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This study explored results of therapy of children with acute lymphoblastic leukemia (ALL) in China, recent progress, and challenges. Included are a survey of therapy outcomes of ALL in Chinese children nationwide, comparison of these data with global ALL therapy outcomes, analyses of obstacles to improving outcomes, and suggestions of how progress can be achieved. Therapy outcomes at many Chinese pediatric cancer centers are approaching those of resource-rich countries. However, nationwide outcomes still need improvement. Obstacles include suboptimal clinical trials participation, children without adequate health care funding, human resource shortages, especially physicians expert in pediatric hematology and oncology, and social-economic disparities. We suggest how these obstacles have been and continue to be remedied including expanded access to protocol-based therapy, improved supportive care, health care reforms, recruitment of trained personnel, and international collaborations. China has made substantial progress treating children with ALL. We envision even better outcomes in the near future.

Purpose: Prediction models for acute myeloid leukemia (AML) are useful, but have considerable inaccuracy and imprecision. No current model includes covariates related to immune cells in the AML microenvironment. Here, an immune risk score was explored to predict the survival of patients with AML. Experimental Design: We evaluated the predictive accuracy of several in silico algorithms for immune composition in AML based on a reference of multi-parameter flow cytometry. CIBERSORTx was chosen to enumerate immune cells from public datasets and develop an immune risk score for survival in a training cohort using least absolute shrinkage and selection operator Cox regression model. Results: Six flow cytometry–validated immune cell features were informative. The model had high predictive accuracy in the training and four external validation cohorts. Subjects in the training cohort with low scores had prolonged survival compared with subjects with high scores, with 5-year survival rates of 46% versus 19% (P < 0.001). Parallel survival rates in validation cohorts-1, -2, -3, and -4 were 46% versus 6% (P < 0.001), 44% versus 18% (P = 0.041), 44% versus 24% (P = 0.004), and 62% versus 32% (P < 0.001). Gene set enrichment analysis indicated significant enrichment of immune relation pathways in the low-score cohort. In multivariable analyses, high-risk score independently predicted shorter survival with HRs of 1.45 (P = 0.005), 2.12 (P = 0.004), 2.02 (P = 0.034), 1.66 (P = 0.019), and 1.59 (P = 0.001) in the training and validation cohorts, respectively. Conclusions: Our immune risk score complements current AML prediction models.

Myelodysplastic syndrome (MDS) is clonal disease featured by ineffective haematopoiesis and potential progression into acute myeloid leukaemia (AML). At present, the risk stratification and prognosis of MDS need to be further optimized. A prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis for MDS patients based on the identified metabolic gene panel in training cohort, followed by external validation in an independent cohort. The patients with lower risk had better prognosis than patients with higher risk. The constructed model was verified as an independent prognostic factor for MDS patients with hazard ratios of 3.721 (1.814‐7.630) and 2.047 (1.013‐4.138) in the training cohort and validation cohort, respectively. The AUC of 3‐year overall survival was 0.846 and 0.743 in the training cohort and validation cohort, respectively. The high‐risk score was significantly related to other clinical prognostic characteristics, including higher bone marrow blast cells and lower absolute neutrophil count. Moreover, gene set enrichment analyses (GSEA) showed several significantly enriched pathways, with potential indication of the pathogenesis. In this study, we identified a novel stable metabolic panel, which might not only reveal the dysregulated metabolic microenvironment, but can be used to predict the prognosis of MDS.

A numerical investigation is performed into the effects of rigid and compliant suspension linkages, respectively, on: the kinematics and handling performance of a lightweight electric vehicle (EV). CAE models of the front and rear suspension systems are first established based on the measured parameters of the target vehicle. The validity of the CAE models is confirmed by comparing the results obtained for the camber angle and kingpin inclination angle with those obtained mathematically using the vector loop method. CAE models are then performed using half-vehicle and whole-vehicle models. Quarter-vehicle simulations are then performed to compare the solutions obtained from the compliance and rigid-body models for the forces acting on the hardpoints of the two suspension systems under pothole impact conditions. Finally, whole-vehicle simulations are conducted using both the rigid-body model and the compliance model to evaluate the handling performance of the EV in impulse steering tests conducted at vehicle speeds of 40, 60 and 80 km h−1, respectively. In general, the results show that the choice of a rigid-body model or a compliance model has a significant effect on the forces computed at some of the hardpoints in the front and rear suspension systems. Furthermore, the rigid-body model predicts a better vehicle body stability following high-speed turns than the compliance model.

