Jianghai Chen

Background: Self-repair of lower limb wounds has always been one of the research hotspots. Flaps and skin graft are the preferred treatment for lower extremity wound reconstruction. However, these treatments have many disadvantages, such as secondary damage, poor healing quality. In recent years, the use of acellular dermal matrix has emerged as an alternative treatment option for extremity ulcers. Methods: This study aimed to explore whether acellular dermal matrix can be used as a single treatment to promote wound healing. 7 patients with lower extremities cutaneous deficiency exposing bone or tendon, were covered by Pelnac, which was an acellular dermal matrix product approved by China Food and Drug Administration. All the wound was treated by Pelnac without flaps and skin graft. The external dressing was changed every 10 days. Results: After a maximum of 20 weeks, all the wounds were completely healed. During the 12 months follow-up period none of the patients developed skin wear on the treatment area. All patients maintained their postoperative ambulatory ability. All patients were satisfied with the appearance and feeling after wound healing. Conclusion: These findings may mean acellular dermal matrix is a novel method offering opportunity for treatment of lower extremities cutaneous deficiency exposing bone or tendon. It also has the potential to close wounds of all uninfected, non-ischemic, full-thickness cutaneous deficiency.

Ferroptosis plays an important role in cancer. However, studies about ferroptosis-related lncRNAs (FRLs) in skin cutaneous melanoma (SKCM) are scarce. Moreover, the relationship between prognostic FRLs and tumor microenvironment (TME) in melanoma remains unclear. This study investigates the potential prognostic value of FRLs and their association with TME in SKCM. The RNA-sequencing data of SKCM were downloaded from The Cancer Genome Atlas (TCGA) database. Melanoma patients were randomly divided into training and testing groups in a 1:1 ratio. A signature composed of 19 FRLs was developed by the least absolute shrinkage and selection operator (LASSO) regression analysis to divide patients into a low-risk group with a better prognosis and a high-risk group with a poor prognosis. Multivariate Cox regression analysis suggested that the risk score was an independent prognostic factor. The Area Under Curve (AUC) value of the risk score reached 0.768 in the training group and 0.770 in the testing group. Subsequent analysis proved that immune-related signaling pathways were significantly enriched in the low-risk group. The tumor immune cell infiltration analysis demonstrated that melanoma in the high-risk group tended to be immunologically “cold”. We identified a novel FRLs signature which could accurately predict the prognosis of patients with melanoma.

Background: Self-repair of lower limb wounds has always been one of the research hotspots. Flaps and skin graft are the preferred treatment for lower extremity wound reconstruction. However, these treatments have many disadvantages, such as secondary damage, poor healing quality. In recent years, the use of acellular dermal matrix has emerged as an alternative treatment option for extremity ulcers. Methods: This study aimed to explore whether acellular dermal matrix can be used as a single treatment to promote wound healing. 7 patients with lower extremities cutaneous deficiency exposing bone or tendon, was covered by Pelnac, which was an acellular dermal matrix product approved by China Food and Drug Administration. All the wound was treated by Pelnac without flaps and skin graft. The external dressing was changed every 10 days. Results: After a maximum of 20 weeks, all the wounds were completely healed. During the 12 months follow-up period none of the patients developed skin wear on the treatment area. All patients maintained their postoperative ambulatory ability. All patients were satisfied with the appearance and feeling after wound healing. Conclusion: These findings may mean acellular dermal matrix is a novel method offering opportunity for treatment of lower extremities cutaneous deficiency exposing bone or tendon. It also has the potential to close wounds of all uninfected, non-ischemic, full-thickness cutaneous deficiency.

