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Background The effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) or trans-arterial chemoembolization (TACE) for cases with single pseudo-capsuled hepatocellular carcinoma (pHCC), as well as their survival outcomes were investigated. Methods 196 cases with single pHCC (diameter > 5 cm) receiving initial HAIC (n = 92) and TACE (n = 104) were enrolled. The propensity score match (PSM) approach based on Cox models was employed to tune any possible imbalance in treatment assignment. The overall survival (OS), objective response rate (ORR), progression-free survival (PFS), and partial response rate (PRR) of the subjects were investigated by using the Log-rank test. The independent risk factors for outcomes were investigated by univariate and multivariate analyses and the results were analyzed by using the Cox regression model. Results The median follow-up of the subjects was 22.3 months. After PSM, no significant difference was found in OS of the HAIC and TACE groups (OS, 16.8 vs. 12.0 months; P = 0.267), while the median PFS of the TACE group was enhanced compared with the HAIC group (PFS, 5.7 vs. 2.8 months; P = 0.003). Moreover, PRR and ORR of the TACE group were enhanced compared with the HAIC group (PRR, 34.6% vs. 21.7%; P = 0.046; ORR, 35.6% vs. 21.7%; P = 0.033). The nomogram model showed high predictive accuracy and significant discrimination. Conclusions TACE therapy could improve the control of tumor progression compared with HAIC for cases with single pHCC.

In this study, different calorimetric and analytical techniques were used to evaluate the thermal behaviour of the preparation of 1-nitronaphthalene through the nitration of naphthalene with mixed acid. Differential scanning calorimetry and adiabatic calorimetry revealed that 1-nitronaphthalene lacks thermal decomposition characteristics. The results of reaction calorimetry, high-performance liquid chromatography, and the density function theory method were combined to analyse the reaction mechanism. An expanded Stoessel criticality diagram was developed to evaluate the process safety of the semibatch nitration reaction. The results revealed a higher degree of risk than that obtained when using the traditional Stoessel criticality diagram. Kinetics parameters of the reaction were investigated.

The fire protection design in a large-scale interchange station is always a great challenge. In this paper, a series of numerical simulations were conducted to investigate the performance of emerge...

The aim of this study was to evaluate the clinical outcome of patients receiving microwave ablation (MWA), either after downstaging of hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE), or without downstaging when meeting initially the Milan criteria. From January 2012 to January 2018, 66 patients with HCC beyond the Milan criteria who were downstaged by TACE previous to MWA comprised the study group. The control group comprised 190 patients who underwent MWA as first-line treatment as they met initially the Milan criteria. Cumulative overall survival (OS) and recurrence-free survival (RFS) rates were compared. The propensity score analysis was performed to reduce potential bias. Baseline characteristics were balanced between the two groups after 1:1 propensity score matching. The OS rates were 100%, 79%, and 73% at 1, 3, and 5 years in the downstaging group and 95%, 83%, and 72%, respectively, in the Milan group. The corresponding RFS rate were 77%, 40%, and 31% in the downstaging group and 76%, 45%, and 34% in the Milan group. There were no significant differences in the OS and RFS rates between the two groups (p = 0.981 and p = 0.586). The long-term therapeutic outcomes of MWA for downstaged HCC with TACE were similar to HCC that initially met the Milan criteria. • Patients treated with MWA of HCC after downstaging with transarterial chemoembolization (TACE) were similar to those with HCC that initially met Milan criteria. • Microwave ablation (MWA) can be an effective treatment for hepatocellular carcinoma (HCC) that is downstaged to the Milan criteria.

Calcium phosphate (CP) nanoparticles (NPs) have been used in various applications for delivery of nucleic acid (NA) cargos with ideal biocompatibility and safety. However, some critical issues such as poor stability and aggregation in water solution hinder the industrial application of CP NPs. To further utilize CP NPs for NA delivery, this study specifically focused on the modification of CP NPs to achieve a rapid synthesis and improvement on dispersibility and colloidal stability by using a bisphosphonate (BP) and BSA (named as BCP NPs). Compared with CP NPs, BCP NPs show better stability and dispersity in the cell culture medium, higher efficiency in cellular uptake, and faster dissolution in acidic environments, which are essential requirements for NA vaccine delivery. The cell viability (MTT) assay indicates that BCP NPs have a similar or lower cytotoxicity than free alendronate and Lipofectamine 2000 reagent (L2K) to macrophages (MΦs), a type of typical antigen-presenting cells (APCs). Furthermore, BCP NPs exhibited 85% plasmid DNA (pDNA) loading efficiency and a good endosome escape property. Using a plasmid expressing enhanced green fluorescent protein (pEGFP) as a model system, we showed that BCP NP transfection resulted in a high-level EGFP expression in MΦs, which was even greater than the commercial L2K and electroporation method. This is the first application of a low amount of BP and BSA to modify CP-based NPs with low MΦ cytotoxicity and favorable dispersity, and our data suggest these BCP NPs are an excellent delivery platform for pDNA to MΦs.

