Machine Learning-assisted Rational Design of Si-rhodamine as Cathepsin-pH Activated Probe for Accurate Fluorescence Navigation.

High-performance fluorescent probes stand as indispensable tools in fluorescence-guided imaging, and are crucial for precise delineation of focal tissue while minimizing unnecessary removal of healthy tissue. Herein, we firstly proposed machine learning-assisted strategy to investigate the current available xanthene dyes, and constructed a quantitative prediction model to guide the rational synthesis of novel fluorescent molecules with desired pH responsivity. We successfully achieved two novel Si-rhodamine derivatives and constructed the Cathepsin/pH sequentially activated probe SiR-CTS-pH. The results reveal that SiR-CTS-pH exhibits higher signal-to-noise ratio of fluorescence imaging, compared to single pH or cathepsin-activate probe. Moreover, SiR-CTS-pH shows strong differentiation abilities for tumor cells and tissues and accurately discriminates the complex hepatocellular carcinoma tissues from normal ones, indicating its significant application potential in clinical practice. Therefore, the continuous development of xanthene dyes and the rational design of superior fluorescent molecules through Machine Learning-assisted model will broaden the path and provide more advanced methods to researchers. This article is protected by copyright. All rights reserved.

Computational evaluation of wire position using separate vertical wire technique and candy box technique for the fixation of inferior pole patellar fractures: a finite element analysis.

The separate vertical wire (SVW) technique and the improved candy box (CB) technique have been proposed for treating inferior pole patellar fractures. However, there is still a lack of clear explanation regarding the location of the wire passing through the patella. Five models of SVW techniques were established in different positions. Finite element analysis was then conducted to determine the optimal bone tunnel position for the SVW technique. Based on these findings, six groups of finite element models were created for CB techniques. The maximum displacement and stress on both the patella and steel wire were compared among these groups under 100-N, 200-N, 300-N, 400-N, and 500-N force loads. The results indicated that, in the SVW technique, the steel wire group near the fracture end of the longitudinal bone tunnel showed minimal displacement and stress on the patella when subjected to different forces. On the other hand, in the CB technique, both the patella and wire experienced minimal stress when a transverse bone tunnel wire was placed near the upper posterior aspect of patella. In conclusion, the SVW technique may require the bone tunnel wire to be positioned near the fractured end of the lower pole of the patella. On the other hand, in CB technique, the transverse bone tunnel wire passing through the patella may be close to its upper posterior aspect. However, further validation is necessary through comprehensive finite element analysis and additional biomechanical experiments.

A novel capitate bone Ilizarov external fixator for treating Kienböck's disease: an anatomical and biomechanical study.

This study aims to measure anatomical data of the capitate bone, develop an external fixator for treating late-stage osteonecrosis of lunate through Ilizarov technique, and evaluate its biomechanical performance. We selected eight wrist joint specimens to measure various parameters of the capitate bone, including its length, the distance from the junction of capitate head and body to the proximal end, as well as the width of its proximal head and distal body. Additionally, we measured these same indicators in 107 patients who had undergone wrist X-ray examination. Based on our measurements, we categorized the capitate bone into two groups and designed two types of capitate bone Ilizarov external fixator (CIEF) for it. Then, we compared it with the orthofix external fixator (OEF) through dynamic fatigue biomechanical experiments and pull-out resistance experiments. The results of the measurement revealed two categories of general patterns in the capitate bone. The first type maintains a consistent longitudinal axis between the proximal and distal ends. The second type is characterized by its proximal end being close to the radial side and its distal end being close to the ulnar side. In the dynamic tensile fatigue test, CIEF-A and CIEF-B had smaller maximum displacement values compared to the OEF (P < 0.05). In the anti-pull-out experiment, both CIEF-A and CIEF-B exhibited higher maximum pull-out force than the OEF (P < 0.05). CIFE is a treatment for advanced osteonecrosis of the lunate bone. It is specifically designed to align with the anatomical characteristics of the capitate bone, providing excellent biomechanical properties and a simple clinical procedure. However, additional clinical experiments are needed to confirm its effectiveness in the future.