Purpose. To evaluate the effect of puncture sites of the portal vein in transjugular intrahepatic portosystemic shunt (TIPS) on long-term clinical efficacy. Methods. A retrospective review was performed, including consecutive 171 patients who underwent TIPS with ePTFE-covered stents. All patients were divided into 3 groups according to the puncture site of the portal vein: intrahepatic bifurcation of the portal vein (group A, n=88), right branch of the portal vein (group B, n=48), and left branch of the portal vein (group C, n=35). The Kaplan-Meier analysis was performed to assess the effect of different puncture sites on primary patency, the incidence of hepatic encephalopathy (HE), and survival. Results. The primary restenosis rate was 29.8% (51/171). The total HE rate was 31.6% (54/171). The cumulative death rate was 19.3% (33/171). The Kaplan-Meier analysis showed that group C versus group A, group C versus group B, and group A versus group B were significantly different on the primary restenosis rate, respectively (χ2 = 11.49, P=0.001; χ2 = 4.54, P=0.033; and χ2 = 4.12, P=0.046), and group C is better than the other two groups. What is more, group C versus group A and group C versus group B were significantly different on the incidence of HE, respectively (χ2 = 8.07, P=0.004; χ2 = 9.44, P=0.002), and group C is better than the other two groups. There was no significant difference on survival. Conclusion. Choosing the left branch of the portal vein as the puncture site to create the shunt in TIPS with ePTFE-covered stents may decrease the incident of primary restenosis and HE significantly.

Purpose: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells epithelial–mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells’ EMT and explored their regulatory mechanisms and clinical significance in UCBs. Experimental Design: We first screened circRNA expression profiles using a circRNA microarray in paired UCB and normal tissues, and then studied the clinical significance of an upregulated circRNA, circPRMT5, in a large cohort of patients with UCB. We further investigated the functions and underlying mechanisms of circPRMT5 in UCB cells’ EMT. Moreover, we evaluated the regulation effect of circPRMT5 on miR-30c, and its target genes, SNAIL1 and E-cadherin, in two independent cohorts from our institute and The Cancer Genome Atlas (TCGA). Results: We demonstrated that upregulated expression of circPRMT5 was positively associated with advanced clinical stage and worse survival in patients with UCB. We further revealed that circPRMT5 promoted UCB cell's EMT via sponging miR-30c. Clinical analysis from two independent UCB cohorts showed that the circPRMT5/miR-30c/SNAIL1/E-cadherin pathway was essential in supporting UCB progression. Importantly, we identified that circPRMT5 was upregulated in serum and urine exosomes from patients with UCB, and significantly correlated with tumor metastasis. Conclusions: CircPRMT5 exerts critical roles in promoting UCB cells’ EMT and/or aggressiveness and is a prognostic biomarker of the disease, suggesting that circPRMT5 may serve as an exploitable therapeutic target for patients with UCB.

Background: Acute myelogenous leukemia (AML) is a heterogeneous disease with recurrent gene mutations and variations in disease-associated gene expression, which may be useful for prognostic prediction.Methods: RNA matrix and clinical data of AML were downloaded from GEO, TCGA, and TARGET databases. Prognostic metabolic genes were identified by LASSO analysis to establish a metabolic model. Prognostic accuracy of the model was quantified by time-dependent receiver operating characteristic curves and the area under the curve (AUC). Survival analysis was performed by log-rank tests. Enriched pathways in different metabolic risk statuses were evaluated by gene set enrichment analyses (GSEA).Results: We identified nine genes to construct a prognostic model of shorter survival in the high-risk vs. low-risk group. The prognostic model showed good predictive efficacy, with AUCs for 5-year overall survival of 0.78 (0.73–0.83), 0.76 (0.62–0.89), and 0.66 (0.57–0.75) in the training, adult external, and pediatric external cohorts, respectively. Multivariable analysis demonstrated that the metabolic signature had independent prognostic value with hazard ratios of 2.75 (2.06–3.66), 1.89 (1.09–3.29), and 1.96 (1.00–3.84) in the training, adult external, and pediatric external cohorts, respectively. Combining metabolic signatures and classic prognostic factors improved 5-year overall survival prediction compared to the prediction by classic prognostic factors (p < 0.05). GSEA revealed that most pathways were metabolism-related, indicating potential mechanisms.Conclusion: We identified dysregulated metabolic features in AML and constructed a prognostic model to predict the survival of patients with AML.

