-
Cellular and Molecular Life Sciences :... Jun 2024Cetuximab resistance has been a major challenge for head and neck squamous cell carcinoma (HNSCC) patients receiving targeted therapy. However, the mechanism that causes...
Cetuximab resistance has been a major challenge for head and neck squamous cell carcinoma (HNSCC) patients receiving targeted therapy. However, the mechanism that causes cetuximab resistance, especially microRNA (miRNA) regulation, remains unclear. Growing evidence suggests that miRNAs may act as "nuclear activating miRNAs" for targeting promoter regions or enhancers related to target genes. This study elucidates a novel mechanism underlying cetuximab resistance in HNSCC involving the nuclear activation of KDM7A transcription via miR-451a. Herein, small RNA sequencing, quantitative real-time polymerase chain reaction (qRT‒PCR) and fluorescence in situ hybridization (FISH) results provided compelling evidence of miR-451a nuclear enrichment in response to cetuximab treatment. Chromatin isolation via RNA purification, microarray analysis, and bioinformatic analysis revealed that miR-451a interacts with an enhancer region in KDM7A, activating its expression and further facilitating cetuximab resistance. It has also been demonstrated that the activation of KDM7A by nuclear miR-451a is induced by cetuximab treatment and is AGO2 dependent. Logistic regression analyses of 87 HNSCC samples indicated the significance of miR-451a and KDM7A in the development of cetuximab resistance. These discoveries support the potential of miR-451a and KDM7A as valuable biomarkers for cetuximab resistance and emphasize the function of nuclear-activating miRNAs.
Topics: Humans; MicroRNAs; Cetuximab; Drug Resistance, Neoplasm; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Jumonji Domain-Containing Histone Demethylases; Argonaute Proteins; Animals; Mice; Cell Nucleus; Female; Mice, Nude
PubMed: 38943031
DOI: 10.1007/s00018-024-05324-x -
Aesthetic Plastic Surgery Jun 2024Sunken eyes have become a most important target of periorbital area aesthetics. Throughout history, the aesthetics of the periorbital region have been emphasized, and...
BACKGROUND
Sunken eyes have become a most important target of periorbital area aesthetics. Throughout history, the aesthetics of the periorbital region have been emphasized, and various surgical techniques related to this region have been described. Most of these techniques provide only soft tissue solutions; therefore, additional surgical interventions may be required. The aim of our study was to introduce an endoscopic supraorbital shaving (SOS) technique for the treatment of individuals with sunken eyes.
METHODS
Between 2020 and 2021, 34 patients (30 females, 4 males; mean age 36.2 years) with sunken eyes were treated with our described technique. All patients underwent an endoscopic SOS procedure under general anesthesia.
RESULTS
A total of 34 patients (30 women and four men), aged 23-59 years old (mean = 36.2 years), underwent the endoscopic SOS procedure. The mean follow-up period was 13 months (range: 12-16 months). Postoperatively, significant improvement in lateral convexity was achieved in all patients. Physical examinations performed at the control visits revealed no functional problems in any patients and no visible or palpable irregularities or contour deformities. No complications were encountered regarding the SOS procedure.
CONCLUSIONS
The technique described here provides significant improvement in lateral convexity compared to other techniques used in patients with sunken eyes. No additional eyelid intervention is needed. Unlike the techniques previously described in the literature, intervention is made in the bone structure, thereby providing more accurate results.
LEVEL OF EVIDENCE V
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
PubMed: 38942952
DOI: 10.1007/s00266-024-04194-9 -
Scientific Reports Jun 2024Telocytes are closely associated with the regulation of tissue smooth muscle dynamics in digestive system disorders. They are widely distributed in the biliary system...
Telocytes are closely associated with the regulation of tissue smooth muscle dynamics in digestive system disorders. They are widely distributed in the biliary system and exert their influence on biliary motility through mechanisms such as the regulation of CCK and their electrophysiological effects on smooth muscle cells. To investigate the relationship between telocytes and benign biliary diseases,such as gallbladder stone disease and biliary dilation syndrome, we conducted histopathological analysis on tissues affected by these conditions. Additionally, we performed immunohistochemistry and immunofluorescence double staining experiments for telocytes. The results indicate that the quantity of telocytes in the gallbladder and bile duct is significantly lower in pathological conditions compared to the control group. This reveals a close association between the decrease in telocyte quantity and impaired gallbladder motility and biliary fibrosis. Furthermore, further investigations have shown a correlation between telocytes in cholesterol gallstones and cholecystokinin-A receptor (CCK-AR), suggesting that elevated cholesterol levels may impair telocytes, leading to a reduction in the quantity of CCK-AR and ultimately resulting in impaired gallbladder motility.Therefore, we hypothesize that telocytes may play a crucial role in maintaining biliary homeostasis, and their deficiency may be associated with the development of benign biliary diseases, including gallstone disease and biliary dilation.