Bladder cancer (BCa) is an increasingly severe clinical and public health issue. Therefore, we aim to investigate BCa susceptibility loci in the Chinese population. In this study, 487 BCa patients and 563 controls were recruited from the First Affiliated Hospital of China Medical University from July 2015 to September 2020. A total of ten single-nucleotide polymorphisms (SNPs) in solute carrier family 15 member 1 (SLC15A1), CWC27 spliceosome associated cyclophilin (CWC27), or UDP glucuronosyltransferase family 1 member A3 (UGT1A3) genes were genotyped. The associations between the candidate SNPs and BCa were analyzed using genotype and haplotype analysis. The results demonstrated that Rs4646227 of SLC15A1 has a significant association with BCa. The patients with CG (OR =2.513, p < 0.05 ) and GG (OR =2.859, p < 0.05 ) genotypes had an increasing risk of BCa compared with the CC genotype. For the CWC27 gene, genotypic frequency analysis revealed that the GT or TT genotype of rs2042329 and the CT or TT genotype of rs1870437 were more frequent in BCa patients than those in the control group, indicating that these genotypes were associated with a higher risk of BCa (all p < 0.05 ). Haplotypes of SLC15A1, UGT1A3, and CWC27 genes found that the C-C-C haplotype of SLC15A1 was associated with a lower risk of BCa while the C-G-C haplotype was associated with a higher risk. For the UGT1A3 gene, a moderate protective effect was observed with the most frequent T-T-C haplotype, and for the CWC27 gene, most of the haplotypes showed no association with BCa, except the G-G-C-T haplotype (order of SNPs: rs2042329-rs7735338-rs1870437-rs2278351, OR =0.81, p =0.038). In sum, this study indicated that rs2042329 and rs1870437 in the CWC27 gene and rs4646227 in the SLC15A1 gene are independent indicators for BCa risk in Chinese people. Further large-scale studies are required to validate these findings. Also, this study provided the theoretical basis for developing new therapeutic drug targeting of BCa.

Plenty of evidence has suggested that long noncoding RNAs (lncRNAs) play a vital role in competing endogenous RNA (ceRNA) networks. Poorly differentiated hepatocellular carcinoma (PDHCC) is a malignant phenotype. This paper aimed to explore the effect and the underlying regulatory mechanism of lncRNAs on PDHCC as a kind of ceRNA. Additionally, prognosis prediction was assessed. A total of 943 messenger RNAs (mRNAs), 86 miRNAs, and 468 lncRNAs that were differentially expressed between 137 PDHCCs and 235 well-differentiated HCCs were identified. Thereafter, a ceRNA network related to the dysregulated lncRNAs was established according to bioinformatic analysis and included 29 lncRNAs, 9 miRNAs, and 96 mRNAs. RNA-related overall survival (OS) curves were determined using the Kaplan-Meier method. The lncRNA ARHGEF7-AS2 was markedly correlated with OS in HCC (P = .041). Moreover, Cox regression analysis revealed that patients with low ARHGEF7-AS2 expression were associated with notably shorter survival time (P = .038). In addition, the area under the curve values of the lncRNA signature for 1-, 3-, and 5-year survival were 0.806, 0.741, and 0.701, respectively. Furthermore, a lncRNA nomogram was established, and the C-index of the internal validation was 0.717. In vitro experiments were performed to demonstrate that silencing ARHGEF7-AS2 expression significantly promoted HCC cell proliferation and migration. Taken together, our findings shed more light on the ceRNA network related to lncRNAs in PDHCC, and ARHGEF7-AS2 may be used as an independent biomarker to predict the prognosis of HCC.

Alternative splicing events (ASEs) play a role in cancer development and progression. We investigated whether ASEs are prognostic for overall survival (OS) in hepatocellular carcinoma (HCC). RNA sequencing data was obtained for 343 patients included in The Cancer Genome Atlas. Matched splicing event data for these patients was then obtained from the TCGASpliceSeq database, which includes data for seven types of ASEs. Univariate and multivariate Cox regression analysis demonstrated that 3,814 OS-associated splicing events (OS-SEs) were correlated with OS. Prognostic indices were developed based on the most significant OS-SEs. The prognostic index based on all seven types of ASEs (PI-ALL) demonstrated superior efficacy in predicting OS of HCC patients at 2,000 days compared to those based on single ASE types. Patients were stratified into two risk groups (high and low) based on the median prognostic index. Kaplan-Meier survival analysis demonstrated that PI-ALL had the greatest capacity to distinguish between patients with favorable vs. poor outcomes. Finally, univariate Cox regression analysis demonstrated that the expression of 23 splicing factors was correlated with OS-SEs in the HCC cohort. Our data indicate that a prognostic index based on ASEs is prognostic for OS in HCC.

