Proteomic profiling of extracellular vesicles derived from human serum for the discovery of biomarkers in Avascular necrosis.

BACKGROUND: Avascular necrosis (AVN) is a medical condition characterized by the destruction of bone tissue due to a diminished blood supply. When the rate of tissue destruction surpasses the rate of regeneration, effective treatment becomes challenging, leading to escalating pain, arthritis, and bone fragility as the disease advances. A timely diagnosis is imperative to prevent and initiate proactive treatment for osteonecrosis. We explored the potential of differentially expressed proteins in serum-derived extracellular vesicles (EVs) as biomarkers for AVN of the femoral head in humans. We analyzed the genetic material contained in serum-derived exosomes from patients for early diagnosis, treatment, and prognosis of avascular necrosis. METHODS: EVs were isolated from the serum of both patients with AVN and a control group of healthy individuals. Proteomic analyses were conducted to compare the expression patterns of these proteins by proteomic analysis using LC-MS/MS. RESULTS: Our results show that the levels of IGHV3-23, FN1, VWF, FGB, PRG4, FCGBP, and ZSWIM9 were upregulated in the EVs of patients with AVN compared with those of healthy controls. ELISA results showed that VWF and PRG4 were significantly upregulated in the patients with AVN. CONCLUSIONS: These findings suggest that these EV proteins could serve as promising biomarkers for the early detection and diagnosis of AVN. Early diagnosis is paramount for effective treatment, and the identification of new osteonecrosis biomarkers is essential to facilitate swift diagnosis and proactive intervention. Our study provides novel insights into the identification of AVN-related biomarkers that can enhance clinical management and treatment outcomes.

Effect of modification methods on the physical properties and immunomodulatory activity of particulate ß-glucan.

ß-Glucan is an immunoenhancing agent whose biological activities are linked to molecular structure. On that basis, the polysaccharide can be physiochemically modified to produce valuable functional materials. This study investigated the physical properties and immunostimulatory activity of modified ß-glucan. Alkali-treated ß-glucan had a distinct shape and smaller particle size than untreated ß-glucan. The reduced particle size was conducive to the stability of the suspension because the ß-glucan appeared to be completely dissolved by this treatment, forming an amorphous mass. Furthermore, alkali treatment improved the immunostimulating activity of ß-glucan, whereas exposure of macrophages to heat-treated ß-glucan decreased their immune activity. ß-Glucan with reduced particle size by wet-grinding also displayed immunomodulatory activities. These results suggested that the particle size of ß-glucan is a key factor in ß-glucan-induced immune responses of macrophages. Thus, the modification of the ß-glucan particle size provides new opportunities for developing immunoenhancing nutraceuticals or pharmacological therapies in the future.

Safety and efficacy of dynamic catheter-directed cerebral digital subtraction angiography for diagnosis of bowhunter syndrome spectrum disorders: A systematic review of the literature.

INTRODUCTION: Dynamic catheter-directed cerebral digital subtraction angiography (dcDSA) is the gold standard for diagnosing dynamic vascular occlusion syndromes such as bowhunter syndrome (BHS). Nonetheless, concerns about its safety exist and no standardized protocols have been published to date. METHODS: We describe our methodology and insights regarding the use of dcDSA in patients with BHS. We also perform a systematic literature review to identify cases of typical and atypical presentations of BHS wherein dcDSA was utilized and report on any procedural complications related to dcDSA. RESULTS: Our study included 104 cases wherein dcDSA was used for the diagnosis of BHS. There were 0 reported complications of dcDSA. DcDSA successfully established diagnosis in 102 of these cases. Thirty-eight cases were deemed atypical presentations of BHS. Fourteen patients endorsed symptoms during neck flexion/extension. In eight cases, there was dynamic occlusion of bilateral vertebral arteries during a single maneuver. Three patients had multiple areas of occlusion along a single vertebral artery (VA). An anomalous entry of the VA above the C6 transverse foramen was observed in four patients. One patient had VA occlusion with neutral head position and recanalization upon contralateral lateral head tilt. CONCLUSION: Our study highlights the safety and diagnostic benefits of dcDSA in characterizing the broad spectrum of BHS pathology encountered in clinical practice. This technique offers a powerful means to evaluate changes in cerebral blood flow and cervical arterial morphology in real time, overcoming the constraints of static imaging methods. Our findings pave the way for further studies on dcDSA to enhance cross-sectional imaging methods for the characterization of BHS and other dynamic vascular occlusion syndromes.

