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Introduction: In patients with pulmonary nodules (PNs), computed tomography (CT)-guided localization is commonly performed prior to the resection of these nodules through video-assisted thoracic surgery (VATS). Aim: To evaluate the relative clinical efficacy of coil and anchored needle (AN) insertion as approaches to preoperative CT-guided PN localization. Material and methods: This single-center, prospective, open-label, randomized controlled trial (registration number: NCT05183945) enrolled consecutive patients from January 2022 to July 2022, assigning these patients at random to undergo either coil or AN localization prior to VATS. Efficacy and safety outcomes in these two groups were then compared. Results: This study enrolled in total 100 patients with 120 PNs who were assigned at random to the coil (patients = 50; PNs = 60) and AN (patients = 50; PNs = 60) localization groups. The respective technical success rates for coil and AN localization were 98.3% (59/60) and 100% (60/60), with no significant difference between the groups (p = 1.000). The coil group had a significantly longer median duration of localization relative to the AN group (16.0 min vs. 8.0 min, p < 0.001). Similar rates of localization-related pneumothorax (8.3% vs. 5.0%, p = 0.715) and pulmonary hemorrhage (5.0% vs. 13.3%, p = 0.110) were observed in both groups. In addition, the VATS resection procedures achieved 100% technical success rates in both of these localization groups. Conclusions: Both coil- and AN-based localization approaches can be successfully employed to localize PNs prior to VATS resection, with the AN localization procedure requiring less time to complete on average as compared to the coil-based approach.
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Catalytic enantioselective preparation of alkene atropisomers with multiple stereogenic elements and discovery of their applications have become significant but challenging issues in the scientific community due to the unique structures of this class of atropisomers. We herein report the first catalytic atroposelective preparation of cyclopentenyl[b]indoles, a new kind of alkene atropisomers, with stereogenic point and axial chirality via an unusual rearrangement reaction of 3-indolylmethanols under asymmetric organocatalysis. Notably, this novel type of alkene atropisomers have promising applications in developing chiral ligands or organocatalysts, discovering antitumor drug candidates and fluorescence imaging materials. Moreover, the theoretical calculations have elucidated the possible reaction mechanism and the non-covalent interactions to control the enantioselectivity. This approach offers a new synthetic strategy for alkene atropisomers with multiple stereogenic elements, and represents the first catalytic enantioselective rearrangement reaction of 3-indolylmethanols, which will advance the chemistry of atropisomers and chiral indole chemistry.
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Background: A common treatment strategy for individuals with multifocal hepatocellular carcinoma (HCC) who are not candidates for surgical resection is transarterial chemoembolization (TACE). Combining TACE with 125I seed insertion (ISI) may offer a means of enhancing therapeutic efficacy. The purpose of this study was to compare the therapeutic efficacy of TACE administered with and without ISI for the treatment of multifocal HCC. Methods: The data from the two centers were analyzed retrospectively. The present study involved 85 consecutive patients with multifocal HCC who underwent TACE between January 2018 and December 2021. Of these patients, 43 were in the combined group, receiving TACE with ISI, and 42 were in the TACE-only group, receiving TACE without ISI. Comparisons of treatment outcomes were made between these groups. Results: No significant differences in baseline data were observed between these groups of patients. Higher rates of complete (60.5% vs. 33.3%, P = 0.016) and total (93.0% vs. 61.9%, P = 0.001) responses were evident in the combined group compared to the TACE-only group. Median progression-free survival (PFS, 13 vs. 10 months, P = 0.014) and overall survival (OS, 22 vs. 17 months, P = 0.035) were also significantly longer in the combined group than in the TACE-only group. Using a Cox regression analysis, risk variables associated with shorter PFS and OS included Child-Pugh B status (P = 0.027 and 0.004) and only TACE treatment (P = 0.011 and 0.022). Conclusion: In summary, these findings suggest that, as compared to TACE alone, combining TACE and ISI can enhance HCC patients' treatment outcomes and survival.