Population-based study for predicting the prognosis for breast cancer liver metastasis (BCLM) is lacking at present. Therefore, the present study aimed to evaluate newly diagnosed BCLM patients of different tumor subtypes and assess potential prognostic factors for predicting the survival for BCLM patients. Specifically, data were collected from the Surveillance, Epidemiology and End Results program from 2010 to 2014, and were assessed, including the data of patients with BCLM. Differences in the overall survival (OS) among patients was compared via Kaplan-Meier analysis. Other prognostic factors of OS were determined using the Cox proportional hazard model. In addition, the breast cancer-specific mortality was assessed using the Fine and Gray's competing risk model. A nomogram was also constructed on the basis of the Cox model for predicting the prognosis of BCLM cases. A total of 2,098 cases that had a median OS of 20.0 months were included. The distribution of tumor subtypes was as follows: 42.2% with human epidermal growth factor receptor 2 (Her2; -)/hormone receptor (HR; +), 12.8% with Her2(+)/HR(-), 19.1% with Her2(+)/HR(+) and 13.5% with triple negative breast cancer (TNBC). Kaplan-Meier analysis revealed that older age (>64 years), unmarried status, larger tumor, higher grade, no surgery, metastases at other sites, and TNBC subtype were associated with shorter OS. Additionally, multivariate analysis revealed that older age (>64 years), unmarried status, no surgery, bone metastasis, brain metastasis and TNBC subtype were significantly associated with worse prognosis. Thus, age at diagnosis, marital status, surgery, bone metastasis, brain metastasis and tumor subtype were confirmed as independent prognosis factors from a competing risk model. We also constructed a nomogram, which had the concordance index of internal validation of 0.685 (0.650-0.720). This paper had carried out the population-based prognosis prediction for BCLM cases. The survival of BCLM differed depending on the tumor subtype. More independent prognosis factors were age at the time of diagnosis, surgery, marital status, bone metastasis, as well as brain metastasis, in addition to tumor subtype. Notably, the as-constructed nomogram might serve as an efficient approach to predict the prognosis for individual patients.

To study the thyroid regeneration and injury of recurrent laryngeal nerve after irreversible electroporation (IRE). 12 pigs were divided into three groups: six pigs underwent IRE, other pigs were used as controls. IRE was performed near tracheoesophageal groove, to ablate most part of thyroid gland. Parathyroid and thyroid function, recurrent laryngeal nerve injury and thyroid computed tomography (CT) imaging were regularly investigated. The histopathology results were analyzed to detect thyroid regeneration. Masson's trichrome method for collagen and immunohistochemistry were performed for Soluble protein-100 (S100) and neurofilaments on nerve section. In IRE group, there were no symptoms of recurrent laryngeal nerve-related injury. No abnormalities of recurrent laryngeal nerve were shown on hematoxylin-eosin (HE) staining, Masson's trichrome staining, Neurofilament (NF) staining and S100 staining. There were no significant changes for thyroid and parathyroid function in all pigs. Immediately after IRE, CT showed hypoattenuation in the ablated thyroid gland and it became swelling. 14 days after IRE, thyroid CT showed hetergenous attenuation in the electroporation zone, and the size and attenuation of thyroid gland were normal after two months. There was cell apoptosis in the thyroid gland after IRE. Seven and 14 days after IRE, there was fragmentation of nucleus within the follicle, and some follicles were empty. Two months later, complete regeneration of thyroid tissue was shown. IRE was shown to be both effective and safe with complete regeneration of thyroid tissue and preservation of the function and structure of the recurrent laryngeal nerve.

Background Blocking the programmed death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in hepatocellular carcinoma (HCC) is a very promising approach in immunotherapy. However, the correlation and prognostic values of serum soluble PD-1 and PD-L1 (sPD-1/sPD-L1) have not been explored conjointly in HCC patients. Methods This study retrospectively included 120 HCC patients receiving radical resection. The serum levels of sPD-1/sPD-L1 and inflammatory cytokines were measured by antibody array assay. Immunohistochemistry was applied to assess both the expression of membrane-bound PD-L1, and the number of CD4+ tumor-infiltrating lymphocytes (TILs) and CD8+ TILs. Results The best cut-off values of sPD-1 and sPD-L1 for predicting disease-free survival (DFS) were 33.0 µg/ml and 11.2 µg/ml, respectively. Multivariable analysis showed that sPD-L1 was a negative independent prognostic factor [DFS, Hazard Ratio (HR) 2.58, 95% CI 1.14–5.84, P = 0.023; overall survival (OS), HR 1.77, 95% CI 1.01–3.12, P = 0.048], while sPD-1 was a favorable independent prognostic factor (DFS, HR 0.32, 95% CI 0.14–0.74, P = 0.007; OS, HR 0.54, 95% CI 0.30–0.98, P = 0.044) in HCC patients. We also observed some similar associations between inflammatory cytokines (IL-10, IL-17, TNF-α) and sPD-1 or sPD-L1, as well as a close positive association between sPD-1 and sPD-L1. No significant associations of sPD-1/sPD-L1 with either intra-tumoral PD-L1 expression, or the numbers of CD4+ TILs and CD8+ TILs were determined. Conclusions Our findings indicate that sPD-1 and sPD-L1 are independent prognostic factors with opposite prognostic roles in predicting both DFS and OS in HCC patients. Electronic supplementary material The online version of this article (10.1007/s00262-018-2271-4) contains supplementary material, which is available to authorized users.