Scalpellum occulta: A rare case of dorsal spinal arachnoid web without the scalpel sign.

Spinal arachnoid web is a rare condition characterized by extramedullary bands of arachnoid tissue at the level of the dorsal thoracic spinal cord that may lead to progressive, permanent neurological deficits. To date, this condition has been radiographically characterized by a scalpel sign, which has been pathognomonic in all reported cases of spinal arachnoid webs. In this case, we report the first known patient with confirmed spinal arachnoid web without radiographic evidence of the scalpel sign. In reporting our finding, we encourage a higher clinical suspicion for spinal arachnoid web in patients presenting with progressive thoracic myelopathy following trauma, and radiographic evidence of ventrally displaced spinal cord and turbulent cerebrospinal fluid flow, even in the absence of a scalpel sign.

Antioxidant and Antimelanogenic Activities of Lactobacillus kunkeei NCHBL-003 Isolated from Honeybees.

Excessive reactive oxygen species production can detrimentally impact skin cell physiology, resulting in cell growth arrest, melanogenesis, and aging. Recent clinical studies have found that lactic acid bacteria have a special effect directly or indirectly on skin organs, but the exact mechanism has not been elucidated. In this study, we investigated the mechanisms underlying the antioxidant protective effect and the inhibitory effect on melanin synthesis of Lactobacillus kunkeei culture supernatant (CSK), isolated from Apis mellifera Linnaeus (the Western honeybee). CSK exhibited notable efficacy in promoting cell migration and wound healing under oxidative stress, surpassing the performance of other strains. CSK pretreatment significantly upregulated the expression of Nrf2/HO-1 (nuclear factor erythroid 2-related factor 2/heme oxygenase-1), a key player in cellular defenses against oxidative stress, relative to the control H2O2-treated cells. The DCF-DA (dichloro-dihydro-fluorescein diacetate) assay results confirmed that CSK's ability to enhance Nrf2 and HO-1 expression aligns with its robust ability to remove H2O2-induced reactive oxygen species. Furthermore, CSK upregulated MAPK (mitogen-activated protein kinase) phosphorylation, an upstream signal for HO-1 expression, and MAPK inhibitors compromised the wound-healing effect of CSK. Additionally, CSK exhibited inhibitory effects on melanin synthesis, downregulating melanogenesis-related genes in B16F10 cells. Thus, the present study demonstrated that CSK exhibited antioxidant effects by activating the Nrf2/HO-1 pathway through MAPK phosphorylation, thereby restoring cell migration and demonstrating inhibitory effects on melanin production. These findings emphasize the antioxidant and antimelanogenic potential of CSK, suggesting its potential use as a therapeutic agent, promoting wound healing, and as an active ingredient in skin-lightening cosmetics.

A rare case of solitary, isolated dural metastasis from hepatocellular carcinoma mimicking a meningioma.

