Objective To evaluate the role of equivalent uniform dose (EUD) in planning optimization of intensity-modulated radiotherapy (IMRT) for prostate cancer.Methods Ten patients with prostate cancer were randomly selected who treated with IMRT.For these patients,the treatment plans were designed with dose-volume objectives.Based on these plans,new plans were designed through replacing the dose-volume objectives with maximum EUD for rectum,bladder and small bowel,while keeping the dosevolume objectives unchanged.Comparison was made between the new plans and the former cones by paired t-test.Results The conformity index of planning target volume was better with EUD optimization compared to dose-volume (1.00 ± 0.04 ∶ 0.94 ± 0.04,t =3.80,P =0.04).The D53,D30 and Dicm3 for rectum was better with EUD optimization compared to dose-volume (24.4 ± 2.7 ∶ 25.5 ± 2.6,t =-3.82,P =0.004,34.1 ±4.3∶39.1±2.1,t=-3.80,P=0.004 and51.4±1.0∶51.8±0.9,t=-2.42,P=0.039),with V10,V20 for bladder and V10,V20,V30,V40 for small bowel also better with EUD optimization (92.2 ±6.2∶99.4±1.1,t=-4.28,P=0.002;70.7±5.7∶78.7±6.3,t=-3.10,P=0.013 and 62.2±30.2∶74.7 ±30.0,t =-4.18,P =0.002;34.3 ±26.3∶46.5 ±30.9,t =-5.46,P =0.000;17.1 ±17.0∶25.1 ±22.6,t=-3.52,P=0.007;10.6± 11.5∶ 15.6± 16.1,t=-2.64,P=0.030).Conclusions The conformity index of planning target volume is better with EUD optimization compared to dose-volume.And the dose to rectum,bladder and small bowel can be reduced through optimization with EUD optimization compared to dose-volume.

Objective The aim of this study was to evaluate the role of multicriteria optimization (MCO) in planning of intensity-modulated radiotherapy (IMRT).Methods Twenty IMRT patients (ten with prostate and ten with lung cancers) were randomly selected.For these patients,the treatment plans were designed with direct machine parameter optimization (DMPO).Based on these plans,new plans were designed with MCO,while keeping the setting conditions unchanged.Comparison was made between the two plans including the dose distribution,the dose volume histogram,the time of optimization and number of monitor unit (MU),but were play by pairing-t test.Results The plan designed in both optimizations satisfied all clinical requirements.For the same or better target coverage,rectum,bladder and small bowel were better with MCO compared with DMPO,MCO reduced 58％ of the time for optimization by average while MU increased 32％ by average for prostate cancer.For lung cancer,the whole lung,heart and spinal cord were better with MCO compared with DMPO,MCO reduced 59％ of the time for optimization by average while MU increased 11％ by average.Conclusions In comparison with DMPO,MCO reduces the dose of organs at risk,shorten the time of optimization.

Pulmonary fibrosis is a fatal progressive disease with no effective therapy. Transforming growth factor (TGF)-beta1 has long been regarded as a central mediator of tissue fibrosis that involves multiple organs including skin, liver, kidney, and lung. Thus, TGF-beta1 and its signaling pathways have been attractive therapeutic targets for the development of antifibrotic drugs. However, the essential biological functions of TGF-beta1 in maintaining normal immune and cellular homeostasis significantly limit the effectiveness of TGF-beta1-directed therapeutic approaches. Thus, targeting downstream mediators or signaling molecules of TGF-beta1 could be an alternative approach that selectively inhibits TGF-beta1-stimulated fibrotic tissue response while preserving major physiological function of TGF-beta1. Recent studies from our laboratory revealed that TGF-beta1 crosstalk with epidermal growth factor receptor (EGFR) signaling by induction of amphiregulin, a ligand of EGFR, plays a critical role in the development or progression of pulmonary fibrosis. In addition, chitotriosidase, a true chitinase in humans, has been identified to have modulating capacity of TGF-beta1 signaling as a new biomarker and therapeutic target of scleroderma-associated pulmonary fibrosis. These newly identified modifiers of TGF-beta1 effector function significantly enhance the effectiveness and flexibility in targeting pulmonary fibrosis in which TGF-beta1 plays a significant role.
Animals ; Drug Design ; Hexosaminidases/antagonists & inhibitors/metabolism ; Humans ; Lung/*drug effects/metabolism/pathology ; Molecular Targeted Therapy ; Pulmonary Fibrosis/*drug therapy/metabolism/pathology ; Receptor Cross-Talk ; Receptor, Epidermal Growth Factor/antagonists & inhibitors/metabolism ; Receptors, Transforming Growth Factor beta/antagonists & inhibitors/metabolism ; Signal Transduction ; Transforming Growth Factor beta1/*antagonists & inhibitors/metabolism

BACKGROUNDThe correlation between angiographic or intravascular ultrasound (IVUS) variables and fractional flow reserve (FFR) in patients with single left anterior descending artery (LAD) lesion has not been studied. The current study aimed at determining the best cutoff value of angiographic and IVUS parameters for defining FFR < 0.80 in patients with LAD lesion.

