Indocyanine green based photodynamic therapy for keloids: Fundamental investigation and clinical improvement.

BACKGROUND: Keloid, a prevalent pathological skin lesion, presents significant challenges in terms of treatment efficacy. Photodynamic therapy (PDT), an increasingly popular adjuvant treatment, has shown significant potential in the management of various disorders, including cancer. However, the therapeutic potential of indocyanine green-mediated photodynamic therapy (ICG-PDT) for keloids has not yet been demonstrated. METHODS: In this study, we divided the experimental groups into control group, Photothermal Therapy group, Photodynamic Therapy group, and Combined Therapy group. The in vitro investigation aimed to optimize the clinical application of PDT for keloid treatment by elucidating its underlying mechanism. Subsequently, on this basis, we endeavored to manage a clinical case of keloid by employing surgical intervention in conjunction with modified ICG-PDT. RESULTS: Our investigation revealed an unexpected outcome that ICG-PDT maximally inhibited the cellular activity and migration of keloid fibroblasts only when photodynamic mechanism took effect. Additionally, the induction of autophagy and apoptosis, as well as the inhibition of collagen synthesis, were particularly evident in this experimental group. Furthermore, the above therapeutic effect could be achieved at remarkably low drug concentrations. Building upon the aforementioned experimental findings, we successfully optimized the treatment modality for the latest case and obtained a more favorable treatment outcome. CONCLUSIONS: This study investigated the mechanism of ICG-PDT treatment and optimized the in vivo treatment regimen, demonstrating the significant therapeutic potential of ICG-PDT treatment in clinical keloid treatment.

Development of Uveal Melanoma-Specific Aptamer for Potential Biomarker Discovery and Targeted Drug Delivery.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. However, challenges in early diagnosis, high risk of liver metastasis, and lack of effective targeted therapy lead to poor prognosis and high mortality of UM. Therefore, generating an effective molecular tool for UM diagnosis and targeted treatment is of great significance. In this study, a UM-specific DNA aptamer, PZ-1, was successfully developed, which could specifically distinguish molecular differences between UM cells and noncancerous cells with nanomolar-range affinity and presented excellent recognition ability for UM in vivo and clinical UM tissues. Subsequently, the binding target of PZ-1 on UM cells was identified as JUP (junction plakoglobin) protein, which held great potential as a biomarker and therapeutic target for UM. Meanwhile, the strong stability and internalization capacity of PZ-1 were also determined, and a UM-specific aptamer-guided "nanoship" was engineered to load and selectively release doxorubicin (Dox) to targeted UM cells, with lower toxicity to nontumor cells. Taken together, the UM-specific aptamer PZ-1 could serve as a molecular tool to discover the potential biomarker for UM and to achieve the targeted therapy of UM.

Development of an Aptamer-Based Molecular Tool for Specifically Targeting Microglia via the CD64 Protein.

Microglial dysfunction has been identified as a key factor in the pathology of several traumatic and neurodegenerative diseases in the central nervous system. Due to the importance of microglia in various pathological processes, the development of molecular tools to target microglia may be of significance for the clinical diagnosis and treatment of these disorders. In this study, a DNA aptamer, ZH-1c, that binds microglia with high affinity was developed by cell-SELEX and truncated strategies. ZH-1c exhibits promising binding ability under physiological temperatures, high serum stability after being modified, and can be internalized by microglia. Also, the binding target of ZH-1c on microglia was identified as the transmembrane protein CD64, which increased in response to inflammatory stimulation via lipopolysaccharide and interferon-gamma, thus enhancing the affinity of ZH-1c for activated microglia. Based on the above experiments, the DNA aptamer ZH-1c exhibits great potential for the targeting of activated inflammatory microglia and may be suitable as a novel and effective molecular tool for diagnosis and microglia-targeted therapies.

Collagen Niches Affect Direct Transcriptional Conversion toward Human Nucleus Pulposus Cells via Actomyosin Contractility.

Cellular niches play fundamental roles in regulating cellular behaviors. However, the effect of niches on direct converted cells remains unexplored. In the present study, the specific combination of transcription factors is first identified to directly acquire induced nucleus pulposus-like cells (iNPLCs). Next, tunable physical properties of collagen niches are fabricated based on various crosslinking degrees. Collagen niches significantly affect actomyosin cytoskeleton and then influence the maturation of iNPLCs. Using gain- and loss of function approaches, the appropriate physical states of collagen niches are found to significantly enhance the maturation of iNPLCs through actomyosin contractility. Moreover, in a rat model of degenerative disc diseases, iNPLCs with collagen niches are transplanted into the lesion to achieve significant improvements. As a result, overexpression of transcription factors in human dermal fibroblasts are efficiently converted into iNPLCs and the optimal collagen niches affect cellular cytoskeleton and then facilitate iNPLCs maturation toward human nucleus pulposus cells. These findings encourage more in-depth studies toward the interactions of niches and direct conversion, which would contribute to the development of direct conversion.

Removal of Small Cavernous Hemangioma in Orbital Apex Through an Endoscopic Transethmoidal-Sphenoidal Approach.