Purpose To utilize a neural architecture search (NAS) approach to develop a convolutional neural network (CNN) method for distinguishing benign and malignant lesions on breast cone-beam CT (BCBCT). Method 165 patients with 114 malignant and 86 benign lesions were collected by two institutions from May 2012 to August 2014. The NAS method autonomously generated a CNN model using one institution’s dataset for training (patients/lesions: 71/91) and validation (patients/lesions: 20/23). The model was externally tested on another institution’s dataset (patients/lesions: 74/87), and its performance was compared with fine-tuned ResNet-50 models and two breast radiologists who independently read the lesions in the testing dataset without knowing lesion diagnosis. Results The lesion diameters (mean ± SD) were 18.8 ± 12.9 mm, 22.7 ± 10.5 mm, and 20.0 ± 11.8 mm in the training, validation, and external testing set, respectively. Compared to the best ResNet-50 model, the NAS-generated CNN model performed three times faster and, in the external testing set, achieved a higher (though not statistically different) AUC, with sensitivity (95% CI) and specificity (95% CI) of 0.727, 80% (66–90%), and 60% (42–75%), respectively. Meanwhile, the performances of the NAS-generated CNN and the two radiologists’ visual ratings were not statistically different. Conclusions Our preliminary results demonstrated that a CNN autonomously generated by NAS performed comparably to pre-trained ResNet models and radiologists in predicting malignant breast lesions on contrast-enhanced BCBCT. In comparison to ResNet, which must be designed by an expert, the NAS approach may be used to automatically generate a deep learning architecture for medical image analysis.

BACKGROUND: Existing research has identified correlations between numerous microRNAs (miRNAs) and the prognosis of hepatocellular carcinoma (HCC). However, the role of a combination of miRNAs in predicting HCC survival requires further elucidation. METHODS: miRNA expression profiles and clinical data from HCC patients were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed (DE) miRNAs in tumor versus normal samples were identified. All HCC patients were randomly assigned to a training cohort or a validation cohort at a ratio of 1 to 1. A least absolute shrinkage and selection operator (LASSO) Cox regression model was subsequently employed to establish the miRNA signature. The constructed miRNA signature was then developed and validated. RESULTS: In total, 127 DE miRNAs were detected between HCC and paracancerous tissue using HCC RNA sequencing (RNA-Seq) data extracted from TCGA database. LASSO Cox regression generated a five-miRNA signature consisting of has-mir-105-2, has-mir-9-3, has-mir-137, has-mir-548f-1, and has-mir-561 in the training cohort. This risk model was significantly related to survival (P=5.682e-6). Log-rank tests and multivariate Cox regression analyses revealed the five-miRNA signature as an independent prognostic indicator [HR =3.285, 95% confidence interval (CI): 1.737–6.213], with the area under curve (AUC) of the miRNA signature being 0.728. The effects of the miRNA signature were further confirmed in the validation cohort and in the OncomiR Cancer Database and Gene Expression Omnibus (GEO) dataset. Functional enrichment analysis revealed the potential effects of the five-miRNA signature in tumor-related biological pathways and processes. Cell Counting Kit-8, Transwell, and wound healing assays, were used to evaluate the role of has-mir-137 in HCC cell proliferation and migration in vitro. CONCLUSIONS: We established a novel five-miRNA signature which reliably predicted prognosis in HCC patients and which could be used to assist in both strategic counseling and personalized management in HCC.

Background Metal foam has been demonstrated numerous advantages in fine chemistry when used as catalyst support. In this research, a novel strategy for the fabrication of copper tungstate (CuWO4) foam as heterogeneous catalysis to conduct dimethyl sulfoxide (DMSO) oxidation reaction in a scale-up microreactor was proposed. Methods A series of three-dimensional skeleton CuWO4 foams were prepared by a continuous sintering approach. The obtained CuWO4 catalysis inherited the porous structure from the copper foam and had a high loading density of CuWO4 crystal particles. Afterwards, DMSO oxidation was employed as a probe reaction to explore the catalytic performance of CuWO4 foam. Significant findings CuWO4 foam showed prefect catalytic activity in a scale-up microreactor. The average crystallite size of CuWO4 were increased from 52.8 to 57.7 nm with extension of sintering time. Under the optimum condition (residence time was 40 min, CuWO4 catalyst was CuWO4F-5 and reaction temperature was 80 oC), a high dimethyl sulfone yield of 65.4% was obtained. The yield of MSM reached nearly 65.3% in the run time of 1 h and showed a value of 50.4% even in the run time of 4 h. Higher reaction contact surface and larger crystal particles of CuWO4 foam are conducive to enhancing the catalytic performance of CuWO4 foam. This research indicates the potential opportunity to apply CuWO4 foam in a scale-up microreactor.