Tension band high-strength suture combined with absorbable cannulated screws for treating transverse patellar fractures: finite element analysis and clinical study.

Objective: Few reports exist on the treatment of transverse patellar fractures (TPFs) using absorbable cannulated screws and high-strength sutures, and most screws and sutures lack good biomechanics and clinical trials. Therefore, this study aimed to demonstrate the biomechanical stability and clinical efficacy of tension-band high-strength sutures combined with absorbable cannulated screws (TBSAS) in treating TPFs (AO/OTA 34 C1). Methods: Finite element models of five internal fixation schemes were established: tension-band wire with K-wire (TBW), TBW with cerclage wire (TBWC), TBW with headless pressure screws (TBWHS), TBW with full-thread screws (TBWFS), and TBSAS. We comprehensively compared the biomechanical characteristics of the TBSAS treatment scheme during knee flexion and extension. Forty-one patients with TPFs in our hospital between January 2020 and August 2022 were retrospectively enrolled and divided into the TBSAS (n = 22) and TBWC (n = 19) groups. Clinical and follow-up outcomes, including operative time, visual analog scale (VAS) pain score, postoperative complications, Bostman score, and final knee range of motion, were compared between both groups. Results: Finite element analysis (FEA) showed that TBWHS and TBWFS achieved the minimum mean fracture interface relative displacement during knee flexion (45°, 0-500 N bending load) and full extension (0°, 0-500 N axial load). There was no significant difference between TBSAS (0.136 mm) and TBWC (0.146 mm) during knee flexion (500 N); however, TBSAS displacement was smaller (0.075 mm) during full extension (500 N). Furthermore, the stress results for the internal fixation and the patella were generally lower when using TBSAS. Retrospective clinical studies showed that the TBSAS group had a shorter operative time, lower VAS pain score at 1 and 2 months postoperatively, better Bostman knee function score at 3 and 9 months postoperatively, and better final knee joint motion than the TBWC group (all p < 0.05). There were five cases (26.3%) of internal fixation stimulation complications in the TBWC group. Conclusion: TBSAS demonstrated excellent safety and effectiveness in treating TPFs. It is sufficient to meet the needs of TPF fixation and early functional exercise and effectively reduces metal internal fixation-induced complications and secondary surgery-induced trauma.

68 Ga-DOTA-IBA Uptake in Breast cancer.

ABSTRACT: A 77-year-old woman with recently diagnosed breast cancer underwent 68 Ga-labeled DOTA-ibandronic acid ( 68 Ga-DOTA-IBA) PET/CT scan for the evaluation of bone metastases. The examination revealed increased tracer uptake, indicating that the cervical vertebrae presented osteoblastic metastasis. Interestingly, the breast cancer also showed enhanced activity of 68 Ga-DOTA-IBA.

Tumor-derived microparticles promoted M2-like macrophages polarization to stimulate osteosarcoma progression.

Microparticles (MPs) are a heterogeneous subpopulation of extracellular vesicles that originate from the plasma membranes of cells. There is increasing evidence that tumor-derived MPs (T-MPs) play a significant role in tumor progression and immune response in cancer. In our study, we found an increased secretion of MPs in osteosarcoma tissues obtained from metastatic patients. These T-MPs promoted polarization of M2-like macrophages and stimulated the migration and chemoresistance of osteosarcoma cells. Mechanistically, T-MPs promoted macrophage polarization to an M2-like phenotype through TBK1-STAT6 signaling. Consequently, these M2-like macrophages mediated osteosarcoma cell migration via CCL18/STAT3 signaling. Blockade of STAT3 signaling pathway improved the outcome of chemotherapy in LM8-bearing osteosarcoma mice model. Thus, our study reveals how tumor cells regulate macrophage polarization by releasing MPs and provides new insights into clinical osteosarcoma therapy.

Molecular Engineering of Sulfone-Xanthone Chromophore for Enhanced Fluorescence Navigation.

