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•Hepatic arterial infusion was proven to be an effective and safe treatment in advanced HCC.•Hepatic arterial infusion therapy was an independent factor for PFS and OS.•Hepatic ...arterial infusion therapy provided a potential benefit of survival in patients with advanced HCC.
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Scope
To investigate the role of endoplasmic reticulum stress (ERS)‐induced autophagy in inflammatory bowel disease (IBD) and the intervention mechanism of Portulaca oleracea L. (POL) extract, a ...medicinal herb with anti‐inflammatory, antioxidant, immune‐regulating, and antitumor properties, in vitro and in vivo.
Methods and Results
An IL‐10‐deficient mouse model is used for in vivo experiments; a thapsigargin (Tg)‐stimulated ERS model of human colonic mucosal epithelial cells (HIECs) is used for in vitro experiments. The levels of ERS‐autophagy‐related proteins are examined by immunofluorescence and Western blot. Cellular ultrastructure is assessed with transmission electron microscopy.
POL extract promotes a healing effect on colitis by regulating ERS‐autophagy through the protein kinase R‐like endoplasmic reticulum kinase (PERK)‐eukaryotic initiation factor 2α (eIF2α)/Beclin1‐microtubule‐associated protein light chain 3II (LC3II) pathway.
Conclusion
Overall, the results of this study further confirm the anti‐inflammatory mechanism and protective effect of POL extract and provide a new research avenue for the clinical treatment of IBD.
ERS‐induced autophagy is involved in inflammation, intestinal mucosal barrier damage, and pathogenesis of IBD. POL extract exerts a therapeutic effect in PAC IL‐10‐/‐ model and Tg‐stimulated ERS model of HIECs by regulating the PERK‐eIF2α/Beclin1‐LC3II pathway.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Lenvatinib combined with programmed cell death protein-1 (PD-1) inhibitors has resulted in good survival outcomes in the treatment of unresectable hepatocellular carcinoma (HCC). Hepatic artery ...infusion chemotherapy (HAIC) has also attracted attention due to its high response rates and favorable survival for advanced HCC patients. The present study aimed to compare the efficacy of HAIC combined with PD-1 inhibitors plus lenvatinib (HPL) and PD-1 inhibitors plus lenvatinib (PL) in patients with advanced HCC.
Between July 2018 and December 2019, patients diagnosed with advanced HCC who initially received HPL or PL treatment were reviewed for eligibility. Efficacy was evaluated according to tumor response and survival.
In total, 70 patients met the criteria and were included in the present study, and they were divided into the HPL group (n = 45) and PL group (n = 25). The overall response rate (40.0
. 16.0%, respectively; p = 0.038) and disease control rate (77.6
. 44.0%, respectively; p < 0.001) were higher in the HPL group than in the PL group. The median overall survival was 15.9 months in the HPL group and 8.6 months in the PL group (p = 0.0015; HR = 0.6; 95% CI 0.43-0.83). The median progression-free survival was 8.8 months in the HPL group and 5.4 months in the PL group (p = 0.0320; HR = 0.74; 95% CI 0.55-0.98).
Compared to PL, HPL was associated with a significantly better treatment response and survival benefits for patients with advanced HCC.
Purpose
To develop a comprehensive PET radiomics model to predict the pathological response after neoadjuvant toripalimab with chemotherapy in resectable stage III non-small-cell lung cancer (NSCLC) ...patients.
Methods
Stage III NSCLC patients who received three cycles of neoadjuvant toripalimab with chemotherapy and underwent
18
F-FDG PET/CT were enrolled. Baseline
18
F-FDG PET/CT was performed before treatment, and preoperative
18
F-FDG PET/CT was performed three weeks after the completion of neoadjuvant treatment. Surgical resection was performed 4–5 weeks after the completion of neoadjuvant treatment. Standardized uptake value (SUV) statistics features and radiomics features were derived from baseline and preoperative PET images. Delta features were derived. The radiologic response and metabolic response were assessed by iRECIST and iPERCIST, respectively. The correlations between PD-L1 expression, driver-gene status, peripheral blood biomarkers, and the pathological responses (complete pathological response CPR; major pathological response MPR) were assessed. Associations between PET features and pathological responses were evaluated by logistic regression.