N6-methyladenosine (m6A) RNA methylation, which is related to cancer initiation and progression, is dynamically regulated by the m6A RNA methylation regulators (including 'writers', 'erasers' and 'readers'). However, the prognostic value of m6A RNA methylation regulators involved in hepatocellular carcinoma (HCC) carcinogenesis and progression remains to be elucidated. The aim of the present study was to determine the prognostic score in predicting the prognosis of HCC patients based on these regulators. In The Cancer Genome Atlas, most of the 13 major m6A RNA methylation regulators were found to be differentially expressed between HCC and normal samples (P

In the process in which high-density passengers need to be evacuated from a multi-exit subway station, not all the exits can be effectively utilized, and the bottlenecks near the exits are often crowded. Therefore, the utilization of different exits and the optimization of congestion at bottlenecks were investigated in this study. To alleviate the congestion of the evacuation in a large-scale and multifunctional subway station, the first underground floor of the station was divided into four regions, referring to the idea of fire compartment division, in which passengers were evacuated from local exits. The results reveal that the evacuation time increases as the initial passenger density increases. The railings have a positive effect on balancing the proportion of different exits for the region with fewer exits in the early evacuation stage. For regions with several exits well-distributed, the symmetrical structure is beneficial to the evacuation and the effective use of different exits. What's more, setting railings can reduce crowding at bottlenecks to a certain extent. The results of the study can guide passenger evacuation in typical multi-exit subway stations.

Objective To assess the safety and effectiveness of computed-tomography-guided (CT-guided) percutaneous radiofrequency ablation (RFA) for lung neoplasms adjacent to the pericardium. Materials and methods This retrospective study was approved by the institutional ethics committee, and all patients provided written informed consent. Between January 1, 2012 and March 31, 2016, 49 consecutive patients (32 men and 17 women; mean age 47.9 years; range 16–67 years) with 51 tumors (mean diameter 17.7 ± 7.2 mm; range 4–30 mm) located within 10 mm of the pericardium underwent percutaneous CT-guided RFA. The technical success rate, local progression-free survival (LPFS), risk factors for local progression, and safety of this technique were evaluated. Results The technical success rate was 96.1% (49/51), and the LPFS was 98.0%, 93.0%, 84.0%, and 77.0% at 3, 6, 12, and 24 months, respectively. A tumor size >2.0 cm (p = .045) and the primary lung tumor types (p = .013) were associated with local progression. No treatment-related deaths occurred. The incidence of major complications was 15.7%; complications included pneumothorax (5.9%, 3/51), pleural effusion (3.9%, 2/51), pneumonitis (3.9%, 2/51), and hemothorax (2.0%, 1/51). Conclusion Percutaneous CT-guided RFA can be a safe and effective option for the treatment of lung malignancies adjacent to the pericardium.

β-Elemene, an anti-cancer drug extracted from traditional Chinese medicinal herb, showed anti-tumor effects on gastric cancer cells. Our previous studies reported gastric cancer cells are insensitive to TRAIL. However, whether β-elemene could enhance anti-cancer effects of TRAIL on gastric cancer cells is unknown. In our present study, β-elemene prevented gastric cancer cell viability in dose-dependent manner, and when combined with TRAIL, obviously inhibited proliferation and promoted apoptosis in gastric cancer cells. Compared to β-elemene or TRAIL alone, treatment with β-elemene and TRAIL obviously promoted DR5 clustering as well as translocation of Caspase-8, DR5 and FADD into lipid rafts. This led to cleavage of Caspase-8 and the formation of death-inducing signaling complex (DISC) in lipid rafts. The cholesterol-sequestering agent nystatin partially reversed DR5 clustering and DISC formation, preventing apoptosis triggered by the combination of β-elemene and TRAIL. Our results suggest that β-elemene increases the sensitivity of gastric cancer cells to TRAIL partially by promoting the formation of DISC in lipid rafts.