Enriching the palette of high-performance fluorescent dyes is vital to support the frontier of biomedical imaging. Although various rhodamine skeletons remain the premier type of small-molecule fluorophores due to the apparent high brightness and flexible modifiability, they still suffer from the inherent defect of small Stokes shift due to the nonideal fluorescence imaging signal-to-background ratio. Especially, the rising class of fluorescent dyes, sulfone-substituted xanthone, exhibits great potential, but low chemical stability is also pointed out as the problem. Molecular engineering of sulfone-xanthone to obtain a large Stokes shift and high stability is highly desired, but it is still scarce. Herein, we present the combination modification method for optimizing the performance of sulfone-xanthone. These redesigned fluorescent skeletons owned greatly improved stability and Stokes shift compared with the parent sulfone-rhodamine. To the proof of bioimaging capacity, annexin protein-targeted peptide LS301 was introduced to the most promising dyes, J-S-ARh, to form the tumor-targeted fluorescent probe, J-S-LS301. The resulting probe, J-S-LS301, can be an outstanding fluorescence tool for the orthotopic transplantation tumor model of hepatocellular carcinoma imaging and on-site pathological analysis. In summary, the combination method could serve as a basis for rational optimization of sulfone-xanthone. Overall, the chemistry reported here broadens the scope of accessible sulfone-xanthone functionality and, in turn, enables to facilitate the translation of biomedical research toward the clinical domain.

Candy box technique for the fixation of inferior pole patellar fractures: finite element analysis and biomechanical experiments.

BACKGROUND: Maintaining effective reduction and firm fixation in inferior pole patellar fractures is a highly challenging task. There are various treatment methods available; although tension-band wiring combined with cerclage wiring (TBWC) is the mainstream approach, its effectiveness is limited. Herein, we propose and evaluate a new technique called candy box (CB), based on separate vertical wiring (SVW), for the treatment of inferior pole patellar fractures. Specifically, we provide biomechanical evidence for its clinical application. METHODS: Five fixation models were built: SVW combined with cerclage wiring (SVWC); TBWC; modified SVW with the middle (MSVW-A) or upper (MSVW-B) 1/3 of the steel wire reserved, and CB. A finite element analysis was performed to compare the displacement and stress under 100-N, 200-N, 300-N, 400-N and 500-N force loads. Three-dimensional printing technology was utilized to create fracture models, and the average displacement of each model group was compared under a 500-N force. RESULTS: The results of the finite element analysis indicate that CB technology exhibits significantly lower maximum displacement, bone stress, and wire stress compared to that with other technologies under different loads. Additionally, in biomechanical experiments, the average force displacement in the CB group was significantly smaller than that with other methods under a 500-N force (P < 0.05). CONCLUSIONS: CB technology has the potential to overcome the limitations of current techniques due to its superior biomechanical characteristics. By incorporating early functional exercise and ensuring strong internal fixation, patient prognosis could be enhanced. However, further clinical trials are needed to fully evaluate the therapeutic effects of CB technology.

Long-term outcome of flexor hallucis longus tendon transfer for chronic Achilles tendon rupture with large defect: A retrospective series.

There are multiple surgical options for treatment of chronic Achilles tendon (AT) rupture according to the classifications and length of defect. However, no gold standard method has been confirmed, and there is no clear evidence to support the superiority of 1 procedure over others. This study aimed to evaluate the long-term clinical outcome of flexor hallucis longus tendon (FHL) transfer for chronic AT rupture with large defect. Clinical data of patients treated with FHL transfer due to chronic AT rupture between January 2009 and October 2019 were reviewed retrospectively. All cases were presented with AT rupture for more than 4 weeks after injury. The gap between ruptured ends was > 5 cm after debridement in all patients. The harvest of FHL was performed through a single incision in accordance with AT rupture debridement in all cases. Clinical outcomes were assessed with AOFAS ankle-hindfoot scale, Achilles tendon total rupture score and AOFAS hallux metatarsophalangeal-interphalangeal scale. Twenty-eight patients were followed successfully for 62.6 ±â€…22.2 months. According to the complete datasets obtained from 28 patients, none of the tendons re-ruptured. The AOFAS ankle-hindfoot scale and Achilles tendon total rupture score at last follow-up visit was 90.4 ±â€…5.7 and 89.8 ±â€…5.3 respectively, which revealed statistically significant improvement from the preoperative score of 61.1 ±â€…6.7 and 53.8 ±â€…8.3. The AOFAS hallux metatarsophalangeal-interphalangeal scale at last follow-up visit was 87.5 ±â€…6.1. The FHL transfer through a single incision for chronic AT rupture with large defect is a safe and simple method with low risk of morbidity and complications.

