Objective Triple-negative breast cancer(TNBC)poses a significant challenge for treatment efficacy.CD8+T cells,which are pivotal immune cells,can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing technology.By leveraging these genes,our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to immunotherapy. Methods Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC databases.In the initial stage,we identified 67 differentially expressed genes associated with immune response in CD8+T cells.Subsequently,we narrowed our focus to three key genes,namely CXCL13,GBP2,and GZMB,which were used to construct a prognostic model.The accuracy of the model was assessed using the validation set data and receiver operating characteristic(ROC)curves.Furthermore,we employed various methods,including Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway,immune infiltration,and correlation analyses with CD274(PD-L1)to explore the model's predictive efficacy in immunotherapeutic responses.Additionally,we investigated the potential underlying biological pathways that contribute to divergent treatment responses. Results We successfully developed a model capable of predicting the prognosis of patients with TNBC.The areas under the curve(AUC)values for the 1-,3-,and 5-year survival predictions were 0.618,0.652,and 0.826,respectively.Employing this risk model,we stratified the samples into high-and low-risk groups.Through KEGG enrichment analysis,we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism,whereas the low-risk group demonstrated significant enrichment in cytokine pathways.Furthermore,immune landscape analysis revealed noteworthy variations between(PD-L1)expression and risk scores, Conclusion Our study demonstrates the potential of CXCL13,GBP2,and GZMB as prognostic indicators of clinical outcomes and immunotherapy responses in patients with TNBC.These findings provide valuable insights and novel avenues for developing immunotherapeutic approaches targeting TNBC.

Objective:To explore the prevalence and independent associated factors of vascular calcification (VC) in non-dialysis chronic kidney disease (CKD) patients of stage 3-5.Methods:It was a single-center cross-sectional observational study. Non-dialysis stage 3-5 CKD patients ≥18 years old who were admitted to the Department of Nephrology, the First Affiliated Hospital of Sun Yat-sen University from May 1, 2022 to December 31, 2022 with VC evaluation were enrolled. The patients' general information, laboratory examination and imaging data were collected. Coronary artery calcification (CAC), thoracic aorta calcification (TAC), abdominal aorta calcification (AAC), carotid artery calcification and aortic valve calcification (AVC) were evaluated by cardiac-gated electron-beam CT (EBCT) scans, lateral lumbar x-ray, cervical macrovascular ultrasound and echocardiography, respectively. The differences in clinical data and the prevalence of VC at different sites of patients with different CKD stages were compared, and the prevalence of VC at different sites of patients in different age groups [youth group (18-44 years old), middle-aged group (45-64 years old) and elderly group (≥65 years old)] and patients with or without diabetes were compared. Multivariate logistic regression analysis was used to analyse the independent associated factors of VC for different areas.Results:A total of 206 patients aged (51±14) years were included, including 129 (62.6%) males. There were 44 patients with CKD stage 3 (21.4%), 51 patients with CKD stage 4 (24.8%), and 111 patients with CKD stage 5 (53.9%). CKD was caused by chronic glomerulonephritis [104 cases (50.5%)], diabetic kidney damage [35 cases (17.0%)], hypertensive kidney damage [29 cases (14.1%)] and others [38 cases (18.4%)]. Among 206 patients, 131 (63.6%) exhibited cardiovascular calcification, and the prevalence of CAC, TAC, AAC, carotid artery calcification, and AVC was 37.9%, 43.7%, 37.9%, 35.9% and 9.7%, respectively. The overall prevalence of VC in young, middle-aged and elderly patients was 24.6%, 73.6% and 97.4%, respectively. With the increase of age, the prevalence of VC in each site gradually increased, and the increasing trend was statistically significant (all P<0.001). The overall prevalence of VC in CKD patients with diabetes was 92.5% (62/67), and the prevalence of VC at each site in the patients with diabetes was significantly higher than that in the patients without diabetes (all P<0.001). Multivariate logistic regression analysis revealed that age (every 10 years increase, OR=2.51, 95% CI 1.77-3.56, P<0.001), hypertension ( OR=5.88, 95% CI 1.57-22.10, P=0.009), and diabetes ( OR=4.66, 95% CI 2.10-10.35, P<0.001) were independently correlated with CAC; Age (every 10 years increase, OR=6.43, 95% CI 3.64-11.36, P<0.001) and hypertension ( OR=6.09, 95% CI 1.33-27.84, P=0.020) were independently correlated with TAC; Female ( OR=0.23, 95% CI 0.07-0.72, P=0.011), age (every 10 years increase, OR=3.90, 95% CI 2.42-6.29, P<0.001), diabetes ( OR=5.37, 95% CI 2.19-13.19, P<0.001) and serum magnesium ( OR=0.01,95% CI 0-0.35, P=0.014) were independently correlated with AAC. Moreover, age and diabetes were independently correlated with carotid artery calcification, AVC and overall VC Conclusions:The prevalence of VC in non-dialysis CKD patients of stage 3-5 is 63.59%, of which CAC reaches 37.9%, TAC is the most common one (43.7%), while AVC is the least one (9.7%). Age and diabetes are the independent associated factors for VC of all sites except TAC, while hypertension is an independent associated factor for both CAC and TAC.

