JPX could directly bind with YTHDF2 and USP10, respectively. YTHDF2 knockdown increased BMP2 and activated the AKT pathway in cutaneous melanoma.
We report two cases of chronic skin ulcers that were misdiagnosed as skin and soft tissue infections and as an inflammatory myofibroblastic tumour before the final diagnosis of epithelioid sarcoma at our institution. Our coverage of this rare but fatal tumour that can cause chronic skin ulcers is critical because early diagnosis and treatment can reduce morbidity and mortality.
Abstract Aberrant long noncoding RNAs just proximal to Xist (lncRNA JPX) expression levels have been detected in multiple tumors. However, whether JPX is involved in melanoma progression remains unclear. Our study showed that JPX expression is significantly increased in melanoma tissues and cell lines. To clarify the effect of JPX on cutaneous melanoma, we successfully generated JPX-overexpressing or JPX-knockdown A375 and A2058 cells. CCK-8, colony formation EdU, Transwell, and cell-cycle phase assays were performed, and subcutaneously implanted tumor models were used to determine the function of JPX in cutaneous melanoma. The results showed that JPX knockdown reduced the proliferation and migration of malignant melanoma cells both in vitro and in vivo. To further elucidate the molecular mechanism of JPX-induced cutaneous melanoma deterioration, we performed RNA pull-down, RNA immunoprecipitation, coimmunoprecipitation, Western blot, and RNA-sequence analyses. JPX can directly interact with YTHDF2 and impede the protection of YTHDF2 from ubiquitin-specific protease 10 (USP10), which promotes its deubiquitination. Thus, JPX decreases protein stability and promotes the degradation of YTHDF2, thereby stabilizing BMP2 mRNA and activating AKT phosphorylation. Overall, our study revealed a novel effect of JPX on YTHDF2 ubiquitination, suggesting the possibility of blocking the JPX/USP10/YTHDF2/BMP2 axis as a prospective therapeutic approach for cutaneous melanoma. Implications: This study highlights the ubiquitination effect of USP10 and JPX on YTHDF2 in cutaneous melanoma, and proposes that the JPX/USP10/YTHDF2/BMP2 axis may be a prospective therapeutic target for cutaneous melanoma.
JPX overexpression induces the proliferation and migration of cutaneous melanoma cells.
Immune checkpoint inhibitors such as anti-PD-1 receptor antibodies have been shown to be effective in patients with advanced gastric cancer. However, there is a growing concern about immune-related adverse events. A case of a patient with gastric adenocarcinoma who developed toxic epidermal necrolysis (TEN) induced by sintilimab and subsequently developed lichenoid dermatitis is reported. TEN was diagnosed according to a history of sintilimab use, clinical symptoms and physical examination. During hospitalization, the patient developed recurrent fever caused by bacteremia and recovered from TEN after anti-infection and anti-inflammatory treatments. However, when TEN was controlled, the patient developed the lesional manifestations of lichenoid dermatitis. To date, no cases of lichenoid dermatitis after TEN have been reported following the use of PD-1 inhibitors.
目的 探讨自制负压引流装置联合加压包扎治疗头部脓肿性穿掘性毛囊周围炎(PCAS)的临床效果.方法 选取2017年6月至2023年6月于该院就诊的PCAS患者49例,其中24例患者应用自制负压引流装置联合局部加压包扎进行治疗(联合组),25例患者采用常规换药(常规组).比较两组患者的换药次数、伤口愈合时间、并发症发生情况、不良反应发生率及痊愈率.结果 与常规组比较,联合组换药次数减少,伤口愈合时间缩短,差异均有统计学意义(P<0.05);随访3个月,均无脓肿复发、窦道、脱发等并发症发生,两组不良反应发生率无明显差异(P>0.05),联合组痊愈率明显高于常规组(91.67%vs.56.00%,P<0.05).结论 该自制负压引流装置联合加压包扎可有效加速头部PCAS患者康复.
BACKGROUND:Condyloma acuminatum (CA) of the anal canal is difficult to treat and subject to relapse.. We investigated the effects of aminolevulinic acid-based photodynamic therapy (ALA-PDT) combined with oral acitretin during therapy of refractory CA in the anal canal. We also conducted a clinical retrospective study for the treatment of intra-anal CA.METHODS:A total of 101 patients diagnosed with intra-anal CA were enrolled. All patients underwent liquid nitrogen cryotherapy as a basic treatment until visible wart clearance. Patients were divided into two groups depending on the treatment modality after cryotherapy. ALA-PDT group with 51 patients was given ALA-PDT treatment, and ALA-PDT plus acitretin group with 50 patients was given ALA-PDT treatment combined with oral acitretin. The cure rate, recurrence rate, and adverse reactions of the two groups were analyzed and recorded.RESULTS:The cure rate in the ALA-PDT plus acitretin group was 94% (47/50), which was significantly higher than 80.4% (41/51) in ALA-PDT group. The recurrence rate in the ALA-PDT plus acitretin group was 6% (3/50), which was lower than 19.6% (10/51) in ALA-PDT group (P<0.05).CONCLUSION:ALA-PDT combined with oral acitretin is effective and safe in the treatment of refractory CA in anal canal, and with further study may become an option for these patients.
Objective To review the advances in the computational fluid dynamics (CFD) in tissue engineering. Methods The latest research of CFD applied to tissue engineering were extensively retrieved and analyzed, the optimization of bioreactor design and the simulation of fluid dynamics and cell growth kinetics during tissue regeneration in vitro were mainly reviewed. Results The simulation and predictive capabilities of CFD can provide important guidance for the optimization of bioreactor design, and the cultivation of engineering tissue. The accuracy of model prediction results can be further improved by combining with experimental research. Conclusion As a new and effective research tool, CFD has its unique advantages in the application of tissue engineering. However, a more comprehensive and accurate simulation of the whole process of tissue regeneration still needs further studies.
