Machine Log File and Calibration Errors-based Patient-specific Quality Assurance (QA) for Volumetric Modulated Arc Therapy (VMAT).

INTRODUCTION: Dose reconstructed based on linear accelerator (linac) log-files is one of the widely used solutions to perform patient-specific quality assurance (QA). However, it has a drawback that the accuracy of log-file is highly dependent on the linac calibration. The objective of the current study is to represent a new practical approach for a patient-specific QA during Volumetric modulated arc therapy (VMAT) using both log-file and calibration errors of linac. METHODS: A total of six cases, including two head and neck neoplasms, two lung cancers, and two rectal carcinomas, were selected. The VMAT-based delivery was optimized by the TPS of Pinnacle^3 subsequently, using Elekta Synergy VMAT linac (Elekta Oncology Systems, Crawley, UK), which was equipped with 80 Multi-leaf collimators (MLCs) and the energy of the ray selected at 6 MV. Clinical mode log-file of this linac was used in this study. A series of test fields validate the accuracy of log-file. Then, six plans of test cases were delivered and log-file of each was obtained. The log-file errors were added to the corresponding plans through the house script and the first reconstructed plan was obtained. Later, a series of tests were performed to evaluate the major calibration errors of the linac (dose-rate, gantry angle, MLC leaf position) and the errors were added to the first reconstruction plan to generate the second reconstruction plan. At last, all plans were imported to Pinnacle and recalculated dose distribution on patient CT and ArcCheck phantom (SUN Nuclear). For the former, both target and OAR dose differences between them were compared. For the latter, γ was evaluated by ArcCheck, and subsequently, the surface dose differences between them were performed. RESULTS: Accuracy of log-file was validated. If error recordings in the log file were only considered, there were four arcs whose proportion of control points with gantry angle errors more than ± 1°larger than 35%. Errors of leaves within ± 0.5 mm were 95% for all arcs. The distinctness of a single control point MU was bigger, but the distinctness of cumulative MU was smaller. The maximum, minimum, and mean doses for all targets were distributed between -6.79E-02-0.42%, -0.38-0.4%, 2.69E-02-8.54E-02% respectively, whereas for all OAR, the maximum and mean dose were distributed between -1.16-2.51%, -1.21-3.12% respectively. For the second reconstructed dose: the maximum, minimum, and mean dose for all targets was distributed between 0.0995~5.7145%, 0.6892~4.4727%, 0.5829~1.8931% separately. Due to OAR, maximum and mean dose distribution was observed between -3.1462~6.8920%, -6.9899~1.9316%, respectively. CONCLUSION: Patient-specific QA based on the log-file could reflect the accuracy of the linac execution plan, which usually has a small influence on dose delivery. When the linac calibration errors were considered, the reconstructed dose was closer to the actual delivery and the developed method was accurate and practical.

Investigation of total skin helical tomotherapy using a 3D-printed total skin bolus.

OBJECTIVE: To investigate the effectiveness of using a 3D-printed total skin bolus in total skin helical tomotherapy for the treatment of mycosis fungoides. MATERIALS AND METHODS: A 65-year-old female patient with a 3-year history of mycosis fungoides underwent treatment using an in-house desktop fused deposition modelling printer to create a total skin bolus made of a 5-mm-thick flexible material, which increased the skin dose through dose building. The patient's scan was segmented into upper and lower sections, with the division line placed 10 cm above the patella. The prescription was to deliver 24 Gy over 24 fractions, given 5 times per week. The plan parameters consisted of a field width of 5 cm, pitch of 0.287 and modulation factor of 3. The complete block was placed 4 cm away from the planned target region to reduce the area of the internal organs at risk, especially the bone marrow. Dose delivery accuracy was verified using point dose verification with a "Cheese" phantom (Gammex RMI, Middleton, WI), 3D plane dose verification with ArcCHECK (Model 1220, Sun Nuclear, Melbourne, FL), and multipoint film dose verification. Megavoltage computed tomography guidance was also utilized to ensure the accuracy of the setup and treatment. RESULTS: A 5-mm-thick 3D-printed suit was used as a bolus to achieve a target volume coverage of 95% of the prescribed dose. The conformity index and homogeneity index of the lower segment were slightly better than those of the upper segment. As the distance from the skin increased, the dose to the bone marrow gradually decreased, and the dose to other organs at risk remained within clinical requirements. The point dose verification deviation was less than 1%, the 3D plane dose verification was greater than 90%, and the multipoint film dose verification was less than 3%, all of which confirmed the accuracy of the delivered dose. The total treatment time was approximately 1.5 h, which included 0.5 h of wearing the 3D-printed suit and 1 h with the beam on. Patients only experienced mild fatigue, nausea or vomiting, low-grade fever, and grade III bone marrow suppression. CONCLUSION: The use of a 3D-printed suit for total skin helical tomotherapy can result in a uniform dose distribution, short treatment time, simple implementation process, good clinical outcomes, and low toxicity. This study presents an alternative treatment approach that can potentially yield improved clinical outcomes for mycosis fungoides.