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Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored. However, it is highly likely to lead to further aggravation of pathological damage to ischemic tissues or the nervous system., and has accordingly been a focus of extensive clinical research. As a traditional Chinese medicinal formulation, Sanhua Decoction has gradually gained importance in the treatment of cerebrovascular diseases. Its main constituents include Citrus aurantium, Magnolia officinalis, rhubarb, and Qiangwu, which are primarily used to regulate qi. In the treatment of neurological diseases, the therapeutic effects of the Sanhua Decoction are mediated via different pathways, including antioxidant, anti-inflammatory, and neurotransmitter regulatory pathways, as well as through the protection of nerve cells and a reduction in cerebral edema. Among the studies conducted to date, many have found that the application of Sanhua Decoction in the treatment of neurological diseases has clear therapeutic effects. In addition, as a natural treatment, the Sanhua Decoction has received widespread attention, given that it is safer and more effective than traditional Western medicines. Consequently, research on the mechanisms of action and efficacy of the Sanhua Decoctions in the treatment of cerebral ischemia-reperfusion injury is of considerable significance. In this paper, we describe the pathogenesis of cerebral ischemia-reperfusion injury and review the current status of its treatment to examine the therapeutic mechanisms of action of the Sanhua Decoction. We hope that the findings of the research presented herein will contribute to a better understanding of the efficacy of this formulation in the treatment of cerebral ischemia-reperfusion, and provide a scientific basis for its application in clinical practice.
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Sporadic or late-onset Alzheimer's disease (LOAD) accounts for more than 95% of Alzheimer's disease (AD) cases without any family history. Although genome-wide association studies have identified associated risk genes and loci for LOAD, numerous studies suggest that many adverse environmental factors, such as social isolation, are associated with an increased risk of dementia. However, the underlying mechanisms of social isolation in AD progression remain elusive. In the current study, we found that 7 days of social isolation could trigger pattern separation impairments and presynaptic abnormalities of the mossy fibre-CA3 circuit in AD mice. We also revealed that social isolation disrupted histone acetylation and resulted in the downregulation of 2 dentate gyrus (DG)-enriched miRNAs, which simultaneously target reticulon 3 (RTN3), an endoplasmic reticulum protein that aggregates in presynaptic regions to disturb the formation of functional mossy fibre boutons (MFBs) by recruiting multiple mitochondrial and vesicle-related proteins. Interestingly, the aggregation of RTN3 also recruits the PP2A B subunits to suppress PP2A activity and induce tau hyperphosphorylation, which, in turn, further elevates RTN3 and forms a vicious cycle. Finally, using an artificial intelligence-assisted molecular docking approach, we determined that senktide, a selective agonist of neurokinin3 receptors (NK3R), could reduce the binding of RTN3 with its partners. Moreover, application of senktide in vivo effectively restored DG circuit disorders in socially isolated AD mice. Taken together, our findings not only demonstrate the epigenetic regulatory mechanism underlying mossy fibre synaptic disorders orchestrated by social isolation and tau pathology but also reveal a novel potential therapeutic strategy for AD.
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Enfermedad de Alzheimer , Fragmentos de Péptidos , Sustancia P/análogos & derivados , Ratones , Animales , Enfermedad de Alzheimer/metabolismo , Inteligencia Artificial , Estudio de Asociación del Genoma Completo , Simulación del Acoplamiento Molecular , Trastornos de la Memoria/metabolismoRESUMEN
Implant abutment fractures are an uncommon mechanical complication, and the removal of the abutment fragment and replacement with a new prosthesis is the best solution. However, successful retrieval of the fractured abutment fragment from the implant is challenging, and effective rescue kits are lacking. This clinical report describes the retrieval of a fractured implant abutment in a conical connection implant using a modified manufacturer-specific instrument.
