Multislice CT angiography in coronary artery disease: Technical developments, radiation dose and diagnostic value

Multislice computed tomography (CT) angiography has been increasingly used in the detection and diagnosis of coronary artery disease because of its rapid technical evolution from the early generation of 4-slice CT scanners to the latest models such as 64-slice, 256-slice and 320-slice CT scanners. Technical developments of multislice CT imaging enable improved diagnostic value in the detection of coronary artery disease, and this indicates that multislice CT can be used as a reliable lessinvasive alternative to invasive coronary angiography in selected patients. In addition, multislice CT angiography has played a significant role in the prediction of disease progression and cardiac events. Despite promising results reported in the literature, multislice CT has the disadvantage of having a high radiation dose which could contribute to the radiation-induced malignancy. A variety of strategies have been currently undertaken to reduce the radiation dose associated with multislice CT coronary angiography while in the meantime acquiring diagnostic images. In this article, the author will review the technical developments, radiation dose associated with multislice CT coronary angiography, and strategies to reduce radiation dose. The diagnostic and prognostic value of multislice CT angiography in coronary artery disease is briefly discussed, and future directions of multislice CT angiography in the diagnosis of coronary artery disease will also be highlighted.

Involvement of Endoplasmic Reticulum Stress in Apoptosis of Testicular Cells Induced by Low-dose Radiation

Summary： The study examined the role of endoplasmic reticulum stress （ERS） and signaling pathways of inositol-requiring enzyme-1 （IRE1）, RNA-activated protein kinase-like ER kinase （PERK） and activating transcription factor-6 （ATF6） in apoptosis of mouse testicular cells treated with low-dose radiation （LDR）. In the dose-dependent experiment, the mice were treated with whole-body X-ray irradiation at different doses （25, 50, 75, 100 or 200 mGy） and sacrificed 12 h later. In the time-dependent experiment, the mice were exposed to 75 mGy X-ray irradiation and killed at different time points （3, 6, 12, 18 or 24 h）. Testicular cells were harvested for experiments. H202 and NO concentrations, and Ca2＋-ATPase activity were detected by biochemical assays, the calcium ion concentration （[Ca2＋]i） by flow cytometry using fluo-3 probe, and GRP78 mRNA and protein expressions by quantitative real-time RT-PCR （qRT-PCR） and Western blotting, respectively. The mRNA expressions of S-XBP1, JNK, caspase-12 and CHOP were measured by qRT-PCR, and the protein expressions of IREla, S-XBP1, p-PERK, p-elF2a, ATF6 p50, p-JNK, pro-caspase-12, cleaved caspase-12 and CHOP by Western blot- ting. The results showed that the concentrations of H202 and NO, the mR_NA expressions of GRP78, S-XBP1, JNK, caspase-12 and CHOP, and the protein expressions of GRP78, S-XBP1, IREla, p-PERK, p-elF2a, ATF6 p50, p-JNK, pro-caspase-12, cleaved caspase-12 and CHOP were significantly increased in a time- and dose-dependent manner after LDR. But the [Ca2]i and Ca2-ATPase activities were sig nificantly decreased in a time and dose-dependent manner. It was concluded that the ERS, regulated by IRE 1, PERK and ATF6 pathways, is involved in the apoptosis of testicular cells in LDR mice, which is associated with ERS-apoptotic signaling molecules of JNK, caspase-12 and CHOP.

