Surgical amputation for patients with diabetic foot ulcers: A Chinese expert panel consensus treatment guide.

Background: Diabetic foot disease is a serious complication of diabetes mellitus. Patients with diabetes mellitus have a 25% lifetime risk for developing a foot ulcer, and between 14% and 24% of patients require a major or minor lower limb amputation due to severe gangrene. However, decisions concerning whether to amputate or whether to perform a major or minor lower limb amputation, and how best to determine the amputation plane remain unclear. Methods: To consolidate the current literature with expert opinion to make recommendations that will guide surgical amputation for patients with diabetic foot ulcers. A total of 23 experts experienced in surgical treatment of patients with diabetic foot ulcers formed an expert consensus panel, and presented the relevant evidence, discussed clinical experiences, and derived consensus statements on surgical amputation for patients with diabetic foot ulcers. Each statement was discussed and revised until a unanimous consensus was achieved. Results: A total of 16 recommendations for surgical amputation for patients with diabetic foot ulcers were formulated. The experts believe that determination of the amputation plane should be comprehensively evaluated according to a patient's general health status, the degree of injury, and the severity of lower limb vasculopathy. The Wagner grading system and the severity of diabetic lower extremity artery disease are important criteria when determining the degree of amputation. The severity of both diabetic foot infection and systemic underlying diseases are important factors when considering appropriate treatment. Moreover, consideration should also be given to a patient's socioeconomic status. Given the complexities of treating the diabetic foot, relevant issues in which consensus could not be reached will be discussed and revised in future. Conclusion: This expert consensus could be used to guide doctors in clinical practice, and help patients with diabetic foot ulcers gain access to appropriate amputation treatment.

DHRS7 is an immune-related prognostic biomarker of KIRC and pan-cancer.

Renal clear cell carcinoma (KIRC) is one malignancy whose development and prognosis have been associated with aberrant DHRS7 expression. However, the catalytic activity and pathophysiology of KIRC are poorly understood, and no sensitive tumor biomarkers have yet been discovered. In our study, we examined the significant influence of DHRS7 on the tumor microenvironment (TME) and tumor progression using an overall predictable and prognostic evaluation approach. We found novel cancer staging, particularly in KIRC, as well as potential therapeutic drugs out of 27 drug sensitivity tests. Using Perl scripts, it was possible to determine the number of somatic mutations present in 33 tumors, as well as the relative scores of 22 immune cells using CIBERSORT, the relationship between immune infiltration and differential expression using TCGA data, and the immune microenvironment score using the estimate technique. Our results show that DHRS7 is abnormally expressed in pan-cancer patients, which influences their survival. Low DHRS7 expression was associated with late clinical stages and a low survival rate in KIRC patients, suggesting a poor prognosis and course of treatment, in HNSG, MESO, and KIRC patients. We also found that DHRS7 was associated with TMB and MSI in certain tumors. Using KIRC as an example, we discovered a negative correlation between DHRS7 expression and immunological assessments, suggesting that this substance might be used as a tumor biomarker.

Identification and verification of the prognostic value of CUL7 in colon adenocarcinoma.

CUL7, a gene composed of 26 exons associated with cullin 7 protein, is also an E3 ligase that is closely related to cell senescence, apoptosis, and cell transformation and also plays an important role in human cancer. However, there is no systematic pan-cancer analysis has been performed to explore its role in prognosis and immune prediction. In this study, the expression of CUL7 in colon adenocarcinoma (COAD) was investigated to determine its prognosis value. First, based on the Cancer Genome Atlas (TCGA), Genotypic-Tissue Expression Project(GTEx), Cancer Cell Line Encyclopedias(CCLE), and TISIDB database, the potential role of CUL7 in different tumors was explored. Subsequently, the expression of CUL7 in COAD was explored and verified by Immunohistochemistry (IHC). Furthermore, the mutation frequency of CUL7 in COAD was analyzed, and the prognostic value of CUL7 in COAD was discussed. In addition, the nomogram was constructed, and its prognostic value was verified by follow-up data from Jiangmen Central Hospital. Finally, PPI network analysis explored the potential biological function of CUL7 in COAD. The results show that CUL7 is upregulated in most tumors, which is significantly associated with poor survival. At the same time, CUL7 is correlated with the clinical stage and immune landscape of various tumors. In colorectal cancer, CUL7 was overexpressed in tumor tissues by IHC with a mutation frequency of about 4%. CUL7 is an independent prognostic factor for colorectal cancer. The nomogram constructed has effective predictive performance, and external databases proved the prognostic value of CUL7. In addition, PPI network analysis showed that CUL7 was closely related to FBXW8, and further pathway enrichment analysis showed that CUL7 was mainly involved in ubiquitin-mediated proteolysis. Therefore, our study provides a comprehensive understanding of the potential role of CUL7 in different tumors, and CUL7 might be a prognostic marker for COAD.