To compare the overall survival (OS) and disease progression free survival (PFS) in patients with advanced hepatocellular carcinoma (Ad-HCC) who are undergoing hepatic arterial infusion (HAI) of oxaliplatin, fluorouracil/leucovorin (FOLFOX) treatment vs. sorafenib.This retrospective study was approved by the ethical review committee, and informed consent was obtained from all patients before treatment. HAI of FOLFOX (HAIF) was recommended as an alternative treatment option for patients who refused sorafenib. Of the 412 patients with Ad-HCC (376 men and 36 women) between Jan 2012 to Dec 2015, 232 patients were treated with sorafenib; 180 patients were given HAIF therapy. The median age was 51 years (range, 16-82 years). Propensity-score matched estimates were used to reduce bias when evaluating survival. Survival curves were calculated by performing the Kaplan-Meier method and compared by using the log-rank test and Cox regression models.The median PFS and OS in the HAIF group were significantly longer than those in the sorafenib group (PFS 7.1 vs. 3.3 months [RECIST]/7.4 vs. 3.6 months [mRECIST], respectively; OS 14.5 vs. 7.0 months; p 0.001 for each). In the propensity-score matched cohorts (147 pairs), both PFS and OS in the HAIF group were longer than those in the sorafenib group (p 0.001). At multivariate analysis, HAIF treatment was an independent factor for PFS (hazard ratio [HR] 0.389 [RECIST]/0.402 [mRECIST]; p 0.001 for each) and OS (HR 0.129; p 0.001).HAIF therapy may improve survival compared to sorafenib in patients with Ad-HCC. A prospective randomized trial is ongoing to confirm this finding.We compared the hepatic arterial infusion of FOLFOX (a combination chemotherapy) with sorafenib (a tyrosine kinase inhibitor) in patients with advanced hepatocellular carcinoma, retrospectively. It was found that hepatic arterial infusion of FOLFOX therapy may improve both progression free and overall survival in patients with advanced hepatocellular carcinoma.

Background Impaired insulin activity in women with polycystic ovary syndrome might differ from that seen in type 2 diabetes mellitus without polycystic ovary syndrome. This study was designed to compare the effects of treatment with metformin, saxagliptin, and their combination in newly diagnosed women with type 2 diabetes mellitus and polycystic ovary syndrome in China. Methods A total of 75 newly diagnosed patients from Shanghai, China with type 2 diabetes mellitus and polycystic ovary syndrome were included in this randomized, parallel, open-label study. All patients received treatment for 24 weeks with metformin, saxagliptin, or their combination. Patients were allocated to one of three treatment groups by a computer-generated code that facilitated equal patient distribution of 25 patients per group. The primary outcome was a change in glycemic control and β-cell function. Results A total of 63 patients completed the study (n = 21, for each group). The reduction in hemoglobin A1c was significant in the combination group, compared to the monotherapy groups (saxagliptin vs. combination treatment vs. metformin: − 1.1 vs. -1.3 vs. -1.1%, P = 0.016), whereas it was comparable between the metformin and saxagliptin groups (P > 0.05). Saxagliptin, metformin, and the combination treatment significantly reduced the homeostasis model assessment- insulin resistance index and increased the deposition index (P 0.05 for all). In addition, saxagliptin and metformin treatments significantly reduced body mass index and high-sensitivity C-reactive protein levels (P

The pyrolysis characteristics of tetrazolo[1,5-a]pyridine were investigated by thermogravimetric analysis (TG) and differential scanning calorimetry (DSC). The apparent activation energy (Eα) was estimated with DSC and various kinetic analysis methods, and it was determined that the decomposition of tetrazolo[1,5-a]pyridine follows the Avarami-Erofeve (A2) reaction pattern. The thermal safety and thermodynamic parameters were calculated. In addition, the thermal runaway behavior and kinetic parameters under adiabatic conditions were studied by employing an adiabatic accelerating calorimeter (ARC). Thermogravimetric-photoionization mass spectrometry (TG-MS) was used to identify the vapor phase products of the pyrolysis process. The different decomposition pathways were analyzed by density functional theory (DFT). The main decomposition products were N2, C2H2 and HCN according to TG-MS experiments and theoretical calculations. The most likely proposed decomposition mechanism proceeded through the opening of the tetrazole ring to dissociate N2 and the rupturing of the pyridine ring to release C2H2 and HCN. The findings of these experiments and theoretical calculations can contribute to the determination of safety precautions for possible heat hazard accidents during the handling, transportation, use and storage of tetrazolo[1,5-a]pyridine.

