Objective:To verify the feasibility of using Elekta accelerated go live (AGL) standard process for the acceptance of multiple accelerators.Methods:The beams of three accelerators were adjusted by PTW Beamscan three-dimensional water tank to reach the AGL standard. Dose verification was performed for three accelerators that met AGL standards. A simple field test example from Cancer Hospital Chinese Academy of Medical Sciences was used to compare the MapCheck 3 surface dose measurement results with the surface dose calculated by the same accelerator model. Images of 10 patients including head and neck, esophagus, breast, lung and rectum were randomly selected. volumetric-modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) treatment techniques were used for planning design, and the measured dose of ArcCheck was compared with the planned dose calculated by the same accelerator model. One-way ANOVA was used to statistically analyze the passing rates of two-dimensional and three-dimensional dose verification.Results:The 6 MV X-ray percentage depth dose at 10 cm underwater (PDD 10) of three accelerators was 67.45%, 67.36%, 67.47%, and the maximum deviation between the three accelerators was 0.11%. The 6 MV flattenting filter free (FFF) mode X-ray PDD 10 was 67.33%, 67.20%, 67.20%, and the maximum deviation between the three accelerators was 0.13%. All required discrete point doses on each energy 30 cm×30 cm Profile spindle of the three accelerator X-rays deviated less than ±1% from the standard data. Absolute γ analysis was performed on the results of MapCheck 3 two-dimensional dose matrix validation. Under the 10% threshold of 2 mm/3% standard, the average passing rate of the test cases in Cancer Hospital Chinese Academy of Medical Sciences was above 99%, and the difference was not statistically significant ( P>0.05). Absolute γ analysis was performed on the ArcCheck verification results. Under the 10% threshold, the pass rate of 2 mm/3% was all above 95%, the maximum average passing rate of the three accelerators with different energy and different treatment techniques was 0.28% (6 MV, VMAT), 0.19%(6 MV FFF, VMAT), 0.56% (6 MV, IMRT) and 0.05% (6 MV FFF, IMRT), and the difference was not statistically significant ( P>0.05). Conclusion:Compared with traditional accelerator acceptance process, the acceptance time of each accelerator is shortened by 4-6 weeks by using the AGL standard process, and the radiotherapy plan of patients can be interchangeably executed among different accelerators.

Objective To evaluate the postoperative survival quality in the patients with heart valve re-placement (HVR) in Three Gorges Reservoir area,and to analyze its main influencing factors.Methods A to-tal of 343 valvular heart disease patients from Three Gorges Reservoir area who received HVR treatment for the first time in this hospital from January 2019 to December 2021 were selected by the convenience sampling method.The general data questionnaire and the MOS 36-item short form health survey (SF-36) were adopted to conduct the survey.The main influencing factors affecting the survival quality were analyzed.Results Af-ter HVR,the physical components summary (PCS) score of SF-36 was 238.0±73.6,and the mental compo-nents summary (MCS) score was 254.8±83.6,and the scores in each dimension were significantly lower than those of the Chinese norm (P<0.05).The multiple stepwise linear regression analysis results showed that the age,gender,place of residence,education level,postoperative time,complications and readmission were the influencing factors of PCS and MCS scores (P<0.05).Conclusion The survival quality of the patients af-ter HVR is different from that of healthy population.The targeted intervention could be carried out according to the influencing factors of the survival quality of the patients,so as to improve their survival quality.

Objective:To explore the knowledge, attitude, and practice of insulin injection among nurses in Beijing and analyze its influencing factors.Methods:From July to August 2019, stratified-random-cluster multi-stage sampling was used to select 7 448 nurses from 30 hospitals of different levels in Beijing as the research subject. The survey was conducted using the General Information Questionnaire and the Insulin Injection Knowledge, Attitude, and Practice Questionnaire. Multiple linear regression was used to analyze the influencing factors of nurses' knowledge, attitude, and practice on insulin injection.Results:A total of 7 448 questionnaires were distributed and 7 448 valid questionnaires were collected, with an effective response rate of 100.00% (7 448/7 448). Among 7 448 nurses, 6 942 had no positions, and the scores of the belief dimension, behavior dimension, and the total score of questionnaire were calculated; the knowledge dimension score was calculated based on the overall sample. The total score of the Insulin Injection Knowledge, Attitude, and Practice Questionnaire was (115.22±10.75), and the scores for each dimension of the questionnaire were (14.14±2.97), (17.29±2.73), and (83.82±7.72), respectively. The proportion of nurses who scored well in all questionnaire dimensions was 19.01% (1 320/6 942). The excellent score rates of each dimension in the questionnaire, from high to low, were the practice dimension [92.71% (6 436/6 942) ], attitude dimension [76.40% (5 304/6 942) ], and knowledge dimension [22.35% (1 665/7 448) ]. Multiple linear regression analysis showed that the influencing factors of insulin injection knowledge, attitude, and practice among nurses were gender, age, professional title and department ( P<0.05). The influencing factors of knowledge were gender, age, years of work, education level, professional title, and department ( P<0.05). The influencing factors of attitude were gender, professional title, and department ( P<0.05). The influencing factors of practice were gender and age ( P<0.05). The above differences were statistically significant. Conclusions:Nurses at all levels of hospitals in Beijing have great beliefs and behaviors in insulin injection but lack knowledge. The knowledge of insulin injection among clinical nurses can be enhanced by improving the training and education standards on insulin injection, regularly providing insulin injection knowledge training and skill assessment to clinical nurses and other methods.