Background: Accurate prediction of prognosis is critical for therapeutic decisions in chondrosarcoma patients. Several prognostic models have been created utilizing multivariate Cox regression or binary classification-based machine learning approaches to predict the 3- and 5-year survival of patients with chondrosarcoma, but few studies have investigated the results of combining deep learning with time-to-event prediction. Compared with simplifying the prediction as a binary classification problem, modeling the probability of an event as a function of time by combining it with deep learning can provide better accuracy and flexibility.Materials and methods: Patients with the diagnosis of chondrosarcoma between 2000 and 2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) registry. Three algorithms—two based on neural networks (DeepSurv, neural multi-task logistic regression [NMTLR]) and one on ensemble learning (random survival forest [RSF])—were selected for training. Meanwhile, a multivariate Cox proportional hazards (CoxPH) model was also constructed for comparison. The dataset was randomly divided into training and testing datasets at a ratio of 7:3. Hyperparameter tuning was conducted through a 1000-repeated random search with 5-fold cross-validation on the training dataset. The model performance was assessed using the concordance index (C-index), Brier score, and Integrated Brier Score (IBS). The accuracy of predicting 1-, 3-, 5- and 10-year survival was evaluated using receiver operating characteristic curves (ROC), calibration curves, and the area under the ROC curves (AUC).Results: A total of 3145 patients were finally enrolled in our study. The mean age at diagnosis was 52 ± 18 years, 1662 of the 3145 patients were male (53%), and mean survival time was 83 ± 67 months. Two deep learning models outperformed the RSF and classical CoxPH models, with the C-index on test datasets achieving values of 0.832 (DeepSurv) and 0.821 (NMTLR). The DeepSurv model produced better accuracy and calibrated survival estimates in predicting 1-, 3- 5- and 10-year survival (AUC:0.895-0.937). We deployed the DeepSurv model as a web application for use in clinical practice; it can be accessed through https://share.streamlit.io/whuh-ml/chondrosarcoma/Predict/app.py.Conclusions: Time-to-event prediction models based on deep learning algorithms are successful in predicting chondrosarcoma prognosis, with DeepSurv producing the best discriminative performance and calibration.

Purpose: Ferroptosis plays a crucial role in the initiation and progression of melanoma. This study developed a robust signature with ferroptosis‐related genes (FRGs) and assessed the ability of this signature to predict OS in patients with skin cutaneous melanoma (SKCM).Methods: RNA‐sequencing data and clinical information of melanoma patients were extracted from TCGA, GEO, and GTEx. Univariate, multivariate, and LASSO regression analyses were conducted to identify the gene signature. A 10 FRG signature was an independent and strong predictor of survival. The predictive performance was assessed using ROC curve. The functions of this gene signature were assessed by GO and KEGG analysis. The statuses of low‐risk and high‐risk groups according to the gene signature were compared by GSEA. In addition, we investigated the possible relationship of FRGs with immunotherapy efficacy.Results: A prognostic signature with 10 FRGs (CYBB, IFNG, FBXW7, ARNTL, PROM2, GPX2, JDP2, SLC7A5, TUBE1, and HAMP) was identified by Cox regression analysis. This signature had a higher prediction efficiency than clinicopathological features (AUC = 0.70). The enrichment analyses of DEGs indicated that ferroptosis‐related immune pathways were largely enriched. Furthermore, GSEA showed that ferroptosis was associated with immunosuppression in the high‐risk group. Finally, immune checkpoints such as PDCD‐1 (PD‐1), CTLA4, CD274 (PD‐L1), and LAG3 were also differential expression in two risk groups.Conclusions: The 10 FRGs signature were a strong predictor of OS in SKCM and could be used to predict therapeutic targets for melanoma.

