A case of nevoid basal cell carcinoma syndrome dominated by facial basal cell carcinoma. / é¢éƒ¨åŸºåº•ç»†èƒžç™Œä¸ºä¸»çš„ç—£æ ·åŸºåº•ç»†èƒžç™Œç»¼åˆå¾1例.

Nevus-like basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disease characterized by the occurrence of multiple maxillofacial keratocysts, basal cell carcinoma, child medulloblastoma, and various skeletal and soft tissue dysplasia. In 2020, a patient with NBCCS dominated by facial basal cell carcinoma was admitted to Xiangya Hospital of Central South University. The patient was an elderly woman. Ten years ago, the systemic mass appeared, especially on the face, but it was not treated. Later, these masses gradually increased in volume and number, and showed invasive properties. The nasal mass was broken and suppurated, seriously affecting the patient's life quality. The patient came to the hospital to improve the symptoms. Staphylococcus aureus and Providencia rettgeri were cultured in the patient's nasal secretions. Nasal sinus enhanced MRI showed that the subcutaneous soft tissue of the right cheek and the anterolateral mucosa of the left nasal cavity were invaded, indicating multiple malignant skin lesions. After admission, local anesthesia was performed and some masses were removed. Pathological examination of the mass showed basal cell carcinoma. After general anesthesia, multiple masses were resected. The postoperative pathological examination showed that multiple basal cell carcinoma invaded the deep dermis near subcutaneous fat layer. Combined with the results of clinical and immunohistochemical examination, the patient was diagnosed as NBCCS. There were no clear tumor thrombus in the vessel and no nerve invasion. No recurrence or new tumor was found after 1 year follow-up. The incidence rate of NBCCS is low and clinical symptoms are different. The patient's life quality is poor and the patient needs long-term individualized treatment.

Application of septal extension grafts with auricular cartilage in rhinoplasty. / 耳廓软骨鼻中隔延伸支架移植物在鼻整形术中的应用.

OBJECTIVES: Rhinoplasty is one of the most common cosmetic surgeries in China. Septal extension grafts (SEG) have been widely used in rhinoplasty, but there are few reports on SEG derived from ear cartilage. This study aims to explore the effectiveness and stability of auricular cartilage nasal SEG transplantation in Chinese rhinoplasty. METHODS: A retrospective analysis of 35 rhinoplasty patients admitted from September 2019 to March 2022 has been conducted. Among them, 29 patients underwent rhinoplasty for the first time and 6 patients underwent rhinoplasty with the age of 18-32 (average 22.4) years old. The postoperative follow-up was 3-28 (average 18.5) months. The improvement of the nose shape was observed. The changes of the nose tip angle, nasolabial angle, and nasofrontal angle were compared between before and after the operation, and the complications were recorded. RESULTS: All patients who underwent rhinoplasty with a septal extension grafts constructed from the concha cavity and concha cartilage showed significant improvement in nasal contour. The preoperative nasal tip angle, nasolabial angle, and nasofrontal angle were significantly improved compared with 3 months after operation (all P<0.001), and there was no significant difference between 3 months and 14 months after operation (all P>0.05). The appearance of nasal cavity was satisfactory in 32 patients after operation. Columella deviation occurred in 2 patients and 1 patient complained of downward rotation of the nasal tip, which was satisfied after readjustment of the graft. CONCLUSIONS: The simplified SEG derived from auricular cartilage can provide stable support for the nasal tip, the nasal shape is natural after operation, and minimal trauma of unilateral auricle cartilage transplantation remains.

Promotion effects of mono-2-ethyhexyl phthalate (MEHP) on migration and invasion of human melanoma cells via activation of TGF-ß signals.