Underlying beneficial effects of Rhubarb on constipation-induced inflammation, disorder of gut microbiome and metabolism.

Background: Constipation is a common syndrome and a worldwide healthy problem. Constipation patients are becoming younger, with a 29.6% overall prevalence in children, which has captured significant attention because of its epigenetic rejuvenation and recurrent episodes. Despite the usage of rhubarb extract to relieve constipation, novel targets and genes implicated in target-relevant pathways with remarkable functionalities should still be sought for. Materials and methods: We established a reliable constipation model in C57B/6N male mice using intragastric administration diphenoxylate, and the eligible subjects received 600 mg/25 g rhubarb extract to alleviate constipation. Resultant constipation was morphological and genetically compared with the specimen from different groups. Results: Constipation mice exhibited thicker muscle layers, higher levels of cytokines, including IL-17 and IL-23, and lower content of IL-22. Bacterial abundance and diversity varied tremendously. Notably, the alterations were reversed following rhubarb extract treatment. Additionally, Constipation also had a substantial impact on short-chain fatty acids (SCFAs), medium- and long-chain fatty acids (MLCFAs), and the expression of SCFA receptors, GPR41 and GPR43. Conclusion: This thesis has provided insight that rhubarb extract promoted the flexibility of collagen fiber, reduced pro-inflammatory cytokines, enhanced anti-inflammatory cytokines, and maintained gut microflora balance with potential impacts on the fatty acid and polyamine metabolism.

Corrigendum: ACE2 in the gut: The center of the 2019-nCoV infected pathology.

[This corrects the article DOI: 10.3389/fmolb.2021.708336.].

Corrigendum: Peroxisome proliferator-activated receptor-α: A pivotal regulator of the gastrointestinal tract.

[This corrects the article DOI: 10.3389/fmolb.2022.864039.].

Corrigendum: Endoplasmic reticulum stress of gut enterocyte and intestinal diseases.

[This corrects the article DOI: 10.3389/fmolb.2022.817392.].

Clinical study of total bone marrow combined with total lymphatic irradiation pretreatment based on tomotherapy in hematopoietic stem cell transplantation of acute leukemia.

Objective: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective method for the treatment of refractory and relapsed acute leukemia, and the preconditioning methods before transplantationis one of the important factors affecting the survival of patients. Radiotherapy combined with chemotherapy is the most commonly used preconditioning method before transplantation. This study evaluated the safety and efficacy of total bone marrow combined with total lymphatic irradiation as a preconditioning method before hematopoietic stem cell transplantation. Methods: Seventeen patients with acute leukemia who were admitted to our center from 2016 to 2020 were selected. The median age was 17 years (8-35). The target area for TMLI includes the total bone marrow and total lymphatic space, and the organs at risk include the lens, lungs, kidneys, intestine, heart, and liver. The patients received a total bone marrow and lymphatic irradiation preconditioning regimen, the related acute adverse reactions were graded, and the prognosis of the patients after transplantation was observed. Results: During patient preconditioning, only grade 1-2 toxicity was observed, and grade 3-4 toxicity did not occur. Except for one patient whose platelets were not engrafted, all the other patients were successfully transplanted. The median time of neutrophil implantation was 14 d (9-15 d), and the median time of platelet implantation was 14 d (13-21 d). With a median follow-up of 9 months (2-48), 4 relapses occurred, 3 died, and 10 leukemia patients survived and were disease-free. One-year overall survival was 69.8%, cumulative recurrence was 19.5%, disease-free-survival was 54.2%. Conclusion: The Allo-HSCT pretreatment regimen of total bone marrow combined with total lymphatic irradiation is safe and effective in the treatment of malignant hematological diseases. Total bone marrow combined with total lymphatic irradiation may completely replace total body irradiation, and the clinically observed incidence of acute toxicity is not high.