Purpose. To evaluate the technical efficacy and safety of the pull-through technique in recanalization of transjugular intrahepatic portosystemic shunt (TIPS) when standard transjugular approach is inaccessible. Materials and Methods. A retrospective review of patients underwent TIPS revision via the pull-through technique was performed. Transhepatic directly punctured stent was conducted if the portal vein could not be accessed via standard transjugular approach. Technical success was defined by recanalization of shunt. Clinical success was defined as bleeding interruption and ascites regression without pharmacological support. All patients were followed up by clinical evaluation and Doppler ultrasound. Results. Between January 2010 and December 2016, a total of 63 patients underwent TIPS revision, and 14 of them could not be accessed via standard transjugular approaches owing to stenosis or occlusion of the hepatic vein. The pull-through technique was successful in 13 patients, and one patient underwent parallel TIPS. No procedure-related complication was observed. One patient died of liver failure one week after the procedure. During the follow-up, three patients developed hepatic encephalopathy, and one patient developed TIPS dysfunction again and experienced variceal bleeding. The primary patency rate after TIPS revision was 92% (11/12) at 12 months. Conclusion. The pull-through technique was effective and safe for recanalization of TIPS inaccessible via standard transjugular approach.

Background There has been no prospective or retrospective studies reporting the comparison outcome between surgery and ablation for resectable-ablative (lesions could be treated by resection or complete ablation) colorectal liver oligometastases (CLOM). The purpose of this study was to compare the efficacy and prognostic difference in patients who underwent R0 resection vs. complete ablation within the resectable-ablative CLOM criteria. Methods From January 2008 to May 2018, a total of 2,367 patients diagnosed with colorectal liver metastases were included in this observational study. The metastasis was characterized by only limited to liver with number ≤5, size ≤5 cm, and resectable-ablative (lesions could be treated by resection or complete ablation). The evaluated indications, including liver progression-free survival (LPFS), overall survival (OS), survival rates, pattern and number of recurrences, and complications, were compared by using propensity score matching (PSM). The Kaplan−Meier curves were generated, and a log-rank test was performed. The Cox regression model was used for univariate and multivariate analyses to identify predictors of outcomes. Results A total of 421 consecutive patients were eligible for this study, with 250 and 171 undergoing R0 resection and complete ablation, respectively. PSM identified 145 patients from each group. The 1-, 3-, 5- and 8-year OS rates in the resection group and the ablation group were 95.8% vs. 95.0%, 69.8% vs. 60.1%, 53.6% vs. 42.5%, and 45.1% vs. 32.9% (p = 0.075), respectively. The median LPFS in the resection group was significantly longer than that in the ablation group (35 months vs. 15 months, p = 0.011). No statistical difference was found in LPFS between the two groups when comparing ≤3 cm liver metastases. For liver metastasis >3 cm, the median LPFS in the resection group and ablation group was 11 months and 5 months, respectively (p = 0.001). In terms of high risk of clinical risk score (CRS), the resection group showed longer LPFS than the ablation group (median 18 months vs. 10 months, p = 0.043). Conclusion For patients within the CLOM criteria suggesting that liver metastases were resectable as well as ablative, resection could result in longer liver recurrence-free survival than ablation in cases with size >3 cm or high risk of CRS. But for ≤3 cm liver metastases, their treatment efficacies were comparable.