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BACKGROUND: The combination of a prosthetic index with Morse taper connection was developed, with the purpose of making prosthetic procedures more precise. However, the presence of the index may compromise the mechanical performance of the abutment. The aim of this study is to evaluate the effect of prosthetic index on stress distribution in implant-abutment-screw system and peri-implant bone by using the 3D finite element methodology. METHODS: Two commercial dental implant systems with different implant-abutment connections were used: the Morse taper connection with platform switching (MT-PS) implant system and the internal hex connection with platform matching (IH-PM) implant system. Meanwhile, there are two different designs of Morse taper connection abutment, namely, abutments with or without index. Consequently, three different models were developed and evaluated: (1) MT-PS indexed, (2) MT-PS non-indexed, and (3) IH-PM. These models were inserted into a bone block. Vertical and oblique forces of 100 N were applied to each abutment to simulate occlusal loadings. RESULTS: For the MT-PS implant system, the maximum stress was always concentrated in the abutment neck under both vertical and oblique loading. Moreover, the maximum von Mises stress in the neck of the MT-PS abutment with index even exceed the yield strength of titanium alloy under the oblique loading. For the IH-PM implant system, however, the maximum stress was always located at the implant. Additionally, the MT-PS implant system has a significantly higher stress level in the abutment neck and a lower stress level around the peri-implant bone compared to the IH-PM implant system. The combined average maximum stress from vertical and oblique loads is 2.04 times higher in the MT-PS indexed model, and 1.82 times for the MT-PS non-indexed model than that of the IH-PM model. CONCLUSIONS: MT-PS with index will cause higher stress concentration on the abutment neck than that of without index, which is more prone to mechanical complications. Nevertheless, MT-PS decreases stress within cancellous bone and may contribute to limiting crestal bone resorption.
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Implantes Dentales , Aleaciones , Fenómenos Biomecánicos , Análisis del Estrés Dental/métodos , Análisis de Elementos Finitos , Humanos , Estrés Mecánico , TitanioRESUMEN
Tumor-targeted delivery and controlled release of antitumor drugs are promising strategies for increasing chemotherapeutic efficacy and reducing adverse effects. Although mesoporous silica nanoparticles (MSNs) have been known as a potential delivery system for doxorubicin (DOX), they have restricted applications due to their uncontrolled leakage and burst release from their large open pores. Herein, we engineered a smart drug-delivery system (smart MSN-drug) based on MSN-drug loading, cell membrane mimetic coating, on-demand pore blocking/opening, and tumor cell targeting strategies. The pore size of DOX-loaded MSNs was narrowed by polydopamine coating, and the pores/channels were blocked with tumor-targeting ligands anchored by tumor environment-rupturable -SS- chains. Furthermore, a cell membrane mimetic surface was constructed to enhance biocompatibility of the smart MSN-drug. Confocal microscopy results demonstrate highly selective uptake (12-fold in comparison with L929 cell) of the smart MSN-drug by HeLa cells and delivery into the HeLa cellular nuclei. Further in vitro IC50 studies showed that the toxicity of the smart MSN-drug to HeLa cells was 4000-fold higher than to the normal fibroblast cells. These exciting results demonstrate the utility of the smart MSN-drug capable of selectively killing tumor cells and saving the normal cells.
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Antineoplásicos/farmacología , Doxorrubicina/farmacología , Portadores de Fármacos/química , Nanopartículas/química , Animales , Antineoplásicos/química , Doxorrubicina/química , Portadores de Fármacos/toxicidad , Liberación de Fármacos , Células HeLa , Humanos , Indoles/química , Indoles/toxicidad , Ratones , Nanopartículas/toxicidad , Fosforilcolina/análogos & derivados , Fosforilcolina/toxicidad , Polímeros/química , Polímeros/toxicidad , Porosidad , Dióxido de Silicio/química , Dióxido de Silicio/toxicidad , Microambiente Tumoral/fisiologíaRESUMEN
BACKGROUND: Mesenchymal stem cells (MSCs) have been proved to drive castration resistant prostate cancer (CRPC). In this study, we aim to investigate the contribution of MSCs to the development of docetaxel resistance in CRPC cells and its potential mechanisms. METHODS: The effect of MSCs on CRPC cells resistance to docetaxel was determined using in vivo and in vitro approaches. CCK8 and PI/Annexin V-FITC assay were used to examined the cell viability and apoptosis. The concentration of transforming growth factor-ß1 was measured by enzyme-linked immunosorbent assay and small interfering RNA was used for functional analyses. RESULTS: MSCs significantly reduced the sensitivity of CRPC cells to docetaxel-induced proliferation inhibition and apoptosis promotion in vivo and in vitro. CRPC cells cocultured with MSCs under docetaxel administration have an increased autophagy activation, while autophagy inhibitor could effectively reversed MSCs-induced resistance to docetaxel. Additionally, MSCs-induced CRPC cell autophagy increase under docetaxel administration depends on MSCs secreting TGF-ß1 and inhibition of TGF-ß1 secretion in MSCs could consequently increase the sensitivity of CRPC cells to docetaxel. CONCLUSIONS: These results suggest that docetaxel administrated CRPC cells may elicit MSCs secreting TGF-ß1 increase, which desensitizes CRPC to docetaxel chemotherapy accelerating chemoresistance occurrence via inducing cell autophagy.