Malignant melanoma is one of the most leading forms of skin cancer associated with a low patient survival rate. There is an urgent need to illustrate risk factors that can trigger the motility of melanoma cancer cells. Our present study revealed that mono-(2-ethylhexyl)phthalate (MEHP) exposure can significantly increase the in vitro migration and invasion of WM983A and A375 cells. Among the tested cytokines, MEHP can increase the expression of transforming growth factor ß (TGF-ß). Inhibition of TGF-ß via its neutralization antibody can attenuate MEHP-induced cell migration and invasion. Further, upregulation of TGF-ß mediated MEHP-induced activation of Smad signals and upregulation of Snail in melanoma cells. Blocking the TGF-ß/Smad signal pathway can attenuate MEHP-induced cell migration. Estrogen receptor α (ERα) was essential for MEHP-induced expression of TGF-ß. In addition, MEHP can increase the expression of ERα in melanoma cells. Collectively, our study found that MEHP can stimulate the progression of melanoma via TGF-ß signals. SIGNIFICANCE: Mono-(2-ethylhexyl)phthalate (MEHP) is the active and most toxic metabolite of di(2-ethylhexyl)phthalate (DEHP). Our present study revealed that MEHP can trigger the in vitro migration and invasion of melanoma cells via upregulation of TGF-ß/Snail signals. It revealed that daily exposure to MEHP might be a risk factor for melanoma patients.

Responses in the crucian carp (Carassius auratus) exposed to environmentally relevant concentration of 17α-Ethinylestradiol based on metabolomics.

17α-ethynylestradiol (EE2), a ubiquitous synthetic endocrine disrupting chemical, was the principal component of contraceptive drugs and one of common hormone medications. The detrimental impact of EE2 on the reproduction of organisms was widely recognized. However, the underlying mechanisms of physiological and metabolome effects of EE2 on freshwater fish are still unclear. This study investigated the toxic effects and related mechanisms of EE2 on freshwater fish crucian carp (Carassius auratus) based on metabolomics. Crucian carp were exposed to EE2 at environmentally relevant concentration for 9 days, 18 days, and 27 days, and the biological responses were explored through analysis of the physiological endpoints, steroid hormones, and metabolome. The physiological endpoints of crucian carp had no distinct change after EE2 exposure. However, metabolomics analysis probed significant deviation based on chemometrics, indicating that the metabolomics approach was more sensitive to the effects of EE2 at environmentally relevant concentration to freshwater fish than the traditional endpoints. The alterations of 24 metabolites in gonad and 16 metabolites in kidney were induced by treatment with EE2, respectively, which suggesting the perturbations in amino acid metabolism, lipid metabolism, energy metabolism, and oxidative stress. Moreover, EE2 exposure could induce the disruption of lipid metabolism and then broke the homeostasis of endogenous steroid hormones. Metabolomics provided a new strategy for the studies on contaminant exposure at a low dose in the short term and gave important information for the toxicology and mechanism of EE2.

MiR-488-3p facilitates wound healing through CYP1B1-mediated Wnt/ß-catenin signaling pathway by targeting MeCP2.

INTRODUCTION: Diabetic wounds are difficult to heal, but the pathogenesis is unknown. MicroRNAs (miRNAs) are thought to play important roles in wound healing. The effect of miR-488-3p in wound healing was studied in this article. MATERIALS AND METHODS: The gene methylation was measured by methylation specific PCR (MSP) assay. A dual-luciferase reporter assay was adopted to analyze the interaction between miR-488-3p and MeCP2. RESULTS: Cytochrome P450 1B1 (CYP1B1) is a monooxygenase belonging to the cytochrome P450 family that aids in wound healing. Our findings showed that the miR-488-3p and CYP1B1 expression levels were much lower in wound tissues of diabetics with skin defects, but the methyl-CpG-binding protein 2 (MeCP2) level was significantly higher than that in control skin tissues. MiR-488-3p overexpression increased cell proliferation and migration, as well as HUVEC angiogenesis, while inhibiting apoptosis, according to function experiments. In vitro, MeCP2 inhibited wound healing by acting as a target of miR-488-3p. We later discovered that MeCP2 inhibited CYP1B1 expression by enhancing its methylation state. In addition, CYP1B1 knockdown inhibited wound healing. Furthermore, MeCP2 overexpression abolished the promoting effect of miR-488-3p on wound healing. It also turned out that CYP1B1 promoted wound healing by activating the Wnt4/ß-catenin pathway. Animal experiments also showed that miR-488-3p overexpression could accelerate wound healing in diabetic male SD rats. CONCLUSIONS: MiR-488-3p is a potential therapeutic target for diabetic wound healing since it improved wound healing by activating the CYP1B1-mediated Wnt4/-catenin signaling cascade via MeCP2.