BACKGROUND Hepatitis B virus (HBV) has been recognized as a leading cause of hepatocellular carcinoma (HCC). Numerous reports suggest that immune infiltration can predict the prognosis of HCC. Nonetheless, no creditable markers for prognosis of HBV-related HCC have been established by systematically assessing the immune-related markers based on tumor transcriptomes. AIM To establish an immune-related marker based on the cell compositions of immune infiltrate obtained based on tumor transcriptomes, so as to enhance the prediction accuracy of HBV-related HCC prognosis. METHODS RNA expression patterns as well as the relevant clinical data of HCC patients were obtained from The Cancer Genome Atlas. Twenty-two immunocyte fraction types were estimated by cell type identification by estimating relative subsets of RNA transcripts. Subsequently, the least absolute shrinkage and selection operator (LASSO) Cox regression model was employed to construct an immunoscore based on the immunocyte fraction types. Afterwards, the receiver operating characteristic (ROC) curve, Kaplan-Meier, and multivariate Cox analyses were performed. Additionally, a nomogram for prognosis that integrated the immunoscore as well as the clinical features was established. Meanwhile, the correlation of immunoscore with immune genes was also detected, and gene set enrichment analysis (GSEA) of the immunoscore was conducted. RESULTS A total of 22 immunocyte fraction types were predicted and compared among the tumor as well as non-tumor samples. An immunoscore was constructed through adopting the LASSO model, which contained eight immunocyte fraction types. Meanwhile, the areas under the ROC curves for the immunoscore biomarker prognostic model were 0.971, 0.912, and 0.975 for 1-, 3-, and 5-year overall survival (OS), respectively. Difference in OS between the high-immunoscore group and the low-immunoscore group was statistically significant [hazard ratio (HR) = 66.007, 95% confidence interval (CI): 8.361-521.105; P < 0.0001]. Moreover, multivariable analysis showed that the immunoscore was an independent factor for predicting the prognosis (HR = 2.997, 95%CI: 1.737-5.170). A nomogram was established, and the C-index was 0.757 (95%CI: 0.648-0.866). The immunoscore showed a significant negative correlation with the expression of PD-1 (P = 0.024), PD-L1 (P = 0.026), PD-L2 (P = 0.029), and CD27 (P = 0.033). Eight pathways were confirmed by GSEA. CONCLUSION The established immunoscore can potentially serve as a candidate marker to estimate the OS for HBV-related HCC cases.

N6-methyladenosine (m6A) RNA methylation, which is related to cancer initiation and progression, is dynamically regulated by the m6A RNA methylation regulators (including ‘writers’, ‘erasers’ and ‘readers’). However, the prognostic value of m6A RNA methylation regulators involved in hepatocellular carcinoma (HCC) carcinogenesis and progression remains to be elucidated. The aim of the present study was to determine the prognostic score in predicting the prognosis of HCC patients based on these regulators. In The Cancer Genome Atlas, most of the 13 major m6A RNA methylation regulators were found to be differentially expressed between HCC and normal samples (P

Immune cells have emerged as key regulators in the occurrence and development of multiple tumor types. However, it is unclear whether immune-related genes (IRGs) and the tumor immune microenvironment can predict prognosis for patients with gastric cancer (GC). The mRNA expression data in GC tissues ( n = 368) were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed IRGs in patients with GC were determined using a computational difference algorithm. A prognostic signature was constructed using COX regression and random survival forest (RSF) analyses. In addition, datasets related to “gemcitabine resistance” and “trastuzumab resistance” (GSE58118 and GSE77346) were obtained for GEO database, and DEGs associated with drug-resistance were screened. Then, we analyzed correlations between gene expression and cancer immune infiltrates via Tumor Immune Estimation Resource (TIMER) site. The cBioportal database was used to analyze drug-resistant gene mutation status and survival. One hundred and fifty-five differentially expressed IRGs were screened between GC and normal tissues, and a prognostic signature consisting of four IRGs (NRP1, PPP3R1, IL17RA, and FGF16) was closely related to the overall survival (OS). According to cutoff value of risk score, patients were divided into high-risk and low-risk group. Patients in the high-risk group had shorter OS compared to the low-risk group in both the training ( p

Pancreatic cancer (PC) is a lethal disease with extremely high mortality. Although surgical resection is the optimal therapeutic approach for PC, about 30%-40% of those patients are not candidates for surgical resection when diagnosed. Chemotherapy and radiotherapy also could not claim a desirable effect on PC. The application of interventional radiology approaches is limited by unavoidable damage to the surrounding vessels or organs. By the superiority of mechanism and technology, IRE could ablate the tumor by creating irreversible pores on the membrane of PC cells with other tissues like vessels and pancreatic ducts untouched. This consensus gathers the theoretical basis and clinical experience from multiple Chinese medical centers, to provide the application principles and experience from Chinese experts in the IRE field.