An Unexpected Alteration Colonic Mucus Appearance in the Constipation Model via an Intestinal Microenvironment.

Due to the lack of research between the inner layers in the structure of colonic mucous and the metabolism of fatty acid in the constipation model, we aim to determine the changes in the mucous phenotype of the colonic glycocalyx and the microbial community structure following treatment with Rhubarb extract in our research. The constipation and treatment models are generated using adult male C57BL/6N mice. We perform light microscopy and transmission electron microscopy (TEM) to detect a Muc2-rich inner mucus layer attached to mice colon under different conditions. In addition, 16S rDNA sequencing is performed to examine the intestinal flora. According to TEM images, we demonstrate that Rhubarb can promote mucin secretion and find direct evidence of dendritic structure-linked mucus structures with its assembly into a lamellar network in a pore size distribution in the isolated colon section. Moreover, the diversity of intestinal flora has noticeable changes in constipated mice. The present study characterizes a dendritic structure and persistent cross-links have significant changes accompanied by the alteration of intestinal flora in feces in models of constipation and pretreatment with Rhubarb extract.

Insight into the Role of Psychological Factors in Oral Mucosa Diseases.

With the development of psychology and medicine, more and more diseases have found their psychological origins and associations, especially ulceration and other mucosal injuries, within the digestive system. However, the association of psychological factors with lesions of the oral mucosa, including oral squamous cell carcinoma (OSCC), burning mouth syndrome (BMS), and recurrent aphthous stomatitis (RAS), have not been fully characterized. In this review, after introducing the association between psychological and nervous factors and diseases, we provide detailed descriptions of the psychology and nerve fibers involved in the pathology of OSCC, BMS, and RAS, pointing out the underlying mechanisms and suggesting the clinical indications.

Peroxisome Proliferator-Activated Receptor-α: A Pivotal Regulator of the Gastrointestinal Tract.

Peroxisome proliferator-activated receptor (PPAR)-α is a ligand-activated transcription factor distributed in various tissues and cells. It regulates lipid metabolism and plays vital roles in the pathology of the cardiovascular system. However, its roles in the gastrointestinal tract (GIT) are relatively less known. In this review, after summarizing the expression profile of PPAR-α in the GIT, we analyzed its functions in the GIT, including physiological control of the lipid metabolism and pathologic mediation in the progress of inflammation. The mechanism of this regulation could be achieved <i>via</i> interactions with gut microbes and further impact the maintenance of body circadian rhythms and the secretion of nitric oxide. These are also targets of PPAR-α and are well-described in this review. In addition, we also highlighted the potential use of PPAR-α in treating GIT diseases and the inadequacy of clinical trials in this field.

Influencing Factors of Total Skin Irradiation With Helical Tomotherapy.

Purpose: To investigate the influencing factors of total skin irradiation (TSI) with helical tomotherapy for guiding the clinical selection of the suitable parameters and optimizing the plan quality and efficiency. Materials and Methods: Six patients with mycosis fungoides (MF) who received TSI were retrospectively selected. They were all dressed with 5 mm thick diving suits during the CT scan and treatment as a bolus to increase the superficial dose through buildup. The dose prescription was 24 Gy in 20 fractions and 5 times per week. During the planned pretreatment, Ring0, Ring1, Ring2, Ring3, and Ring4 of 1 cm thick away from the planning target volume (PTV) at the distances of 0, 1, 2, 3, and 4 cm and other normal tissues (NTs) were generated, respectively. The auxiliary structures were completely blocked during planning; while the field widths were 5 and 2.5 cm, the pitches were 0.287 and 0.215, the modulation factors were 4 and 3, and the other parameters remained consistent. Finally, the dose parameters of PTV and auxiliary structures, as well as the beam on time (BOT) and gantry period, were compared and analyzed. Results: when the auxiliary structures were completely blocked with distance to PTV (dPTV) above 3 cm were used, the mean dose (Dmean), conformity index (CI), and heterogeneity index (HI) of the PTV met the clinical requirements. As the dPTV gradually increased, the BOT decreased while the volume of normal tissue that received excessive radiation increased correspondingly. If the dPTV was less than 3 cm, the clinical requirements were not met. The field widths (FWs), pitches, and modulation factors (MFs) had no effect on PTVmean and the HI. The FW of 2.5 cm was slightly better than 5 cm for the CI. The FW and MF had a significant impact on the BOT, which gradually increased with decreasing FW and increasing MF. Pitch had no effect on the BOT. Conclusion: During planning with TSI patients, dPTV is the key factor that has a significant influence on the plan quality. We found that the plan with the dPTV above 3 cm can meet clinical objectives. The BOT increases as the dPTV increases. The FWs also have an effect on the CI and BOT. Therefore, it is necessary to comprehensively balance these factors to optimize the quality and efficiency of the plan. We also found that different MFs and pitches have no obvious effect on the results.