Selenium alleviates cadmium and copper toxicity in Gracilaria lemaneiformis (rhodophyta) with contrasting detoxification strategies.

Selenium (Se) is a beneficial element for plants, and can be used to mitigate the toxicity of heavy metals. However, the detoxification of Se in macroalgae, a crucial part of aquatic ecosystem productivity, has rarely been reported. In the present study, a red macroalga Gracilaria lemaneiformis was exposed to non-essential metal cadmium (Cd) or essential metal copper (Cu) with addition of different levels of Se. We then examined the changes in growth rate, metal accumulation, metal uptake rate, subcellular distribution, as well as thiol compound induction in this alga. Se addition alleviated Cd/Cu-induced stress in G. lemaneiformis by regulating cellular metal accumulation and intracellular detoxification. Specifically, supplementation of low-level Se displayed a significant decrease in Cd accumulation, and thus alleviated the growth inhibition induced by Cd. This may be caused by the inhibitory effect of endogenous Se instead of exogenous Se on Cd uptake. Although Se addition increased bioaccumulation of Cu in G. lemaneiformis, the important intracellular metal chelators, phytochelatins (PCs), were massively induced to alleviate Cu-induced growth inhibition. High-dose Se addition did not deteriorate but failed to normalize the growth of algae under metal stress conditions. Reduction in Cd accumulation or induction of PCs by Cu could not suppress the toxicity of Se above safe levels. Se addition also altered metal subcellular distribution in G. lemaneiformis, which might affect the subsequent metal trophic transfer. Our results demonstrated that the detoxification strategies of Se between Cd and Cu were different in macroalgae. Elucidating the protective mechanisms of Se against metal stress may help us better apply Se to regulate metal accumulation, toxicity, and transfer in aquatic environment.

HI-MViT: A lightweight model for explainable skin disease classification based on modified MobileViT.

Objective: To develop an explainable lightweight skin disease high-precision classification model that can be deployed to the mobile terminal. Methods: In this study, we present HI-MViT, a lightweight network for explainable skin disease classification based on Modified MobileViT. HI-MViT is mainly composed of ordinary convolution, Improved-MV2, MobileViT block, global pooling, and fully connected layers. Improved-MV2 uses the combination of shortcut and depth classifiable convolution to substantially decrease the amount of computation while ensuring the efficient implementation of information interaction and memory. The MobileViT block can efficiently encode local and global information. In addition, semantic feature dimensionality reduction visualization and class activation mapping visualization methods are used for HI-MViT to further understand the attention area of the model when learning skin lesion images. Results: The International Skin Imaging Collaboration has assembled and made available the ISIC series dataset. Experiments using the HI-MViT model on the ISIC-2018 dataset achieved scores of 0.931, 0.932, 0.961, and 0.977 on F1-Score, Accuracy, Average Precision (AP), and area under the curve (AUC). Compared with the top five algorithms of ISIC-2018 Task 3, Marco's average F1-Score, AP, and AUC have increased by 6.9%, 6.8%, and 0.8% compared with the suboptimal performance model. Compared with ConvNeXt, the most competitive convolutional neural network architecture, our model is 5.0%, 3.4%, 2.3%, and 2.2% higher in F1-Score, Accuracy, AP, and AUC, respectively. The experiments on the ISIC-2017 dataset also achieved excellent results, and all indicators were better than the top five algorithms of ISIC-2017 Task 3. Using the trained model to test on the PH2 dataset, an excellent performance score is obtained, which shows that it has good generalization performance. Conclusions: The skin disease classification model HI-MViT proposed in this article shows excellent classification performance and generalization performance in experiments. It demonstrates how the classification outcomes can be applied to dermatologists' computer-assisted diagnostics, enabling medical professionals to classify various dermoscopic images more rapidly and reliably.