Cutaneous blastomycosis is endemic to North America and is often caused by dimorphic fungi with spores that are inhaled, inoculated spores, or hyphae that infect immunosuppressed and healthy people. It is sporadic and described as a universal imitator with morphological manifestations as erythema, nodules, and ulcers. Our case demonstrated a 69-year-old female bitten by her pet dog who was then diagnosed with cutaneous blastomycosis through social history and detailed laboratory examinations. She experienced a prolonged failure with antibacterial treatment, negative stool and tissue culture, and chronic inflammatory cell infiltrates on tissue pathology. High-throughput sequencing was performed and showed evidence of Blastomyces dermatitidis aetiology. Photodynamic therapy combined with oral itraconazole was administered, and the patient recovered in a short time. Our case presents inoculated cutaneous blastomycosis and a treatment approach in which photodynamic therapy combined with oral itraconazole significantly reduced the duration of disease treatment and affords a promising choice for the treatment of cutaneous blastomycosis.
Objective To observe and evaluate the effect of different perfusion frequencies on the survival of human skin specimens in a quasi-static planar homogeneous flow field. Methods The foreskin skin grafts in size of 4 mm were placed a quasi-static planar homogeneous flow field, and randomly divided into experimental group (perfused with high frequency) and the control group (perfused with low frequency). After 12 days' culture, PAS staining and VG staining were used to observe the changes of basement membrane, cell morphology and dermal collagen fibers. Moreover, the number of total cells and the apoptotic cells in the 2 groups were separately determined by HE staining and TUNEL assay. The dissolved oxygen concentration in culture medium was measured by a dissolved oxygen meter. Results In the low frequency perfusion group, gross observation showed characteristic features of necrosis; PAS and VG staining results indicated that the epidermis was severely separated, basement membrane structure disappeared and collagen fibers accumulated. Significant differences were seen in total cell number (249.35±13.00 vs 37.50±9.18, P < 0.001) and apoptotic rate between the experimental group and the control group. The dissolved oxygen level was higher in the former group than the latter group. Conclusion In the quasi-static planar homogeneous flow field, high frequency perfusion is suitable for the culture of free skin grafts in vitro.
Hidradenitis Suppurativa (HS) is a distressing painful chronic inflammatory skin follicular condition. It is a challenge to achieve better therapeutic effect and lower recurrence rate. In this report, ALA-PDT combined with surgery for the treatment achieved ulcer healing, pain elimination, with no relapse during our follow-up.
Cultured skin has been used extensively for testing therapeutic drugs because it replicates the physical and biochemical properties of whole skin. However, traditional static culture cannot fully maintain cell viability and skin morphology because of the limitations involved with nutrient transmission. Here, we develop a new dynamic perfusion platform for skin culture and compare it with a static culture device. Rat skins were cultured in either static or dynamic condition for 0, 3, 6, 9 and 12 days. H&E, periodic acid–Schiff (PAS) and picrosirius red (PSR) staining were used for skin morphology detection, immunostaining against cytokeratin 10 (CK10) for differentiation detection, immunostaining against proliferating cell nuclear antigen (PCNA) for cell proliferation detection and TUNEL staining for apoptosis detection. After culturing for 12 days, the epidermis, basement membrane, hair follicles and connective tissue were disrupted in the static group, whereas these features were preserved in the dynamic group. Moreover, compared to the static group, proliferation in the epidermis and hair follicles was significantly improved and apoptosis in dermis was significantly decreased in the dynamic group. These findings suggest that our device is effective for extending the culture period of rat skin to maintain its characteristics and viability in vitro.
AIM:To investigate the effects of ALA-PDT on biofilm structure, virulence factor secretion, and quorum sensing (QS) in Pseudomonas aeruginosa.MATERIALS AND METHODS:We used confocal laser scanning microscopy (CLSM), an XTT assay, scanning electron microscopy (SEM), a virulence factor assay and qRT-PCR in this study.RESULTS:The XTT assay showed that ALA-PDT significantly inhibited the growth of planktonic P. aeruginosa. CLSM and SEM showed that ALA-PDT destroyed both bacterial and biofilm structures. The virulence factor assay showed that pyocyanin and elastase secretion were significantly inhibited in the ALA-PDT groups. qRT-PCR assays demonstrated that ALA-PDT significantly reduced the mRNA expression of QS-related genes.CONCLUSION:ALA-PDT kills planktonic and viable biofilm-associated P. aeruginosa cells, destroys biofilm structures, reduces virulence factor secretion and affects QS system gene expression.
组织工程是一门生物科学和工程科学密切交叉的前沿学科,组织工程生物反应器已广泛地应用于人体器官修复领域.组织工程皮肤是通过组织工程相关技术来构建人工皮肤替代物,并具有暂时性乃至永久性替代自身皮肤的功效,目前主要有人工表皮、人工真皮和人工复合皮等.灌注式生物反应器是成功培养组织工程皮肤的关键技术,具有培养基的连续供给、气液界面的维持和相对低的应力环境等优点.
A 46-year-old male presented with yellow-red plaques and nodules on the face for 2 years. Histopathological examination showed a dense dermal infiltrate of histiocytes with scattered lymphocytes and plasma cells. Emperipolesis could be seen in histiocytes. Histiocytes stain were positive for S100 protein and CD68,but negative for CDla. Thus, the diagnosis of cutaneous Rosai-Dorfman disease was made. The lesions had a good response to the treatment of thalidomide and intralesional injection of corticosteroid in 2 years.