Rational Design of pH-Independent and High-Fidelity Near-Infrared Tunable Fluorescent Probes for Tracking Leucine Aminopeptidase In Vivo.

Accurate detection of target analytes and generation of high-fidelity fluorescence signals are particularly critical in life sciences and clinical diagnostics. However, the majority of current NIR-I fluorescent probes are vulnerable to pH effects resulting in signal distortion. In this work, a series of fluorescence-tunable and pH-independent probes are reported by combining optically tunable groups of unsymmetric Si-rhodamines and introducing the methoxy instead of the spiro ring on the benzene ring at position 9. To validate the concept, the leucine aminopeptidase response site was introduced into Si-2,6OMe-NH2 with the best optical properties to synthesize Si-LAP for monitoring the intrahepatic LAP in vivo. Therefore, the design approach may provide a new and practical strategy for designing innovative functional fluorescent probes and generating high-stability and high-fidelity fluorescent signals.

Unexpected Solitary Subcutaneous Metastasis From Esophageal Carcinoma Revealed by MDP Bone Scintigraphy.

ABSTRACT: A 60-year-old man with back pain underwent 99m Tc-MDP to evaluate bone metastases from newly esophageal carcinoma. No bone metastasis was found on the whole-body bone scan. Unexpectedly, subcutaneous metastasis revealed increased 99m Tc-MDP activity.

Early Detection of Gastric Intramucosal Adenocarcinoma on 68 Ga-FAPI PET/CT.

ABSTRACT: 18 F-FDG PET/CT may sometimes not be an ideal imaging method for gastric adenocarcinoma. Because of the unstable physiological uptake of 18 F-FDG in the gastrointestinal tract and muscles, it may interfere with the detection of lesions. We present a case of gastric intramucosal adenocarcinoma detected by 68 Ga-FAPI PET/CT in a patient with nasopharyngeal carcinoma.

Denosumab for giant cell tumors of bone from 2010 to 2022: a bibliometric analysis.

Giant cell tumors of the bone (GCTB) are considered moderately malignant bone tumors. Denosumab, as a neoadjuvant therapy, provides new possibilities for treating GCTB. However, even after multiple studies and long-term clinical trials, there are limitations in the treatment process. Research data and Medical Subject Headings terms related to denosumab and GCTB were collected from January 2010 to October 2022 using the Web of Science and MeSH ( https://meshb.nlm.nih.gov ) browsers. These data were imported into CiteSpace and VOSviewer softwares for bibliometric analysis. Overall, 445 publications on denosumab and GCTB were identified. Over the last 12 years, the growth rate of the total number of publications has remained relatively stable. The USA published the highest number of articles (83) and had the highest centrality (0.42). Amgen Inc. and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) First Ortoped Rizzoli were identified as the most influential institutions. Many authors have made outstanding contributions to this field. Lancet Oncology had the highest journal impact factor (54.433). Local recurrence and drug dosage are current research hotspots, and future development trends will mainly focus on prognostic markers of GCTB and the development of new therapies. Further research is required to analyze denosumab's safety and efficacy and understand its local recurrence of GCTB, to identify the optimal dose. Future progress in this field will likely focus on exploring new diagnostic and recurrence markers to monitor disease progression and examine new therapeutic targets and treatment strategies.