Topics: Telocytes; Cholelithiasis; Humans; Gallbladder; Female; Male; Bile Ducts; Middle Aged; Aged; Dilatation, Pathologic
PubMed: 38942924
DOI: 10.1038/s41598-024-65776-w -
Journal of Hand Therapy : Official... Jun 2024Therapy use is common following carpal tunnel release (CTR), trigger finger release, ganglion cyst excision, De Quervain tenosynovitis release, carpometacarpal...
BACKGROUND
Therapy use is common following carpal tunnel release (CTR), trigger finger release, ganglion cyst excision, De Quervain tenosynovitis release, carpometacarpal arthroplasty, and distal radius fracture, open reduction internal fixation or percutaneous pinning (DRF). Policy that improves coverage influences the cost and use of health care services.
PURPOSE
This study aims to evaluate changes to the cost and use of postoperative hand therapy by race and procedure following the repeal of a longstanding annual Medicare outpatient therapy cap.
STUDY DESIGN
Retrospective cohort study.
METHODS
This is a longitudinal retrospective cohort study using a quasi-experimental interrupted time series design, including patients who underwent common hand surgeries from January 1, 2016-December 31, 2019.
RESULTS
This study included 203,672 patients with a mean age of 71.4 years. Neither White (1.00, 95% confidence interval [CI]: 0.999-1.007, p = 0.45) nor non-White (1.00, 95% CI: 1.00-1.01, p = 0.06) patients experienced monthly changes in therapy use before policy implementation. Therapy frequency increased following CTR (odds ratio [OR] 1.12, 95% CI: 1.11-1.14, p < 0.001), trigger finger release (OR 1.09, 95% CI: 1.07-1.10, p < 0.001), and DRF (OR 1.05, 95% CI: 1.03-1.06, p < 0.001) following implementation.
CONCLUSIONS
This study found that improved coverage was associated with increased postoperative therapy use among some subsets, including CTR and DRF, suggesting the need to optimize coverage by means such as prior authorization or bundled payments, rather than only increasing coverage benefits.
PubMed: 38942653
DOI: 10.1016/j.jht.2024.05.002 -
Asian Journal of Surgery Jun 2024
PubMed: 38942633
DOI: 10.1016/j.asjsur.2024.06.032 -
Cellular Signalling Jun 2024Keloid formation, characterized by aberrant fibroproliferation and immune dysregulation, remains a challenging clinical concern. This study aims to elucidate the...
Keloid formation, characterized by aberrant fibroproliferation and immune dysregulation, remains a challenging clinical concern. This study aims to elucidate the neuroimmune mechanisms underlying keloid pathogenesis and explores the efficacy of a combined treatment approach involving modulation of the α7 nicotinic acetylcholine receptor (α7nAchR), a key player in neural transmission, and programmed death ligand 1 (PD-L1), an immune checkpoint molecule, for keloid intervention. A key innovation lies in the identification of signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) as a potential target gene influenced by this dual treatment. We elucidate the underlying mechanism, wherein the hypoxic keloid microenvironment fosters an upsurge in SCUBE3 secretion. Subsequently, SCUBE3 forms complexes with TGF-β, initiating the activation of the PI3K/AKT/NF-κB signaling pathway. Notably, SCUBE3 is secreted in the form of exosomes, thereby exerting a profound influence on the differentiation of T cells and macrophages within the keloid milieu. This research not only provides a comprehensive understanding of the molecular mechanisms involved but also offers a promising avenue for the development of targeted therapies to address keloid-associated fibrosis and immune dysregulation. In conclusion, the combined inhibition of α7nAchR and PD-L1 represents a promising therapeutic strategy with SCUBE3 as a pivotal molecular target in the complex landscape of keloid pathophysiology.
PubMed: 38942343
DOI: 10.1016/j.cellsig.2024.111275 -
Medical Image Analysis Jun 2024The conventional pretraining-and-finetuning paradigm, while effective for common diseases with ample data, faces challenges in diagnosing data-scarce occupational...
The conventional pretraining-and-finetuning paradigm, while effective for common diseases with ample data, faces challenges in diagnosing data-scarce occupational diseases like pneumoconiosis. Recently, large language models (LLMs) have exhibits unprecedented ability when conducting multiple tasks in dialogue, bringing opportunities to diagnosis. A common strategy might involve using adapter layers for vision-language alignment and diagnosis in a dialogic manner. Yet, this approach often requires optimization of extensive learnable parameters in the text branch and the dialogue head, potentially diminishing the LLMs' efficacy, especially with limited training data. In our work, we innovate by eliminating the text branch and substituting the dialogue head with a classification head. This approach presents a more effective method for harnessing LLMs in diagnosis with fewer learnable parameters. Furthermore, to balance the retention of detailed image information with progression towards accurate diagnosis, we introduce the contextual multi-token engine. This engine is specialized in adaptively generating diagnostic tokens. Additionally, we propose the information emitter module, which unidirectionally emits information from image tokens to diagnosis tokens. Comprehensive experiments validate the superiority of our methods.