Background: Distinguishing an isolated metastatic dural tumor from a meningioma on imaging is challenging and may lead to a delay in treatment. Here, we present the first known case of isolated, solitary dural metastasis from hepatocellular carcinoma (HCC) mimicking a meningioma. Case Description: A 64-year-old male with a history of liver cirrhosis presented with a 5.8 cm enhancing left parafalcine hemorrhagic dural-based mass extending across the midline. Cerebral angiography revealed a distal left anterior pseudoaneurysm, and tumor contrast blush with feeders from the left ophthalmic and right middle meningeal artery. The pseudoaneurysm was successfully embolized to stop the bleeding, followed by an uneventful bi-coronal frontal craniotomy for falcine tumor resection to relieve brain compression. Histopathological analysis of the dural-based tumor showed poorly differentiated carcinoma with positive albumin in situ hybridization and cytokeratin tumor markers, consistent with dural metastases from HCC. Conclusion: When encountering a solitary, highly vascular mass bearing resemblance to a meningioma, it may be prudent to consider the possibility of a dural-based metastatic carcinoma.

Extracellular Vesicles from Human Adipose Tissue-Derived Mesenchymal Stem Cells Suppress RANKL-Induced Osteoclast Differentiation via miR122-5p.

Researchers are increasingly interested in cell therapy using mesenchymal stem cells (MSCs) as an alternative remedy for osteoporosis, with fewer side effects. Thus, we isolated and characterized extracellular vesicles (EVs) from human adipose tissue-derived MSCs (hMSCs) and investigated their inhibitory effects on RANKL-induced osteoclast differentiation. Purified EVs were collected from the supernatant of hMSCs by tangential flow filtration. Characterization of EVs included typical evaluation of the size and concentration of EVs by nanoparticle tracking analysis and morphology analysis using transmission electron microscopy. hMSC-EVs inhibited RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by EV treatment of osteoclasts. In addition, EVs decreased RANKL-induced phosphorylation of p38 and JNK and expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. To elucidate which part of the hMSC-EVs plays a role in the inhibition of osteoclast differentiation, we analyzed miRNA profiles in hMSC-EVs. The results showed that has-miR122-5p was present at significantly high read counts. Overexpression of miR122-5p in BMDMs significantly inhibited RANKL-induced osteoclast differentiation and induced defects in F-actin ring formation and bone resorption. Our results also revealed that RANKL-induced phosphorylation of p38 and JNK and osteoclast-specific gene expression was decreased by miR122-5p transfection, which was consistent with the results of hMSC-EVs. These findings suggest that hMSC-EVs containing miR122-5p inhibit RANKL-induced osteoclast differentiation via the downregulation of molecular mechanisms and could be a preventive candidate for destructive bone diseases.

Long-term adjuvant metronomic chemotherapy in a dog with recurrent maxillofacial osteosarcoma.

Osteosarcoma (OSA) is the most common malignant bone tumour in dogs; however, OSA of the maxilla is uncommon compared to appendicular OSA. Oral melanoma also commonly occurs in dogs with frequent distant metastasis. The role of adjuvant chemotherapy has been questioned in maxillary OSA and melanoma. A 17-year-old English Cocker Spaniel was referred with a growing mass on the right maxilla and a right lower lip mass. Osteosarcoma was diagnosed after partial maxillectomy, and the right lower lip mass was diagnosed as oral melanoma. Metronomic chemotherapy (MC) was performed, and the number of doses was tapered due to side effects at 5 weeks after initiation of MC. After 130 weeks of MC, chemotherapy was suspended due to kidney disease. After the suspension of chemotherapy, findings suggesting recurrence and metastasis were detected. The dog suddenly died 193 weeks after surgery, which was 8-14 times longer than the expected survival time. To the best of our knowledge, this is the first case report of successful long-term combination therapy, including surgery and MC, in a dog with maxillary OSA and lip melanoma. Our results show that the survival time can be greatly extended if MC is performed with proper management.

Evaluation of Silk Fibroin/Gellan Gum Hydrogels with Controlled Molecular Weight through Silk Fibroin Hydrolysis for Tissue Engineering Application.

