Dose tracking assessment for magnetic resonance guided adaptive radiotherapy of rectal cancers.

BACKGROUND: Magnetic resonance-guided adaptive radiotherapy (MRgART) at MR-Linac allows for plan optimisation on the MR-based synthetic CT (sCT) images, adjusting the target and organs at risk according to the patient's daily anatomy. Conversely, conventional linac image-guided radiotherapy (IGRT) involves rigid realignment of regions of interest to the daily anatomy, followed by the delivery of the reference computed tomography (CT) plan. This study aims to evaluate the effectiveness of MRgART versus IGRT for rectal cancer patients undergoing short-course radiotherapy, while also assessing the dose accumulation process to support the findings and determine its usefulness in enhancing treatment accuracy. METHODS: Nineteen rectal cancer patients treated with a 1.5 Tesla MR-Linac with a prescription dose of 25 Gy (5 Gy x 5) and undergoing daily adapted radiotherapy by plan optimization based on online MR-based sCT images, were included in this retrospective study. For each adapted plan ([Formula: see text]), a second plan ([Formula: see text]) was generated by recalculating the reference CT plan on the daily MR-based sCT images after rigid registration with the reference CT images to simulate the IGRT workflow. Dosimetry of [Formula: see text] and[Formula: see text]was compared for each fraction. Cumulative doses on the first and last fractions were evaluated for both workflows. The dosimetry per single fraction and the cumulative doses were compared using dose-volume histogram parameters. RESULTS: Ninety-five fractions delivered with MRgART were compared to corresponding simulated IGRT fractions. All MRgART fractions fulfilled the target clinical requirements. IGRT treatments did not meet the expected target coverage for 63 out of 94 fractions (67.0%), with 13 fractions showing a V95 median point percentage decrease of 2.78% (range, 1.65-4.16%), and 55 fractions exceeding the V107% threshold with a median value of 15.4 cc (range, 6.0-43.8 cc). For the bladder, the median [Formula: see text] values were 18.18 Gy for the adaptive fractions and 19.60 Gy for the IGRT fractions. Similarly the median [Formula: see text] values for the small bowel were 23.40 Gy and 25.69 Gy, respectively. No statistically significant differences were observed in the doses accumulated on the first or last fraction for the adaptive workflow, with results consistent with the single adaptive fractions. In contrast, accumulated doses in the IGRT workflow showed significant variations mitigating the high dose constraint, nevertheless, more than half of the patients still did not meet clinical requirements. CONCLUSIONS: MRgART for short-course rectal cancer treatments ensures that the dose delivered matches each fraction of the planned dose and the results are confirmed by the dose accumulation process, which therefore seems redundant. In contrast, IGRT may lead to target dose discrepancies and non-compliance with organs at risk constraints and dose accumulation can still highlight notable dosimetric differences.

Spatially fractionated radiotherapy (Lattice SFRT) in the palliative treatment of locally advanced bulky unresectable head and neck cancer.

Objectives: Locally advanced bulky unresectable head neck cancer causes significant tumor mass effects, leading to severe symptoms. This study aims to report the safety and outcomes in patients undergoing Lattice spatially fractionated radiotherapy (Lattice SFRT) for locally advanced bulky unresectable head and neck cancer. Methods: Patients with bulky head and neck cancer received Lattice SFRT between June 2022 and June 2023. Lattice SFRT was administered in 2-3 fractions of 12 Gy (Gy) using 6-megavolt (MV) photon beams through a multileaf collimator (MLC) based on VMAT technology. The primary endpoints were symptomatic and tumor response rates. Secondary endpoints were overall survival, local control, and acute and late toxicity rates. Results: 19 consecutive patients meeting the study criteria were identified, predominantly with squamous cell carcinoma histology. The median patient age was 62 years (range 39-79 years), and the median tumor volume was 208 cc (cc) (range 48-701 cc). All patients completed radiotherapy. Among all investigated patients, 16 of 19 (84.2 %) patients achieved an objective response, including 10 individuals achieved a partial response (PR), with 3 of them exhibiting regression exceeding 75 %. 17 patients showed symptom improvement to varying degrees. Acute toxicity of Radiation Therapy Oncology Group (RTOG) grade 1 or higher occurred in 5 patients, while no grade 3 adverse events was observed. Conclusions: Lattice SFRT proves to be a viable treatment option for the palliative management of bulky head and neck cancer. In the palliative setting, Lattice SFRT offers timely symptom relief, enhancing patient quality of life. Treatment toxicity remains within an acceptable range. Continued optimization of Lattice SFRT delivery and patient selection can benefit from further data on the feasibility and efficacy of this radiation modality.

