A single-cell analysis reveals tumor heterogeneity and immune environment of acral melanoma.

Acral melanoma is a dismal subtype of melanoma occurring in glabrous acral skin, and has a higher incidence in East Asians. We perform single-cell RNA sequencing for 63,394 cells obtained from 5 acral and 3 cutaneous melanoma samples to investigate tumor heterogeneity and immune environment. We define 5 orthogonal functional cell clusters that are involved in TGF-beta signaling, Type I interferon, Wnt signaling, Cell cycle, and Cholesterol efflux signaling. Signatures of enriched TGF-beta, Type I interferon, and cholesterol efflux signaling are significantly associated with good prognosis of melanoma. Compared with cutaneous melanoma, acral melanoma samples have significantly severe immunosuppressive state including depletion of cytotoxic CD8+ T cells, enrichment of Treg cells, and exhausted CD8+ T cells. PD1 and TIM-3 have higher expression in the exhaustive CD8+ T cells of acral melanoma. Key findings are verified in two independent validation sets. This study contributes to our better understanding of acral melanoma.

Postoperative Adjuvant Radiotherapy Can Delay the Recurrence of Desmoid Tumors After R0 Resection in Certain Subgroups.

Background: When patients with desmoid tumors (DTs) present uncontrolled clinical symptoms, surgery is an effective treatment, but the high postoperative recurrence rate is a major problem. The significance of adjuvant radiotherapy has been debated for many years, and the significance of aggressive surgery has not been reported. Methods: Medical records for DT patients were collected. KM analysis and the Mann-Whitney U-test were performed to evaluate the role of radiotherapy and aggressive surgery in the entire cohort and different subgroups. Results: Of 385 DT patients, 267 patients with R0 resection were included in the final analysis. A total of 53 patients (19.85%) experienced recurrence. Although radiotherapy showed no significant effect on recurrence-free survival (RFS) or time to recurrence (TTR) in the entire cohort, radiotherapy delayed recurrence in the age ≤ 30 years old subgroup (TTR = 35 months with surgery plus radiotherapy, TTR = 11 months with surgery alone; p = 0.014) and the tumor diameter >5 cm subgroup (TTR = 26 months with surgery plus radiotherapy, TTR = 11 months with surgery alone; p = 0.02) among patients with a single tumor. Aggressive surgery improved RFS in the tumor diameter >5 cm subgroup (p = 0.049) but not the entire cohort. Conclusions: Although radiotherapy cannot improve RFS, it can delay recurrence in the age ≤ 30 years old subgroup and the tumor diameter >5 cm subgroup among patients with a single tumor. For patients with large invasive tumors and multiple involved sites, aggressive surgery could be selected to achieve complete tumor resection to improve RFS.

Corrigendum: Development, Validation, and Visualization of A Web-Based Nomogram for Predicting the Recurrence-Free Survival Rate of Patients With Desmoid Tumors.

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Efficiency comparison of B6(Cg)-Tyrc-2j /J and C57BL/6NTac embryos as hosts for the generation of knockout mice.

Careful selection of the host embryo is critical to the efficient production of knockout (KO) mice when injecting mouse embryonic stem (mES) cells into blastocysts. B6(Cg)-Tyrc-2j/J (B6 albino) and C57BL/6NTac (B6NTac) strains of mice are widely used to produce host blastocysts for such procedures. Here, we tested these two strains to identify an appropriate match for modified agouti C57BL/6N (JM8A3.N1) mES cells. When comparing blastocyst yield, super-ovulated B6NTac mice produced more injectable blastocysts per female than B6 albino mice (8.2 vs. 5.4). There was no significant difference in birth rate when injected embryos were transferred to the same pseudopregnant recipient strain. However, the live birth rate was significantly higher for B6NTac blastocysts than B6 albino blastocysts (62.7% vs. 50.2%). In addition, the proportion of pups exhibiting high-level and complete chimerism, as identified by coat color, was also significantly higher in the B6NTac strain. There was no obvious difference in the efficiency of germline transmission (GLT) when compared between B6NTac and B6 albino host embryos (61.5% vs. 63.3% for mES clones; 64.5% vs. 67.9% for genes, respectively), thus suggesting that an equivalent GLT rate could be obtained with only a few blastocyst injections for B6NTac embryos. In conclusion, our data indicate that B6NTac blastocysts are a better choice for the microinjection of JM8A3.N1 mES cells than B6 albino blastocysts.

Development, Validation, and Visualization of A Web-Based Nomogram for Predicting the Recurrence-Free Survival Rate of Patients With Desmoid Tumors.

