Radix Tetrastigma Hemsleyani Flavone represses cutaneous squamous cell carcinoma via Janus kinase/signal transducer and activator of transcription 3 pathway inactivation.

Cutaneous squamous cell carcinoma (CSCC) is the second most common malignant skin tumor and significantly affects patients' quality of life and health. The Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway activation is involved in CSCC development. Radix Tetrastigma hemsleyani flavone (RTHF) is an active Radix Tetrastigma extract (RTE), which was recently reported to have promising inhibitory effects on CSCC. However, the underlying functional mechanisms of this inhibition remain unknown. In the present study, A431 cells or SCL-1 cells were incubated with 1, 5, and 10 mg/mL RTHF for 48 h, respectively. A significantly increased wound closure rate, decreased number of migrated and invaded cells, decreased colony number, and elevated apoptotic rate were observed after treatment with 1, 5, and 10 mg/mL RTHF. Furthermore, after incubation with RTHF, p-JAK1/JAK1, p-JAK2/JAK2, and p-STAT3/STAT3 levels were drastically reduced. An A431 xenograft model was constructed, followed by oral administration of 15, 30, or 60 mg/kg RTHF for 21 consecutive days. A significantly lower increase in tumor volume and reduced tumor weight were observed in all RTHF-treated groups. In addition, JAK/STAT3 signaling was drastically repressed in tumor tissues. Collectively, RTHF inhibited CSCC progression, which may be associated with JAK/STAT3 pathway inactivation.

The role of PKP1 in tumor progression in melanoma: Analysis of a cell adhesion-related model.

The incidence rate of melanoma varies across regions, with Europe, the United States, and Australia having 10-25, 20-30, and 50-60 cases per 1 00 000 people. In China, patients with melanoma exhibit different clinical manifestations, pathogenesis, and outcomes. Current treatments include surgery, adjuvant therapy, and immune checkpoint inhibitors. Nonetheless, complications may arise during treatment. Melanoma development is heavily reliant on cell adhesion molecules (CAMs), and studying these molecules could provide new research directions for metastasis and progression. CAMs include the integrin, immunoglobulin, selectin, and cadherin families, and they affect multiple processes, such as maintenance, morphogenesis, and migration of adherens junction. In this study, a cell adhesion-related risk prognostic signature was constructed using bioinformatics methods, and survival analysis was performed. Plakophilin 1 (PKP1) was observed to be crucial to the immune microenvironment and has significant effects on melanoma cell proliferation, migration, invasion, and the cell cycle. This signature demonstrates high reliability and has potential for clinical applications.

The predictive efficacy of programmed cell death in immunotherapy of melanoma: A comprehensive analysis of gene expression data for programmed cell death biomarker and therapeutic target discovery.

In this study, genes linked to prognosis in skin cutaneous melanoma (SKCM) involved in programmed cell death (PCD) were identified and confirmed and prognostic models based on these genes were constructed. Acquisition and analysis of clinical data and RNA sequencing information from The Cancer Genome Atlas-SKCM (TCGA-SKCM) and Sangerbox databases, gene expression data for 477 tumor samples and 2 normal samples were successfully gathered. The patients were separated into two clusters based on consensus clustering of PCD-related genes, with Cluster A having greater tumor purity, ESTIMATE score, immune score, and matrix score, and Cluster B having a significantly distinct pattern of immune cell infiltration. The use of gene set enrichment analysis and weighted correlation network analysis showed significant associations between certain genes and factors such as tumor mutation burden, age, stage, grade, and tumor subtype. Finally, based on the 12 genes selected by Least Absolute Shrinkage and Selection Operator regression analysis (STAT3, IRF2, SLC7A11, ZEB1, LIPT1, PML, GCH1, GYS1, ABCC1, XBP1, TFAP2C, NOX4), a prognostic model of PGD-related genes was constructed. The effectiveness of the model's prognostic value was confirmed through survival analysis, time-dependent receiver operating characteristic curve, single-factor Cox regression analysis, and nomogram. We also verified the relationship between the GCH1 and MKI67 expression by wet experiment. This model has high prediction accuracy in SKCM patients and can provide a reference for clinical treatment.

The clinical effect of modified slow Mohs circular skin biopsy on penoscrotal extramammary Paget's disease.