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Ankle fractures are common injuries. If an ankle fracture is combined with tibiofibular syndesmosis separation, then tibiofibular transfixation should be used to stabilize the syndesmosis; in such cases, flexible (suture-button) fixation is an option. We surgically treated a male patient's unstable ankle fracture with internal fixation devices, including a suture-button fixator, and observed the development of a flexor hallucis longus checkrein deformity in the postoperative period. The aim of this report is to describe this rare postoperative complication associated with the use of suture-button transfixation of the tibiofibular syndesmosis.
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Fracturas de Tobillo/cirugía , Deformidades Adquiridas del Pie/etiología , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/instrumentación , Hallux , Anclas para Sutura/efectos adversos , Adulto , Humanos , MasculinoRESUMEN
Background: Circular RNAs (circRNAs) have been identified as essential regulators in a plethora of cancers. Nonetheless, the mechanistic functions of circRNAs in Renal Cell Carcinoma (RCC) remain largely unknown. Methods: In this study, we aimed to identify novel circRNAs that regulate RCC epithelial-mesenchymal transition (EMT), and to subsequently determine their regulatory mechanisms and clinical significance. Results: circPRRC2A was identified by circRNA microarray and validated by qRT-PCR. The role of circPRRC2A in RCC metastasis was evaluated both in vitro and in vivo. We found that increased expression of circPRRC2A is positively associated with advanced clinical stage and worse survivorship in RCC patients. Mechanistically, our results indicate that circPRRC2A prevents the degradation of TRPM3, a tissue-specific oncogene, mRNA by sponging miR-514a-5p and miR-6776-5p. Moreover, circPRRC2A promotes tumor EMT and aggressiveness in patients with RCC. Conclusions: These findings infer the exciting possibility that circPRRC2A may be exploited as a therapeutic and prognostic target for RCC patients.
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Carcinoma de Células Renales , Transición Epitelial-Mesenquimal , Neoplasias Renales , Proteínas/metabolismo , ARN Circular/metabolismo , Canales Catiónicos TRPM/metabolismo , Adulto , Animales , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana EdadRESUMEN
Metastatic cholangiocarcinoma (CCA) to the gastrointestinal tracts has rarely been described in the literature. We report a 54-year-old male patient with radical resection of an extrahepatic CCA who underwent uncommon metastatic pattern. After a recurrence-free period of 2 years, an elevated CA19- 9 initiated a CT scan, showing a tumor at the junction of rectum and sigmoid with enlarged lymph nodes around colon, mimicking a primary colon cancer. Histological diagnosis was adenocarcinoma, and the patient was treated with surgery as a primary colon cancer, but post-operative immunohistochemistry revealed the same pattern as the CCA. As colon is not the common organ for distant spread that makes some challenge to distinguish the colonic metastatic CCA between primary colon carcinoma. Biomarkers (CA 19-9), immunohistological and pathological features play an important role in distinguishing CCA from primary colon cancer. This case taught us a lesson how cancers can spread to unusual sites and mimic other tumor types, that may change the treatment and prognostication significantly.