Objective On the premise of meeting the image quality requirements of simulated location for pediatric radiotherapy,the simulated localizable CT parameters are optimized through phantom scanning to reduce the radiation dose.Methods CatPhan700 phantom was used to simulate the child's body,Philip 24-row large-aperture spiral simulated localizable CT was performed,and the CT images were obtained by scanning the phantom at different mAs and tube voltages.The mAs range was set at 60-400 mAs,the scanning was performed every 20 mAs interval,and the kV was set at 80,100,and 120 kV.Image evaluation was carried out using parameters such as image noise(N10 and mean SD),uniformity,low contrast resolution,high contrast resolution,and the stabilities of HU values of Air,Acrylic,50%bone,LDPE,20%bone,Teflon,Polystyrene,DelrinTM,Lung,PMP and Water.The CTDIVol and DLP automatically calculated by the simulated localizable CT system were read to evaluate the radiation dose.Results At 100 kV,as mAs increased,both CTDI and DLP showed upward trends,and the fitting results were linear correlated,with slopes of 0.034 5 and 0.932 4.Image noise was decreased nonlinearly with the increasing mAs.When mAs increased from 60 to 140 mAs,N10 decreased from 0.25%to 0.14%,and SD reduced from 3.74 HU to 2.54 HU.When mAs reached 180 mAs or higher,N10 fluctuated between 0.1%and 0.12%,the mean SD fluctuated between 2.0 and 2.5 HU,and the downward trends obviously slowed down.When mAs increased from 60 to 200 mAs,the low contrast resolution of the image dropped from 0.53 to 0.29.The image uniformity,high contrast resolution and HU values of different substances were less affected by mAs.The image quality of 100 kV and 200 mAs scanning was close to that of 120 kV scanning,but the image quality of 80 kV scanning failed to meet the clinical requirements.Conclusion In order to reduce the radiation dose as much as possible,the mAs should be set at 200 mAs when the tube voltage is set at 100 kV for a simulated cylinder with a diameter of 20 cm.In the actual simulation scanning for pediatric radiotherapy,the scanning parameters should be fine-tuned according to the phantom results and the actual physical characteristics of children to satisfy the optimization principle for radiation protection.

Using high-energy proton to image the region of interest can directly obtain the accurate estimation of the proton stopping power of the lesions,which is of great significance to reduce the range uncertainty in proton therapy.As a fundamental function of proton computed tomography(CT),radiographic imaging plays a crucial role in assisting clinical positioning.The study develops a compact proton CT detector based on an active array pixel CMOS chip in Monte-Carlo simulation toolkit Geant4,and evaluates the radiographic imaging capability of the system using 180 MeV protons.The angles of tracks are successfully reconstructed.CTP404,CTP528,and the CTP515 of specific materials are used for simulation,obtaining the spatial and density resolutions,and measuring the proton relative stopping power(RSP).The image signal-to-noise ratio is improved when using 2° proton scattering angle cut-off value.The spatial resolution is 3-4 lp/cm measured using CTP528 module.The density resolution is better than 0.05 g/cm3,and the RSP resolution is within 5%when CTP404 module is used.Through the imaging of CTP515 phantom of specific material,it is demonstrated that the system has potential for imaging common human tissues.

OBJECTIVE: To explore the genetic basis for a patient with Alport syndrome (AS) and confirm the existence of a splicing variant. METHODS: An AS patient diagnosed at the Affiliated Hospital of Inner Mongolia Medical University on January 8, 2021 for significant proteinuria and occult hematuria was selected as the study subject. Clinical data was collected. Peripheral blood samples were collected for the extraction of genomic DNA. Whole exome sequencing and Sanger sequencing were carried out to identify potential genetic variants. An in vitro experiment was also conducted to verify the abnormal mRNA splicing. Bioinformatic software was used to analyze the conservation of amino acids of the variant sites and simulate the 3D structure of the variant collagen IV protein. Immunofluorescence and immunohistochemistry were carried out on renal tissues from the patient to confirm the presence of AS kidney injury. RESULTS: The patient, a 21-year-old male, had a 24-hour urine protein of 3.53 g/24 h, which fulfilled the diagnostic criteria for proteinuria. His blood uric acid has also increased to 491 μmol/L. DNA sequencing revealed that he has harbored a c.835-9T>A splice variant of the COL4A5 gene, which was not found in either of his parents. In vitro experiment confirmed that the variant has removed 57 bp from the exon 15 of the mRNA of the COL4A5 gene. The deletion may cause loss of amino acid residues from positions 279 to 297, which in turn may affect the stability of the secondary structure of the α5 chain encoded by the COL4A5 gene. The amino acids are conserved across various species. The result of homology modeling indicated that the trimerization of Col-IV with the mutated α5 chain could be achieved, however, the 3D structure was severely distorted. The AS kidney damage was confirmed through immunofluorescence assays. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.835-9T>A variant was classified as likely pathogenic (PVS1_Moderate+PS3_Moderate+PM2_Supporting+PS2+PP3+PP4). CONCLUSION The c.835-9T>A variant of the COL4A5 gene probably underlay the AS in this patient. In vitro experiment has confirmed the abnormal splicing caused by the variant. Histopathological examination of the kidney tissue has provided in vivo evidence for its pathogenicity. Above finding has expanded the mutational spectrum of the COL4A5 gene.
Humans ; Male ; Young Adult ; Amino Acids ; China ; Collagen Type IV/genetics* ; Exons ; Nephritis, Hereditary/genetics* ; RNA Splicing