Regulation mechanism of microRNAs in cardiac cells-derived exosomes in cell crosstalk.

The heart is a multicellular system, and the intercellular crosstalk mechanism is very important for the growth and development of the heart and even the organs, tissues, and cells at a distance. As a kind of extracellular vesicle, exosomes are released by different types of cells and can carry specific genetic material, endosomal proteins, cytokines, etc., which are the main material basis for mediating cell crosstalk mechanism. Among them, microRNA carried by cardiac cells-derived exosomes have highly conserved sequences and play a key role in regulating the function of organs, tissues, and cells related to cardiovascular diseases and their complications and comorbidities, which have attracted extensive attention in the medical community in recent years. Following up on the latest research progress at home and abroad, this review systematically summarized the regulatory role of microRNA from cardiac cells-derived exosomes in various cell crosstalk, including not only cardiac cells (including cardiomyocytes, fibroblasts, myofibroblast, cardiac progenitor cells, cardiac microvascular endothelial cells, cardiosphere-derived cells, etc.) but also tumor cells, bone marrow progenitor cells, and other tissue cells, in order to provide a reference for the prevention and treatment of cardiovascular diseases and their complications and comorbidities.

Overview of pyroptosis mechanism and in-depth analysis of cardiomyocyte pyroptosis mediated by NF-κB pathway in heart failure.

The pyroptosis of cardiomyocytes has become an essential topic in heart failure research. The abnormal accumulation of these biological factors, including angiotensin II, advanced glycation end products, and various growth factors (such as connective tissue growth factor, vascular endothelial growth factor, transforming growth factor beta, among others), activates the nuclear factor-κB (NF-κB) signaling pathway in cardiovascular diseases, ultimately leading to pyroptosis of cardiomyocytes. Therefore, exploring the underlying molecular biological mechanisms is essential for developing novel drugs and therapeutic strategies. However, our current understanding of the precise regulatory mechanism of this complex signaling pathway in cardiomyocyte pyroptosis is still limited. Given this, this study reviews the milestone discoveries in the field of pyroptosis research since 1986, analyzes in detail the similarities, differences, and interactions between pyroptosis and other cell death modes (such as apoptosis, necroptosis, autophagy, and ferroptosis), and explores the deep connection between pyroptosis and heart failure. At the same time, it depicts in detail the complete pathway of the activation, transmission, and eventual cardiomyocyte pyroptosis of the NF-κB signaling pathway in the process of heart failure. In addition, the study also systematically summarizes various therapeutic approaches that can inhibit NF-κB to reduce cardiomyocyte pyroptosis, including drugs, natural compounds, small molecule inhibitors, gene editing, and other cutting-edge technologies, aiming to provide solid scientific support and new research perspectives for the prevention and treatment of heart failure.

[SWOT analysis of risk prevention and control of microorganism pollution in shopping malls and supermarkets].

OBJECTIVE: To understand the status and problems of microbial pollution in shopping malls and supermarkets in China. METHODS: Microbial pollution in shopping malls and supermarkets was assessed by literature search, key information extraction and analysis. The strengths, weaknesses, opportunities and threats(SWOT) of risk control of pathogenic microorganisms in shopping malls and supermarkets were analyzed by SWOT analysis. RESULTS: Common bacteria in the indoor air of shopping malls and supermarkets included staphylococcus and Bacillus, and common fungi include Aspergillus and Penicillium. The bacteria detected in dust samples, escalator surfaces and floor surfaces were mainly Proteobacteria and Actinomyces. The complete public places laws and regulations, standards and health supervision system were the advantages of the risk prevention and control countermeasures of microbial contamination in shopping malls and supermarkets. At the same time, it also had the disadvantages of incomplete microbial-related indexes in the premises, and insufficiently detailed countermeasures for prevention and control in the premises. There were opportunities for multi-sectoral participation and post-licensing risk prevention, and it was also facing challenges brought by many factors affecting the health microenviroment and over-disinfection. CONCLUSION: The main sites for microbial risk prevention and control in superstore-type public places included high-frequency contact areas, key public supplies and utensils, indoor air, etc. , which could be prevented and controlled through a variety of measures such as controlling the release of the source, dilution and reduction, disinfection and denaturation, etc. , and exploring a comprehensive prevention and control system that involves the autonomy of the organization, industry self-regulation, collaboration of multi-government departments, and participation of the whole society.