OBJECTIVE: Determining the tumor margin is the main problem in penoscrotal extramammary Paget's disease (PEMPD) surgery. This study aimed to explore the role of modified slow Mohs circular skin biopsy in determining the tumor margin in patients with PEMPD before operation. METHODS: Thirty-six PEMPD patients were divided into the control group and the observation group according to the simple randomization method. The control group, which consisted of 16 patients, underwent wide local excision, and the observation group, which consisted of 20 patients, underwent a modified slow Mohs circular skin biopsy to determine the tumor margin before surgery. The duration of surgery, number of frozen sections, satisfaction with the appearance of the skin, tumor recurrence rate, and incidence of functional sequelae were statistically analyzed. RESULTS: The number of frozen sections, duration of surgery, incidence of functional sequelae, and tumor recurrence rate in the observation group were lower than in the control group. The satisfaction with the appearance of the skin was higher in the observation group than in the control group, and the difference was statistically significant (P < 0.05). CONCLUSION: Modified slow Mohs circular skin biopsy can determine the tumor margin before surgery and reduce the number of frozen sections, tumor recurrence rate, and the incidence of functional sequelae. It also increases the postoperative satisfaction of patients.

PGAM5: A necroptosis gene associated with poor tumor prognosis that promotes cutaneous melanoma progression.

Cutaneous melanoma is the deadliest type of skin cancer, and its highly aggressive and metastatic nature leads to an extremely poor prognosis. Necrotizing apoptosis, a specific form of programmed cell death, has been extensively studied in recent years. In this study, we analyzed the relationship between necroptosis-related functional genes and cutaneous melanoma in order to identify the biomarkers associated with the prognosis and progression of cutaneous melanoma. Cutaneous melanoma samples were classified into three subgroups on the basis of a necroptosis gene set. These subgroups were subjected to a prognostic survival analysis, and the greatest differences were observed between subgroups C1 and C3. Between these subgroups, 28 necrotizing apoptosis-related genes were significantly differently expressed. Among these, 16 necrotizing apoptosis-related genes were associated with cutaneous melanoma prognosis. Downscaling analysis and prognostic modeling using the least absolute shrinkage and selection operator analysis yielded nine pivotal genes and revealed phosphoglycerate translocase 5 (PGAM5) as the key gene. Then, qRT-PCR was used to verify the expression level of PGAM5. The results showed that PGAM5 was highly expressed in cutaneous melanoma tissues. In this study, a bioinformatics approach was used to identify PGAM5, a biomarker whose high expression is associated with the poor prognosis of cutaneous melanoma.

Case report: Lower eyelid Reconstruction with the rotation flap pedicled by orbicularis oculi muscle.

Background: Loss of eyelid tissue can be caused by trauma, congenital defects or tumors. Eyelid reconstruction is complicated and challengingly difficult because of the complex anatomy of the eyelid. Several types of surgical procedures for the reconstruction of eyelid defects are available. Objective: To describe reconstruction of lower-eyelid defects using a rotation flap pedicled by the orbicularis oculi. Methods: Fourteen patients (mean age = 67 years old; ages range of 53-86 years old) who suffered from tumor excision from the lower eyelid were treated by the method. Results: The mean duration of follow-up was 14 (range, 12-16) months. Ectropion, abnormal eyelid position and donor-site morbidity were not observed during follow-up. Conclusion: A rotation flap pedicled by the orbicularis oculi can be a good choice for single-stage reconstruction of lower-eyelid defects.

The application of electrolysis of depigmented hair using a trichiasis electrolyzer combined with single hair follicle transplantation for the treatment of vitiligo-associated leukotrichia.

Leukotrichia is one of the difficulties of vitiligo treatment. Hair follicle transplantation is an efficient method to treat vitiligo-associated leukotrichia. A trichiasis electrolyzer, commonly used for treating trichiasis, can be used to damage and remove the depigmented hair follicles. To evaluate the efficacy of the electrolysis of depigmented hair using a trichiasis electrolyzer combined with single hair follicle transplantation for the treatment of vitiligo-associated leukotrichia. A total of 15 patients with stable vitiligo-associated eyebrow and eyelash leukotrichia were enrolled from Department of Dermatology, Hangzhou Third People's Hospital between January 2020 and January 2021. All patients were treated using a trichiasis electrolyzer combined with single hair follicle transplantation. The patients were followed up at the first week, the first month, the third month, and the sixth month after surgery. The texture and growth state of the transplanted hair were observed, and the number of surviving transplanted follicles and regenerating depigmented follicles were recorded. The transplanted hair grew as expected with natural shape. No local infection or obvious scar was observed. Most of the depigmented hair in the lesion area re-pigmented and only a few depigmented hairs regenerated. The average survival rate of the transplanted hair follicles was 71.6%, and the average regeneration rate of the depigmented hair was 11.6%. The electrolysis of depigmented hair using a trichiasis electrolyzer combined with single hair follicle transplantation was an effective and safe method to treat vitiligo-associated leukotrichia.

