is bound to be an efficient and convenient therapeutic method to improve the dental implantation success rate and expand clinical implant indications.