Background Microsurgical reconstruction of extremity defects with free flaps has been carried out for many years. The aim of this retrospective study is to characterize free flap surgery on children of 1 to 7 years old by evaluating a series of 20 cases of free flap surgeries that have been performed in pediatric patients. Methods From February 2014 to January 2018, 20 patients, 10 boys and 10 girls aged from 1 to 7 years (average, 4.6 years), were engaged in this study. Several types of free flaps were used, including anterolateral thigh flaps (ALT), inferior ulnar collateral artery flap, latissimus dorsi flap, medial plantar flap, fibular osteocutaneous flap and hallux toenail flap. After operations, follow-up period was at least for 2 years and the average follow-up period was 48.5 months. The long-term outcomes were estimated by questionnaires derived from the American Academy of Orthopaedic Surgeons Pediatric Outcomes Data Collection Instrument (PODCI). Results A total of 21free-flap reconstructions were performed on 20patients, including 15 ALT, 3 composite flaps, and 3 other cutaneous flaps. The size of the tissue flap ranged from 1.5 to 280 cm2 (average, 74.1cm2). The diameter of the anastomosed artery of the flap ranged from 0.7 to 1.2 mm. Among the 21 flaps, 20 survived and the success rate was about 95 %. Contour adaption was achieved in all flaps. Fifteen children received a secondary operation for debulking or functional improvement. Secondary deformity was present in 3 children, among which ankle joint valgus was seen in two children and a flexion deformity of injured toe occurred in one child. The mean global functioning score of PODCI was 94 (ranging from 81 to 98, maximum 100). Conclusion The success rate of free-flap surgery in pediatric patients was comparable to that achieved in adults. Post-operative caring for pediatric patients was easier than expected. For pediatric patients, the final outcomes were not varied remarkably from different types of free tissue transfer. Methoden Von Februar 2014 bis Januar 2018 nahmen 20 Patienten, 10 Jungen und 10 Mädchen im Alter von 1 bis 7 Jahren (Durchschnittsalter 4,6 Jahre), an dieser Studie teil. Es wurden mehrere Arten von freien Lappenplastiken verwendet, darunter anterolaterale Oberschenkellappen (ALT), Lappen der A. collateralis ulnaris inferior, des M. latissimus dorsi und der A. plantaris medialis sowie osteokutane Fibulalappen und Lappen des Großzehnnagels. Nach den Operationen wurden die Patienten über einen Mindestzeitraum von 2 Jahren nachbeobachtet, wobei der durchschnittliche Nachbeobachtungszeitraum bei 38,5 Monaten lag. Die Langzeitergebnisse wurden anhand von Fragebögen in Anlehnung an das Pediatric Outcomes Data Collection Instrument (PODCI) der American Academy of Orthopaedic Surgeons beurteilt. Ergebnisse Insgesamt wurden 21 Rekonstruktionen mittels freier Lappenplastiken bei 20 Patienten durchgeführt, darunter 15 ALT, 3 zusammengesetzte Lappen und 3 andere kutane Lappenplastiken. Die Größe der Gewebelappen lag zwischen 1,5 und 280 cm² (Durchschnitt 74.1 cm²). Der Durchmesser der anastomosierten Arterien der Lappen lag zwischen 0,7 und 1,2 mm. Von den 21 Lappen blieben 20 erhalten und die Erfolgsrate betrug etwa 95 %. Bei allen Lappenplastiken gelang die Konturenanpassung. Fünfzehn Kinder wurden zur Reduktion der Tumormasse oder zur Funktionsverbesserung ein zweites Mal operiert. Sekundäre Deformitäten lagen bei 3 Kindern vor, bei 2 Kindern ein Valgus des Sprunggelenks und bei einem eine Flexionsdeformität des verletzten Zehs. Der mittlere globale PODCI-Score zur Funktionsfähigkeit lag bei 94 (Spannweite 81 bis 98, Maximum 100). Schlussfolgerung Die Erfolgsrate chirurgischer Eingriffe mit freien Lappenplastiken bei pädiatrischen Patienten war mit der von Erwachsenen vergleichbar. Die postoperative Versorgung der pädiatrischen Patienten gestaltete sich einfacher als erwartet. Bei pädiatrischen Patienten unterschieden sich die Endergebnisse der verschiedenen Arten von freiem Gewebetransfer nicht nennenswert voneinander. Received: 26 September 2020 Accepted: 21 December 2020 Publication Date: 09 August 2021 (online) © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Purpose: Skin cutaneous melanoma (SKCM) is the most aggressive skin cancer that results in high morbidity and mortality rate worldwide. Immune-related long non-coding RNAs (IRlncRs) play an important role in regulating gene expression in tumors. Therefore, in this study, we aimed to identify IRlncRs signature that could predict prognosis and therapeutic targets for melanoma irrespective of the gene expression