The Application of Modified Kite Flap in Repairing Facial Skin Defects After Tumor Resection.

INTRODUCTION: The kite flap is widely used in the repair of facial skin defects because of its high survival rate and simple operation. However, the flap mobility of traditional kite flap is limited and needs to be improved. We conducted this survey to evaluate clinical efficacy of modified kite flap in repairing facial skin defects after tumor resection. METHODS: Clinical data of 25 patients with facial skin tumors were collected and analyzed. All patients received skin defect repair with modified kite flaps after Mohs surgery. The survival conditions of the flaps were observed 24 hours after the surgery. The patients were followed up at the first month and the third month after surgery and then every 3 months thereafter. The shape and texture of the flaps, as well as the matching degree with surrounding tissues, were evaluated. RESULTS: All the flaps were survived without infection and healed by the first intervention. The shape and color of the flaps were all good without obvious scar. Satisfactory functional and cosmetic results were achieved in both donor sites and recipient sites. CONCLUSIONS: The modified kite flap is effective for the repair of facial skin defects, which has a high survival rate and larger mobility.

Defect detection in code characters with complex backgrounds based on BBE.

Computer vision technologies have been widely implemented in the defect detection. However, most of the existing detection methods generally require images with high quality, and they can only process code characters on simple backgrounds with high contrast. In this paper, a defect detection approach based on deep learning has been proposed to efficiently perform defect detection of code characters on complex backgrounds with a high accuracy. Specifically, image processing algorithms and data enhancement techniques were utilized to generate a large number of defect samples to construct a large data set featuring a balanced positive and negative sample ratio. The object detection network called BBE was build based on the core module of EfficientNet. Experimental results show that the mAP of the model and the accuracy reach 0.9961 and 0.9985, respectively. Individual character detection results were screened by setting relevant quality inspection standards to evaluate the overall quality of the code characters, the results of which have verified the effectiveness of the proposed method for industrial production. Its accuracy and speed are high with high robustness and transferability to other similar defect detection tasks. To the best of our knowledge, this report describes the first time that the BBE has been applied to defect inspections for real plastic container industry.

The Therapeutic Effects of Baicalin on Vitiligo Mice.

Vitiligo is a commom disease of skin. Its pathogenesis is complex, resulting in the incapacity to find a targeted cure. Baicalin, which is isolated from Scutellariae radix, has been known to exhibit a number of pharmacological effects on autoimmune diseases. In this study, we explored the effects of Baicalin on the recovery of vitiligo stimulated by monophenylketone in mice. We observed that Baicalin slowed down the progression of depigmentation, decreased the incidence of depigmentation, and reduced the area of depigmentation. Moreover, reflectance confocal microscopy (RCM) shown that Baicalin increased the epidermal melanocytes in depigmented skin. Baicalin decreased CD8 + T cell infiltration in mice skin, and decreased the expression of CXCL10 and CXCR3. Baicalin significantly decreased the levels of serum cytokine (interleukin [IL]-6, tumor necrosis factor [TNF]-α, interferon-γ [IFN-γ], and IL-13). Collectively, these data suggest that Baicalin play an important role in the occurrence and development of vitiligo.

Radix Tetrastigma Hemsleyani Flavone Suppresses Cutaneous Squamous Cell Carcinoma A431 Cells via Proteasome Inhibition.

BACKGROUND Radix Tetrastigma Hemsleyani Flavone (RTHF) has detoxification and anti- inflammation activity and is widely used. Here, we report that RTHF inhibits cell proliferation and induces apoptosis in cutaneous squamous cell carcinoma A431 cells and is a potential strategy for cancer therapy. MATERIAL AND METHODS A431 cells were cultured in different concentrations of RTHF. The inhibition of cell proliferation was assessed by MTT assay, cell apoptosis was shown through FCM, and cell invasion was assessed by Transwell methods. Enzyme proteasome assay was used to detect the activity of proteasome and DUB. Expression of apoptosis-related and ubiquitin proteasome pathway-associated proteins were assessed by PCR and Western blot. RESULTS RTHF obviously suppressed the proliferation and induced apoptosis of A431 cells in a dose-dependent manner. Transwell assay showed that RTHF inhibited the cell metastasis significantly. Enzyme proteasome assay show that the RTHF treatment of activity of proteasome and DUB was significantly lower than in control. RTHF increased the expression of Bax and inhibited Bcl-2, pro-caspase3, and pro-caspase9 activity. The expression of USP14, UCHL5, and POH1 decreased and ub-prs increased significantly in the treatment group. CONCLUSIONS Our study reveals that RTHF-mediated inhibition of DUBs and proteasome may provide a potential strategy for cancer therapy.