CLP1 is a Prognosis-Related Biomarker and Correlates With Immune Infiltrates in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, heterogeneous autoimmune disease with a high disability rate that seriously affects society and individuals. However, there is a lack of effective and reliable diagnostic markers and therapeutic targets. In this study, we identified diagnostic markers of RA based on RNA modification and explored its role as well as degree of immune cell infiltration. We used the gene expression profile data of three synovial tissues (GSE55235, GSE55457, GSE77298) from the Gene Expression Omnibus (GEO) database and the gene of 5 RNA modification genes (including m6A, m1A, m5C, APA, A-1), combined with cluster analysis, identified four RNA modifiers closely related to RA (YTHDC1, LRPPRC, NOP2, and CLP1) and five immune cells namely T cell CD8, CD4 memory resting, T cells regulatory (Tregs) Macrophages M0, and Neutrophils. Based on the LASSO regression algorithm, hub genes and immune cell prediction models were established respectively in RA and a nomogram based on the immune cell model was built. Around 4 key RNA modification regulator genes, miRNA-mRNA, mRNA-TF networks have been established, and GSEA-GO, KEGG-GSEA enrichment analysis has been carried out. Finally, CLP1 was established as an effective RA diagnostic marker, and was highly positively correlated with T cells follicular helper (Tfh) infiltration. On the other hand, highly negatively correlated with the expression of mast cells. In short, CLP1 may play a non-negligible role in the onset and development of RA by altering immune cell infiltration, and it is predicted to represent a novel target for RA clinical diagnosis and therapy.

Efficacy of topical and systemic transplantation of mesenchymal stem cells in a rat model of diabetic ischemic wounds.

BACKGROUND: Mesenchymal stem cells (MSCs) exert positive effects in chronic wounds. However, critical parameters, such as the most effective administration routes, remain unclear. Accordingly, the purpose of this study was to compare the effects of topical and systemic transplantation MSCs on diabetic ischemic wound healing and explored the underlying mechanisms. METHOD: A diabetic ischemic wound model was created on the dorsal foot of type 2 diabetes mellitus (T2DM) rat. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were administered via two routes: topical injection and intravenous (IV) infusion. Wound healing outcomes and blood glucose level were assessed dynamically. Meanwhile, blood flow recovery was evaluated in ischemic gastrocnemius muscles. The homing and transdifferentiation of mKate2-labeled BM-MSCs were assessed by fluorescence imaging and immunohistochemistry (IHC) analysis. RESULT: Both topical and systemic treatments had a positive effect on the diabetic ischemic wound showing a significant reduction in wound area at day 14. Histological results showed an increase in the length of epithelial edges, collagen content, microvessel density in the wound bed, and a higher expression of vascular endothelial growth factor (VEGF). Meanwhile, systemic administration can ameliorate hyperglycemia and improve the blood perfusion of the ischemic hindlimb. BM-MSCs administered systemically were found distributed in wounded tissue and transdifferentiated into endothelial cells. Furthermore, BM-MSCs stimulated angiogenesis at wound sites by downregulating phosphatase and tensin homolog (PTEN) and activation of AKT signaling pathway. CONCLUSIONS: The results demonstrated that both transplantation delivery method (topical and systemic) of BM-MSCs accelerated wound healing remarkably under pathological conditions. Nevertheless, systemic administration has the potential to ameliorate hyperglycemia and repair the damaged tissue.