The impact of physical activity on social anxiety among college students: the chain mediating effect of social support and psychological capital.

Objective: As a topic of widespread concern in the fields of mental health and public health, social anxiety has many negative impacts on the physical and mental health of contemporary college students. Therefore, this study aims to provide new ideas for solving the problem of social anxiety among college students by exploring the potential mediating role of social support and psychological capital in the relationship between physical activity and social anxiety. Methods: A cross-sectional survey was conducted on 874 college students from five universities in Shandong Province. Various self-report tools such as physical activity rating scale, social support scale, positive psychological capital scale, and social anxiety scale were used to collect information needed for this study. Related data. Use this to conduct descriptive statistical analysis, correlation analysis, and mediation effect analysis. Results: The results showed that physical activity was significantly positively correlated with college students' social support (r = 0.354, p < 0.01) and psychological capital (r = 0.448, p < 0.01), and social support was significantly positively correlated with psychological capital (r = 0.556, p < 0.01), the above three are significantly negatively correlated with social anxiety (r = -0.326, -0.381, -0.432, p < 0.01); the mediation effect analysis shows that physical activity has a significant direct effect on college students' social anxiety The effect value is -0.136, accounting for 43.31% of the total effect; social support and psychological capital both play a separate mediating role between physical activity and social anxiety among college students, with effect values of -0.064 and -0.073 respectively, accounting for the total effect. 20.38, 23.25%, and also played a chain intermediary role, with an effect value of -0.041, accounting for 13.05% of the total effect. Conclusion: Current research shows that physical activity can not only directly reduce social anxiety among college students, but also indirectly alleviate social anxiety among college students by increasing the level of social support and psychological capital. This has important reference significance for helping college students in China and even around the world overcome social anxiety.

Optimal exercise modality and dose to improve depressive symptoms in adults with major depressive disorder: A systematic review and Bayesian model-based network meta-analysis of RCTs.

Depression is a growing public health concern, and exercise is an adjunctive treatment modality to improve depression, but the optimal form of exercise and the optimal dose are still unclear. This systematic review examined the efficacy of four major types of exercise (aerobic, resistance, mixed, and mind-body) on depression, as well as the dose-response relationship between total and specific exercise and depressive symptoms. We included randomized controlled trials that included participants aged 18 years or older with a diagnosis of major depressive disorder or a depressive symptom score above a threshold as determined by a validated screening measure, implemented one or more exercise therapy groups, and assessed depressive symptoms at baseline and follow-up. Forty-six studies (3164 patients) were included in the meta-analysis. Aerobic (standardised mean difference (SMD) = -0.93; 95% CI: -1.25 to -0.62) and mind-body exercise (SMD) = -0.81; 95% CI: -1.19 to -0.42) improved depressive symptoms better compared to controls, followed by mixed (SMD = -0.77; 95% CI: -1.20 to -0.34) and resistance exercise (SMD = -0.76; 95% CI: -1.24 to -0.28). This dose-response meta-analysis showed a U-shaped curve between exercise dose and depressive symptoms. The minimum effective dose was estimated to be 320 metabolic equivalent (METs) -min per week and the optimal response was 860 METs-min per week. These findings lead us to advocate that clinicians carefully select the appropriate dose of exercise based on the patient's individual characteristics and needs, in conjunction with psychological care interventions.