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Colangiocarcinoma/complicaciones , Colon/patología , Neoplasias del Colon/secundario , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la NeoplasiaRESUMEN
The study assessed the pelvic dimensions by computed tomography (CT) performed for gluteal muscle contracture women, and evaluated the impact of malformations on several essential obstetric parameters.The CT pelvimetry was retrospectively performed in 25 gluteal muscle contracture women selected consecutively whether they had delivery history or not. Among the pelvic inlet plane, the mid plane and the outlet plane, 12 indicators including the transverse diameter of the pelvic inlet, the conjugate vera, the diagonal conjugate, the biischial diameter, the anteroposterior diameter of the middle pelvis, transverse outlet, the posterior sagittal diameter of outlet, the conjugate of the outlet, the anterior sagittal diameter of the outlet, the curvature and length of the sacrum, the angle of pubic arch were collected.Finally, the mean age of these women was 26.6â±â5.0 years. Most pelvises had anteroposterior elliptical appearance in inlet and size of the female pelvis. The most statistically different and most clinically significant indicator was the biischial diameter, gluteal muscle contracture women were 95.6â±â9.3âmm and the normal women from other study were 105.0â±â7.9âmm, the comparison showed a significant difference (Pâ<â.001).Generally, most gluteal muscle contracture women had features of anthropoid pelvis which were quite different from normal Chinese female. These results may serve as a basis for future studies to assess its utility and prognostic value for a safe vaginal delivery in gluteal muscle contracture women.
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Nalgas/diagnóstico por imagen , Distocia/etiología , Músculo Esquelético/diagnóstico por imagen , Huesos Pélvicos/diagnóstico por imagen , Adolescente , Adulto , Nalgas/patología , Nalgas/fisiopatología , Femenino , Fibrosis , Humanos , Músculo Esquelético/fisiopatología , Huesos Pélvicos/patología , Embarazo , Síndrome , Adulto JovenRESUMEN
PURPOSE: To investigate whether tenofovir disoproxil fumarate (TDF) treatment that started from the second trimester had an advantage over TDF treatment that started from the third trimester. PATIENTS AND METHODS: Twenty 35-year-old pregnant women with hepatitis B virus (HBV) DNA >2×106 IU/mL were prospectively enrolled in this study. All participants were divided into two subgroups: the second trimester group who started TDF treatment at 24-27 weeks and the third trimester group who started TDF treatment at 28-30 weeks. The primary outcome was the change in serum HBV DNA level from baseline to delivery. Each parameter was tested every 4 weeks from TDF initiation to 3 months postpartum. RESULTS: There were 80 pregnant women in the second trimester group and 49 pregnant women in the third trimester group. The decline in HBV DNA from baseline to delivery was more obvious in the second trimester group (4.8±1.2 log10 IU/mL) than that in the third trimester group (4.3±1.1 log10 IU/mL, p=0.041). The downward shift of haemoglobin (HB) from baseline to delivery was greater in the second trimester group (10.6±10.7 g/L) than in the third trimester group (6.3±12.3 g/L, p=0.041). The decline in HBV DNA from baseline to delivery was linearly related to the start of TDF treatment from the second trimester (ß=0.50 and 95% CI: 0.26-0.75, p<0.001). There were no significant differences between the two groups regarding HBV serologic markers and safety indicators. CONCLUSION: Starting TDF treatment from the second trimester achieved better viral suppression than starting TDF treatment from the third trimester in highly viraemic pregnant women without increasing additional adverse reactions. HB level needed frequent monitoring during treatment to avoid anaemia. REGISTRY NUMBER: Clinical Trial No. NCT02719808.
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Os acromiale is a developmental defect which results from the lack of an osseous union between the ossification centers of the acromion, leading to the fibrocartilaginous tissue connection. The prevalence of os acromiale is 1% to 15%, and is quite common in the African American population. Os acromiale in adults is easily diagnosed by symptoms and X-ray, particularly on the axillary view; however, the differential diagnosis of adolescents may require MRI or SPECT-CT. Generally, nonoperative therapy for symptomatic os acromiale should be started, including physiotherapy, nonsteroidal anti-inflammatory drugs, and injections. Surgical treatment is indicated after failed conservative treatment. In symptomatic patients with fixable acromiale, the tension band technique should be used to make the anterior aspect of the acromion elevated from the humerus head. In patients with small fragments which are unsuitable for reattachment, excision might be the best therapeutic option and lead to good outcomes. Whether using internal fixation or resection, the arthroscopic technique results in a better outcome and fewer complications, especially in older patients or athletes with overhead movement, because of the high incidence of shoulder impingement or rotator cuff tears which can be treated concurrently.