Radiation dose to patients during endoscopic retrograde cholangiopancreatography

Endoscopic retrograde cholangiopancreatography (ERCP) is an important tool for the diagnosis and treatment of the hepatobiliary system. The use of fluoroscopy to aid ERCP places both the patient and the endoscopy staff at risk of radiation-induced injury. Radiation dose to patients during ERCP depends on many factors, and the endoscopist cannot control some variables, such as patient size, procedure type, or fluoroscopic equipment used. Previous reports have demonstrated a linear relationship between radiation dose and fluoroscopy duration. When fluoroscopy is used to assist ERCP, the shortest fluoroscopy time possible is recommended. Pulsed fluoroscopy and monitoring the length of fluoroscopy have been suggested for an overall reduction in both radiation exposure and fluoroscopy times. Fluoroscopy time is shorter when ERCP is performed by an endoscopist who has many years experience of performing ERCP and carried out a large number of ERCPs in the preceding year. In general, radiation exposure is greater during therapeutic ERCP than during diagnostic ERCP. Factors associated with prolonged fluoroscopy have been delineated recently, but these have not been validated.

Correlation between Low Tube Voltage in Dual Source CT Coronary Artery Imaging with Image Quality and Radiation Dose

The influence of low tube voltage in dual source CT（DSCT） coronary artery imaging on image quality and radiation dose and its application value in clinical practice were investigated. Totally, 300 cases of chest pain with low body mass index（BMI 〈18.5 kg/m2） subjected to DSCT coronary artery imaging were prospectively enrolled. The heart rate in all patients were greater than 65/min. The retrospective ECG gated scanning mode and simple random sampling method were used to assign the patients into groups A, B and C（n=100 each）. The patients in groups A, B and C experienced 120-, 100-, and 80-kV tube voltage imaging respectively, and the image quality was evaluated. The CT volume dose index（CTDIvol） and dose length product（DLP） were recorded, and the effective dose（ED） was calculated in each group. The image quality scores and radiation doses in groups were compared, and the influence of tube voltage on image quality and radiation dose was analyzed. The results showed that the excellent rate of image quality in groups A, B and C was 95.69%, 94.72% and 96.33% respectively with the difference being not statistically significant among the three groups（P〉0.05）. The CTDIvol values in groups A, B and C were 51.35±12.21, 21.28±7.13 and 6.34±3.34 mGy, respectively, with the difference being statistically significant（P〈0.05）. The ED values in groups A, B and C were 9.27±1.63, 4.56±2.29 and 2.29±1.69 mSv, respectively, with the difference being statistically significant（P〈0.05）. It was suggested that for the patients with low BMI, the application of DSCT coronary artery imaging with low tube voltage can obtain satisfactory image quality, and simultaneously, significantly reduce the radiation dose.

Increased Levels of p53 and PARP-1 in EL-4 Cells Probably Related with the Immune Adaptive Response Induced by Low Dose Ionizing Radiation in vitro

Objective This paper is to explore the DNA repair mechanism of immune adaptive response （AR） induced by low dose radiation （LDR）, the changes of mRNA levels and protein expressions of p53, ATM, DNA-PK catalytic subunit （DNA-PKcs） and PARP-1 genes in the LDR-induced AR in EL-4 cells. Methods The apoptosis and cell cycle progression of EL-4 cells were detected by flow cytometry in 12 h after the cells received the pre-exposure of 0.075 Gy X-rays （inductive dose, D 1） and the succeeding high dose irradiation （challenge dose, D2; 1.0, 1.5, and 2.0 Gy X-rays, respectively） with or without wortmannin （inhibitor of ATM and DNA-PK） and 3-aminobenzamid （inhibitor of PARP-1）. And the protein expressions and mRNA levels related to these genes were detected with flow cytometry and reverse transcription-polymerase chain reaction in 12 h after irradiation with D2. Results The mRNA and protein expressions of p53 and PARP-1 in EL-4 cells in the D1 ＋ D2 groups were much lower than those in the D2 groups, and those of PARP-1 in the 3-AB ＋ D2 and the 3-AB ＋ D1 ＋ D2 groups were much lower than those in the D2 and the D1 ＋ D2 groups. The percentage of apoptotic EL-4 cells in the 3-AB ＋ D1 ＋ D2 groups was much higher than that in the D1 ＋ D2 groups, that in the G0/G1 and the G2 ＋ M phases was much higher, and that in the S phase were much lower. Although the ATM and DNA-PKcs mRNA and protein expressions in wortmannin ＋ D1 ＋ D2 groups were much lower than those in the D1 ＋ D2 groups, there were no significant changes in the apoptosis and cell cycle progression between the wortmannin ＋ D1 ＋ D2 and the D1 ＋ D2 groups. Conclusion PARP-1 and p53 might play important roles in AR induced by LDR.

