Background
Small intestine cancer (SIC) is difficult to diagnose early and presents a poor prognosis due to distant metastasis. This study aimed to develop nomograms for diagnosing and assessing the ...prognosis of SIC with distant metastasis.
Methods
Patients diagnosed with SIC between 2010 and 2015 were included from the Surveillance, Epidemiology and End Results database. Univariate and multifactor analysis determined independent risk factors for distant metastasis and prognostic factors for overall and cancer‐specific survival. We then constructed the corresponding three nomograms and assessed the diagnostic accuracy of the nomograms by net reclassification improvement, receiver operating characteristic curves and calibration curves, assessed the clinical utility by decision curve analysis.
RESULTS
The cohort consisted of 6697 patients, of whom 1299 had distant metastasis at diagnosis. Tstage, Nstage, age, tumor size, grade, and histological type were independent risk factors for distant metastasis. Age, histological type, T stage, N stage, grade, tumor size, whether receiving surgery, number of lymph nodes removed, and the presence of bone or lung metastases were predictors of both overall survival and cancer‐specific survival. The nomograms showed excellent accuracy in predicting distant metastasis and prognosis.
Conclusion
Nomograms were developed and validated for SIC patients with distant metastasis, aiding physicians in making rational and personalized clinical decisions.
Introduction
Compared with traditional fundus examination techniques, ultra-widefield fundus (UWF) images provide 200° panoramic images of the retina, which allows better detection of peripheral ...retinal lesions. The advent of UWF provides effective solutions only for detection but still lacks efficient diagnostic capabilities. This study proposed a retinal lesion detection model to automatically locate and identify six relatively typical and high-incidence peripheral retinal lesions from UWF images which will enable early screening and rapid diagnosis.
Methods
A total of 24,602 augmented ultra-widefield fundus images with labels corresponding to 6 peripheral retinal lesions and normal manifestation labelled by 5 ophthalmologists were included in this study. An object detection model named You Only Look Once X (YOLOX) was modified and trained to locate and classify the six peripheral retinal lesions including rhegmatogenous retinal detachment (RRD), retinal breaks (RB), white without pressure (WWOP), cystic retinal tuft (CRT), lattice degeneration (LD), and paving-stone degeneration (PSD). We applied coordinate attention block and generalized intersection over union (GIOU) loss to YOLOX and evaluated it for accuracy, sensitivity, specificity, precision,
F
1 score, and average precision (AP). This model was able to show the exact location and saliency map of the retinal lesions detected by the model thus contributing to efficient screening and diagnosis.
Results
The model reached an average accuracy of 96.64%, sensitivity of 87.97%, specificity of 98.04%, precision of 87.01%,
F
1 score of 87.39%, and mAP of 86.03% on test dataset 1 including 248 UWF images and reached an average accuracy of 95.04%, sensitivity of 83.90%, specificity of 96.70%, precision of 78.73%,
F
1 score of 81.96%, and mAP of 80.59% on external test dataset 2 including 586 UWF images, showing this system performs well in distinguishing the six peripheral retinal lesions.
Conclusion
Focusing on peripheral retinal lesions, this work proposed a deep learning model, which automatically recognized multiple peripheral retinal lesions from UWF images and localized exact positions of lesions. Therefore, it has certain potential for early screening and intelligent diagnosis of peripheral retinal lesions.
Background and Objective
Recent advancements in immunotherapy led to the development of Chimeric antigen receptor (CAR) T‐cell therapy. CAR‐T cell therapy in non‐small cell lung cancer (NSCLC) is ...hindered by overexpression of transforming growth factor (TGFβ) in the cancer cells that have a negative regulatory role on T‐cells activity. This study characterized CAR‐T with overexpression of mothers against decapentaplegic homologue 7 (SMAD), a negative regulator of TGFβ downstream signalling.
Methods
We have generated three types of CAR‐T: epidermal growth factor receptor (EGFR)‐CAR‐T, EGFR‐dominant‐negative TGFbeta receptor 2 (DNR)‐CAR‐T, and EGFR‐SMAD7‐CAR‐T by transducing human T‐cells with the lentivirus constructs. We characterized the proliferation, expression of proinflammatory cytokines, activation profile, and lysis capacity in co‐cultures with A549 lung carcinoma cells with and without TGFβ neutralizing antibodies. We also tested the therapeutic potential of EGFR‐SMAD7‐CAR‐T in the A549 cells tumour‐bearing mice model.
Results
Both EGFR‐DNR‐CAR‐T and EGFR‐SMAD7‐CAR‐T demonstrated a higher proliferation rate and lysis capacity to A549 than traditional EGFR‐CAR‐T. Neutralization of TGFβ by the antibodies resulted in increased performance of EGFR‐CAR‐T. In vivo, both EGFR‐DNR‐CAR‐T and EGFR‐SMAD7‐CAR‐T resulted in complete tumour resorption by day 20, whereas conventional CAR‐T only has a partial effect.