The RET C611Y mutation causes MEN 2A and associated cutaneous

Background: Cutaneous lichen amyloidosis (CLA) has been reported in some multiple endocrine neoplasia type 2A (MEN 2A) families affected by specific germline RET mutations C634F/G/R/W/Y or V804M, as a characteristic of the clinical manifestation in 'MEN 2A with CLA', one of four variants of MEN 2A, which was strictly located in the scapular region of the upper back. Patient Findings: This study reports a large south-eastern Chinese pedigree with 17 individuals carrying the MEN 2A-harboring germline C611Y (c.1832G>A) RET mutation by Sanger sequencing. One individual presented MEN 2A-related clinical features, including typical CLA in the interscapular region; another individual exhibited neurological pruritus and scratching in the upper back but lacked CLA skin lesions. Both subjects presented with CLA or pruritic symptoms several years before the onset of medullary thyroid carcinoma (MTC) and/or pheochromocytoma. The remaining 15 RET mutation carriers did not exhibit CLA; of these, one presented with MTC and pheochromocytoma, nine with MTC only, two with elevated serum calcitonin and three younger subjects with normal serum calcitonin levels. This family's clinical data revealed a later diagnosis of MTC (mean age, 45.9 (range: 23­73) years), a lower penetrance of pheochromocytoma (2/17, 11.8%) and CLA (1/17, 5.9%). However, no hyperparathyroidism and Hirschsprung disease were reported in this family. Summary and Conclusions: This is the first description of a family with MEN 2A-related CLA due to a germline RET C611Y mutation, which might exhibit a novel and diversified genotype­phenotype spectrum in MEN 2A.

A Clinical Trial Using Attrition Combined with 5-Aminolevulinic Acids Based Photodynamic Therapy in Treating Squamous Cell Carcinoma.

BACKGROUND Squamous cell carcinoma (SCC) is the second most common type of skin cancer, for which non- or mini-invasive treatment is of critical importance. 5-aminolevulinic acids based photodynamic therapy (ALA-PDT) is a mini-invasive approach that causes focal tumor cell injury, apoptosis, and necrosis through light sensitivity. The efficacy of combining ALA-PDT and surgery in treating SCC, however, has not been demonstrated. MATERIAL AND METHODS A total of 60 SCC patients were randomly assigned into attrition plus ALA-PDT group (experimental group) and single ALA-PDT treatment group (control group). Clinical efficacy, recurrence rate, and adverse effects were analyzed in conjunction with H&E staining and immunohistochemistry (IHC) staining for p53 expression. RESULTS The overall effective rate of the experimental group was 73.3%, which was significantly higher than that of the control group (46.7%). The experimental group also had a lower recurrence rate (16.6% versus 30.0%, p<0.05). Similar rates of adverse effects existed between the two groups. After treatment, abnormal cells disappeared, while the p53 positive rate after treatment was elevated in the two groups (p<0.05 comparison of before and after treatment). The experimental group had a higher p53 positive rate compared to the control group (p<0.05). CONCLUSIONS Combined therapy of attrition with ALA-PDT significantly elevated the effective treatment rate and can decrease the recurrence rate with reliable safety in treating SCC, thus ALA-PDT can be used as an optimal plan for SCC treatment.

Analysis of debrided and non-debrided invasive squamous cell carcinoma skin lesions by in vivo reflectance confocal microscopy before and after therapy.

Hyperkeratosis hinders the application of reflectance confocal microscopy (RCM) to image squamous cell carcinoma (SCC). Not all lesions with SCC show hyperkeratosis, and these lesions can be directly imaged. However, lesions with hyperkeratosis can be treated by debriding the hyperkeratotic surface for further imaging. RCM was used to investigate patients with suspected SCC. Lesions without obvious keratosis underwent direct RCM examinations. Lesions with obvious keratosis were treated by debriding the hyperkeratotic surface. The following main RCM criteria were used to diagnose invasive SCC: atypical keratinocytes arranged in nests, islands, and disarrangement patterns; an atypical honeycomb pattern; the absence of a cobblestone pattern; and non-edged dermal papillae. Other characteristics of invasive SCC observed by confocal microscopy included keratin pearl structures, hyperkeratosis, and inflammatory cell infiltration. During the follow-up period after treatment, both the cobblestone pattern and edged dermal papillae were as important as the typical honeycomb pattern in suggesting a normal skin structure. Our findings indicate RCM is a valuable tool to noninvasively examine the histology of invasive SCC before and after therapy.