Application of Low Tube Voltage, Low-concentration Contrast Agent Using a 320-row CT in Coronary CT Angiography: Evaluation of Image Quality, Radiation Dose and Iodine Intake

The effect of low voltage and low concentration contrast agent on image quality of coronary CT angiography,radiation dose and iodine intake was evaluated.A total of 121 patients with body mass index(BMI)<26 kg/m2 and heart rate(HR)<70 beats/min were randomly divided into four groups:group A(n=31,80 kVp,270 mgl/mL);group B(n=33,100 kVp,270 mgl/mL);group C(h=30,100 kVp,320 mgl/mL);group D(w=27,100 kVp,400 mgl/mL).The automatic current modulation system and the iterative algorithm for reconstruction were adopted in each group.The CT values and SD values of the aortic root(AR),subcutaneous fat,left coronary artery opening(LCA),and right coronary artery opening(RCA)were measured in all groups,the signalto-noise ratio(SNR)and contrast noise ratio(CNR)were calculated,and effective radiation dose and iodine intake were recorded.The subjective assessment for image quality was performed by two physicians using a 4-point scale.The results were compared using the one-way ANOVA and rank sum tests.The image quality of the four groups met the clinical diagnostic requirements.The CT values of AR in groups A,B,C,and D were 537.6±71.4,447.2±81.9,445.2±64.9 and 518.5±94.9 Hu,respectively,with no significant difference between group A and group D,or between group B and group C,while CT values in groups B and C were significantly lower than those in groups A and D(P<0.05).In groups A,B,C,and D,the LCA SNR values were 22.7±9.1,23.3±9.1,23.3±7.7 and 26.6±8.9,and the RCA CNR values were 26.9±9.&28.5±11.4,27.7土&8 and 32」±10.6,respectively.The AR visual scores in groups A,B,C and D were 3.8±0.2,3.9±0.3,3.9±0.3 and 4.0±0.3,respectively.There were no significant differences in SNR,CNR and visual score among the four groups(P>0.05).The radiation doses in groups A,B,C and D were 2.6±1.4,3.6±1.&4.9±3.5 and 4.9±2.8 mSv,respectively.The radiation dose in group A was significantly less than that in the rest three groups(P<0.05).The iodine intakes in groups A,B,C and D were 14.9±1.5,15.0±1.5,17.7±2.0 and 18.1±2.5 g,respectively.There was no significant difference in the intake of iodine between groups C and D,or between groups A and B,while iodine intake in groups A and B were significantly reduced as compared with that in groups C and D(P<0.05).It was concluded that for patients with low BMI and controlled HR,compared to 100 kVp tube voltage combined with multiple concentration contrast agents,80 kVp combined with 270 mgl/mL contrast agent is enough to ensure the quality of the images,and can reduce the radiation dose significantly,while reducing the amount of iodine intake notably,thus reducing the incidence of adverse reaction.

Radiation dose measurements in coronary CT angiography

Coronary computed tomography(CT)angiography is associated with high radiation dose and this has raised serious concerns in the literature.Awareness of various parameters for dose estimates and measurements of coronary CT angiography plays an important role in increasing our understanding of the radiation exposure to patients,thus,contributing to the implementation of dose-saving strategies.This article provides an overview of the radiation dose quantity and its measurement during coronary CT angiography procedures.

