Corilagin Restrains NLRP3 Inflammasome Activation and Pyroptosis through the ROS/TXNIP/NLRP3 Pathway to Prevent Inflammation.

Corilagin, a gallotannin, shows excellent antioxidant and anti-inflammatory effects. The NLRP3 inflammasome dysfunction has been implicated in a variety of inflammation diseases. However, it remains unclear how corilagin regulates the NLRP3 inflammasome to relieve gouty arthritis.

Clinical Implementation and Initial Experience of Real-Time Motion Tracking With Jaws and Multileaf Collimator During Helical Tomotherapy Delivery.

Purpose: This work reports the clinical implementation of a real-time motion tracking and correction system using dynamic multileaf collimator and jaws during helical tomotherapy delivery (Synchrony on Radixact; Accuray, Inc).

Methods And Materials: The first clinical Synchrony on Radixact system was recently installed and tested at our institution. Various clinical workflows, including fiducial implantation, computed tomography simulation, treatment planning, delivery quality assurance, treatment simulation, and delivery, for both fiducial-free and fiducial-based motion tracking methods were developed.

4D-MRI driven MR-guided online adaptive radiotherapy for abdominal stereotactic body radiation therapy on a high field MR-Linac: Implementation and initial clinical experience.

Background And Purpose: In this report, we describe our implementation and initial clinical experience using 4D-MRI driven MR-guided online adaptive radiotherapy (MRgOART) for abdominal stereotactic body radiotherapy (SBRT) on the Elekta Unity MR-Linac.

Materials And Methods: Eleven patients with abdominal malignancies were treated with free-breathing SBRT in three to five fractions on a 1.5 T MR-Linac.

Technical Note: Comprehensive performance tests of the first clinical real-time motion tracking and compensation system using MLC and jaws.

Purpose: To evaluate the performance of the first clinical real-time motion tracking and compensation system using multileaf collimator (MLC) and jaws during helical tomotherapy delivery.

Methods: Appropriate mechanical and dosimetry tests were performed on the first clinical real-time motion tracking system (Synchrony on Radixact, Accuray Inc) recently installed in our institution. kV radiography dose was measured by CTDIw using a pencil chamber.

A daily end-to-end quality assurance workflow for MR-guided online adaptive radiation therapy on MR-Linac.

Purpose: Magnetic Resonance (MR)-guided online adaptive radiation therapy (MRgOART), enabled with MR-Linac, has potential to revolutionize radiation therapy. MRgOART is a complex process. This work is to introduce a comprehensive end-to-end quality assurance (QA) workflow in routine clinic for MRgOART with a high-magnetic-field MR-Linac.

Bmi1 Overexpression in Mesenchymal Stem Cells Exerts Antiaging and Antiosteoporosis Effects by Inactivating p16/p19 Signaling and Inhibiting Oxidative Stress.

We previously demonstrated that Bmi1 deficiency leads to osteoporosis phenotype by inhibiting the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs), but it is unclear whether overexpression of Bmi1 in MSCs stimulates skeletal development and rescues Bmi1 deficiency-induced osteoporosis. To answer this question, we constructed transgenic mice (Bmi1 ) that overexpressed Bmi1 driven by the Prx1 gene and analyzed their skeletal phenotype differences with that of wild-type littermates. We then hybridized Bmi1 to Bmi1 mice to generate Bmi1 mice overexpressing Bmi1 in MSCs and compared their skeletal phenotypes with those of Bmi1 and wild-type mice using imaging, histopathological, immunohistochemical, histomorphometric, cellular, and molecular methods.

DNA damage checkpoint pathway modulates the regulation of skeletal growth and osteoblastic bone formation by parathyroid hormone-related peptide.

We previously demonstrated that parathyroid hormone-related peptide (PTHrP) 1-84 knockin ( KI) mice, which lacked a PTHrP nuclear localization sequence (NLS) and C-terminus, displayed early senescence, defective osteoblastic bone formation, and skeletal growth retardation. However, the mechanism of action of the PTHrP NLS and C-terminus in regulating development of skeleton is still unclear. In this study, we examined alterations of oxidative stress and DNA damage response-related molecules in KI skeletal tissue.