Cardiovascular diseases is the leading cause of threat to human life and health worldwide. Early risk assessment, timely diagnosis, and prognosis evaluation are critical to the treatment of cardiovascular diseases. Currently, the evaluation of diagnosis and prognosis of cardiovascular diseases mainly relies on imaging examinations such as coronary CT and coronary angiography, which are expensive, time-consuming, partly invasive, and require high professional competence of the operator, making it difficult to promote in the community or in areas where medical resources are scarce. The fundus microcirculation is a part of the human microcirculation and has similar embryological origins and physiopathological features to cardiovascular circulation. Several studies have revealed fundus imaging biomarkers associated with cardiovascular diseases, and developed and validated intelligent diagnosis and treatment models for cardiovascular diseases based on fundus imaging data. Fundus imaging is expected to be an important adjunct to cardiovascular disease diagnosis and treatment given its noninvasive and convenient nature. The purpose of this review is to summarize the current research status, challenges, and future prospects of the application of artificial intelligence based on multimodal fundus imaging data in cardiovascular disease diagnosis and treatment.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

OBJECTIVE: To explore the genetic etiology of a fetus with Cornelia de Lange syndrome type 1. METHODS: Clinical data of the fetus was collected. Genomic DNA was extracted from amniotic fluid and peripheral blood samples of the parents and subjected to low-depth copy number variant sequencing, whole exome sequencing (WES) and Sanger sequencing. Pathogenicity of the candidate variant was predicted based on the guidelines of American College of Medical Genetics and Genomics (ACMG). Minigene assay was used to assess the effect of the variant on mRNA splicing. RESULTS: WES revealed that the fetus has harbored a heterozygous c.5808+5gG>A variant in the intron of the NIPBL gene, which was predicted to affect the mRNA splicing. The same variant was not detected in either parent. The variant was not recorded in ExAC, 1000G and dbSNP databases. Comprehensive analysis showed that the variant was deleterious and may result in skipping of exon 31 during mRNA splicing. CONCLUSION The fetus was diagnosed with Cornelia de Lange syndrome type 1. Splicing variant identified by WES may be verified by minigene assay in vitro, which can provide more evidence for the prediction of its pathogenicity.
Cell Cycle Proteins/genetics* ; De Lange Syndrome/genetics* ; Female ; Fetus ; Humans ; Mutation ; Pregnancy ; Prenatal Diagnosis ; RNA, Messenger

ObjectiveTo explore the effect of home visit based on empowerment education on psychotic symptoms， self-management ability and well-being of schizophrenia patients in home rehabilitation. MethodsA total of 87 cases of schizophrenia patients who met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） and were recovering at home in Caiba town， Yibin city from January to July 2021 were selected by random sampling method as research subjects. They were divided into experimental group （n=43） and control group （n=44） according to the random number table method. The two groups received routine family visits， and the experimental group received family visits based on empowerment education. The intervention cycle of the two groups was 6 months. Before and after the intervention， the severity of psychotic symptoms， self-management ability and well-being of the patients in the two groups were assessed with the Brief Psychiatric Rating Scale （BPRS）， the Schizophrenia Self-Management Instrument Scale （SSMIS） and the Index of Well-Being Scale （IWB）. ResultsAfter intervention， the intra group comparison showed that the BPRS score in the experimental group was lower than that before the intervention （t=4.550， P<0.01）， the SSMIS scores in both groups were higher than those before intervention （t=-17.107， -6.367， P<0.01）， and the IWB score in the experimental group was higher than that before intervention （t=-9.239， P<0.01）. The comparison between groups showed that the BPRS score of the experimental group was lower than that of the control group， and the SSMIS and IWB scores were higher than those of the control group （t=-3.899， 10.564， 9.690， P<0.01）. ConclusionThe implementation of family visit based on empowerment education may help to improve the psychotic symptoms of home rehabilitation schizophrenia， and improve their self-management ability and well-being.