levels. Methods: RNA-sequencing data were obtained from The Cancer Genome Atlas (TCGA). IRlncRs were identified using co-expression analysis and recognized using univariate analysis. The impact of IRlncRs on survival was analyzed using a modified least absolute shrinkage and selection operator (Lasso) regression model. A 1-year survival receiver operating characteristic curve was constructed, and the area under the curve was calculated to identify the optimal cut-off point to distinguish between high and low-risk groups in patients with SKCM. Furthermore, integrative analysis was performed to identify the impact of clinicopathological features, chemotherapeutic treatment, tumor-infiltrating immune cells, and mutant genes on survival. Results: A total of 28 IRlncRs significantly associated with survival were identified. Seventeen IRlncRs pairs were used to build a survival risk model that could be used to distinguish between low and high-risk groups. The high-risk group was negatively associated with tumor-infiltrating immune cells and had a higher half inhibitory centration for chemotherapeutic agents such as cisplatin and vinblastine. Additionally, the high-risk group had a positive correlation with the expression of specific mutant genes such as BRAF and KIT. Conclusion: Our findings demonstrate that some IRlncRs have a significant correlation with survival and therapeutic targets for SKCM patients and may provide new insight into the clinical diagnosis and treatment strategies for SKCM patients.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has progressed to a pandemic associated with substantial morbidity and mortality. The WHO and the United States Center for Disease Control and Prevention (CDC) have issued interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19), but there is limited data on the virologic and clinical characteristics for prognosis of severe COVID-19. Methods: A total of 50 patients with severe COVID-19 were divided into good and poor recovery groups. The dynamic viral shedding and serological characteristics of SARS-CoV-2 were explored. The risk factors associated with poor recovery and lung lesion resolutions were identified. In addition, the potential relationships among the viral shedding, the pro-inflammatory response, and lung lesion evolutions were characterized. Results: A total of 58% of the patients had poor recovery and were more likely to have a prolonged interval of viral shedding. The longest viral shedding was 57 days after symptom onset. Older age, hyperlipemia, hypoproteinemia, corticosteroid therapy, consolidation on chest computed-tomography (CT), and prolonged SARS-CoV-2 IgM positive were all associated with poor recovery. Additionally, the odds of impaired lung lesion resolutions were higher in patients with hypoproteinemia, hyperlipemia, and elevated levels of IL-4 and ferritin. Finally, viral shedding and proinflammatory responses were closely correlated with lung lesion evolutions on chest CT. Conclusions: Patients with severe COVID-19 have prolonged SARS-CoV-2 infection and delayed intermittent viral shedding. Older age, hyperlipemia, hypoproteinemia, corticosteroid usage, and prolonged SARS-CoV-2 IgM positive might be utilized as predicative factors for the patients with poor recovery.

Full-thickness skin wounds are common accidents. Although healing can be achieved by treatments like autologous skin grafts, donor site morbidity is hardly evitable. In this article, we provide compelling evidence demonstrating that artificial dermal template (ADT)-treated wound healing is achieved by regrowth of skin epidermis as well as adnexa without skin grafts by use of rodent models. First, by fixating a chamber to the wound edge, we confirmed that wound healing was achieved by regeneration instead of contracture. We found highly proliferative cells in adnexa in the newly formed skin. In the distal edge of newly formed skin, we identified immature hair follicles at early developing stages, suggesting they were newly regenerated. Second, we observed that the Lgr5-positive hair follicle stem cells contributed to formation of new hair follicles through a lineage tracing model. Also, Lgr6-positive cells were enriched in distal edge of newly developed skin. Finally, WNT signaling pathway mediators were highly expressed in the new skin epidermis and adnexa, implying a potential role of WNT signaling during ADT treatment-stimulated skin regrowth. Taken together, our findings demonstrated that full skin regrowth can be induced by ADT treatment alone, thus arguing for its wide clinical application in skin wound treatment.