Machine learning based gray-level co-occurrence matrix early warning system enables accurate detection of colorectal cancer pelvic bone metastases on MRI.

Objective: The mortality of colorectal cancer patients with pelvic bone metastasis is imminent, and timely diagnosis and intervention to improve the prognosis is particularly important. Therefore, this study aimed to build a bone metastasis prediction model based on Gray level Co-occurrence Matrix (GLCM) - based Score to guide clinical diagnosis and treatment. Methods: We retrospectively included 614 patients with colorectal cancer who underwent pelvic multiparameter magnetic resonance image(MRI) from January 2015 to January 2022 in the gastrointestinal surgery department of Gezhouba Central Hospital of Sinopharm. GLCM-based Score and Machine learning algorithm, that is,artificial neural net7work model(ANNM), random forest model(RFM), decision tree model(DTM) and support vector machine model(SVMM) were used to build prediction model of bone metastasis in colorectal cancer patients. The effectiveness evaluation of each model mainly included decision curve analysis(DCA), area under the receiver operating characteristic (AUROC) curve and clinical influence curve(CIC). Results: We captured fourteen categories of radiomics data based on GLCM for variable screening of bone metastasis prediction models. Among them, Haralick_90, IV_0, IG_90, Haralick_30, CSV, Entropy and Haralick_45 were significantly related to the risk of bone metastasis, and were listed as candidate variables of machine learning prediction models. Among them, the prediction efficiency of RFM in combination with Haralick_90, Haralick_all, IV_0, IG_90, IG_0, Haralick_30, CSV, Entropy and Haralick_45 in training set and internal verification set was [AUC: 0.926,95% CI: 0.873-0.979] and [AUC: 0.919,95% CI: 0.868-0.970] respectively. The prediction efficiency of the other four types of prediction models was between [AUC: 0.716,95% CI: 0.663-0.769] and [AUC: 0.912,95% CI: 0.859-0.965]. Conclusion: The automatic segmentation model based on diffusion-weighted imaging(DWI) using depth learning method can accurately segment the pelvic bone structure, and the subsequently established radiomics model can effectively detect bone metastases within the pelvic scope, especially the RFM algorithm, which can provide a new method for automatically evaluating the pelvic bone turnover of colorectal cancer patients.

[Clinical effect of multicenter multidisciplinary treatment in children with renal malignant tumors].

OBJECTIVE: To study the long-term clinical effect of multicenter multidisciplinary treatment (MDT) in children with renal malignant tumors. METHODS: A retrospective analysis was performed on the medical data of 55 children with renal malignant tumors who were diagnosed and treated with MDT in 3 hospitals in Hunan Province from January 2015 to January 2020, with GD-WT-2010 and CCCG-WT-2016 for treatment regimens. A Kaplan-Meier survival analysis was used to analyze the survival of the children. RESULTS: Of the 55 children, 10 had stage I tumor, 14 had stage Ⅱ tumor, 22 had stage Ⅲ tumor, 7 had stage IV tumor, and 2 had stage V tumor. As for pathological type, 47 had FH type and 8 had UFH type. All children underwent complete tumor resection. Of the 55 children, 14 (25%) received preoperative chemotherapy. All children, except 1 child with renal cell carcinoma, received postoperative chemotherapy. Among the 31 children with indication for radiotherapy, 21 (68%) received postoperative radiotherapy. One child died of postoperative metastasis. The incidence rate of FH-type myelosuppression was 94.4%, and the incidence rate of UFH-type myelosuppression was 100%. The median follow-up time was 21 months and the median survival time was 26 months for all children, with an overall survival rate of 98% and an event-free survival rate of 95%. CONCLUSIONS: Multicenter MDT has the advantages of high success rate of operation and good therapeutic effect of chemotherapy in the treatment of children with renal malignant tumors, with myelosuppression as the most common side effects, and radiotherapy is safe and effective with few adverse events. Therefore, MDT has good feasibility, safety, and economy.

Optimization of the adipose-derived mesenchymal stem cell delivery time for radiation-induced lung fibrosis treatment in rats.

The present study attempts to identify the optimal time duration for the administration of Ad-MSCs, in order to maximize its therapeutic benefits, and compare the degree of fibrosis among three different administration time points using the RILF rat model system. Ad-MSCs were delivered to Sprague-Dawley rats through the tail vein at the following different time points after thorax irradiation: two hours, seven days, and two hours + seven days. Post Ad-MSCs transplantation and the histopathological analysis of the lungs were performed along with analysis of inflammatory cytokine levels, including interleukin (IL)-1, IL-2, IL-6, IL-10 and tumor necrosis factor-α (TNF-α). In particular, pro-fibrotic factors (TGF-ß1 and α-SMA) were also evaluated in serum and lung tissues. In addition, it was also determined whether Ad-MSCs had any role in inhibiting the transition of type II alveolar epithelial cells into fibroblasts in the lungs of injured rats. The present results demonstrated that the intravenous delivery of Ad-MSCs twice at the 2-hour and 7-day (R + MSC2h+7d group) was effective in reducing lung fibrosis for long term durations, when compared with single delivery either at the two-hour or 7-day time points. In addition, a marked anti-inflammatory effect was also observed in RILF rats in the R + MSC2h+7d group, as indicated by the reduced serum levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) and increased levels of anti-inflammatory cytokines IL-10 and IL-2. Rats that were delivered twice with Ad-MSCs (R + MSC2h+7d group) exhibited significantly reduced TGF-ß1 and α-SMA levels, in contrast to rats in the R + MSC7d or R + MSC2h groups, after four weeks. Furthermore, it was also noted that after four weeks, Ad-MSCs increased the number of lung epithelial cells (SP-C) and inhibited the lung fibroblastic cells (α-SMA) of rats in the R + MSC2h and R + MSC2h+7d groups. The present study concluded that two injections of Ad-MSCs (R + MSC2h+7d group) appear to be optimal for therapeutic efficacy and safety during RILF.