Reducing radiation dose and enhancing imaging quality of 4DCT for radiation therapy using iterative reconstruction algorithms.

Purpose: Four-dimensional computed tomography (CT) images are typically used to quantify the necessary internal target volumes for thoracic and abdominal tumors. However, 4-dimensional CT is typically associated with excessive imaging dose to patients and the situation is exacerbated when using repeat 4-dimensional CT imaging on a weekly or daily basis throughout fractionated therapy. The aim of this work is to evaluate an iterative reconstruction (IR) algorithm that helps reduce the imaging dose to the patient while maintaining imaging quality as quantified by point spread function and contrast-to-noise ratios (CNRs).

Technical Note: Dose effects of 1.5 T transverse magnetic field on tissue interfaces in MRI-guided radiotherapy.

Purpose: The integration of MRI with a linear accelerator (MR-linac) offers great potential for high-precision delivery of radiation therapy (RT). However, the electron deflection resulting from the presence of a transverse magnetic field (TMF) can affect the dose distribution, particularly the electron return effect (ERE) at tissue interfaces. The purpose of the study is to investigate the dose effects of ERE at air-tissue and lung-tissue interfaces during intensity-modulated radiation therapy (IMRT) planning.

Technical Note: Development and performance of a software tool for quality assurance of online replanning with a conventional Linac or MR-Linac.

Purpose: To develop an integrated quality assurance (QA) software tool for online replanning capable of efficiently and automatically checking radiation treatment (RT) planning parameters and gross plan quality, verifying treatment plan data transfer from treatment planning system (TPS) to record and verify (R&V) system, performing a secondary monitor unit (MU) calculation with or without a presence of a magnetic field from MR-Linac, and validating the delivery record consistency with the plan.

Methods: The software tool, named ArtQA, was developed to obtain and compare plan and treatment parameters from both the TPS and the R&V system database. The TPS data are accessed via direct file reading and the R&V data are retrieved via open database connectivity and structured query language.

Radiation-induced CT number changes in GTV and parotid glands during the course of radiation therapy for nasopharyngeal cancer.

Objective: To investigate the changes in CT number (CTN) in gross tumour volume (GTV) and organs at risk (OARs) during the course of radiation therapy (RT) for nasopharyngeal cancer (NPC).

Methods: Daily megavoltage CT (MVCT) data collected from 30 patients with NPC treated with a prescription dose of 70 Gy in 30-33 fractions using helical tomotherapy were retrospectively analyzed. The contours of GTV and OARs on daily MVCTs were obtained by populating the planning contours from planning CT to daily MVCTs with manual editing, if necessary.

Deficiency of the parathyroid hormone-related peptide nuclear localization and carboxyl terminal sequences leads to premature skin ageing partially mediated by the upregulation of p27.

We previously reported that deficiency of the PTHrP nuclear localization sequence (NLS) and C-terminus in PTHrP knockin (PTHrP KI) mice resulted in premature ageing of skin. P27, a cyclin-dependent kinase inhibitor, was upregulated in PTHrP KI mice and acted as a downstream target of the PTHrP NLS to regulate the proliferation of vascular smooth muscle cells. To determine the effects of p27 deficiency on premature skin ageing of PTHrP KI mice, we compared the skin phenotypes of PTHrP KI mice to those of p27 knockout (p27(-/-) ) mice and to those of double homozygous p27-deficient and PTHrP KI (p27(-/-) PTHrP KI) mice at 2 weeks age.

A planning comparison of 7 irradiation options allowed in RTOG 1005 for early-stage breast cancer.

This study compared the 7 treatment plan options in achieving the dose-volume criteria required by the Radiation Therapy Oncology Group (RTOG) 1005 protocol. Dosimetry plans were generated for 15 representative patients with early-stage breast cancer (ESBC) based on the protocol-required dose-volume criteria for each of the following 7 treatment options: 3D conformal radiotherapy (3DCRT), whole-breast irradiation (WBI) plus 3DCRT lumpectomy boost, 3DCRT WBI plus electron boost, 3DCRT WBI plus intensity-modulated radiation therapy (IMRT) boost, IMRT WBI plus 3DCRT boost, IMRT WBI plus electron boost, IMRT WBI plus IMRT boost, and simultaneous integrated boost (SIB) with IMRT. A variety of dose-volume parameters, including target dose conformity and uniformity and normal tissue sparing, were compared for these plans.