PubMed: 38941859
DOI: 10.1016/j.media.2024.103248 -
Journal of Plastic, Reconstructive &... Jun 2024Spinal anesthesia (SA) is commonly used within the specialties of orthopedic surgery, obstetrics and gynecology, spine surgery, and general surgery, and offers several... (Review)
Review
INTRODUCTION
Spinal anesthesia (SA) is commonly used within the specialties of orthopedic surgery, obstetrics and gynecology, spine surgery, and general surgery, and offers several benefits over general anesthesia (GA). However, SA is used much less frequently in plastic surgery. This review analyzed currently existing data on SA use across various surgical specialties and compared the benefits and complications of SA to those of GA, to assess its utility and potential for more widespread use in plastic surgery.
METHODS
A comprehensive literature review was conducted using the PubMed and Cochrane Library databases to evaluate the utility of SA in plastic surgery. Indications, contraindications, and data on the use of SA across various surgical specialties were reviewed. Benefits, complications, and cost-effectiveness were also assessed. Finally, the utility of SA in plastic surgery was evaluated based on the available literature.
RESULTS
SA has been shown to yield several benefits and fewer risks than GA, including a higher possibility of early discharge, decreased costs, better pain and postoperative nausea and vomiting control, and decreased risk of deep venous thrombosis and pulmonary embolism.
CONCLUSION
Although commonly used for procedures across various surgical specialties such as obstetrics and gynecology, urology, and orthopedic surgery, SA is less frequently used within plastic surgery. Plastic surgery procedures that would benefit from the use of SA include those below the umbilicus such as liposuction, lower extremity procedures, and perineal procedures, and owing to its benefits, we recommend that SA be used more often within plastic surgery under appropriate clinical circumstances.
PubMed: 38941780
DOI: 10.1016/j.bjps.2024.05.059 -
Journal of Plastic, Reconstructive &... Jun 2024Grafts play key roles in functional and aesthetic rhinoplasty. Autologous grafts are generally preferred for their biocompatibility and less visibility when used in a... (Review)
Review
INTRODUCTION
Grafts play key roles in functional and aesthetic rhinoplasty. Autologous grafts are generally preferred for their biocompatibility and less visibility when used in a fragmented fashion. The aim of this study was to review mechanically fragmented cartilage grafts techniques described in the literature, outlining indications, outcomes, and complications.
MATERIAL AND METHODS
A systematic review of articles published from 1999 until December 2022 was conducted, using the following key words: "rhinoplasty," "cartilage," and "graft." Studies were selected according to the inclusion and exclusion criteria, and data were extracted and grouped for subgroup analysis. Rates of partial resorption, total resorption, surgical revision, and major and minor complications were statistically analyzed.
RESULTS
Thirty eligible studies were included. Three cartilage fragmentation methods were identified: diced, shaved, and crushed. Cartilage grafts were further divided into injectable and noninjectable grafts. Diced cartilage was the most commonly used. Dorsal irregularities were the main indication. Overall, 1.68% of patients experienced partial resorption, 0.27% experienced total resorption, and 1.46% needed revision. The partial resorption rate in the diced group was significantly lower than that in the shaved group. Injectable grafts showed a higher rate of partial resorption. The revision rate was higher with noninjectable grafts.
CONCLUSION
The partial resorption rate was lower in patients treated with diced cartilage. Injectable grafts are malleable and suitable for the correction of minimal irregularities, although they are affected by a higher rate of partial resorption. Wrapping materials may be used when significant augmentation is required.
PubMed: 38941779
DOI: 10.1016/j.bjps.2024.05.036 -
ACS Nano Jun 2024Three-dimensional (3D) bioprinting has advantages for constructing artificial skin tissues in replicating the structures and functions of native skin. Although many...
Three-dimensional (3D) bioprinting has advantages for constructing artificial skin tissues in replicating the structures and functions of native skin. Although many studies have presented improved effect of printing skin substitutes in wound healing, using hydrogel inks to fabricate 3D bioprinting architectures with complicated structures, mimicking mechanical properties, and appropriate cellular environments is still challenging. Inspired by collagen nanofibers withstanding stress and regulating cell behavior, a patterned nanofibrous film was introduced to the printed hydrogel scaffold to fabricate a composite artificial skin substitute (CASS). The artificial dermis was printed using gelatin-hyaluronan hybrid hydrogels containing human dermal fibroblasts with gradient porosity and integrated with patterned nanofibrous films simultaneously, while the artificial epidermis was formed by seeding human keratinocytes upon the dermis. The collagen-mimicking nanofibrous film effectively improved the tensile strength and fracture resistance of the CASS, making it sewable for firm implantation into skin defects. Meanwhile, the patterned nanofibrous film also provided the biological cues to guide cell behavior. Consequently, CASS could effectively accelerate the regeneration of large-area skin defects in mouse and pig models by promoting re-epithelialization and collagen deposition. This research developed an effective strategy to prepare composite bioprinting architectures for enhancing mechanical property and regulating cell behavior, and CASS could be a promising skin substitute for treating large-area skin defects.
PubMed: 38941540
DOI: 10.1021/acsnano.4c04088