Low contrast medium and radiation dose for hepatic computed tomography perfusion of rabbit VX2 tumor

AIM:To evaluate the feasibility of low contrast medium and radiation dose for hepatic computed tomography(CT) perfusion of rabbit VX2 tumor.METHODS:Eleven rabbits with hepatic VX2 tumor underwent perfusion CT scanning with a 24-h interval between a conventional tube potential(120 k Vp) protocol with 350 mg I/m L contrast medium and filtered back projection,and a low tube potential(80 k Vp) protocol with 270 mg I/m L contrast medium with iterative reconstruction.Correlation and agreement among perfusion parameters acquired by the conventional and low dose protocols were assessed for the viable tumor component as well as whole tumor.Image noise and tumor-to-liver contrast to noise ratio during arterial and portal venous phases were evaluated.RESULTS:A 38% reduction in contrast medium dose(360.1 ± 13.3 mg I/kg vs 583.5 ± 21.5 mg I/kg,P < 0.001) and a 73% decrease in radiation dose(1898.5 m Gy·cm vs 6951.8 m Gy·cm) were observed.Interestingly,there was a strong positive correlation in hepatic arterial perfusion(r = 0.907,P < 0.001;r = 0.879,P < 0.001),hepatic portal perfusion(r = 0.819,P = 0.002;r = 0.831,P = 0.002),and hepatic blood flow(r = 0.945,P < 0.001;r = 0.930,P < 0.001) as well as a moderate correlation in hepatic perfusion index(r = 0.736,P = 0.01;r = 0.636,P = 0.035) between the low dose protocol with iterative reconstruction and the conventional protocol for the viable tumor component and the whole tumor.These two imaging protocols provided a moderate but acceptable agreement for perfusion parameters and similar tumorto-liver CNR during arterial and portal venous phases(5.63 ± 2.38 vs 6.16 ± 2.60,P = 0.814;4.60 ± 1.27 vs 5.11 ± 1.74,P = 0.587).CONCLUSION:Compared with the conventional protocol,low contrast medium and radiation dose with iterative reconstruction has no significant influence on hepatic perfusion parameters for rabbits VX2 tumor.

Radiation dose detection using a high-power portable optically stimulated luminescence real-time reading system

Optically stimulated luminescence(OSL) reading systems are becoming smaller and capable of real-time detection. To improve real-time and multipurpose radiation dosimetry readings, we built a real-time continuous-wave(RCW) OSL reading system. This system is both small and lightweight, and it employs powerful laser excitation(478 mW/cm^2) at the dosimetry probe location. We investigate the possibility of using the RCW mode to read the radiation luminescence(RL) or OSL by using a singlecrystal Al_2O_3:C dosimeter in a low-dose-rate137 Cs y field.Our results indicate that the RL/OSL follows a stable and uniform distribution. The minimum detected doses associated with the RL, OSL, and RL + OSL signals are2.1 9 10^(-2), 3.17 9 10^(-1), and 5.7 9 10^(-2) l Gy, respectively. This device provides a framework for the future development of applications for practical radiation dose measurements.

Paediatric computed tomography radiation dose: A review of the global dilemma

Computed tomography(CT)has earned a well-deserved role in diagnostic radiology,producing crosssectional and three-dimensional images which permit enhanced diagnosis of many pathogenic processes.The speed,versatility,accuracy,and non-invasiveness of this procedure have resulted in a rapid increase in its use.CT imaging,however,delivers a substantially higher radiation dose than alternative imaging methodologies,particularly in children due to their smaller body dimensions.In addition,CT use in children produces an increased lifetime risk of cancer,as children’s developing organs and tissues are inherently more vulnerable to cellular damage than those of adults.Though individual risks are small,the increasing use of CT scans in children make this an important public health problem.Various organizations have recommended measures to minimize unnecessary exposures to radiation through CT scanning.These include elimination of multiple or medically unnecessary scans,development of patientspecific dosing guidelines,and use of alternative radiographic methodology wherever possible.Another important factor in excessive CT exposures,however,is a documented lack of awareness among medical practitioners of the doses involved in CT usage as well as itssignificant potential dangers.This review examines the effects of paediatric CT radiation,discusses the level of medical practitioner awareness of these effects,and offers recommendations on alternative diagnostic methods and practitioner education.