Background: Surgery is an important treatment option for desmoid tumor (DT) patients, but how to decrease and predict the high recurrence rate remains a major challenge. Methods: Desmoid tumor patients diagnosed and treated at Tianjin Cancer Institute & Hospital were included, and a web-based nomogram was constructed by screening the recurrence-related risk factors using Cox regression analysis. External validation was conducted with data from the Fudan University Shanghai Cancer Center. Results: A total of 385 patients were identified. Finally, after excluding patients without surgery, patients who were lost to follow-up, and patients without complete resection, a total of 267 patients were included in the nomogram construction. Among these patients, 53 experienced recurrence, with a recurrence rate of 20.15%. The 3-year and 5-year recurrence-free survival (RFS) rates were 82.5% and 78%, respectively. Age, tumor diameter, admission status, location, and tumor number were correlated with recurrence in univariate Cox analysis. In multivariate Cox analysis, only age, tumor diameter and tumor number were independent risk factors for recurrence and were then used to construct a web-based nomogram to predict recurrence. The concordance index (C-index) of the nomogram was 0.718, and the areas under the curves (AUCs) of the 3-year and 5-year receiver operating characteristic (ROC) curves were 0.751 and 0.761, respectively. In the external validation set, the C-index was 0.706, and the AUCs of the 3-year and 5-year ROC curves are 0.788 and 0.794, respectively. Conclusions: Age, tumor diameter, and tumor number were independent predictors of recurrence for DTs, and a web-based nomogram containing these three predictors could accurately predict RFS (https://stepforward.shinyapps.io/Desmoidtumor/).

Endothelial progenitor cells as the target for cardiovascular disease prediction, personalized prevention, and treatments: progressing beyond the state-of-the-art.

Stimulated by the leading mortalities of cardiovascular diseases (CVDs), various types of cardiovascular biomaterials have been widely investigated in the past few decades. Although great therapeutic effects can be achieved by bare metal stents (BMS) and drug-eluting stents (DES) within months or years, the long-term complications such as late thrombosis and restenosis have limited their further applications. It is well accepted that rapid endothelialization is a promising approach to eliminate these complications. Convincing evidence has shown that endothelial progenitor cells (EPCs) could be mobilized into the damaged vascular sites systemically and achieve endothelial repair in situ, which significantly contributes to the re-endothelialization process. Therefore, how to effectively capture EPCs via specific molecules immobilized on biomaterials is an important point to achieve rapid endothelialization. Further, in the context of predictive, preventive, personalized medicine (PPPM), the abnormal number alteration of EPCs in circulating blood and certain inflammation responses can also serve as important indicators for predicting and preventing early cardiovascular disease. In this contribution, we mainly focused on the following sections: the definition and classification of EPCs, the mechanisms of EPCs in treating CVDs, the potential diagnostic role of EPCs in predicting CVDs, as well as the main strategies for cardiovascular biomaterials to capture EPCs.

Association of the presence of microangiopathy with adverse pregnancy outcome in type 1 diabetes: A meta-analysis.

OBJECTIVE: Microangiopathy is common after a long duration in type 1 diabetes mellitus (T1DM). Pregnancies with end-age vascular complications are a big challenge to multidisciplinary physicians. The objective of this study was to assess the risk of microangiopathy for adverse pregnancy outcome in T1DM. MATERIALS AND METHODS: PubMed, EMBASE, and Cochrane Library databases were searched for relevant articles appearing in the literature up to October 1, 2017. Analysis of cohort studies were performed with Review Manager 5.3 and Newcastle Ottawa Scale (NOS) was chosen to evaluate the risk of bias. RESULTS: A total of 10 studies involving 3239 pregnancies were retrieved and analyzed. Microangiopathy for diabetic nephropathy (DN), microalbuminuria and diabetic retinopathy (DR) significantly increased the risk of preeclampsia (PE) (OR of 7.19, [95%CI: 5.15, 10.03], 4.19, [95%CI: 2.78, 6.31] and 3.02, [95%CI: 2.24, 4.07], respectively). Significant association of the presence of DN with preterm delivery was demonstrated (OR = 4.14, 95%CI [2.84, 6.02]), with small for gestation age was demonstrated (OR = 6.23, 95%CI [2.75, 14.14]) and with large for gestation age was demonstrated (OR = 0.41, 95%CI [0.27, 0.62]). A mild association of the presence of DR with preterm delivery was demonstrated (OR = 1.57, 95%CI [1.08, 2.29]). CONCLUSION: The presence of microangiopathy before or in early pregnancy increased the risk of adverse pregnancy outcome in T1DM. We highlighted it was important that White's classification and a full assessment of vasculopathy should be carry out before pregnancy to ensure a well-planned pregnancy. Further work should be designed to establish risks model involving microangiopathy and find out whether early intervention with strict blood sugar control or medication such as low-dose aspirin will reduce the incidence of PE in T1DM.