Hydrogel is a versatile material that can be manipulated to achieve the desired physicochemical properties, such as stiffness, pore size, and viscoelasticity. Traditionally, these properties have been controlled through parameters such as concentration and pH adjustments. In this study, we focused on exploring the potential of hydrolyzed silk fibroin (HSF) as a molecular weight-modulating agent to control the physicochemical properties of double-composite hydrogels. We developed a synergistic dual-crosslinked hydrogel by combining ionically crosslinked silk fibroin with gellan gum (GG). The hydrolysis of silk fibroin not only enhanced its hydrophilicity but also enabled adjustments in its mechanical properties, including the pore size, initial modulus elasticity, and relaxation time. Moreover, biocompatibility assessments based on cell viability tests confirmed the potential of these hydrogels as biocompatible materials. By highlighting the significance of developing an HSF/GG dual-crosslinked hydrogel, this study contributes to the advancement of novel double-composite hydrogels with remarkable biocompatibility. Overall, our findings demonstrate the capability of controlling the mechanical properties of hydrogels through molecular weight modulation via hydrolysis and highlight the development of a biocompatible HSF/GG dual-crosslinked hydrogel with potential biomedical applications.

Deep Learning-Enabled Detection of Pneumoperitoneum in Supine and Erect Abdominal Radiography: Modeling Using Transfer Learning and Semi-Supervised Learning.

OBJECTIVE: Detection of pneumoperitoneum using abdominal radiography, particularly in the supine position, is often challenging. This study aimed to develop and externally validate a deep learning model for the detection of pneumoperitoneum using supine and erect abdominal radiography. MATERIALS AND METHODS: A model that can utilize "pneumoperitoneum" and "non-pneumoperitoneum" classes was developed through knowledge distillation. To train the proposed model with limited training data and weak labels, it was trained using a recently proposed semi-supervised learning method called distillation for self-supervised and self-train learning (DISTL), which leverages the Vision Transformer. The proposed model was first pre-trained with chest radiographs to utilize common knowledge between modalities, fine-tuned, and self-trained on labeled and unlabeled abdominal radiographs. The proposed model was trained using data from supine and erect abdominal radiographs. In total, 191212 chest radiographs (CheXpert data) were used for pre-training, and 5518 labeled and 16671 unlabeled abdominal radiographs were used for fine-tuning and self-supervised learning, respectively. The proposed model was internally validated on 389 abdominal radiographs and externally validated on 475 and 798 abdominal radiographs from the two institutions. We evaluated the performance in diagnosing pneumoperitoneum using the area under the receiver operating characteristic curve (AUC) and compared it with that of radiologists. RESULTS: In the internal validation, the proposed model had an AUC, sensitivity, and specificity of 0.881, 85.4%, and 73.3% and 0.968, 91.1, and 95.0 for supine and erect positions, respectively. In the external validation at the two institutions, the AUCs were 0.835 and 0.852 for the supine position and 0.909 and 0.944 for the erect position. In the reader study, the readers' performances improved with the assistance of the proposed model. CONCLUSION: The proposed model trained with the DISTL method can accurately detect pneumoperitoneum on abdominal radiography in both the supine and erect positions.

Toxicity and Biodistribution of Fragmented Polypropylene Microplastics in ICR Mice.

Currently, polypropylene (PP) is used in various products, thus leading to high daily exposure in humans. Thus, it is necessary to evaluate the toxicological effects, biodistribution, and accumulation of PP microplastics in the human body. In this study, administration of two particle sizes of PP microplastics (approximately 5 and 10-50 µm) did not lead to any significant changes in several toxicological evaluation parameters, including body weight and pathological examination, compared with the control group in ICR mice. Therefore, the approximate lethal dose and no-observed-adverse-effect level of PP microplastics in ICR mice were established as ≥2000 mg/kg. Furthermore, we manufactured cyanine 5.5 carboxylic acid (Cy5.5-COOH)-labeled fragmented PP microplastics to monitor real-time in vivo biodistribution. After oral administration of the Cy5.5-COOH-labeled microplastics to the mice, most of the PP microplastics were detected in the gastrointestinal tract and observed to be out of the body after 24 h in IVIS Spectrum CT. Therefore, this study provides a new insight into the short-term toxicity, distribution, and accumulation of PP microplastics in mammals.