OBJECTIVES: In light of the rise in the global aging population, this study investigated the potential of the oxidative balance score (OBS) as an indicator of phenotypic age acceleration (PhenoAgeAccel) to better understand and potentially slow down aging. METHODS: Utilizing data from the National Health and Nutrition Examination Survey collected between 2001 and 2010, including 13,142 United States adults (48.7% female and 51.2% male) aged 20 and above, OBS and PhenoAgeAccel were calculated. Weighted generalized linear regression models were employed to explore the associations between OBS and PhenoAgeAccel, including a sex-specific analysis. RESULTS: The OBS demonstrated significant variability across various demographic and health-related factors. There was a clear negative correlation observed between the higher OBS quartiles and PhenoAgeAccel, which presented sex-specific results: the negative association between OBS and PhenoAgeAccel was more pronounced in male than in female. An analysis using restricted cubic splines revealed no significant non-linear relationships. Interaction effects were noted solely in the context of sex and hyperlipidemia. CONCLUSIONS A higher OBS was significantly associated with a slower aging process, as measured by lower PhenoAgeAccel. These findings underscore the importance of OBS as a biomarker in the study of aging and point to sex and hyperlipidemia as variables that may affect this association. Additional research is required to confirm these results and to investigate the biological underpinnings of this relationship.

Objective:To analyze the clinical phenotype and molecular pathogenesis of nine patients with hereditary factor Ⅴ (FⅤ) deficiency.Methods:Nine patients with hereditary FⅤ deficiency who were admitted to the Institute of Hematology and Blood Diseases Hospital from April 1999 to September 2019 were analyzed. The activated partial thromboplastin time, prothrombin time, and FⅤ procoagulant activity (FⅤ∶C) were measured for phenotypic diagnosis. High-throughput sequencing was employed for the F5 gene mutation screening, Sanger sequencing was adopted to confirm candidate variants and parental carrying status, Swiss-model was used for three-dimensional structure analysis, and ClustalX v.2.1 was used for homologous analysis.Results:The FⅤ∶C of the nine patients ranged from 0.1 to 10.6. Among them, eight had a hemorrhage history, with kin/mucosal bleeding as the most common symptom (three cases, 37.5%) , whereas one case had no bleeding symptom. There were five homozygotes and four compound heterozygotes. A total of 12 pathogenic or likely pathogenic mutations were detected, of which c.6100C>A/p.Pro2034Thr, c.6575T>C/p.Phe2192Ser, c.1600_1601delinsTG/p. Gln534*, c.4713C>A/p.Tyr1571*, and c.952+5G>C were reported for the first time.Conclusion:The newly discovered gene mutations enriched the F5 gene mutation spectrum associated with hereditary FⅤ deficiency. High-throughput sequencing could be an effective method to detect F5 gene mutations.