Total dose radiation response of modified commercial silicon-on-insulator materials with nitrogen implanted buried oxide

Nitrogen ions of various doses are implanted into the buried oxide （BOX） of commercial silicon-on-insulator （SOI） materials, and subsequent annealings are carried out at various temperatures. The total dose radiation responses of the nitrogen-implanted SOI wafers are characterized by the high frequency capacitance-voltage （C-V） technique after irradi- ation using a Co-60 source. It is found that there exist relatively complex relationships between the radiation hardness of the nitrogen implanted BOX and the nitrogen implantation dose at different irradiation doses. The experimental results also suggest that a lower dose nitrogen implantation and a higher post-implantation annealing temperature are suitable for improving the radiation hardness of SOI wafer. Based on the measured C V data, secondary ion mass spectrometry （SIMS）, and Fourier transform infrared （FTIR） spectroscopy, the total dose responses of the nitrogen-implanted SOI wafers are discussed.

Radiation-Associated Cardiotoxicity during Breast Cancer Treatment with Ionizing Radiation

Introduction: Breast cancer is the most common cancer in women. The treatment of breast carcinoma has advanced in the last decade and nowadays there are treatment protocols for all stages of the disease. Depending on the histopathology and stage breast cancer is treated with surgery, chemotherapy and radiotherapy. Regarding radiation, the field of irradiation includes the chest wall in patients with mastectomy, or the breast glandular tissue in patients with conserving surgical approaches. It is often treated with radiation therapy with two opposing tangential fields, and when indicated supraclavicular lymph nodes have to be irradiated. In this case an additional anterior field is applied. The tangential as well as the other radiation beams have a potential damaging effect on the healthy surrounding tissues, particularly over the heart in the left breast irradiation and in the lungs as well. Material and Methods: The study included 25 patients with left breast carcinoma, all post surgery, treated with radiation therapy, with the Elekta accelerator at our department. For academic purpose the treatment plans were generated following two methods. The first one with two tangential opposite beams plus a supraclavicular beam. In this method the angles of the tangential internal and external create an angle that is equal to 180&#730;{310&#730;& 130&#730;};no further changes were made to the beam geometry. Even though this is not the best option from the dose distribution point of view, it is still the most applied method, probably because of the semplicity of it. For each patient, a second plan was generated using two opposite tangential beams plus the supraclavicular beam. The angles of the internal and external beam were changed from 1&#730;to 3&#730;, depending on the surface of the body, so that the resulting angle was 180&#730;± 3&#730;{310&#730;± 3&#730;& 130&#730;± 3&#730;} with the aim to adapt the beam geometry as much as possible to the shape of the thoracic wall and to spare the OAR-s. Results and Discussion: The data show that the dose in the organs at risk, in terms of dose percentage, is lower when the angles of the beams are changed with 1&#730;- 3&#730;, compared to the classic method where the internal and external angles equal 180&#730;. This dose is not only non-negligible but significant;for every angle change from 1&#730;to 3&#730;, there is a significant reduction in the integral dose in the radiated volume, expressed in percentage, up to 5%. Conclusion: In most centers, the radiation treatment of breast is realized with two tangential opposite beams, which usually are mirror beams, or in other words, the internal and external beam angles create an angle of 180&#730;{α + β = 180&#730;}. This is a simple method, which provides a good dose distribution, but leaves a relatively high dose in the organs at risk. This study shows the difference in the dose percentage in the heart and lung when the beam angles are changed adapting to the anatomy of the patient. Reducing these doses allows for better overall treatment and less longtime toxicity, particularly for the heart tissues.