Conclusion
We demonstrated the high efficacy and resistance to negative TGFβ regulation of EGFR‐SMAD7‐CAR‐T comparable with EGFR‐DNR‐CAR‐T and without the systemic effect of TGFβ inhibition.
The efficacy of TGF‐β signalling‐resistant CAR‐T based on SMAD7 overexpression is restricted to CAR‐T cells themselves and potentially reduces systemic effects on TGF‐β signalling. SMAD7‐CAR‐T demonstrates complete elimination of cancer in vivo, high levels of SMAD7‐CAR‐T proliferation, and activation that are not significantly different from the DNR‐CAR‐T design.
Purpose
This study aimed to explore the role and underlying mechanism of action of Endoplasmic reticulum oxidoreductin‐1 L (ERO1L) in lung adenocarcinoma (LUAD).
Materials and Methods
The Gene ...expression profiling interactive analysis database was used to analyze the expression of ERO1L in LUAD cases. The expression of ERO1L and Wnt2 in LUAD tissue was evaluated using immunohistochemistry. We also used western blotting to assess the expression of ERO1L or Wnt2 and the phosphorylation of β‐catenin in LUAD cell lines. Plasmid transfection and small interfering RNA were used for overexpression and knockdown of ERO1L in LUAD cells, respectively. The proliferation, invasion and migration of LUAD cells were analyzed using cell viability, Transwell invasion and wound healing assays. The growth of LUAD tumors in animal models was assessed using tumor xenograft experiments.
Results
This study revealed that elevated ERO1L expression was associated with a poor prognosis in LUAD patients. In addition, ERO1L expression was significantly associated with lymph‐node metastasis, TNM stage and tumor size. The expression of Wnt2 was positively associated with ERO1L expression in LUAD tissue samples and cell lines. ERO1L overexpression upregulated the expression of Wnt2 and β‐catenin phosphorylation in vitro. Additionally, ERO1L was essential for the ubiquitination of Wnt2. Last, ERO1L promoted the proliferation and metastasis of LUAD via the Wnt2 signaling pathway in vitro and in vivo.
Conclusion
These findings suggest that ERO1L was highly expressed in LUAD tissue, and it promoted the proliferation and metastasis of LUAD by activating the Wnt2/β‐catenin signaling pathway.
One novel ruthenium polypyridyl complex, Ru(bpy)2(icip)(2+) (1), and two previously reported ruthenium polypyridyl complexes, Ru(bpy)2(pdppz)(2+) ()2 and Ru(bpy)2(tactp)(2+) (3) (bpy = ...2,2'-bipyridine, icip = 2-(indeno2,1-bchromen-6-yl)-1H-imidazo4,5-f1,10phenanthroline, pdppz = phenanthro4,5-abcdipyrido3,2-h:2',3'-jphenazine, tactp = 4,5,9,18-tetraazachryseno9,10-b-triphenylene), have been synthesised. As expected, these complexes show inhibition towards telomerase by inducing and stabilising the G-quadruplex structure, and behave as topoisomerase I/II poisons at the same time. Additionally, the acute and chronic cytotoxicities of the complexes are considered. Furthermore, cell apoptosis experiments are used to briefly study the mechanism. Because studies involving multi-target inhibition towards topoisomerase and telomerase of Ru(II) complexes have not been reported previously, the present research may help to develop innovative chemical strategies and therapies.
Two novel ruthenium polypyridyl complexes, Ru(bpy)2(pedppz)(2+) (1) and Ru(bpy)2(pemitatp)(2+) (2) (bpy = 2'2-bipyridine, pdeppz = 10-(2-(piperidin-1-yl)ethoxy)dipyrido3,2-a:2',3'-cphenazine, ...pemitatp = 5-methoxy-1-(2-(piperidin-1-yl)ethyl)-isatino1,2-b-1,4,8,9-tetraazatriphenylene), bearing large planar π-delocalized aromatic systems with flexible chains have been synthesised and characterised. As expected, these complexes show inhibition towards telomerase by inducing and stabilising the G-quadruplex structure.
The intelligent diagnosis of thyroid nodules in ultrasound image is an important research issue. Automatically locating the region of interest (ROI) of thyroid nodules and providing pre-diagnosis ...results can help doctors to diagnose faster and more accurate.
This study aims to propose a model, which can detect multiple nodules stably and accurately in order to avoid missed detection and misjudgment. In addition, the detection speed of the model needs to be fast for real-time diagnosis in ultrasound images.
Based on the object detection technology, we propose an accurate, robust and high-speed network with multiscale fusion strategy called Efficient-YOLO, which can realize the localization and recognition of nodules at the same time. Finally, multiple metrics are used to measure the diagnostic ability of the model.