Objective: To develop the methodology for using TLD and radiochromic film to measure the planned target volume (PTV) and organ at risk (OAR) doses and 2D dose distribution in IMRT, in order to provide technical guidance on the dose quality audit in IMRT at home. Methods: China has participated in the research project launched by the international multi-radiotherapy centre (IMRC). IMRT polystyrene phantom provided by IAEA was scanned by CT scanner and then the scanned images were transmitted to TPS to outline prescribed dose to PTV and to OAR. The former was limited to 400 cGy while the latter limited to 200 cGy. IMRT was implemented with the phantom irradiated using 6 MV X-ray. The irradiated TLDs and films were sent to IAEA dosimerty laboratory for measurement and calculation. Jiangsu, Sichuan, Hubei and Henan provinces were selected to engage with this study for their variety of accelerators and highly skilled physicists. The procedures used were the same as in the IMRC and the irradiated TLDs and films were required to send to external audit group for measurement and calculation. Results: According to IAEA requirement, the relative deviations of the TLD-measured and TPS planned doses are within ±7.0% for PTV and OAR. The China′s research results at the IMRC have shown that the relative deviation of TLD-measured and TPS-planned values for the upper and lower PTV were -0.2% and 0.8%, respectively, consistent with the IAEA requirement, and the values for upper and lower OAR were -0.6% and -1.0%, respectively, consistent with the requirement. As the results have shown in four provinces, the relative deviations of the TLD-measured and TPS-planned were within 0 to 10.6% for upper and lower PTV and -0.6% to 20.9% for upper and lower OAR. According to IAEA requirement, the passing rate should be greater than 90% for 3 mm /3% for 2D dose distribution. China′s result at the IMRC is 100%, being excellent. The four provinces′ results have shown that 2D dose distribution pass rate of 3 mm/3% was in the range of 45.0%-100.0%. Conclusions The uses of TLD in quality audit for PTV and OAR doses and the radiochromic film in 2D dose distribution pass rate in IMRT are characterized by scientific feasibility, strong operability, easy-to-mail and data realibility. They are can be applied to quality assurance and audit in medical institutions in the country to on a large scale.

Objective: To validate the method for measuring the TPV and OAR doses and 2D dose distribution in IMRT through using TLD and radiochromic film. Methods: Eight medical linear accelerators (Valian, Elekta, Siemens) were selected. The polystyrene phantom provided by IAEA was CT scanned and the image obtained was transferred to TPS for formulation of treatment plan, prescription of PTV and OAR doses and calculation of corresponding monitoring unit (MU), IMRT was performed on the phantom using 6 MV X-ray. Irradiated TLDs and films were measured and evaluated at the Secondary Standard Dosimetry Laboratory at the Radiation Safety Institute of Chinese Center for Disease Control and Prevention. Results: According to IAEA requirement, the relative deviations between TLD-measured and TPS-planned doses were within ±7.0% for the prescribed PTV and OAR doses. As measured result, the PTV values for 8 accelerators were in the range of 0.6% to 5.9%, consistent with the IAEA requirements, whereas the OAT values for 8 accelerators were within -0.6% to 7.0%, consistent the requirements. As IAEA required, the 2D dose distribution passing rate of 3 mm/3% should be higher than 90%. The film-measured and TPS-planned values for 8 accelerators were within 90.2% to 100.0%, consistent with the requirements. Conclusions TLD and radiochromic film are feasible in validating the PTV and OAR doses and the 2D dose distribution pass rate in IMRT. This method can be widely used in quality audit and internal verification in IMRT in medical institutiions on a large scale.

Objective: To use TLDs and radiochromic films to verify the prescribed doses to both planned target volume (PTV) and organ at risk (OAR) and the 2D dose distribution in IMRT. Methods: Eight accelerators of different models were selected in Henan province. The polystyrene phantom provided by IAEA was scanned using CT scanners and then the scanned images were transmitted to treatment planning system (TPS) for prescribing respectively the doses to PTV and OAR. IMRT was performed with phantom exposed to a 6 MV X-rays. The irradiated TLDs and films were delivered for measurement and estimation at Secondary Standard Dosimetry Laboratory at National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention. Results: According to IAEA requirements, the relative deviations of the TLD-measured and TPS-planned values were within ±7.0% for the prescribed doses to PTV and OAR. The measured results for PTV have shown that the relative deviation of TLD-measured and TPS-planned values were within -0.3% to 6.9% for 8 accelerators, all consistent with the IAEA requirements. For OAR, the relative deviations of TLD-measured and TPS-planned were within -7.0% to 0.3% for 6 accelerators, consistent with the requirements, whereas those for other 2 accelerators were within -10.8% to -8.4%, not up to the requirements. IAEA required that, for 2D dose distribution, the pass rate of 3 mm/3% be ≥90%. The measured values for 7 accelerators were from 90.2% to 99.9%, consistent with the requirements, whereas that for another one was 70.0%, not meeting the requirement. Conclusions The method to verify, using radiochromic film and TLD, the prescribed doses to PTV and OAR and the pass rate of 2D dose distribution is simple and reliable. It is an important step to implement quality control for IMRT and can provide effective support for medical or third-party service institution to verify clinically prescribed dose.