Regulation of optimized new Shengmai powder on cardiomyocyte apoptosis and ferroptosis in ischemic heart failure rats: The mediating role of phosphatidylinositol-3-kinase/protein kinase B/tumor protein 53 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Optimized New Shengmai Powder (ONSMP) is a sophisticated traditional Chinese medicinal formula renowned for bolstering vital energy, optimizing blood circulation, and mitigating fluid retention. After years of clinical application, ONSMP has shown a significant impact in improving myocardial injury and cardiac function and has a positive effect on treating heart failure. However, many unknowns exist about the molecular biological mechanisms of how ONSMP exerts its therapeutic effects, which require further research and exploration. AIM OF THE STUDY: Exploring the potential molecular biological mechanisms by which ONSMP ameliorates cardiomyocyte apoptosis and ferroptosis in ischemic heart failure (IHF). MATERIALS AND METHODS: First, we constructed a rat model of IHF by inducing acute myocardial infarction through surgery and using echocardiography, organ coefficients, markers of heart failure, antioxidant markers, and histopathological examination to assess the effects of ONSMP on cardiomyocyte apoptosis and ferroptosis in IHF rats. Next, we used bioinformatics analysis techniques to analyze the active components, signaling pathways, and core targets of ONSMP and calculated the interactions between core targets and corresponding elements. Finally, we detected the positive expression of apoptosis and ferroptosis markers and core indicators of signaling pathways by immunohistochemistry; detected the mean fluorescence intensity of core indicators of signaling pathways by immunofluorescence; detected the protein expression of signaling pathways and downstream effector molecules by western blotting; and detected the mRNA levels of p53 and downstream effector molecules by quantitative polymerase chain reaction. RESULTS: ONSMP can activate the Ser83 site of ASK by promoting the phosphorylation of the PI3K/AKT axis, thereby inhibiting the MKK3/6-p38 axis and the MKK4/7-JNK axis signaling to reduce p53 expression, and can also directly target and inhibit the activity of p53, ultimately inhibiting p53-mediated mRNA and protein increases in PUMA, SAT1, PIG3, and TFR1, as well as mRNA and protein decreases in SLC7A11, thereby inhibiting cardiomyocyte apoptosis and ferroptosis, effectively improving cardiac function and ventricular remodeling in IHF rat models. CONCLUSION: ONSMP can inhibit cardiomyocyte apoptosis and ferroptosis through the PI3K/AKT/p53 signaling pathway, delaying the development of IHF.

Decoding ferroptosis: Revealing the hidden assassin behind cardiovascular diseases.

The discovery of regulatory cell death processes has driven innovation in cardiovascular disease (CVD) therapeutic strategies. Over the past decade, ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has been shown to drive the development of multiple CVDs. This review provides insights into the evolution of the concept of ferroptosis, the similarities and differences with traditional modes of programmed cell death (e.g., apoptosis, autophagy, and necrosis), as well as the core regulatory mechanisms of ferroptosis (including cystine/glutamate transporter blockade, imbalance of iron metabolism, and lipid peroxidation). In addition, it provides not only a detailed review of the role of ferroptosis and its therapeutic potential in widely studied CVDs such as coronary atherosclerotic heart disease, myocardial infarction, myocardial ischemia/reperfusion injury, heart failure, cardiomyopathy, and aortic aneurysm but also an overview of the phenomenon and therapeutic perspectives of ferroptosis in lesser-addressed CVDs such as cardiac valvulopathy, pulmonary hypertension, and sickle cell disease. This article aims to integrate this knowledge to provide a comprehensive view of ferroptosis in a wide range of CVDs and to drive innovation and progress in therapeutic strategies in this field.

The Best Exercise Modality and Dose for Reducing Pain in Adults With Low Back Pain: A Systematic Review With Model-Based Bayesian Network Meta-analysis.

OBJECTIVE: To quantify the dose-response relationship between overall and specific exercise modalities and pain, in patients with nonspecific chronic low back pain (LBP). DESIGN: Systematic review with Bayesian network meta-analysis. LITERATURE SEARCH: We searched the Medline, Embase, Web of Science, Cochrane Library, Scopus, and SPORTDiscus databases from inception to June 2023. STUDY SELECTION CRITERIA: We included randomized controlled trials of exercise interventions in adults with nonspecific chronic LBP and at least 1 pain outcome reported at the main trial end point. DATA SYNTHESIS: A random-effects network meta-analysis was conducted. We assessed risk of bias using the Cochrane Risk of Bias Tool 2.0, and used the GRADE approach to judge the certainty of evidence for each outcome. RESULTS: Eighty-two trials were included (n = 5033 participants). We found a nonlinear dose-response relationship between total exercise and pain in patients with nonspecific chronic LBP. The maximum significant response was observed at 920 MET minutes (standardized mean difference = -1.74; 95% credible intervals: -2.43, -1.04). The minimal clinically important difference for achieving meaningful pain improvement was 520 MET minutes per week. The dose to achieve minimal clinically important difference varied by type of exercise; Pilates was the most effective. The certainty of the evidence was very low to moderate for all outcomes. CONCLUSION: The dose-response relationship of different exercise modalities to improve pain in patients with nonspecific chronic LBP had a U-shaped trajectory and low- to moderate-certainty evidence. The clinical effect was most pronounced with Pilates exercise. J Orthop Sports Phys Ther 2024;54(5):1-13. Epub 8 March 2024. doi:10.2519/jospt.2024.12153.