Experimental results conducted on 3,562 ultrasound images show that our new model greatly increases the accuracy and speed of the detection compared with the baseline model. The best mAP is 92.64%, and the fastest detection speed is 45.1 frames per second.
This study proposed an effective method to diagnosis thyroid nodules automatically, which can meet the real-time requirements, indicating that its effectiveness and feasibility for future clinical application.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
One novel ruthenium polypyridyl complex, Ru(bpy)
2
(icip)
2+
(
1
), and two previously reported ruthenium polypyridyl complexes, Ru(bpy)
2
(pdppz)
2+
(
2
) and Ru(bpy)
2
(tactp)
2+
(
3
) (bpy = ...2,2′-bipyridine, icip = 2-(indeno2,1-
b
chromen-6-yl)-1
H
-imidazo4,5-
f
1,10phenanthroline, pdppz = phenanthro4,5-
abc
dipyrido3,2-
h
:2′,3′-
j
phenazine, tactp = 4,5,9,18-tetraazachryseno9,10-
b
-triphenylene), have been synthesised. As expected, these complexes show inhibition towards telomerase by inducing and stabilising the G-quadruplex structure, and behave as topoisomerase I/II poisons at the same time. Additionally, the acute and chronic cytotoxicities of the complexes are considered. Furthermore, cell apoptosis experiments are used to briefly study the mechanism. Because studies involving multi-target inhibition towards topoisomerase and telomerase of Ru(
ii
) complexes have not been reported previously, the present research may help to develop innovative chemical strategies and therapies.
Three ruthenium(
ii
) polypyridyl complexes, Ru(bpy)
2
(icip)
2+
(
1
), Ru(bpy)
2
(pdppz)
2+
(
2
), and Ru(bpy)
2
(tactp)
2+
(
3
), were selected to inhibit telomerase by inducing and stabilising the G-quadruplex structure, and behave as topoisomerase I/II poisons at the same time.
Two novel ruthenium polypyridyl complexes, Ru(bpy)
2
(pedppz)
2+
(
1
) and Ru(bpy)
2
(pemitatp)
2+
(
2
) (bpy = 2′2-bipyridine, pdeppz = 10-(2-(piperidin-1-yl)ethoxy)dipyrido3,2-
a
:2′,3′-
c
...phenazine, pemitatp = 5-methoxy-1-(2-(piperidin-1-yl)ethyl)-isatino1,2-
b
-1,4,8,9-tetraazatriphenylene), bearing large planar π-delocalized aromatic systems with flexible chains have been synthesised and characterised. As expected, these complexes show inhibition towards telomerase by inducing and stabilising the G-quadruplex structure.
Two ruthenium(
ii
) polypyridyl complexes, Ru(bpy)
2
(pedppz)
2+
(
1
) and Ru(bpy)
2
(pemitatp)
2+
(
2
), show inhibition towards telomerase by inducing and stabilising the human telomeric d(TTAGGG)
n
quadruplex.
Due to the excellent anti-inflammatory effect, ibuprofen and naproxen have been widely used in the people's daily life, which inevitably leads to their pollution in natural water environment. The ...removal of these chemicals from water has drawn great interests. Here, a new Cu-doped Mil-101(Fe) was synthesized through a one-step solvothermal method and successfully applied for the adsorption removal of ibuprofen and naproxen from water. A series of characterization techniques (FESEM, TEM, N2 adsorption-desorption analysis, XRD and FT-IR) were applied to explore the physicochemical properties of the prepared Cu-doped Mil-101(Fe). The adsorption performances of the Cu-doped Mil-101(Fe) for ibuprofen and naproxen, including the adsorption kinetics and isotherms, and effects of diverse influencing factors (pH, ionic strength, and natural organic matter) were examined through batch experiments. The adsorption kinetics and isotherms of ibuprofen and naproxen on the Cu-doped Mil-101(Fe) fitted well with the pseudo-second-order model and Langmuir model, respectively. The maximum adsorption capacities of Cu-doped Mil-101(Fe) were 497.3 and 396.5 mg/g for ibuprofen and naproxen, respectively. The pH of solution in a range of 3-9 exerted no significant effects on the adsorption process. The adsorption was almost unaffected by the ionic strength and humic acid. The π-π interaction and hydrogen bond interaction between the adsorbent and adsorbates were found to be accountable for adsorption. The Cu-doped Mil-101(Fe) was readily regenerated by ethanol and could be repeatedly used.
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•A novel Cu-doped Mil-101(Fe) was synthesized through a one-step solvothermal method.•The Cu-doped Mil-101(Fe) exhibited fast adsorption rate and high adsorption capacity.•The adsorption was almost unaffected by ionic strength and humic acid.•The as-synthesized material can be readily regenerated by ethanol with excellent stability.