Objective To develop measurement methodology using film for the positioning accuracy of MLC leaves in IMRT.Methods The solid water phantom of 30 cm x 30 cm was scanned and the scanned images were transferred to TPS for treatment plan formulation.The five MLC strip picket fence pattern was formed by MLC leaves,each 3.0 cm long × 6.0 mm wide.The separation between strip and strip is 3.0 cm.SAD is 100 cm at dmax for 6 MV X-ray,with 250 MU per MLC strip.EBT2 radiochomic film was put on the phantom for delivery of IMRT,for each MLC strip.The present study focused on 30 accelerators of Varian,Elekta and Siemens designs at 27 hospitals with highly skilled physicists all over Jiangsu,Sichuan,Hubei and Henan provinces.The study was conducted in the same way as used in international multi-radiotherapy center (IMRC).The irradiated films were sent respectively to IAEA dosimetry laboratory and external audit group (EGA) of China for measurement,analysis and calculation.Results According to IAEA requirements,the differenc of film-measured and TPS-planned of MLC leaf position for each strip should be within ±0.5 mm.China had participated in the research of IMRC,with the result of 0.3,0.2,0.0,-0.1,and-0.2 mm,respectively.For 30 accelerators in four provinces involved in the study,the IAEA's verification results of MLC leaf position were within 0.6-1.0 mm for 5 accelerators and within ± 0.5 mm for other 25 ones.Whereas the verification results of EAG were within 0.6-1.0 mm for 6 accelerators and within ±0.5 mm for other 24 ones.According to IAEA requirements,the film-measured MLC leaf position deviation for each pair of leaves and average all pairs of leaves should be within ±0.5 mm.China had participated in IMRC's research,with the measured result being 0.04 mm.The verification result of EGA for 30 accelerators showed the measured MLC leaf position deviations were all ＜0.3 mm per strip,consistent with IAEA requirements.The IAEA's result showed the measured deviations of MLC leaf position for 29 accelerators were within ±0.5 mm,with only other one being-0.7 mm not consistent with the IAEA requirements.As required by IAEA,the difference of film-measured difference of MLC opening width should be within ±0.75 mm between each pair and average all pairs of leaves.China's result in research of IMRC showed the difference of minimum width to mean width was-0.2 mm whereas the difference of maximum width to mean width was 0.4 mm.For 30 accelerators involved in IAEA'verification study,the measured result shown that the difference between maximum and average of filmmeasured of MLC leaf width,and between minmum and average,were within ± 0.75 mm for 24 accelerators,in line with the IAEA requirements.For other 6 ones,the values were beyond ±0.75 mm,not in line with the IAEA requirements.For the verification result of EAG,the difference between maximum and average widths and between minmum and average widths for 25 accelerators were within ±0.75 mm as required by IAEA,whereas for other 5 ones the value were beyond ±0.75 mm,not consistent with IAEA requirements.The standard deviation of film-measured MLC opening width between each pair and average all pairs should be within 0.3 mm as required by IAEA.China's IMRC result was 0.12 mm.The verification result of IAEA shown the standard deviation of MLC opening position were ＜0.3 mm for 26 accelerators and ＞ 0.3 mm for other 4 accelerators.EAG verification result were the same as IAEA result.Conclusions The method using radiochromic film for measuring accuracy of MLC leaf position is convenient and practicable as a quality audit.It is suitable for quality verification in medical institutions owing to easy to post and repeated measurements.