Targeting MAPK-ERK/JNK pathway: A potential intervention mechanism of myocardial fibrosis in heart failure.

Myocardial fibrosis is a significant pathological basis of heart failure. Overactivation of the ERK1/2 and JNK1/2 signaling pathways of MAPK family members synergistically promotes the proliferation of myocardial fibroblasts and accelerates the development of myocardial fibrosis. In addition to some small molecule inhibitors and Western drugs, many Chinese medicines can also inhibit the activity of ERK1/2 and JNK1/2, thus slowing down the development of myocardial fibrosis, and are generally safe and effective. However, the specific biological mechanisms of ERK1/2 and JNK1/2 signaling pathways in myocardial fibrosis still need to be fully understood, and there is no systematic review of existing drugs and methods to inhibit them from improving myocardial fibrosis. This study aims to summarize the roles and cross-linking mechanisms of ERK1/2 and JNK1/2 signaling pathways in myocardial fibrosis and to systematically sort out the small-molecule inhibitors, Western drugs, traditional Chinese medicines, and non-pharmacological therapies that inhibit ERK1/2 and JNK1/2 to alleviate myocardial fibrosis. In the future, we hope to conduct more in-depth research from the perspective of precision-targeted therapy, using this as a basis for developing new drugs that provide new perspectives on the prevention and treatment of heart failure.

Characterization and childhood exposure assessment of toxic heavy metals in household dust under true living conditions from 10 China cities.

Health hazards caused by metal exposure in household dust are concerning environmental health problems. Exposure to toxic metals in household dust imposes unclear but solid health risks, especially for children. In this multicenter cross-sectional study, a total of 250 household dust samples were collected from ten stratified cities in China (Panjin, Shijiazhuang, Qingdao, Lanzhou, Luoyang, Ningbo, Xi'an, Wuxi, Mianyang, Shenzhen) between April 2018 and March 2019. Questionnaire was conducted to gather information on individuals' living environment and health status in real-life situations. Multivariate logistic regression and principal component analysis were conducted to identify risk factors and determine the sources of metals in household dust. The median concentration of five metals in household dust from 10 cities ranged from 0.03 to 73.18 µg/g. Among the five heavy metals, only chromium in household dust of Mianyang was observed significantly both higher in the cold season and from the downwind households. Mercury, cadmium, and chromium were higher in the third-tier cities, with levels of 0.08, 0.30 and 97.28 µg/g, respectively. There were two sources with a contribution rate of 38.3 % and 25.8 %, respectively. Potential risk factors for increased metal concentration include long residence time, close to the motorway, decoration within five years, and purchase of new furniture within one year. Under both moderate and high exposure scenarios, chromium showed the highest level of exposure with 6.77 × 10-4 and 2.28 × 10-3 mg·kg-1·d-1, and arsenic imposed the highest lifetime carcinogenic risk at 1.67 × 10-4 and 3.17 × 10-4, respectively. The finding highlighted the priority to minimize childhood exposure of arsenic from household dust.

Optimized New Shengmai Powder modulation of cAMP/Rap1A signaling pathway attenuates myocardial fibrosis in heart failure.

BACKGROUND: Optimized New Shengmai Powder (ONSMP) is a traditional Chinese medicine formula with significant anti-heart failure and myocardial fibrosis effects, but the specific molecular biological mechanisms are not fully understood. METHODS: In this study, we first used network pharmacology to analyze the ONSMP's active ingredients, core signaling pathways, and core targets. Second, calculate the affinity and binding modes of the ONSMP components to the core targets using molecular docking. Finally, the heart failure rat model was established by ligating the left anterior descending branch of the coronary artery and assessing the effect of ONSMP on myocardial fibrosis in heart failure using echocardiography, cardiac organ coefficients, heart failure markers, and pathological sections after 4 weeks of drug intervention. The cAMP level in rat myocardium was determined using Elisa, the α-SMA and FSP-1 positive expression determined by immunohistochemistry, and the protein and mRNA levels of the cAMP/Rap1A signaling pathway were detected by Western Blotting and quantitative real-time PCR, respectively. RESULTS: The result shows that the possible mechanism of ONSMP in reducing myocardial fibrosis also includes the use of 12 active ingredients such as baicalin, vitamin D, resveratrol, tanshinone IIA, emodin, 15,16-dihydrotanshinone-i to regulate ß1-AR, AC6, EPAC1, Rap1 A, STAT3, and CCND1 on the cAMP/Rap1A signaling pathway, thereby inhibiting the proliferation of cardiac fibroblasts and reduce the excessive secretion of collagen, effectively improve cardiac function and ventricular remodeling in heart failure rats. CONCLUSION: This research shows that ONSMP can inhibit myocardial fibrosis and delay heart failure through the cAMP/Rap1A signaling pathway.