Modified gellan gum-based hydrogel with enhanced mechanical properties for application as a cell carrier for cornea endothelial cells.

Recently, the number of people suffering from visual loss due to eye diseases is increasing rapidly around the world. However, due to the severe donor shortage and the immune response, corneal replacement is needed. Gellan gum (GG) is biocompatible and widely used for cell delivery or drug delivery, but its strength is not suitable for the corneal substitute. In this study, a GM hydrogel was prepared by blending methacrylated gellan gum with GG (GM) to give suitable mechanical properties to the corneal tissue. In addition, lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), a crosslinking initiator, was added to the GM hydrogel. After the photo-crosslinking treatment, it was named GM/LAP hydrogel. GM and GM/LAP hydrogels were analyzed for physicochemical properties, mechanical characterization, and transparency tests to confirm their applicability as carriers for corneal endothelial cells (CEnCs). Also, in vitro studies were performed with cell viability tests, cell proliferation tests, cell morphology, cell-matrix remodeling analysis, and gene expression evaluation. The compressive strength of the GM/LAP hydrogel was improved compared to the GM hydrogel. The GM/LAP hydrogel showed excellent cell viability, proliferation, and cornea-specific gene expression than the GM hydrogel. Crosslinking-improved GM/LAP hydrogel can be applied as a promising cell carrier in corneal tissue engineering.

Development of Gelatin-Based Shape-Memory Polymer Scaffolds with Fast Responsive Performance and Enhanced Mechanical Properties for Tissue Engineering Applications.

Shape-memory polymers (SMPs) can be defined as a reversibly changing form through deformation and recovery by external stimuli. However, there remain application limitations of SMPs, such as complicated preparation processes and slow shape recovery. Here, we designed gelatin-based shape-memory scaffolds by a facile dipping method in tannic acid solution. The shape-memory effect of scaffolds was attributed to the hydrogen bond between gelatin and tannic acid, which acts as the net point. Moreover, gelatin (Gel)/oxidized gellan gum (OGG)/calcium chloride (Ca) was intended to induce faster and more stable shape-memory behavior through the introduction of a Schiff base reaction. The chemical, morphological, physicochemical, and mechanical properties of the fabricated scaffolds were evaluated, and those results showed that the Gel/OGG/Ca had improved mechanical properties and structural stability compared with other scaffold groups. Additionally, Gel/OGG/Ca exhibited excellent shape-recovery behavior of 95.8% at 37 °C. As a consequence, the proposed scaffolds can be fixed to the temporary shape at 25 °C in just 1 s and recovered to the original shape at 37 °C within 30 s, implying a great potential for minimally invasive implantation.

A Huge Gastric Angiolipoma Presenting with Acute Upper Gastrointestinal Hemorrhage: A Case Report.

BACKGROUND: Angiolipoma is a benign neoplasm mainly composed of adipose tissue and proliferating blood vessels and is relatively rare in the gastrointestinal tract. And among them, gastric angiolipomas are extremely rare and tend to be small. CASE PRESENTATION: We report the clinical and imaging features of a patient with a huge angiolipoma in the stomach and an episode of hematemesis and melena, caused by the ulceration of the gastric mucosa overlying the gastric subepithelial angiolipoma revealed by the endoscopic evaluation. The patient was anemic, and the anemia resolved after local surgical resection of the tumor. We also reviewed the imaging and histological features of the presenting gastric angiolipoma. CONCLUSION: Radiologists should be aware of this rare benign gastric tumor that may present with gastrointestinal hemorrhage.

Foot-and-mouth disease virus non-structural protein 2B downregulates the RLR signaling pathway via degradation of RIG-I and MDA5.

