Revealing mitf functions and visualizing allografted tumor metastasis in colorless and immunodeficient Xenopus tropicalis.

Transparent immunodeficient animal models not only enhance in vivo imaging investigations of visceral organ development but also facilitate in vivo tracking of transplanted tumor cells. However, at present, transparent and immunodeficient animal models are confined to zebrafish, presenting substantial challenges for real-time, in vivo imaging studies addressing specific biological inquiries. Here, we employed a mitf-/-/prkdc-/-/il2rg-/- triple-knockout strategy to establish a colorless and immunodeficient amphibian model of Xenopus tropicalis. By disrupting the mitf gene, we observed the loss of melanophores, xanthophores, and granular glands in Xenopus tropicalis. Through the endogenous mitf promoter to drive BRAFV600E expression, we confirmed mitf expression in melanophores, xanthophores and granular glands. Moreover, the reconstruction of the disrupted site effectively reinstated melanophores, xanthophores, and granular glands, further highlighting the crucial role of mitf as a regulator in their development. By crossing mitf-/- frogs with prkdc-/-/il2rg-/- frogs, we generated a mitf-/-/prkdc-/-/il2rg-/- Xenopus tropicalis line, providing a colorless and immunodeficient amphibian model. Utilizing this model, we successfully observed intravital metastases of allotransplanted xanthophoromas and migrations of allotransplanted melanomas. Overall, colorless and immunodeficient Xenopus tropicalis holds great promise as a valuable platform for tumorous and developmental biology research.

Is It Necessary to Cross the Cervicothoracic Junction in Posterior Cervical Decompression and Fusion for Multilevel Degenerative Cervical Spine Disease? A Systematic Review and Meta-Analysis.

BACKGROUND: Posterior cervical decompression and fusion (PCF) is a common procedure for treating patients with multilevel degenerative cervical spine disease. The selection of lower instrumented vertebra (LIV) relative to the cervicothoracic junction (CTJ) remains controversial. This study aimed to compare the outcomes of PCF construct terminating at the lower cervical spine and crossing the CTJ. METHODS: A comprehensive literature search was performed for relevant studies in the PubMed, EMBASE, Web of Science, and Cochrane Library database. Complications, rate of reoperation, surgical data, patient-reported outcomes (PROs), and radiographic outcomes were compared between PCF construct terminating at or above C7 (cervical group) and at or below T1 (thoracic group) in patients with multilevel degenerative cervical spine disease. A subgroup analysis based on surgical techniques and indications was performed. RESULTS: Fifteen retrospective cohort studies comprising 2071 patients (1163 in the cervical group and 908 in the thoracic group) were included. The cervical group was associated with a lower incidence of wound-related complications (RR, 0.58; 95% CI 0.36 to 0.92, p = 0.022; 831 patients in cervical group vs. 692 patients in thoracic group), a lower reoperation rate for wound-related complications (RR, 0.55; 95% CI 0.32 to 0.96, p = 0.034; 768 vs. 624 patients), and less neck pain at the final follow-up (WMD, -0.58; 95% CI -0.93 to -0.23, p = 0.001; 327 vs. 268 patients). However the cervical group also developed a higher incidence of overall adjacent segment disease (ASD, including distal ASD and proximal ASD) (RR, 1.87; 95% CI 1.27 to 2.76, p = 0.001; 1079 vs. 860 patients), distal ASD (RR, 2.18; 95% CI 1.36 to 3.51, p = 0.001; 642 vs. 555 patients), overall hardware failure (including hardware failure of LIV and hardware failure occurring at other instrumented vertebra) (RR, 1.48; 95% CI 1.02 to 2.15, p = 0.040; 614 vs. 451 patients), and hardware failure of LIV (RR, 1.89; 95% CI 1.21 to 2.95, p = 0.005; 380 vs. 339 patients). The operating time was reasonably shorter (WMD, -43.47; 95% CI -59.42 to -27.52, p < 0.001; 611 vs. 570 patients) and the estimated blood loss was lower (WMD, -143.77; 95% CI -185.90 to -101.63, p < 0.001; 721 vs. 740 patients) when the PCF construct did not cross the CTJ. CONCLUSIONS: PCF construct crossing the CTJ was associated with a lower incidence of ASD and hardware failure but a higher incidence of wound-related complications and a small increase in qualitative neck pain, without difference in neck disability on the NDI. Based on the subgroup analysis for surgical techniques and indications, prophylactic crossing of the CTJ should be considered for patients with concurrent instability, ossification, deformity, or a combination of anterior approach surgeries as well. However, long-term follow-up outcomes and patient selection-related factors such as bone quality, frailty, and nutrition status should be addressed in further studies.

Disruption of tp53 leads to cutaneous nevus and melanoma formation in Xenopus tropicalis.

In humans, germline TP53 mutations predispose carriers to a wide spectrum of cancers, which is known as Li-Fraumeni syndrome (LFS). To date, the association of melanomas with LFS remains unestablished. No melanomas have been reported in any P53-modified mouse models either. In this study, we show that targeted disruption of P53 at the DNA-binding domain in Xenopus tropicalis recapitulates LFS, with the formation of soft-tissue sarcomas and pancreatic ductal adenocarcinoma. Interestingly, 19% of the 14-month-old tp53Δ7/Δ7 homozygotes and 18% of tp53+/Δ7 heterozygotes spontaneously developed small nevi and non-invasive melanomas. Large invasive melanomas were also observed in other older homozygous mutants, with about 7.9% penetrance. Our data suggest that more dermatologic investigation of LFS patients should be able to settle the association of melanoma with LFS in epidemiology. Our model is also valuable for further investigation of the molecular mechanism underlying melanoma progression upon germline alteration of the tp53 locus.