OBJECTIVE: To investigate the feasibility, efficacy, and safety of an endoscopic transethmoidal-sphenoidal approach in removing a small cavernous hemangioma (CH) located in the deep lateral orbital apex. METHODS: This study involved 19 patients diagnosed with a CH located in the deep lateral orbital apex. All patients underwent an endoscopic transethmoidal-sphenoidal approach for removal of the CH. The best-corrected visual acuity (BCVA), visual field, and surgery-related complications were analyzed and compared. RESULTS: All tumors in this study were completely removed. The mean BCVA was LogMAR 0.97 ± 0.97 preoperatively and LogMAR 0.38 ± 0.64 postoperatively (p < 0.05). The mean visual field index was 52.26% ± 33.26% preoperatively and 75.47% ± 30.49% postoperatively (p < 0.05). The mean deviation index was -17.48 ± 12.43 dB preoperatively and -10.10 ± 10.85 dB postoperatively (p < 0.05), and the pattern standard deviation was 6.37 ± 3.77 dB preoperatively and 4.90 ± 3.56 dB postoperatively (p > 0.05). Four (21.1%) patients developed oculomotor limitations and two (10.5%) patients developed ptosis after surgery. All of these symptoms resolved spontaneously, and no other complications occurred. The mean follow-up time was 6.71 ± 3.89 months. CONCLUSION: The endoscopic transethmoidal-sphenoidal approach is an effective and minimally invasive treatment for removing small CH in the deep lateral orbital apex. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1743-1749, 2022.

Endoscopic Transconjunctival Deep Lateral Wall Decompression for Thyroid-associated Orbitopathy: A Minimally Invasive Alternative: Transconjunctival Endoscopic with Wall Decompression for TAO.

PURPOSE: To investigate the feasibility, efficacy, and safety of endoscopic transconjunctival transorbital deep lateral wall decompression for thyroid-associated orbitopathy (TAO). DESIGN: Prospective single-surgeon interventional case series. METHODS: Twenty-two patients (39 orbits) diagnosed with thyroid-associated orbitopathy without dysthyroid optic neuropathy were enrolled in this study. All patients underwent endoscopic transconjunctival transorbital deep lateral wall decompression for proptosis reduction. The data, including measurement on exophthalmometry, volumetric change on computed tomography, and surgery-related complications, were analyzed. RESULTS: We observed a proptosis reduction (mean, 3.42 ± 0.87 mm; range, 2.10-5.52 mm) and a corresponding decrease in the bony volume of the greater wing of the sphenoid bone (mean, 1.89 ± 0.81 cm3; range, 0.56-3.79 cm3) postoperatively. Preexisting diplopia improved in 5 patients (22.73%). Transient zygomaticotemporal hypoesthesia developed in all patients, and cerebrospinal fluid leakage occurred in 1 orbit (2.56%). No patient complained of temporal hollowing, oscillopsia, or new-onset or worsening diplopia during follow-up. CONCLUSIONS: Endoscopic transconjunctival transorbital deep lateral wall decompression is an effective and minimally invasive treatment for proptosis reduction in patients with thyroid-associated orbitopathy. The surgery-related complications with this technique were fewer compared with traditional approaches.

Therapeutic difference between orbital decompression and glucocorticoids administration as the first-line treatment for dysthyroid optic neuropathy: a systematic review.

To assess all available data to compare the efficacy of glucocorticoids treatment and orbital decompression for dysthyroid optic neuropathy (DON). PubMed, EMBASE, the Cochrane Library databases as well as other sources were searched by two independent reviewers followed by extensive hand-searching for the identification of relevant studies. The primary outcomes were the improvement in visual acuity and responder rate. Secondary outcomes were the proptosis reduction, change in diplopia, and clinical activity score (CAS). One randomized controlled trial, three retrospective case series and one prospective case series met the inclusion criteria. They were divided into intravenous high-dose glucocorticoids (ivGC) group and orbital decompression (OD) group. Both groups demonstrated improvement in visual acuity. In addition, the proportion of patients with improved vision in OD group was higher than that in ivGC group (P<0.001). Post-treatment proptosis reduction was also reported in both groups. Overall, weighted mean in proptosis reduction estimated at 1.64 and 5.45 mm in patients treated with ivGC and OD respectively. This study also presented results regarding pre-existing and new-onset diplopia. Apart from diplopia, a wide variety of minor and major complications were noted in 5 included studies. The most common complication in ivGC group and OD group was Cushing's syndrome and epistaxis respectively. The present systematic review shows that both glucocorticoids treatment and OD are effective in treating DON and OD may work better in improving visual acuity and reducing proptosis. However, high-quality, large-sample, controlled studies need to be performed in the future.

Modified endoscopic transnasal orbital apex decompression in dysthyroid optic neuropathy.