Results
Thirty patients underwent surgery and 29 of them performed preoperative PET/CT. Twenty patients achieved MPR and 16 of them achieved CPR. In univariate analysis, five SUV statistics features and two radiomics features were significantly associated with pathological responses. In multi-variate analysis, SUV
max
, SUV
peak
, SUL
peak
, and End-PET-GLDM-LargeDependenceHighGrayLevelEmphasis (End-GLDM-LDHGLE) were independently associated with CPR. SUV
peak
and SUL
peak
performed better than SUV
max
and SUL
max
for MPR prediction. No significant correlation, neither between the radiologic response and the pathological response, nor among PD-L1, driver gene status, and baseline PET features was found. Inflammatory response biomarkers by peripheral blood showed no difference in different treatment responses.
Conclusion
The logistic regression model using comprehensive PET features contributed to predicting the pathological response after neoadjuvant toripalimab with chemotherapy in resectable stage III NSCLC patients.
Background
Microvascular invasion (MVI) is a risk factor for tumor recurrence after hepatectomy in hepatocellular carcinoma (HCC) patients.
Objective
This study aimed to investigate the efficacy and ...safety of postoperative adjuvant transarterial infusion chemotherapy (TAI) with the FOLFOX regimen for HCC patients with MVI.
Methods
In this prospective, phase III, randomized, open-label, controlled clinical trial, HCC patients with histologically confirmed MVI were randomly assigned (1:1) after hepatectomy to receive either one to two cycles of adjuvant TAI (AT group) or follow-up without any adjuvant treatment (FU group). The primary endpoint was disease-free survival (DFS), while secondary endpoints were overall survival (OS) and safety.
Results
Between June 2016 and April 2019, 127 patients were randomly assigned to the AT group (
n
= 63) or FU group (
n
= 64). Clinicopathological characteristics of the two groups were well-balanced. The 6-, 12-, and 18-month OS rates for the AT group were 100.0%, 97.7%, and 97.7%, respectively, and 94.5%, 89.6%, and 78.5% for the FU group, respectively. The 6-, 12-, and 18-month DFS rates for the AT and FU groups were 84.7%, 61.8%, and 58.7%, and 62.9%, 48.1%, and 38.6%, respectively. OS and DFS were significantly better in the AT group than in the FU group (
p
= 0.037 and 0.023, respectively). No patients in the AT group experienced grade 3 or more severe adverse events.
Conclusions
Adjuvant TAI after hepatectomy may bring survival benefits to HCC patients with MVI.
Trial registration
Trial number: NCT03192618.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•The authors propose a novel approach to invert temperature of cable joint.•Indirect temperature measurement of conductor of the cable joint is realized.•The verification experiment was carried ...out.•Inversed results match with measured ones, and the relative errors do not exceed 6%.