Effect of high-intensity interval training on cardiorespiratory in children and adolescents with overweight or obesity: a meta-analysis of randomized controlled trials.

Objective: This meta-analysis aimed to examine the effect of high-intensity interval training on cardiorespiratory fitness in children and adolescents with overweight or obesity, and to explore the optimal dose of high-intensity interval training to improve cardiorespiratory fitness in children and adolescents with overweight or obesity. Methods: Randomized controlled trials on the effects of HIIT on cardiorespiratory fitness in children and adolescents with overweight or obesity were retrieved from six electronic databases, including PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP. The quality assessment of the included studies was conducted following the revised quality evaluation method based on the PRISMA principles. Keywords for literature search mainly include high-intensity interval, cardiorespiratory fitness, overweight, obese, children, and adolescent, etc. Results: (1) A total of 18 studies, comprising 581 participants (288 in the intervention group and 293 in the control group), were included and all of them were of moderate to high quality. (2) HIIT had a positive effect on the cardiorespiratory fitness levels of in children and adolescents with overweight or obesity (SMD = 0.91; 95% CI: 0.66, 1.15; p < 0.00001). (3) The improvement in cardiorespiratory fitness was more significant when the HIIT intervention lasted for more than 10 weeks (SMD = 1.04; 95% CI: 0.74, 1.34; p < 0.00001), was conducted 3 times per week, with 2 to 8 sets per session (SMD = 1.13; 95% CI: 0.71, 1.55; p < 0.00001), and maintained a ratio of approximately 1:1 between exercise and rest intervals (SMD = 1.11; 95% CI: 0.73, 1.50; p < 0.00001). Conclusion and recommendations: (1) Long-term HIIT can improve cardiorespiratory fitness in children and adolescents with overweight or obesity. (2) To achieve significant improvements in cardiorespiratory fitness in a short period, children and adolescents with overweight or obesity can engage in HIIT programs lasting for more than 10 weeks, conducted 3 times per week, with 2 to 8 sets per session, and a ratio of approximately 1:1 between exercise and rest intervals. Systematic Review Registration: Identifier: INPLASY202350033.

Potential dosimetric error in the adaptive workflow of a 1.5 T MR-Linac from patient movement relative to immobilisation systems.

In magnetic resonance- (MR-) based adaptive workflows for an MR-linac, the treatment plan is optimized and recalculated online using the daily MR images. The Unity MR-linac is supplied with a patient positioning device (ppd) using pelvic and abdomen thermoplastic masks attached to a board with high-density components. This study highlights the dosimetric effect of using this in such workflows when there are relative patient-ppd displacements, as these are not visualized on MR imaging and the treatment planning system assumes the patient is fixed relative to the ppd. The online adapted plans of two example rectum cancer patients treated at a Unity MR-linac were perturbed by introducing relative patient-ppd displacements, and the effect was evaluated on plan dosimetry. Forty-eight perturbed clinical adapted plans were recalculated, based on online MR-based synthetic computed tomography, and compared with the original plans, using dose-volume histogram parameters and gamma analysis. The target volume covered by the prescribed dose ( D pre ) and by at least 107% of D pre varied up to - 1.87% and + 3.67%, respectively for 0.5 cm displacements, and to - 3.18% and + 4.96% for 2 cm displacements; whilst 2%-2 mm gamma analysis showed a median value of 92.9%. The use of a patient positioning system with high-density components in a Unity MR-based online adaptive treatment workflow can introduce unrecognized errors in plan dosimetry and it is recommended not to use such a device for such treatments, without modifying the device and the workflow, followed by careful clinical evaluation, or alternatively to use other immobilization methods.

Convenient determination of serum HER-2 status in breast cancer patients using Raman spectroscopy.