Role of PPARbeta in fibroblast response to heat injury.

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family of ligand-inducible transcription factors. Our previous study has shown that in human umbilical vein endothelial cells PPARbeta initiates a protective mechanism that limits the extent of damage due to H2O2-induced injury. Although fibroblasts are one of the main cell types involved in wound repair, the role of PPARbeta in the fibroblast response to heat injury has not been investigated. Thus, in this study, we examined possible protective role of PPARbeta in fibroblasts from heat injury. We developed a novel dermal fibroblast heat injury model to characterize the mechanisms of the heat injury healing response that involved PPARbeta. The specific PPARbeta ligand GW0742, a PPARbeta activator and a short hairpin RNA (shRNA) plasmid against PPARbeta were used to reveal the action mechanism of PPARbeta in heat injury-induced fibroblast changes in morphology and increased proliferation. In response to heat injury (52 degrees C for 30 s), fibroblast activation of PPARbeta increased 1.56-fold. Administration of GW0742 significantly induced a protective effect on heat injury-induced fibroblasts by minimizing the structural damage and increasing the cell proliferation response. Likewise, inhibition of PPARbeta using shRNA exacerbated the damage by inhibiting the de novo synthesis of PPARbeta. These results indicated that heat injury enhanced PPARbeta expression and PPARbeta protected fibroblast structure and proliferation.

LncRNA-ZNF252P-AS1/miR-15b-5p promotes the proliferation of keloid fibroblast by regulating the BTF3-STAT3 signaling pathway.

BACKGROUND: JAK2/STAT3 signaling pathway plays an important role in keloid formation, but the upstream mechanism of their activation remains unclear. OBJECTIVE: This study aims to investigate the possible mechanism of lncRNA-ZNF252P-AS1 in keloid. METHODS: The differentially expressed genes in keloid and their upstream regulatory miRNAs and long non-coding RNAs (lncRNAs) were analyzed by bioinformatics database, and the targeting relationship was further verified by dual-luciferase reporter gene assay. LncRNA function as competitive endogenous RNA (ceRNA) in keloid was further verified by in keloid fibroblasts (KFs) and in nude mice with subcutaneous keloids. RESULTS: BTF3 expression was up-regulated in keloid tissues. The targeting relationship between BTF3 and miR-15b-5p was confirmed by dual-luciferase reporter gene assay. miR-15b-5p overexpression inhibited BTF3, Bcl-2, Cyclin D1, C-myc, Collagen I, MMP2, MMP9, N-cadherin, and ZEB2 expressions in KFs, inhibited cell proliferation and migration, while promoted E-cadherin levels. BTF3 overexpression reversed miR-15b-5p effects on KFs. Bioinformatics analysis as well as clinical and cellular experiments confirmed that the lncRNA ZNF252P-AS1 was highly expressed in keloid/KFs. Dual-luciferase reporter gene assays confirmed the targeting relationship between lncRNA ZNF252P-AS1 and miR-15b-5p. LncRNA ZNF252P-AS1 overexpression inhibited miR-15b-5p and E-cadherin levels, upregulated BTF3, Bcl-2, Cyclin D1, C-myc, Collagen I, MMP2, MMP9, N-cadherin, and ZEB2 expressions, increased cell proliferation and migration, and activated JAK2/STAT3 pathway, while miR-15b-5p overexpression reversed this effect. The in vivo results were consistent with in vitro results. In vivo experiments further confirmed that lncRNA ZNF252P-AS1 reduced keloid volume and weight. CONCLUSION: lncRNA ZNF252P-AS1 is a potential target for keloid treatment.