Monitoring temperature inside the power cable joint is of great meaning to the safety of power distribution, while measuring it directly is infeasible. In this paper, the authors propose a new method to invert real-time hot spot temperature of conductor in the single-core power cable joint. This method consists of two parts, the radial-direction temperature inversion (RDTI) in the cable and axial-direction temperature inversion (ADTI) in the conductor. With this method, hot spot temperature of conductor in the cable joint could be figured out with the surface temperatures of the cable nearby the cable joint and load current, both of which are measurable. Then, the authors carry it out on an actual power cable joint in the laboratory, and the inversed temperatures are compared with experiment data, which come from the indoor experiment platform, to validate the availability of this method. The maximum error of this method is 6%, and it shows that this method for temperature inversion is feasible in laboratory scale.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Energy consumption, monitor, and the control are key prerequisites for an energy conservation process. When energy consumption occurs is known by the users and exactly where it takes place and able ...to make more informed decisions about how to lower their energy consumption. Renewable energy and optimization of energy are integrated and these are the key enablers of sustainable energy transitions and mitigating. Integration of advances in building design, importance of energy efficiency and VR technology have led the research to focus on thermal simulation which results in a virtual environment for the optimization of building design. In order to reduce building energy consumption in our country, the influence of building an online key technology of virtual reality scene based on Virtual Reality Modeling Language (VRML) technology. The combination of Extensible Markup Language (XML) and Active Server Pages (ASP) programming method puts forward the online virtual scene. The energy conservation and environmental protection building design reality used for online virtual reality environment of green building prototype. Through online and virtual reality technology and VRML combination design of the system, the implementation of green building in the most intuitive way to show in front of a remote (network) user, a performance on the Internet which can interact with the user and can be designed by the user via the extensible platform. The proposed model is useful to meet people's living and working environment and also useful to promote the sustainable development of the country.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Mirabilis himalaica
(Edgew.) Heimerl is among the most important genuine medicinal plants in Tibet. However, the biosynthesis mechanisms of the active compounds in this species are unclear, severely ...limiting its application. To clarify the molecular biosynthesis mechanism of the key representative active compounds, specifically rotenoid, which is of special medicinal value for
M. himalaica
, RNA sequencing and TOF-MS technologies were used to construct transcriptomic and metabolomic libraries from the roots, stems, and leaves of
M. himalaica
plants collected from their natural habitat. As a result, each of the transcriptomic libraries from the different tissues was sequenced, generating more than 10 Gb of clean data ultimately assembled into 147,142 unigenes. In the three tissues, metabolomic analysis identified 522 candidate compounds, of which 170 metabolites involved in 114 metabolic pathways were mapped to the KEGG. Of these genes, 61 encoding enzymes were identified to function at key steps of the pathways related to rotenoid biosynthesis, where 14 intermediate metabolites were also located. An integrated analysis of metabolic and transcriptomic data revealed that most of the intermediate metabolites and enzymes related to rotenoid biosynthesis were synthesized in the roots, stems and leaves of
M. himalaica
, which suggested that the use of non-medicinal tissues to extract compounds was feasible. In addition, the
CHS
and
CHI
genes were found to play important roles in rotenoid biosynthesis, especially, since
CHS
might be an important rate-limiting enzyme. This study provides a hypothetical basis for the screening of new active metabolites and the metabolic engineering of rotenoid in
M. himalaica
.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Inflammation is known to have an intricate relationship with tumorigenesis and tumor progression while it is also closely related to tumor immune microenvironment. Whereas the role of ...inflammation‐related genes (IRGs) in lung squamous carcinoma (LUSC) is barely understood. Herein, we recognized IRGs associated with overall survival (OS), built an IRGs signature for risk stratification and explored the impact of IRGs on immune infiltration landscape of LUSC patients.
Methods
The RNA‐sequencing and clinicopathological data of LUSC patients were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, which were defined as training and validation cohorts. Cox regression and least absolute shrinkage and selection operator analyses were performed to build an IRG signature. CIBERSORT, microenvironment cell populations‐counter and tumor immune dysfunction and rejection (TIDE) algorithm were used to perform immune infiltration analysis.
Results
A two‐IRG signature consisting of KLF6 and SGMS2 was identified according to the training set, which could categorize patients into two different risk groups with distinct OS. Patients in the low‐risk group had more anti‐tumor immune cells infiltrated while patient with high‐risk had lower TIDE score and higher levels of immune checkpoint molecules expressed. The IRG signature was further identified as an independent prognostic factor of OS. Subsequently, a prognostic nomogram including IRG signature, age, and cancer stage was constructed for predicting individualized OS, whose concordance index values were 0.610 (95% CI: 0.568–0.651) in the training set and 0.652 (95% CI: 0.580–0.724) in validation set. Time‐dependent receiver operator characteristic curves revealed that the nomogram had higher prediction accuracy compared with the traditional tumor stage alone.
Conclusion
The IRG signature was a predictor for patients with LUSC and might serve as a potential indicator of the efficacy of immunotherapy. The nomogram based on the IRG signature showed a relatively good predictive performance in survival.
Based on a variety of bioinformatics and immune infiltration analyses, we found the expression of inflammation‐related genes was associated with the prognosis. And the inflammation‐related genes signature can be a potential indicator of the effectiveness of immunotherapy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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