METHODSQuantitative coronary analysis, IVUS and FFR measurements were undergone in 169 patients with single LAD lesion. The best angiographic and IVUS cutoff value and their predictive value for FFR < 0.80 were compared using area under the receiver-operator characteristic curve (AUC) in overall patients or in subgroups stratified by lesion sites.

RESULTSFFR < 0.80 was found in 99 lesions (58.6%). Minimal lumen area (MLA), and plaque burden (PB) were two predictors of FFR < 0.80. Lesion length had less value in predicting FFR < 0.80. The cutoff value of PB and MLA for FFR < 0.80 was 75.4% and 3.03 mm(2). MLA and PB had similar high diagnostic value for proximal (cutoff value 3.04 mm(2) and 76.5%) and distal LAD lesion (2.82 mm(2) and 80.6%). Combination of MLA (2.82 mm(2)) and PB (80.6%) had increased diagnostic value for distal LAD lesion.

CONCLUSIONSMLA and plaque burden had equivalent diagnostic value for FFR < 0.80 when lesion localized in LAD. The predictive value of combination of MLA and plaque burden for distal LAD lesion was strengthened.

Coronary Angiography ; methods ; Coronary Artery Disease ; diagnostic imaging ; Coronary Vessels ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Plaque, Atherosclerotic ; diagnostic imaging ; Ultrasonography, Interventional ; methods

BACKGROUNDThe mechanisms responsible for the occurrence of a kissing unsatisfied (KUS) result after classical crush stenting remain unclear. The present study aimed at analyzing the mechanisms and clinical significance of KUS.

METHODSTwo hundred and thirteen patients with true bifurcation lesions treated with classical crush stenting and final kissing balloon inflation (FKBI) were assigned to upper, middle, and lower groups according to the position of the side branch re-wiring assessed by visual estimation, quantitative coronary analysis (QCA) and intravascular ultrasound (IVUS). Angiographic follow-up was indexed at 12 months.

RESULTSThe upper group was characterized by a larger bifurcation angle of 55.53 degrees +/- 25.25 degrees (P = 0.030) and a longer procedural time (42.43 +/- 23.92) minutes (P = 0.015). The overall rate of KUS by visual estimation was 10.48%, with 5.4% in the upper group, 3.9% in middle group, and 36.1% in lower group (P < 0.001). For the diagnosis of KUS, visual inspection demonstrated a good correlation with both QCA and IVUS. Smaller stent diameter was the main reason for KUS in the upper group, while extra-stent side wire location, or re-wire in a low position was the main mechanism attributed to KUS in the lower group. The Lower group had more restenosis, with most restenotic lesions at a lower position of the side branch ostium. KUS (HR 1.652, 95% CI 1.332 - 2.088, P < 0.001) and re-wiring position (HR 2.341, 95% CI 1.780 - 4.329, P < 0.001) were two independent predictors of side branch restenosis. Re-wiring position (OR 0.458, 95%CI 0.336 - 0.874, P = 0.001) and side stent expansion (OR 3.122, 95%CI 2.883 - 5.061, P = 0.014) were factors predicting the findings of KUS.

CONCLUSIONSSide wire outside side stents resulted in more KUS and restenosis. Different restenotic lesion types reflected individual mechanisms contributing to the development of plaque proliferation.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Coronary Disease ; therapy ; Female ; Humans ; Male ; Middle Aged ; Stents ; Treatment Outcome

COVID-19 ; Housing ; Humans ; Pandemics ; SARS-CoV-2

We have previously shown that high expression of the nucleic acid binding factor YB-1 is strongly associated with poor prognosis in a variety of cancer types. The 3-dimensional protein structure of YB-1 has yet to be determined and its role in transcriptional regulation remains elusive. Drug targeting of transcription factors is often thought to be difficult and there are very few published high-throughput screening approaches. YB-1 predominantly binds to single-stranded nucleic acids, adding further difficulty to drug discovery. Therefore, we have developed two novel screening assays to detect compounds that interfere with the transcriptional activation properties of YB-1, both of which may be generalizable to screen for inhibitors of other nucleic acid binding molecules. The first approach is a cell-based luciferase reporter gene assay that measures the level of activation of a fragment of the promoter by YB-1. The second approach is a novel application of the AlphaScreen system, to detect interference of YB-1 interaction with a single-stranded DNA binding site. These complementary assays examine YB-1 binding to two discrete nucleic acid sequences using two different luminescent signal outputs and were employed sequentially to screen 7360 small molecule compounds leading to the identification of three putative YB-1 inhibitors.