Ultrasound diagnosis and follow-up of Takayasu arteritis with femoral vein involvement.

Takayasu arteritis (TA) is a form of chronic vasculitis that mainly affects the aorta and its main branches, most commonly in young female patients. The pathogenesis of the disease remains unclear, and the clinical manifestations are nonspecific. Therefore, misdiagnosis of the disease is considered to be common. Moreover, to the best of our knowledge, TA affecting veins has not been reported. Here we report a case of an adolescent with TA affecting the femoral vein as diagnosed by ultrasound.

Salt-inducible Kinase (SIK1) regulates HCC progression and WNT/ß-catenin activation.

BACKGROUND & AIMS: In this study, we investigated the role of salt-inducible kinase 1 (SIK1) and its possible mechanisms in human hepatocellular carcinoma (HCC). METHODS: Immunoprecipitation, immunohistochemistry, luciferase reporter, Chromatin immunoprecipitation, in vitro kinase assays and a mouse model were used to examine the role of SIK1 on the ß-catenin signaling pathway. RESULTS: SIK1 was significantly downregulated in HCC compared with normal controls. Its introduction in HCC cells markedly suppresses epithelial-to-mesenchymal transition (EMT), tumor growth and lung metastasis in xenograft tumor models. The effect of SIK1 on tumor development occurs at least partially through regulation of ß-catenin, as evidenced by the fact that SIK1 overexpression leads to repression of ß-catenin transcriptional activity, while SIK1 depletion has the opposite effect. Mechanistically, SIK1 phosphorylates the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) at threonine (T)1391, which promotes the association of nuclear receptor corepressor (NCoR)/SMRT with transducin-beta-like protein 1 (TBL1)/transducing-beta-like 1 X-linked receptor 1 (TBLR1) and disrupts the binding of ß-catenin to the TBL1/TBLR1 complex, thereby inactivating the Wnt/ß-catenin pathway. However, SMRT-T1391A reverses the phenotype of SIK1 and promotes ß-catenin transactivation. Twist1 is identified as a critical factor downstream of SIK1/ß-catenin axis, and Twist1 knockdown (Twist1(KD)) reverses SIK1(KD)-mediated changes, whereas SIK1(KD)/Twist1(KD) double knockdown cells were less efficient in establishing tumor growth and metastasis than SIK1(KD) cells. The promoter activity of SIK1 were negatively regulated by Twist1, indicating that a double-negative feedback loop exists. Importantly, levels of SIK1 inversely correlate with Twist1 expression in human HCC specimens. CONCLUSIONS: Our findings highlight the critical roles of SIK1 and its targets in the regulation of HCC development and provides potential new candidates for HCC therapy.

Intravenous delivery of adipose-derived mesenchymal stromal cells attenuates acute radiation-induced lung injury in rats.

BACKGROUND AIMS: Radiation-induced lung injury (RILI) commonly occurs in patients with thoracic cancer. However, an effective treatment option has not yet been established. Adipose-derived mesenchymal stromal cells (Ad-MSCs) have significant potential for clinical use, but their role in RILI is currently unknown. We aimed to evaluate the therapeutic capacity of Ad-MSCs to heal acute RILI in rats. METHODS: Sprague-Dawley rats were used in this study. Rat Ad-MSCs were delivered through the tail veins of rats 2 h after thorax irradiation. Lung histopathologic findings, pulmonary levels of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-10 and tumor necrosis factor-α), pro-fibrotic factors (transforming growth factor [TGF]-ß1, connective tissue growth factor, α-smooth muscle actin and type 1 collagen), pro- or anti-apoptotic mediators (Bcl-2, Bax and caspase-3) and the multifunctional factor hepatocyte growth factor were evaluated after Ad-MSC transplant. RESULTS: Intravenous delivery of Ad-MSCs attenuated acute RILI. Further studies showed that Ad-MSCs had anti-inflammation and anti-fibrotic effects and maintained lung epithelium integrity, as indicated by reduced serum levels of the pro-inflammatory cytokines IL-1, IL-6 and tumor necrosis factor-α, increased levels of the anti-inflammatory cytokine IL-10, and downregulated transforming growth factor -ß1, α-smooth muscle actin and type 1 collagen levels in irradiated lung tissues. Ad-MSCs also regulated the expression of pro- and anti-apoptotic mediators (Bcl-2, Bax and caspase-3) to protect lung cells from apoptosis. CONCLUSIONS: Intravenous Ad-MSC delivery attenuated acute RILI through anti-inflammation, anti-fibrosis and anti-apoptosis mechanisms.