Foot-and-mouth disease virus (FMDV) is a single-stranded, positive-sense RNA virus containing at least 13 proteins. Many of these proteins show immune modulation capabilities. As a non-structural protein of the FMDV, 2B is involved in the rearrangement of the host cell membranes and the disruption of the host secretory pathway as a viroporin. Previous studies have also shown that FMDV 2B plays a role in the modulation of host type-I interferon (IFN) responses through the inhibition of expression of RIG-I and MDA5, key cytosolic sensors of the type-I IFN signaling. However, the exact molecular mechanism is poorly understood. Here, we demonstrated that FMDV 2B modulates host IFN signal pathway by the degradation of RIG-I and MDA5. FMDV 2B targeted the RIG-I for ubiquitination and proteasomal degradation by recruiting E3 ubiquitin ligase ring finger protein 125 (RNF125) and also targeted MDA5 for apoptosis-induced caspase-3- and caspase-8-dependent degradation. Ultimately, FMDV 2B significantly inhibited RNA virus-induced IFN-ß production. Importantly, we identified that the C-terminal amino acids 126-154 of FMDV 2B are essential for 2B-mediated degradation of the RIG-I and MDA5. Collectively, these results provide a clearer understanding of the specific molecular mechanisms used by FMDV 2B to inhibit the IFN responses and a rational approach to virus attenuation for future vaccine development.

A Trade-Off Analysis between Sensor Quality and Data Intervals for Prognostics Performance.

In safety-critical systems such as industrial plants or aircraft, failure occurs inevitably during operation, and it is important to prevent it in order to maintain high availability. To reduce this risk, a lot of efforts are directed from developing sensing technologies to failure prognosis algorithms to enable predictive maintenance. The success of effective and reliable predictive maintenance not only relies on robust prognosis algorithms but also on the selection of sensors or data acquisition strategy. However, there are not many in-depth studies on a trade-off between sensor quality and data storage in the view of prognosis performance. The information about (1) how often data should be measured and (2) how good sensor quality should be for reliable failure prediction can be highly impactful for practitioners. In this paper, the authors evaluate the efficacy of the two factors in terms of remaining useful life (RUL) prediction accuracy and its uncertainty. In addition, since knowing true degradation information is almost impossible in practice, the authors validated the use of the prognosis metric without requiring the true degradation information. A numerical case study is conducted to identify the relationship between sensor quality and data storage. Then, real bearing run-to-failure (RTF) datasets acquired from accelerometer (contact type) and microphone (non-contact type) sensors are evaluated based on the prognosis performance metric and compared in terms of the sensors' cost-effectiveness for predictive maintenance.

Validation of deep learning-based fully automated coronary artery calcium scoring using non-ECG-gated chest CT in patients with cancer.

This study aimed to demonstrate clinical feasibility of deep learning (DL)-based fully automated coronary artery calcium (CAC) scoring software using non-electrocardiogram (ECG)-gated chest computed tomography (CT) from patients with cancer. Overall, 913 patients with colorectal or gastric cancer who underwent non-contrast-enhanced chest CT between 2013 and 2015 were included. Agatston scores obtained by manual segmentation of CAC on chest CT were used as reference. Reliability of automated CAC score acquisition was evaluated using intraclass correlation coefficients (ICCs). The agreement for cardiovascular disease (CVD) risk stratification was assessed with linearly weighted k statistics. ICCs between the manual and automated CAC scores were 0.992 (95% CI, 0.991 and 0.993, p<0.001) for total Agatston scores, 0.863 (95% CI, 0.844 and 0.880, p<0.001) for the left main, 0.964 (95% CI, 0.959 and 0.968, p<0.001) for the left anterior descending, 0.962 (95% CI, 0.956 and 0.966, p<0.001) for the left circumflex, and 0.980 (95% CI, 0.978 and 0.983, p<0.001) for the right coronary arteries. The agreement for cardiovascular risk was excellent (k=0.946, p<0.001). Current DL-based automated CAC software showed excellent reliability for Agatston score and CVD risk stratification using non-ECG gated CT scans and might allow the identification of high-risk cancer patients for CVD.