Dosimetric Comparison of Integral Radiation Dose: Anisotropic Analytical Algorithm and Acuros XB in Breast Radiotherapy

The impact of the difference between Anisotropic Analytical Algorithm (AAA) and Acuros XB (AXB) in breast radiotherapy is not clearly due to different uses and further research is required to explain this effect. The aim of this study is to investigate the contribution of calculation differences between AAA and AXB to the integral radiation dose (ID) on critical organs. Seven field intensity modulated radiotherapy (IMRT) plans were generated using with AAA and AXB algorithms for twenty patients with early stage left breast cancer after breast conserving surgery. Volumetric and dosimetric differences, as well as, the Dmean, V5, V20 doses of the left and right-sided lung, the Dmean, V10, V20, V30 doses of heart and the Dmean, V5, V10 doses of the contralateral breast were investigated. The mean dose (Dmean), V5, V20 doses of the left-sided lung, the Dmean, V5, V10 doses of right-sided lung, the Dmean, V10, V20, V30 doses of heart and the Dmean, V5, V10 doses of the contralateral breast were found to be significantly higher with AAA. In this research integral dose was also higher in the AAA recalculated plan and the AXB plan with the average dose as follows left lung 2%, heart 2%, contralateral breast 8%, contralateral lung 4% respectively. Our study revealed that the calculation differences between Acuros XB (AXB) and Anisotropic Analytical Algorithm (AAA) in breast radiotherapy caused serious differences on the stored integral doses on critical organs. In addition, AXB plans showed significantly dosimetric improvements in multiple dosimetric parameters.

Comparison of radiation doses between hepatic artery infusion chemotherapy and transarterial chemoembolization for liver cancer

Objective:To analyze the radiation dose received by patients during hepatic artery infusion chemotherapy(HAIC)and transarterial chemoembolization(TACE)procedures and the related influencing factors.Methods:Data of 162 cases in the HAIC group and 230 cases in the TACE group were collected.The included covariates were Age(<45/45-59/≥60 years),BMI levels(underweight/normal weight/obesity),focus Dye of tumor(present/absent),lesion size(<5 cm/≥5 cm),superselection(present/absent),hepatic vascular variation(present/absent).The endpoints were postoperative dose-area product(DAP),exposure time and Air kerma(AK).Results:Of all included patients,the HAIC group patients were younger than those in the TACE group(P=0.028).The proportion of patients with large lesions in the HAIC group was higher than the TACE group(45.7%vs.33.9%,P=0.019).The proportion of patients who had superselection was lower in the HAIC group as compared to the TACE group(61.7%vs.82.2%,P<0.001).Generally,the HAIC group has lower DAP,exposure time and AK by 36.3%(P<0.001),38.2%(P<0.001),and 41.3%(P<0.001)than the TACE group,respectively.Linear regression analysis showed the procedure method(HAIC/TACE,P<0.001),type of DSA machine(Pheno/FD20,P<0.001),BMI levels(P<0.001),age(P=0.021),lesion size(<5 cm/≥5 cm,P=0.031)significantly correlated with low DAP.In the HAIC group,the type of DSA machine and BMI correlated with the radiation dose,while in the TACE group,the type of DSA machine,BMI,and lesion size correlated with the radiation dose.Conclusion:Compared with TACE,HAIC enables doctors and patients to receive lower radiation doses.Obese patients in both HAIC and TACE groups increase the radiation exposure in interventional doctors and patients,but large lesions only affect the radiation dose in the TACE procedure.

Study of total ionizing dose radiation effects on enclosed gate transistors in a commercial CMOS technology

This paper studies the total ionizing dose radiation effects on MOS （metal-oxide-semiconductor） transistors with normal and enclosed gate layout in a standard commercial CMOS （compensate MOS） bulk process. The leakage current, threshold voltage shift, and transconductance of the devices were monitored before and after γ-ray irradiation. The parameters of the devices with different layout under different bias condition during irradiation at different total dose are investigated. The results show that the enclosed layout not only effectively eliminates the leakage but also improves the performance of threshold voltage and transconductance for NMOS （n-type channel MOS） transistors. The experimental results also indicate that analogue bias during irradiation is the worst case for enclosed gate NMOS. There is no evident different behaviour observed between normal PMOS （p-type channel MOS） transistors and enclosed gate PMOS transistors.