Given the significant therapeutic efficacy of anti-HER-2 treatment, the HER-2 status is a crucial piece of information that must be obtained in breast cancer patients. Currently, as per guidelines, HER-2 status is typically acquired from breast tissue of patients. However, there is growing interest in obtaining HER-2 status from serum and other samples due to the convenience and potential for dynamic monitoring. In this study, we have developed a serum Raman spectroscopy technique that allows for the rapid acquisition of HER-2 status in a convenient manner. The established HER-2 negative and positive classification model achieved an area under the curve of 0.8334. To further validate the reliability of our method, we replicated the process using immunohistochemistry and in situ hybridization. The results demonstrate that serum Raman spectroscopy, coupled with artificial intelligence algorithms, is an effective technical approach for obtaining HER-2 status.

Physical activity on executive function in sedentary individuals: Systematic review and meta-analysis of randomized controlled trials.

Physical activity has been demonstrated to promote cognitive performance. However, the relationship between physical activity and executive function (EF) in sedentary individuals is not fully understood. This meta-analysis examined the impact of physical activity on EF in sedentary individuals and evaluated potential moderators of the relationship between physical activity and EF. In accordance with the PRISMA guidelines, the electronic databases MEDLINE, Embase, PsycINFO and Web of Science were searched. Included studies had to report sedentary individuals randomized to either a physical activity group or a control group. Subgroup analyses of EF sub-domains, exercise prescription and age were conducted alongside the overall meta-analysis. Thirteen RCT studies were included, with a total of 752 participants. Results showed a small to moderate beneficial effect of physical activity on EF (SMD = 0.24, 95% CI 0.08 to 0.40). In subgroup analysis by EF sub-domains, physical activity enhanced inhibitory control (SMD = 0.38, 95% CI 0.12 to 0.63) and working memory (SMD = 0.22, 95% CI -0.05 to 0.49), but not cognitive flexibility (SMD = 0.11, 95% CI -0.18 to 0.41). Interventions with an intervention length > 12 weeks improved overall EF (SMD = 0.26, 95% CI 0.06 to 0.46), but intervention length ≤ 12 weeks did not (SMD = 0.20, 95% CI -0.08 to 0.47). Interventions with session time ≥ 45 minutes improved overall EF (SMD = 0.47, 95% CI 0.22 to 0.77), but session time < 45 minutes did not (0.17, 95% CI -0.11 to 0.44). Physical activity improves EF for older adults (age ≥ 60 years) (SMD = 0.25, 95% CI 0.08 to 0.42), but not for younger individuals (age < 60 years) (SMD = 0.17, 95% CI -0.25 to 0.59). Overall, physical activity has a beneficial effect on EF in sedentary individuals, although the influence may be domain specific and influenced by exercise prescription and age. These findings have practical implications for those seeking to improve EF in sedentary individuals through physical activity.

Entropy-driven reactions for controlling CRISPR/Cas12a and constructing an electrochemical biosensor for cardiac biomarkers detection.

An electrochemical biosensor is reported for controlling CRISPR/Cas12a activity through the utilization of entropy-driven reactions, alongside the construction of a highly sensitive biosensor for B-type natriuretic peptide (BNP) detection. In the biosensor, entropy-driven reactions are employed to regulate the activity of CRISPR/Cas12a - a gene editing tool - capable of nonspecific cleavage of single-stranded DNA (ssDNA). The biosensor architecture encompasses an electrode that is modified with ssDNA probes designed to hybridize with target BNP aptamers. These aptamers, furnished with labeled ssDNA triggers, facilitate the activation of CRISPR/Cas12a through interaction with its guide RNA. Upon the presence of BNP, it associates with the aptamers, subsequently liberating the triggers that instigate the entropy-driven reactions. As a consequence of these reactions, more stable duplexes emerge between the triggers and guide RNA, thereby activating CRISPR/Cas12a. The activated CRISPR/Cas12a subsequently executes cleavage of ssDNA probes residing on the electrode surface, culminating in the generation of an electrochemical signal directly (the calibration plots of differential pulse voltammetric detection were acquired at a working potential of 0.2 V (vs. ref. electrode)) proportional to the BNP concentration. Validation of the biosensor's performance is undertaken, wherein BNP detection is demonstrated in both buffer and human serum samples. Evident in the findings is the biosensor's discernible sensitivity and specificity for BNP detection, exemplified by a detection limit of 13.53 fM and a lack of interference originating from other cardiac biomarkers, respectively. Furthermore, the biosensor's potential to discriminate between healthy individuals and those afflicted by heart failure, predicated on distinctive BNP levels, is illustrated.

[Establishment of a Rat Model of Hypotension Induced by Reserpine].