Fast stress relaxing gellan gum that enhances the microenvironment and secreting function of bone mesenchymal stem cells.

This study shows tunable stress relaxing gellan gum (GG) hydrogel for enhanced cell growth and regenerative medicine. The molecular weight and physical crosslinking density of GG were tuned and characterized with physicochemical analysis and mechanical tests. The result showed that a decrease in the molecular weight of the GG correlated with a decline in the mechanical properties but faster stress relaxing character. We also discovered that human-derived bone marrow stem cells (hBMSC) showed active viability, proliferation, and remodeling in the fast stress relaxing GG hydrogel. In particular, hBMSC showed an enhanced release profile of growth factors and exosomes (Exo) in the fast stress relaxing GG hydrogel. The secretome obtained from hBMSC embedded in hydrogel exhibited similar cytotoxicity and wound healing properties to that of secretome extracted from hBMSC cultured in a tissue culture plate (TCP) a standard culture condition. Thus, this work demonstrates the potential of fast stress relaxing GG hydrogels for medical application.

Fabrication and Evaluation of Gellan Gum/Hyaluronic Acid Hydrogel for Retinal Tissue Engineering Biomaterial and the Influence of Substrate Stress Relaxation on Retinal Pigment Epithelial Cells.

Cell therapies for age-related macular degeneration (AMD) treatment have been developed by integrating hydrogel-based biomaterials. Until now, cell activity has been observed only in terms of the modulus of the hydrogel. In addition, cell behavior has only been observed in the 2D environment of the hydrogel and the 3D matrix. As time-dependent stress relaxation is considered a significant mechanical cue for the control of cellular activities, it is important to optimize hydrogels for retinal tissue engineering (TE) by applying this viewpoint. Herein, a gellan Gum (GG)/Hyaluronic acid (HA) hydrogel was fabricated using a facile physical crosslinking method. The physicochemical and mechanical properties were controlled by forming a different composition of GG and HA. The characterization was performed by conducting a mass swelling study, a sol fraction study, a weight loss test, a viscosity test, an injection force study, a compression test, and a stress relaxation analysis. The biological activity of the cells encapsulated in 3D constructs was evaluated by conducting a morphological study, a proliferation test, a live/dead analysis, histology, immunofluorescence staining, and a gene expression study to determine the most appropriate material for retinal TE biomaterial. Hydrogels with moderate amounts of HA showed improved physicochemical and mechanical properties suitable for injection into the retina. Moreover, the time-dependent stress relaxation property of the GG/HA hydrogel was enhanced when the appropriate amount of HA was loaded. In addition, the cellular compatibility of the GG/HA hydrogel in in vitro experiments was significantly improved in the fast-relaxing hydrogel. Overall, these results demonstrate the remarkable potential of GG/HA hydrogel as an injectable hydrogel for retinal TE and the importance of the stress relaxation property when designing retinal TE hydrogels. Therefore, we believe that GG/HA hydrogel is a prospective candidate for retinal TE biomaterial.

Proliferating Pilar Tumor of the Cheek Misdiagnosed as Squamous Cell Carcinoma.

Proliferating pilar tumours, also known as trichilemmal tumours, are rare tumours that arise from the external root sheath of hair follicles. These lesions usually have a firm-to-soft texture and form small nodules, but may grow gradually, causing pressure ulceration or hyperkeratinisation. Because of this feature, care should be taken to differentiate proliferating pilar tumours from squamous cell carcinoma. An 89-year-old woman presented with a protruding horn-shaped mass on her left malar area, which was first misdiagnosed as squamous cell carcinoma and then revealed to be a low-grade malignant proliferating pilar tumour. We report this case due to its rarity and clinically atypical characteristics.