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Acromion/patología , Acromion/cirugía , Anomalías Musculoesqueléticas/cirugía , Acromion/diagnóstico por imagen , Artroscopía , Diagnóstico Diferencial , Humanos , Fijadores Internos , Anomalías Musculoesqueléticas/diagnóstico por imagen , RadiografíaRESUMEN
It has become increasingly clear that the development of cancer, a multifactorial disease, cannot be explained by a single molecule or gene mutation. As a new discipline, metabolomics focuses on the body's metabolite changes, and attempts to find differences to explain the development of cancer; it has proven to be effective and credible. Metabolic studies of bladder cancer (BCa) lag behind those of other tumors. This review systematically outlines the specific process of metabolomics and the use of metabolomics in BCa studies in recent years. We have reviewed the in vitro cell line, bladder tumor tissue and biofluid (urine, plasma and serum) studies used in metabolomics analyses of BCa. The advantages and drawbacks of the use of different samples were compared. Based on the available studies, we have further described the aberrant metabolic pathways of BCa and have suggested some metabolites that may be potential biomarkers for BCa detection.
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Biomarcadores de Tumor/metabolismo , Metabolómica/métodos , Neoplasias de la Vejiga Urinaria/metabolismo , Humanos , Flujo de TrabajoRESUMEN
OBJECTIVE: To explore function and related molecular mechanism of osteopractic total flavone (OTF) on tendon healing in rats. METHODS: Ten male rats aged for 8 weeks were collected and weighted from 180 to 220 g. Tendon stem cells were cultivated, the third tendon stem cells were used for experiment. OTP treated with 0, 0.1, 1, 10 ng/ml were added into tendon stem cells, and expression change of ALP, Runx2, OCN, VEGF, P-S6, P-4E/BP1 were detected after 14 days. Forty male rats aged for 8 weeks (weighted 180 to 220 g) were established extra-articular tendon-bone transplanting healing model, and divided into experimental group and control group. Experimental group were treated with OTF(100 mg·kg⻹·d⻹), while control group was treated by normal saline with the same volume. Tendon-bone healing degree were detected by biomechanical testing at 3 and 6 weeks after surgery, histological detection were applied to detect tendon-bone healing and number of new vessles. RESULTS: After treated by OTP, ALP staining and active index detection showed there were statistical differences among 0, 0.1, 1, 10 ng/ml group. After 14 days' cultivation, western blotting results showed mTOR downstream marker protein P-S6 protein expression were gradually increased with increase of density of OTP, expression of P-4E/BP1 was reduced, while expression of Runx2, OCN, VEGF were increased. Biological detection results showed that there was no significant difference in mechanical strength between experimental group(0.78±0.05) N/mm and control group (0.51±0.02) N/mm at 3 weeks after surgery, while mechanical strength in experimental group (1.36±0.09) N/mm was higher than control group (1.01±0.08) N/mm at 6 weeks after surgery. Histological results showed maturity of tendon-bone surface cell were higher at 3 and 6 weeks in experimental group, sharpey fiber growth more density, calcification extent of mesenchyme was high, and new bone, vessels were increased. CONCLUSIONS: OTF could promote osteogenic differentiation of tendon stem cells through mTOR signaling in vitro, and stimulate tendon-bone healing in bone tunnel and enhance connection quality between tendon and bone.
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Trasplante Óseo , Flavonas/farmacología , Osteogénesis , Células Madre/citología , Serina-Treonina Quinasas TOR/metabolismo , Cicatrización de Heridas , Animales , Fenómenos Biomecánicos , Diferenciación Celular , Células Cultivadas , Masculino , Ratas , Tendones/citología , Tendones/trasplanteRESUMEN
Impingement, tibial erosions, and "painful hardware" caused by a lag screw used for malleolar fracture stabilization are rare occurrences. We report a case of a symptomatic lag screw, used to fix a distal fibular fracture, that impinged on the distal tibial and causing symptoms. Awareness of the condition and early diagnosis based on thoughtful review of CT images are key to symptom alleviation. A review of the published data on the complication of "painful hardware" following ankle fracture fixation is also presented.