A planning and delivery study of a rotational IMRT technique with burst delivery.

Purpose: A novel rotational IMRT (rIMRT) technique using burst delivery (continuous gantry rotation with beam off during MLC repositioning) is investigated. The authors evaluate the plan quality and delivery efficiency and accuracy of this dynamic technique with a conventional flat 6 MV photon beam.

Methods: Burst-delivery rIMRT was implemented in a planning system and delivered with a 160-MLC linac.

Development of an online adaptive solution to account for inter- and intra-fractional variations.

Purpose: The current IGRT repositioning cannot fully account for the organ deformation and rotation. We introduce a comprehensive solution using gated IMRT with online adaptive replanning to manage both inter- and intra-fractional variations.

Methods And Materials: The solution includes (1) generating respiration-gated IMRT plans based on 4DCT, (2) acquiring daily gated CT in treatment position prior to the treatment using a diagnostic-quality in-room CT (CTVision, Siemens) with the same gating window as that for the planning CT, (3) performing online repositioning or adaptive replanning based on the gated CT of the day, and (4) delivering the treatment with gating.

Validation of an online replanning technique for prostate adaptive radiotherapy.

We have previously developed an online adaptive replanning technique to rapidly adapt the original plan according to daily CT. This paper reports the quality assurance (QA) developments in its clinical implementation for prostate cancer patients. A series of pre-clinical validation tests were carried out to verify the overall accuracy and consistency of the online replanning procedure.

Characterizing interfraction variations and their dosimetric effects in prostate cancer radiotherapy.

Purpose: To quantitatively characterize the interfraction variations and their dosimetric effects in radiotherapy for prostate cancer.

Methods And Materials: A total of 486 daily computed tomography (CT) sets acquired for 20 prostate cancer patients treated with daily CT-guided repositioning using a linear accelerator and CT-on-rail combination were analyzed. The prostate, rectum, and bladder, delineated on each daily CT data set, were compared with those from the planning CT scan.

An on-line replanning scheme for interfractional variations.

Ability of online adaptive replanning is desirable to correct for interfraction anatomic changes. A full-scope replanning/reoptimization with the current planning techniques takes too long to be practical. A novel online replanning strategy to correct for interfraction anatomic changes in real time is presented.

Automated computer optimization for 3D treatment planning of breast irradiation.

A software package, capable of optimizing beam energy and weight and wedge angle and orientation in conjunction with commercial treatment planning system, has been developed to effectively generate three-dimensional conformal radiation therapy (3DCRT) plans for breast irradiation with complicated dosimetry requirements. A nonlinear optimization procedure was utilized for the optimization. The study with 15 patient cases shows that the technique can reduce treatment planning time and effort significantly and can give comparable or slightly better dosimetry results.

Development of an inverse optimization package to plan nonuniform dose distributions based on spatially inhomogeneous radiosensitivity extracted from biological images.

An inverse optimization package which is capable of generating nonuniform dose distribution with subregional dose escalation is developed to achieve maximum equivalent uniform dose (EUD) for target while keeping the critical structure doses as low as possible. Relative cerebral blood volume (rCBV) maps obtained with a dynamic susceptibility contrast-enhanced MRI technique were used to delineate spatial radiosensitivity distributions. The voxel rCBV was converted to voxel radiosensitivity parameters (e.

Direct aperture optimization-based intensity-modulated radiotherapy for whole breast irradiation.

Purpose: To investigate the technical and dosimetric advantages and the efficacy of direct aperture optimized intensity-modulated radiation therapy (DAO-IMRT) over standard (e.g., beamlet optimized) IMRT and conventional three-dimensional conformal radiotherapy (3D-CRT) for whole breast irradiation in supine and prone positions.