Objective To determine the optimal dosage and intervention duration of reserpine to establish a rat model of hypotension.Methods According to the body weight and systolic blood pressure (SBP),60 male Wistar rats were assigned to six groups (n=10),including a control group and five observation groups with different doses.The control group was administrated with 10 ml/kg 0.5% sodium carboxymethyl cellulose solution,and the observation groups with 0.016,0.032,0.064,0.128,and 0.160 mg/kg reserpine suspensions,respectively.All the groups were administrated by gavage twice a day,and the body weights of rats were monitored daily.SBP and heart rate (HR) were measured before modeling and 1-6 weeks after administration.After 6 weeks of administration,the blood samples of inner canthus were collected.The levels of lactate dehydrogenase (LDH),creatine kinase MB isoenzyme (CK-MB),alanine aminotransferase,aspartate aminotransferase (AST),serum creatinine,and blood urea nitrogen (BUN) were measured by an autoanalyzer.Three rats in each group were randomly selected for observation of the changes in SBP after drug withdrawal and the rest rats were sacrificed for measurement of the levels of norepinephrine and dopamine in the brain.Results Compared with the control group,different doses of reserpine lowered the SBP of rats (F=28.492,P<0.001).The decline in SBP increased in a concentration-dependent manner.SBP reached the lowest value after 1 week,rose slightly later,and was stable after 3 weeks of administration.There was no significant difference in SBP between 0.016 mg/kg reserpine group and the control group after the 5th week (P>0.05).The SBP levels of rats in 0.032,0.064,0.128,and 0.160 mg/kg reserpine groups showed no significant difference between each other (P=0.204) and were lower than that in the control group (all P<0.001).One week after drug withdrawal,the SBP of rats in the observation groups rose to the baseline level and remained stable.HR showed similar changes among groups,first increasing and then decreasing.There was no significant difference in HR among different groups at the same time point (F=0.922,P=0.475).Compared with the control group,reserpine of different doses reduced the norepinephrine content in the hippocampus (all P<0.001),and 0.128 mg/kg (P=0.045) and 0.160 mg/kg (P=0.042) reserpine lowered the dopamine level in the striatum,which showed no significant differences between different reserpine groups(P=0.343,P=0.301).The levels of LDH,CK-MB,and BUN in the serum increased with the increase in reserpine concentration,and the levels of LDH (P=0.001),CK-MB (P=0.020),AST (P=0.007),and BUN (P=0.001) in the 0.160 mg/kg reserpine group were significantly different from those in the control group.Conclusions The rat model of hypotension can be induced by gavage with reserpine.The gavage with reserpine at a dose of 0.032 mg/kg,twice a day for three consecutive weeks is the optimal scheme for the modeling.After the model establishment,continuous administration is essential to maintain the hypotension.

Risk Prediction Models and Novel Prognostic Factors for Heart Failure with Preserved Ejection Fraction: A Systematic and Comprehensive Review.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) have large individual differences, unclear risk stratification, and imperfect treatment plans. Risk prediction models are helpful for the dynamic assessment of patients' prognostic risk and early intensive therapy of high-risk patients. The purpose of this study is to systematically summarize the existing risk prediction models and novel prognostic factors for HFpEF, to provide a reference for the construction of convenient and efficient HFpEF risk prediction models. METHODS: Studies on risk prediction models and prognostic factors for HFpEF were systematically searched in relevant databases including PubMed and Embase. The retrieval time was from inception to February 1, 2023. The Quality in Prognosis Studies (QUIPS) tool was used to assess the risk of bias in included studies. The predictive value of risk prediction models for end outcomes was evaluated by sensitivity, specificity, the area under the curve, C-statistic, C-index, etc. In the literature screening process, potential novel prognostic factors with high value were explored. RESULTS: A total of 21 eligible HFpEF risk prediction models and 22 relevant studies were included. Except for 2 studies with a high risk of bias and 2 studies with a moderate risk of bias, other studies that proposed risk prediction models had a low risk of bias overall. Potential novel prognostic factors for HFpEF were classified and described in terms of demographic characteristics (age, sex, and race), lifestyle (physical activity, body mass index, weight change, and smoking history), laboratory tests (biomarkers), physical inspection (blood pressure, electrocardiogram, imaging examination), and comorbidities. CONCLUSION: It is of great significance to explore the potential novel prognostic factors of HFpEF and build a more convenient and efficient risk prediction model for improving the overall prognosis of patients. This review can provide a substantial reference for further research.