Purpose To establish an image-based M1 category subdivision system for personalized prognosis prediction and treatment planning in patients with metastatic nasopharyngeal carcinoma (NPC). Materials and Methods A total of 1172 patients with metachronous metastasic NPC were retrospectively enrolled (the dataset is from Sun Yat-sen University Cancer Center for derivation, and the combined datasets are from Guangzhou Medical University Cancer Center and the Fifth Affiliated Hospital of Sun Yat-sen University for validation). The Ethics Committee of the three centers approved this study. A general subdivision system of the M1 category was established on the basis of the most influential metastatic features for overall survival (OS). The following multilevel subdivision system for precise subdivision of the M1 category was designed: M [number of locations]-Location [number of lesions], with B indicating bone, L indicating the lung, H indicating the liver, and N indicating a node. The correlation of the M1 subdivisions with OS was determined with Cox regression. The best treatment response was assessed with Response Evaluation Criteria in Solid Tumors 1.1 guidelines and modified Response Evaluation Criteria in Solid Tumors criteria. Results Multivariate analysis in the derivation cohort showed that the number of metastatic lesions (multiple or single), the number of metastatic locations (multiple or single), liver involvement, and bone involvement were independent prognostic factors for OS. In general, subdividing the cohort by the number of metastatic lesions and the number of metastatic locations resulted in three subcategories of differential OS: M1a, a single lesion in a single organ or location; M1b, multiple lesions in a single organ or location; and M1c, metastases in multiple locations (for M1b vs M1a, hazard ratio [HR] = 2.28, 95% confidence interval [CI]: 1.71, 3.05; for M1c vs M1a, HR = 3.65, 95% CI: 2.75, 4.85); these subdivisions were externally validated. The multilevel subdivision system could be further used to discriminate among subgroups of differential OS under the M1b subcategory. Findings from analysis of multilevel subgroups suggested that patients with a single metastatic lesion (M1-B1, M1-L1, M1-H1, M1-N1) or two lesions in the liver only (M1-H2) had high rates of complete response (CR) or complete surgical resection (CSR) and 3-year OS after treatment (CR plus CSR rates >30%, and 3-year OS rates >50%); there were high 3-year OS rates (>50%) in patients with stage M1-B2, M1-L2, or M1-H3 disease but relatively low rates of CR or CSR. Conclusion Use of the multilevel M1 subdivision system in patients with NPC could facilitate more precise prognosis prediction and better identification of patients who will respond well to treatment than the conventional subdivision strategy. (©) RSNA, 2016 Online supplemental material is available for this article.

Aim The aim of this study was to investigate whether the number of removed lymph nodes was associated with survival of patients with node-negative early cervical cancer and to analyze the prognostic significance of clinical and pathologic features in these patients. Methods Patients with FIGO stage IA–IIB cervical cancer who underwent radical hysterectomy with lymphadenectomy without receiving preoperative therapy were reviewed retrospectively. Patients were all proved to have lymph-node-negative disease and classified into five groups based on the number of nodes removed. The Kaplan–Meier method and Cox's proportional hazards regression model were used in prognostic analysis. Results The final dataset included 359 patients: 45 (12.5%) patients had ≤10 nodes removed, 93 (25.9%) had 11–15, 98 (27.3%) had 16–20, 64 (17.8%) had 21–25, and 59 (16.4%) had >25 nodes removed. There was no association between the number of nodes removed and survival of patients with node-negative early cervical cancer (χ2 = 6.19, P = 0.185). Similarly, subgroup analyses for FIGO stage IB1–IIB also showed that the number of lymph nodes was not significantly related to survival in each stage. Multivariate analyses showed that histology and depth of invasion were independent prognostic factors for survival in these patients. Conclusion If a standardized lymphadenectomy is performed, the number of lymph nodes removed is not an independent prognostic factor for patients with node-negative early cervical cancer. Our study suggests that there is inconclusive evidence to support survival benefit of complete lymphadenectomy among these patients.

Background Existing research has identified correlations between numerous microRNAs (miRNAs) and the prognosis of hepatocellular carcinoma (HCC). However, the role of a combination of miRNAs in predicting HCC survival requires further elucidation. Methods miRNA expression profiles and clinical data from HCC patients were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed (DE) miRNAs in tumor versus normal samples were identified. All HCC patients were randomly assigned to a training cohort or a validation cohort at a ratio of 1 to 1. A least absolute shrinkage and selection operator (LASSO) Cox regression model was subsequently employed to establish the miRNA signature. The constructed miRNA signature was then developed and validated. Results In total, 127 DE miRNAs were detected between HCC and paracancerous tissue using HCC RNA sequencing (RNA-Seq) data extracted from TCGA database. LASSO Cox regression generated a five-miRNA signature consisting of has-mir-105-2, has-mir-9-3, has-mir-137, has-mir-548f-1, and has-mir-561 in the training cohort. This risk model was significantly related to survival (P=5.682e-6). Log-rank tests and multivariate Cox regression analyses revealed the five-miRNA signature as an independent prognostic indicator [HR =3.285, 95% confidence interval (CI): 1.737-6.213], with the area under curve (AUC) of the miRNA signature being 0.728. The effects of the miRNA signature were further confirmed in the validation cohort and in the OncomiR Cancer Database and Gene Expression Omnibus (GEO) dataset. Functional enrichment analysis revealed the potential effects of the five-miRNA signature in tumor-related biological pathways and processes. Cell Counting Kit-8, Transwell, and wound healing assays, were used to evaluate the role of has-mir-137 in HCC cell proliferation and migration in vitro. Conclusions We established a novel five-miRNA signature which reliably predicted prognosis in HCC patients and which could be used to assist in both strategic counseling and personalized management in HCC.