Endoplasmic Reticulum Stress of Gut Enterocyte and Intestinal Diseases.

The endoplasmic reticulum, a vast reticular membranous network from the nuclear envelope to the plasma membrane responsible for the synthesis, maturation, and trafficking of a wide range of proteins, is considerably sensitive to changes in its luminal homeostasis. The loss of ER luminal homeostasis leads to abnormalities referred to as endoplasmic reticulum (ER) stress. Thus, the cell activates an adaptive response known as the unfolded protein response (UPR), a mechanism to stabilize ER homeostasis under severe environmental conditions. ER stress has recently been postulated as a disease research breakthrough due to its significant role in multiple vital cellular functions. This has caused numerous reports that ER stress-induced cell dysfunction has been implicated as an essential contributor to the occurrence and development of many diseases, resulting in them targeting the relief of ER stress. This review aims to outline the multiple molecular mechanisms of ER stress that can elucidate ER as an expansive, membrane-enclosed organelle playing a crucial role in numerous cellular functions with evident changes of several cells encountering ER stress. Alongside, we mainly focused on the therapeutic potential of ER stress inhibition in gastrointestinal diseases such as inflammatory bowel disease (IBD) and colorectal cancer. To conclude, we reviewed advanced research and highlighted future treatment strategies of ER stress-associated conditions.

Simulation of dosimetric consequences of intrafraction variation of tumor drift in lung cancer stereotactic body radiotherapy.

Objective: The purpose of this study was to investigate the target dose discrepancy caused by intrafraction variation during stereotactic body radiotherapy (SBRT) for lung cancer. Methods: Intensity-modulated radiation therapy (IMRT) plans were designed based on average computed tomography (AVG CT) utilizing the planning target volume (PTV) surrounding the 65% and 85% prescription isodoses in both phantom and patient cases. Variation was simulated by shifting the nominal plan isocenter along six directions from 0.5 mm to 4.5 mm with a 1-mm step size to produce a series of perturbed plans. The dose discrepancy between the initial plan and the perturbed plans was calculated as the percentage of the initial plan. Dose indices, including ΔD99 for internal target volume (ITV) and gross tumor volume (GTV), were adopted as endpoint samples. The mean dose discrepancy was calculated under the 3-dimensional space distribution. Results: We found that motion can lead to serious dose degradation of the target and ITV in lung SBRT, especially during SBRT with PTV surrounding the lower isodose line. Lower isodose line may lead to larger dose discrepancy, while make steeper dose fall-off gradient. This phenomenon was compromised when 3-dimensional space distribution was considered. Discussion: This result may provide a prospective reference for target dose degradation due to motion during lung SBRT treatment.

ACE2 in the Gut: The Center of the 2019-nCoV Infected Pathology.

The 2019-nCoV is a rapidly contagious pneumonia caused by the recently discovered coronavirus. Although generally the most noticeable symptoms are concentrated in the lungs, the disorders in the gastrointestinal tract are of great importance in the diagnosis of 2019-nCoV. The angiotensin-converting enzyme 2 (ACE2), an important regulator of many physiological functions, including blood pressure and nutrients absorption, is recently identified as a vital entry for 2019-nCoV to enter host cells. In this review, we summarize its functions both physiologically and pathologically. We also elaborate its conflicting roles from the clews of contemporary researches, which may provide significant indications for pharmacological investigations and clinical uses.

GLP-1 and Underlying Beneficial Actions in Alzheimer's Disease, Hypertension, and NASH.