Migration from Lysosome to Nucleus: Monitoring Lysosomal Alkalization-Related Biological Processes with an Aminofluorene-Based Probe.

Aberrant lysosomal alkalization is associated with various biological processes, such as oxidative stress, cell apoptosis, ferroptosis, etc. Herein, we developed a novel aminofluorene-based fluorescence probe named FAN to monitor the lysosomal alkalization-related biological processes by its migration from lysosome to nucleus. FAN possessed NIR emission, large Stokes shift, high pH stability, and high photostability, making it suitable for real-time and long-term bioimaging. As a lysosomotropic molecule, FAN can accumulate in lysosomes first and then migrate to the nucleus by right of its binding capability to DNA after lysosomal alkalization. In this manner, FAN was successfully used to monitor these physiological processes which triggered lysosomal alkalization in living cells, including oxidative stress, cell apoptosis, and ferroptosis. More importantly, at higher concentrations, FAN could also serve as a stable nucleus dye for the fluorescence imaging of the nucleus in living cells and tissues. This novel multifunctional fluorescence probe shows great promise for application in lysosomal alkalization-related visual research and nucleus imaging.

Finite element analysis of a novel anatomical locking plate for scapular neck fracture.

OBJECTIVES: Reconstruction plates (RPs) are commonly used in scapular neck fractures (SNFs): however, RPs have many defects. In this study, we evaluated a newly designed scapular neck anatomical locking compression plate (SNALCP). METHODS: An SNF finite element model (Miller-type IIB) was constructed. Plates were subsequently implanted into the scapula and fixed with screws that were grouped according to the plate used: SNALCP (A) and RP (B). Finally, loads were applied to record and analyze performance. RESULTS: Under lateral, anteroposterior, and vertical compression loads, the maximum von Mises stresses on the scapula and implants of group A were smaller than those of group B. There were some differences in stress distribution between the two groups. CONCLUSIONS: SNALCP can effectively reduce the stress of the scapula and implant, making stress distribution more uniform and continuous, and has mechanical conduction advantages. Compared to RP, it provides improved stability and more reliable fixation.

A retrospective analysis of minimally invasive internal fixation versus nonoperative conservative management of pelvic ring fragility fractures and the elderly.

OBJECTIVE: We aimed to investigate the adoption of treatment patterns for hip fractures combined with minimally invasive surgical treatment of fragility fractures of the pelvis in older individuals and reviewed and analysed the treatment efficacy and feasibility. METHODS AND DATA: From September 2017 to February 2021, 135 older individuals with fragility fractures of the pelvis were admitted to our hospital. We retrospectively analysed patients who received surgical or conservative treatments. The general preoperative data, including sex, age, disease duration, cause of injury, AO/OTA type, BMI, bone mineral density, time from injury to admission, time from injury to surgery, ASA classification, number of underlying diseases, mean bed rest, clinical fracture healing, VAS score and Majeed functional score, were recorded. RESULTS: The mean follow-up time for all 135 patients was 10.5 ± 3.6 months. Among 135 patients, 95 survived, and 11 and 29 patients passed after the surgical (mortality rate = 17.74%) and conservative (mortality rate = 39.73%) treatments, respectively. The average follow-up time for the 95 surviving patients was 14.5 ± 1.8 months. The Majeed and VAS scores for the operation group were significantly better than those of the conservative group. The bed rest and fracture healing times were also shorter in the surgical treatment group than in the conservative group. CONCLUSION: The use of a minimally invasive surgical treatment combined with the geriatric hip fracture treatment model to treat fragility fractures of the pelvis improved the quality of life in older patients.

γ-Glutamyltranspeptidase and pH based "AND" logic gate fluorescent probe for orthotopic breast tumor imaging.

An "AND" logic gate-based NIR fluorescent probe Si-NH2-Glu was developed based on novel meso-amine Si-Rhodamine, which combined γ-glutamyl transpeptidase and pH dual-responsive sites. The features of Si-NH2-Glu enable it to be applied in orthotopic tumor imaging and fluorescence-guided surgery.