Intensity modulated radiation therapy with simultaneous integrated boost based dose escalation on neoadjuvant chemoradiation therapy for locally advanced distal esophageal adenocarcinoma

AIM:To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost(IMRT-SIB).METHODS:We retrospectively reviewed the patients who underwent four-dimensional-based IMRT-SIBbased neoadjuvant chemoradiation protocol.During the concurrent chemoradiation therapy,radiation therapy was through IMRT-SIB delivered in 28 consecutive daily fractions with total radiation doses of 56 Gy to tumor and 5040 Gy dose-painted to clinical tumor volume,with a regimen at the discretion of the treating medical oncologist.This was followed by surgical tumor resection.We analyzed pathological completion response(p CR) rates its relationship with overall survival and event-freesurvival.RESULTS:Seventeen patients underwent dose escalation with the IMRT-SIB protocol between 2007 and 2014 and their records were available for analysis.Among the IMRT-SIB-treated patients,the toxicity appeared mild,the most common side effects were grade 1-3 esophagitis(46%) and pneumonitis(11.7%).There were no cardiac events.The Ro resection rate was 94%(n = 16),the p CR rate was 47%(n = 8),and the postoperative morbidity was zero.There was one mediastinal failure found,one patient had local failure at the anastomosis site,and the majority of failures were distant in the lung or bone.The 3-year diseasefree survival and overall survival rates were 41%(n = 7) and 53%(n = 9),respectively.CONCLUSION:The dose escalation through IMRT-SIB in the chemoradiation regimen seems responsible for down-staging the distal esophageal with well-tolerated complications.

Effect of Stereotactic Body Radiation Therapy on Diverse Organ Lesions in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors

Objective The combination of stereotactic body radiation therapy(SBRT)and immune checkpoint inhibitors(ICIs)is actively being explored in advanced non-small-cell lung cancer(NSCLC)patients.However,little is known about the optimal fractionation and radiotherapy target lesions in this scenario.This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs.Methods The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec.2015 to Sep.2021.Patients were grouped according to radiation sites.Progression-free survival(PFS)and overall survival(OS)were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank(Mantel-Cox)test.Results A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study.Radiation sites included lung lesions(lung group,n=43),bone metastases(bone group,n=24),and brain metastases(brain group,n=57).Compared with the brain group,the mean PFS(mPFS)in the lung group was significantly prolonged by 13.3 months(8.5 months vs.21.8 months,HR=0.51,95%CI:0.28–0.92,P=0.0195),and that in the bone group prolonged by 9.5 months with a 43%reduction in the risk of disease progression(8.5 months vs.18.0 months,HR=0.57,95%CI:0.29–1.13,P=0.1095).The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group.The mean OS(mOS)in the lung and bone groups was longer than that of the brain group,and the risk of death decreased by up to 60%in the lung and bone groups as compared with that of the brain group.When SBRT was concurrently given with ICIs,the mPFS in the lung and brain groups were significantly longer than that of the bone group(29.6 months vs.16.5 months vs.12.1 months).When SBRT with 8–12 Gy per fraction was combined with ICIs,the mPFS in the lung group was significantly prolonged as compared with that of the bone and brain groups(25.4 months vs.15.2 months vs.12.0 months).Among patients receiving SBRT on lung lesions and brain metastases,the mPFS in the concurrent group was longer than that of the SBRT→ICIs group(29.6 months vs.11.4 months,P=0.0003 and 12.1 months vs.8.9 months,P=0.2559).Among patients receiving SBRT with<8 Gy and 8–12 Gy per fraction,the mPFS in the concurrent group was also longer than that of the SBRT→ICIs group(20.1 months vs.5.3 months,P=0.0033 and 24.0 months vs.13.4 months,P=0.1311).The disease control rates of the lung,bone,and brain groups were 90.7%,83.3%,and 70.1%,respectively.Conclusion The study demonstrated that the addition of SBRT on lung lesions versus bone and brain metastases to ICIs improved the prognosis in advanced NSCLC patients.This improvement was related to the sequence of radiotherapy combined with ICIs and the radiotherapy fractionation regimens.Dose fractionation regimens of 8–12 Gy per fraction and lung lesions as radiotherapy targets might be the appropriate choice for advanced NSCLC patients receiving ICIs combined with SBRT.