Preoperative lymph node (LN) status is important for the treatment of bladder cancer (BCa). Here, we report a genomic-clinicopathologic nomogram for preoperatively predicting LN metastasis in BCa. In the discovery stage, 325 BCa patients from TCGA were involved and LN-status-related mRNAs were selected. In the training stage, multivariate logistic regression analysis was used to developed a genomic-clinicopathologic nomogram for preoperative LN metastasis prediction in the training set (SYSMH set, n = 178). In the validation stage, we validated the nomogram using two independent sample sets (SYSUCC set, n = 142; RJH set, n = 104) with respect to its discrimination, calibration and clinical usefulness. As results, we identified five LN-status-related mRNAs, including ADRA1D, COL10A1, DKK2, HIST2H3D and MMP11. Then, a genomic classifier was developed to classify patients into high- and low-risk groups in the training set. Furthermore, a nomogram incorporating the five-mRNA-based classifier, image-based LN status, transurethral resection (TUR) T stage, and TUR lymphovascular invasion (LVI) was constructed in the training set, which performed well in the training and validation sets. Decision curve analysis demonstrated the clinical value of our nomogram. Thus, our genomic-clinicopathologic nomogram shows favorable discriminatory ability and may aid in clinical decision-making, especially for cN-patients. Keywords: Genomics, Lymphatic metastasis, Nomogram, Urinary bladder neoplasms

Background: The present prognosis for AML mainly rely on the cyto- and molecular genetic features. However, the bone marrow microenvironment also plays a critical role in the development and progression of the disease, and the immune signature within the bone marrow microenvironment of AML remains unknown, and should be clarified. Patients and methods: Here, we applied the robust algorithm CIBERSORT method to generate the distribution and frequency of 22 immune subsets in the bone marrow of AML from public datasets. The associations between the overall survival and proportions of putative marrow immune cell types were analyzed to generate an immune risk score in a public training cohort according to LASSO cox regression model and validated in other validation cohorts. Gene Set Enrichment Analysis was adopted to analyze the immune risk score associated biological phenotypes. Results: Data from GSE37642 (n = 531) were used for immune model estimation, and samples from GSE425 (n =81) and TCGA (n =111) were served as external cohorts for validation. We first derived the 22 immune subsets through CIBERSORT, and found that monocytes, resting mast cells, eosinophils, CD8+T cells, resting NK cells, resting dendritic cells and resting memory CD4+ T cells were the most represented cell fractions within AML bone marrow microenvironment. LASSO cox regression was then applied to identify a total of 10 immune subsets to generate the immune risk score that may predict the survival prognosis of AML patients. This model has an excellent reproducibility, with the area under curve of the immune risk score at 5- year OS of 0.65, 0.84 and 0.74 in the training, external 1 and external 2 cohort. Patients with low immune risk score had a significant survival advantage than those with high immune risk score (5-year OS: 39.2 vs 19.6%, P < 0.001 for the training cohort; 77.4 vs 20.1%, P = 0.004 for the external cohort 1; 27.2 vs 0.0%, P = 0.006 for the external cohort 2). After adjusting the confounding variables of the classic ELN risk category and other clinical factors, the multivariable analysis revealed that immune risk score remained an independent prognostic factor for OS in all the three cohorts (HR: 1.34, 5.42 and 2.16 for the training, external cohort1 and 2 cohorts; all P < 0.05). Next, we explored the related biological phenotypes to immune risk score and found that the immune risk score was significantly associated with the markers of immune checkpoint (HMGB1, CEACAM1, LAG3 and CTLA-4), cell proliferation (NOTCH1, LYN, TSC2, SETBP1, TGFBR2, MAP3K14, TP53, NFKB2 and FOXO1), DNA repairment (RAD50 and BRCA1), epigenetic regulation and transcriptional regulation (SRSF6, DNMT3, TLE1). Furthermore, GSEA analysis indicated a significant enrichment of active immune-related pathways in low immune risk group. Finally, we noted that the immune risk score consistently increased follow the increased cytogenetic risk level. Conclusions: The study identified a novel immune prognostic category of AML, which may be used as another prognostic tool that complements the existing genetic risk classification. Figure Disclosures No relevant conflicts of interest to declare.