BACKGROUND: To describe the surgical technique and assess the clinical efficacy and safety of modified endoscopic transnasal orbital apex decompression in the treatment of dysthyroid optic neuropathy. METHODS: In this retrospective research, forty-two subjects (74 orbits) who underwent modified endoscopic transnasal orbital apex decompression for the treatment of dysthyroid optic neuropathy were enrolled. Preoperative and postoperative best-corrected visual acuity (BCVA), visual field mean deviation (MD), Hertel exophthalmometry, and new onset diplopia were assessed before and after the intervention. The Wilcoxon test was used for differential analysis. Linear mixed-models' analyses were conducted to assess the potential predictors for BCVA change. RESULTS: Postoperatively, the mean BCVA improved from 0.70 ± 0.62 logMAR to 0.22 ± 0.33 logMAR. BCVA significantly improved in 69 eyes (93%), remained stable in 4 eyes (5%) and deteriorated in 1 eye (1%). MD of visual fields improved from -13.73 ± 9.22 dB to -7.23 ± 7.04 dB. Proptosis decreased from 19.57 ± 3.38 mm to 16.35 ± 3.01 mm. Preoperative BCVA, MD of visual fields and medical rectus diameter were independent factors associated with improvements in BCVA (P < 0.05) by linear mixed-models' analyses. Eighteen patients (42.9%) developed new diplopia postoperatively. CONCLUSION: Modified endoscopic transnasal orbital apex decompression effectively restores vision in dysthyroid optic neuropathy.

The role of FOS-mediated autophagy activation in the indocyanine green-based photodynamic therapy for treating melanoma.

The morbidity and mortality of melanoma which accounts for 90% of cutaneous neoplasm-related deaths is growing over the last few decades. Common treatments for melanoma are limited to poor tissue selectivity, high toxicity and drug resistance. Photodynamic therapy (PDT) is an effective adjuvant therapy and could be a promising therapy for melanoma. Multiple mechanisms are involved in PDT2 and programmed cell death (PCD) which comprises of autophagy and apoptosis is likely to be a critical one. Whereas, the molecular mechanism and subsequent effect of PDT-induced autophagy in melanoma are still unclear. In this study, we first analyzed gene expression data in the TCGA3 and GEO4 databases to clarify that PDT-induced-autophagy improved the prognosis of melanoma. The expression of FOS which generally defined as an immediate-early gene (IEG) and related to cell autophagy was found significantly elevated after PDT. To further investigate whether FOS played a key role in PDT-induced-autophagy of melanoma, we first determined the optimum concentration of ICG solution for autophagy observation. Then, relative FOS expression was detected at mRNA and protein level and cell autophagy was observed by western blot and flow cytometry. We found that ICG-PDT treatment could significantly elevate FOS expression in SKCM5 B16 cells, and FOS promoted ICG-PDT-induced cell autophagy. To sum up, our data indicated that FOS was involved in ICG-PDT-induced-autophagy in melanoma and furthermore improved the prognosis of melanoma.

Endoscopic transnasal canaliculorhinostomy for refractory common canalicular obstruction with an unidentifiable lacrimal sac.

AIM: To describe the role of endoscopic transnasal canaliculorhinostomy (ETC) in refractory common canalicular obstruction (CCO) associated with an absent or unidentifiable lacrimal sac. METHODS: The records of patients with refractory CCO who underwent ETC at the Eye Hospital of Wenzhou Medical University from October 2007 to December 2016 were retrospectively reviewed. RESULTS: Fifty-six patients (56 eyes) with refractory CCO were recruited into the study. Eight patients were excluded due to the presence of a residual lacrimal sac or failure to complete the follow-up duration. The anatomic and functional success rates were both 85.4% (41/48) at a mean follow-up of 18.6mo. Five cases failed as a result of ostial synechia and two failed because of ostial obstruction by granulation. Postoperative complications included mild nasal bleeding in 5 cases, dried nasal feeling in 8 cases, and olfactory dysfunction in 4 cases. CONCLUSION: Although being surgically challenging, ETC has comparable findings to its external approach counterpart or conjunctivodacryocystorhinostomy (CDCR) with Jones tube. And it may prove to be a novel alternate surgical technique for patients with refractory CCO without identifiable lacrimal sac.

pH-insusceptible cobalt-manganese immobilizing mesoporous siliceous MCM-41 catalyst for ozonation of dimethyl phthalate.

Mesoporous siliceous MCM-41 immobilized with Co and Mn metal ions (Co-Mn-MCM-41) was synthesized using a hydrothermal method. The structural regularity and the valence states of the metal species were measured by X-ray diffractometer and X-ray photoelectron spectrometer. The resultant bimetallic Co-Mn-MCM-41 catalyst was tested for the degradation of dimethyl phthalate (DMP) via a catalytic ozonation mechanism, demonstrating that the catalytic properties of Co-Mn-MCM-41 catalyst significantly accelerated the ozonation process. Total organic carbon (TOC) and DMP removal efficiency reached 94% and 99.7% at 15min under the optimal conditions. The oxidation pathways were proposed after identifying the intermediate products from ozonation using a gas chromatography-mass spectrometer. The enhanced catalytic reactivity was attributed to the highly-dispersive cobalt and manganese species in MCM-41 scaffolds, which promoted the ozone decomposition and hydroxyl radicals' generation in catalytic ozonation and accelerated the degradation of DMP. Bimetallic Co-Mn-MCM-41 catalyst remained stable in mild acidic conditions and continued to show high activity after repeated runs.