Effect of Cycloheximide on the Adaptive Response Induced by Low Dose Radiation

Human lymphocytes pre-exposed to 10 mGy or 50 mGy of X-rays become less sensitive to subsequent large dose irradiation, exhibited lower rate of chromosome aberration than expected. This adaptive response could be inhibited by cycloheximide, a protein synthesis inhibitor for successive 2 h period ranging from 0.5h before to 4h after the low dose exposure, indicating that the adaptive response was directly related with the protein synthesis.

Effect of Low Dose Radiation on Intracellular Calcium and Protein Kinase C in Lymphocytes

It is first reported in the present paper that whole-body irradiation (WBI) with low dose X-rays could increase intracellular calcium ions ([Ca2+]i) and stimulate protein kinase C (PKC) activity of mouse lymphocytes. Following WBI of male Kunming micc With 75 mGy X-rays at a dose rate of 12.5 mGy/min the mobilization of [Ca2+]i with Con A in CD4+ and CD8+ Cells in the thymus and spleen was potentiated and the amplitude of [Ca2+], mobilization in thymocytes in response to anti-CD3 monoclonal antibody increased with time from 4 to 24 h following low dose radiation. The PKC activity in the homogenate of spleen was markedly stimulated 12 h after WBl with 75 mGy, reaching its peak value at 24-48 h and coming down to lower than normal on day 7. However, the PKC activity in the separated T lymphocytes reached its peak value at 12 h and that in the B lymphocytes reached its peak value on day 4, both coming down to below control on day 7. The implications of this facilitation of signal transduction in T lymphocytes in the mechanism of immunoenhancement after low dose radiation were discussed

Mitochondrial Modulation of Apoptosis Induced by Low-dose Radiation in Mouse Testicular Cells

Objective To investigate whether apoptosis induced by low-dose radiation （LDR） is regulated by mitochondrial pathways in testicular cells. Methods Male mice were exposed to whole-body LDR, and changes in mitochondrial function and in expression of apoptotic factors were analyzed in the testicular cells as follows. Total nitric-oxide synthase （T-NOS） and Na＋/K＋ ATPase activities were biochemically assayed. Reactive oxygen species （ROS） and mitochondrial membrane potential （Adjm） were determined by flow cytometry using fluorescent probes. Levels of mRNAs encoding cytochrome c （Cyt c） and apoptosis-inducing factor （AIF） were quantified by real-time reverse-transcription PCR （RT-PCR）. Expression of Cyt c, AIF, caspase-9, and caspase-3 at the protein level was assessed by western blotting and immunohistochemistry. Results LDR induced an increase in T-NOS activity and ROS levels, and a decrease in Na＋/K~ ATPase activity and mitochondrial A^m, in the testicular cells. The intensity of these effects increased with time after irradiation and with dose. The cells showed remarkable swelling and vacuolization of mitochondria, and displayed a time- and dose-dependent increase in the expression of Cyt c, AIF, procaspase-9, and procaspase-3. Activation of the two procaspases was confirmed by detection of the cleaved caspases. The changes in expression of the four apoptotic factors were mostly limited to spermatogonia and spermatocytes. Conclusion LDR can induce testicular cell apoptosis through mitochondrial signaling pathways