GLP-1 is derived from intestinal L cells, which takes effect through binding to GLP-1R and is inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Since its discovery, GLP-1 has emerged as an incretin hormone for its facilitation in insulin release and reduction of insulin resistance (IR). However, GLP-1 possesses broader pharmacological effects including anti-inflammation, neuro-protection, regulating blood pressure (BP), and reducing lipotoxicity. These effects are interconnected to the physiological and pathological processes of Alzheimer's disease (AD), hypertension, and non-alcoholic steatohepatitis (NASH). Currently, the underlying mechanism of these effects is still not fully illustrated and a better understanding of them may help identify promising therapeutic targets of AD, hypertension, and NASH. Therefore, we focus on the biological characteristics of GLP-1, render an overview of the mechanism of GLP-1 effects in diseases, and investigate the potential of GLP-1 analogues for the treatment of related diseases in this review.

Commissioning and clinical implementation of an Autoencoder based Classification-Regression model for VMAT patient-specific QA in a multi-institution scenario.

BACKGROUND AND PURPOSE: To commission and implement an Autoencoder based Classification-Regression (ACLR) model for VMAT patient-specific quality assurance (PSQA) in a multi-institution scenario. MATERIALS AND METHODS: 1835 VMAT plans from seven institutions were collected for the ACLR model commissioning and multi-institutional validation. We established three scenarios to validate the gamma passing rates (GPRs) prediction and classification accuracy with the ACLR model for different delivery equipment, QA devices, and treatment planning systems (TPS). The prediction performance of the ACLR model was evaluated using mean absolute error (MAE) and root mean square error (RMSE). The classification performance was evaluated using sensitivity and specificity. An independent end-to-end test (E2E) and routine QA of the ACLR model were performed to validate the clinical use of the model. RESULTS: For multi-institution validations, the MAEs were 1.30-2.80% and 2.42-4.60% at 3%/3 mm and 3%/2 mm, respectively, and RMSEs were 1.55-2.98% and 2.83-4.95% at 3%/3 mm and 3%/2 mm, respectively, with different delivery equipment, QA devices, and TPS, while the sensitivity was 90% and specificity was 70.1% at 3%/2 mm. For the E2E, the deviations between the predicted and measured results were within 3%, and the model passed the consistency check for clinical implementation. The predicted results of the model were the same in daily QA, while the deviations between the repeated monthly measured GPRs were all within 2%. CONCLUSIONS: The performance of the ACLR model in multi-institution scenarios was validated on a large scale. Routine QA of the ACLR model was established and the model could be used for VMAT PSQA clinically.

Restraint Stress in Hypertensive Rats Activates the Intestinal Macrophages and Reduces Intestinal Barrier Accompanied by Intestinal Flora Dysbiosis.

PURPOSE: Hypertension (HTN) is a major risk factor for cardiovascular disease. In recent years, there were numerous studies on the function of stress in HTN. However, the gut dysbiosis linked to hypertension in animal models under stress is still incompletely understood. Purpose of this study is to use multiple determination method to determine the juvenile stage intestinal bacteria, cytokines and changes in hormone levels. METHODS: Four groups of juvenile male spontaneously hypertensive rats (SHRs) and age-matched male Wistar-Kyoto (WKY) rats were randomly selected as control and experimental groups. Rats in the two stress groups were exposed to restraint stress for 3 hours per day for 7 consecutive days. In one day three times in the method of non-invasive type tail-cuff monitoring blood pressure. The detailed mechanism was illuminated based on the intestinal change using immunohistochemical and immunofluorescence staining and the stress-related hormone and inflammation factors were analyzed via ELISA method. The integrity of the epithelial barrier was assessed using FITC/HRP and the expression levels of proteins associated with the tight junction was detected by Western blot. The alteration of stress-related intestinal flora from ileocecal junction and distal colon were also analyzed using its 16S rDNA sequencing. RESULTS: The results indicate that acute stress rapidly increases mean arterial pressure which is positive correlation to hormone concentration, especially in SHR-stress group. Meanwhile, stress promoted the enhancement of epithelial permeability accompanied with a reduced expression of the tight junction-related protein and the macrophages (Mφ) aggregation to the lamina propria. There were remarkable significant increase of stress-related hormones and pro-inflammatory factor interleukin (IL)-6 along with a decrease in the diversity of intestinal flora and an imbalance in the F/B ratio. CONCLUSION: Our results reveal that stress accompanied with HTN could significantly disrupt the domino effect between intestinal flora and homeostasis.