The treatment options for patients with acute myeloid leukemia (AML) under inferior performance status (i.e. senior patients, MDS transformed AML, and patients with proven invasive fungal disease) are limited. The conventional "3+7" (idarubicin plus cytarabine) induction for those patients can be either too toxic, which leads to higher mortality rate, or requires prolonged recovery time thus raise medical cost. And the delay of consolidation may compromise outcome thus cause early relapse in such patients. Giving the rationale from the designing art of CPX-351, the prolonged IV time requirement for cytarabine, as well as mini-transplantation for AML treatment, at least in part, reflects the philosophy of a longer exposure to the chemo agent can be a more effective treatment approach for leukemia. On the other hand, the D-CAG protocol, which indicated an encouraging result for elderly patients with AML, indicated effectiveness of the strategy with reduced intensity. However, the cyto-toxic effect of decitabine with standard dose (20mg/m2) could still lead to severe treatment adverse events (AEs) thus raise the need of optimization of D-CAG regimen for patients with inferior PS. When considering the low dose hypo-methylation agent (HMA) can trigger the innate immunity response, the unique effect of homoharringtonine, as well as the effectiveness of CAG, we designed this DHCAG protocol following the principle of "longer exposure, lower intensity preceded by priming" and observed an unexpected excellent outcome with high CR rate, low induction failure and treatment mortality, as well as a higher cost effective value for patients with AML, when compared to "3+7" protocol, whom under inferior PS. From March 2016 - January 2018, we initiated this pilot study and investigated the safety and efficiency of this DHCAG protocol in patients with AML under poor PS. We enrolled 25 patients and administer the regimen as followings: i) G-CSF: 5μg/kg used when WBC 1*10^9/L then increase the dosage of homoharringtonine to 2mg/m2); iv) Cytarabine:10mg/m2 q12h at day 1-14 subcutaneous injection (if WBC >20*10^9/L then increase to 100mg/m2 by 24h CIV, or 50mg/m2 q12h by subcutaneous injection). The primary end point was complete hematologic remission, defined as a bone marrow blast cells ≤5%, Neutrophils in peripheral blood ≥1.0X109 /L, hemoglobin≥90g/L, and platelets ≥100X109/L and no any evidence of extramedullary leukemic infiltration; Secondary end points included numbers of adverse events, length of hospital stay, medical costs, and quality of life as measured with the use of the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire. Among the 25 patients in the study, 23 completed the induction therapy. And 21/25 patients had a hematologic complete remission after a median time of 19 days. Once complete remission had occurred, all 21 patients received post-remission treatment for another 5 cycles of DHCAG. Median follow-up was 14 months (range, 8 to 19) by June 2018. Interestingly, regardless of grade 3-4 myelo-suppression occurred all of our patients during induction, eight patients did not experienced grade 3-4 myelo-suppression during the following cycles. The median hospital stay is 22 days. The median of total medical costs for induction was $9,815 (range, $5,053 to $16,336) vs $14,705 for "3+7" induction protocol (history control. Data unpublished). Patients resumed their usual lifestyle during post-remission therapy, and their quality of life was rated as nearly normal on the FACT-G questionnaire. At the time of the last follow-up, seven patients had had a hematologic relapse. The results of our pilot study, in which we tested a priming based, low dose and longer exposure in 25 patients with AML under poor PS, showed that the treatment was safe, effective, and economical. A prospective multicenter, randomized trial comparing DHCAG with IA is now under way in China. Disclosures No relevant conflicts of interest to declare.

Silver nanoparticles were deposited on the surface of polycrystalline silicon wafer via vacuum thermal evaporation and metal-catalyzed chemical etching (MCCE) was conducted in a HF-H2O2 etching system. Treatment of the etched silicon wafer with HF transformed the textured structure on the surface from nanorods into nanocones. An etching time of 30 s and treatment with HF resulted in nanocones with uniform size distribution and a reflectivity as low as 1.98% across a spectral range from 300 to 1000 nm.