Objective To develop the methodology for using TLDs and films to measure absorbed dose and 2D dose distribution produced by the multi-leaf collimator (MLC) in intensity modulated radiotherapy (IMRT),in order to provide the guidance on dose quality audit in IMRT.Methods A total of 30 different-typed accelerators were selected from 27 hospitals in Jiangsu,Sichuan,Hubei and Henan provinces,including 17 Varian accelerators,10 Elektas and 3 Simens.The same batch of films and TLDs were put in a 2 cm-thick solid plate for fixation and then loaded in a 15 cm × 15 cm × 15 cm polysyrene solid phantom supplied by International Atomic Energy Agency(IAEA) in terms of 90 cm SSD,19 cm depth,10 cm × 10 cm field at different doses.The standard dose curves wcrc established for film and TLD,respectively.The irradiated film was measured and then sent to the External Audit Group (EAG) in China.The TLD-and film-absorbed doses were compared with TPS-calculated doses.The 2D dose distribution on the IRMT MLC field was measured using films.The homogeneous phanton of 30 cn × 30 cm was scanned by CT and the image was transferred to the TPS.The IMRT was implemented with 6 Gy fractionated irradiation by placing a 25 cm × 25 cm film on the phantom surface at 95 cm SSD and at 5 cm depth.The irradiated film was sent to the IAEA dosimetry laboratory for measurement and calculation.2D dose distribution verification was conducted in thc same way consistent with the procedure of international multi-radiotherapy center.The 3 mm/3％ passing rate was calculated for 2D dose distribution and compared with the film-measured and TPS calculated result.Results IAEA requires the relative deviation of TLD and film measured absorbed dose are with in ± 5％.The relative deviation of TLD-and filmmeasured to TPS-calculated absorbed dose was within the range of ±0.7％-± 8.5％ and within ±0.3％ ±7.8％ in Jiangsu,Sichuan,Hubei and Henan provinces,respectively.IAEA requires the 3 mm/3％ passing rate of film-measured 2D distribution to be 90％.The result of the present study were up to 94.0％.The verification result of 2D dose distribution were within 70.0％-99.9％ in Sichuan,Jiangsu,Hubei and Henan provinces.Conclusions The adsorbed dose and 2D distribution can be audited using TLDs and films for MLC in IRMT.The method is scientific and applicable,economical and convenient for development of dose quality audit for a wide range of IRMT.

Objective To measure the doses to eye lens and hands of workers,using thermo luminescent dosimeter (TLD) and optically stimulated luminescence dosimeter (OSLD).Methods TLDs in the same batch were annealed,packed and stuck to the flat abdomen of Alderson-Phantom at a distance of about 15 cm from 125I seed source,while irradiated at different doses:1.0,1.5,3.0,5.0,10.0,12.0,20.0,25.0,30.0,50.0 and 60.0 μ Gy.And then TLDs were measured by dosimeters to establish a dose calibration curve.By implanting seed source into the selected lung for 14 cases,belly for 10 cases,pelvic for 5 case and neck for 6 cases while placing calibrated TLDs on the left,middle and right above eyes,left and right hands of the workers to obtain the location-specific kerma values.Finally,the conversion factors Hp (3) and Hp (0.07) were used to calculate the values of dose equivalent to eye lens and hands.Additionally,OSLDs were used to measure the doses to workers in the same way.Results The TLD-measured eye lens dses to the operator and his assistant were 0.8 and 1.6 mSv in lungs,1.3 and 1.2 mSv in bellies,0.9 and 0.6 mSv in pelves,0.3 mSv in necks,respectively.Meanwhile,hand doses to the operator and his assistant were 1.4 and 2.1 mSv in lungs,1.2 and 1.0 mSv in bellies,0.5 and 0.9 mSv in pelves,0.1 mSv in necks,respectively.The maximum doses to eye lens and hands were 1.2 and 1.0 mSv,respectively in a single treatment.OSLD-measured dose equivalents from lung therapy were 0.2 and 0.1 mSv for eye lens of the operator and his assistant and 0.4 and 0.6 mSv for hands.For belly therapy,the accumulated dose equivalent to hands of the operator was 0.1 mSv while those for other types of therapy were 0 mSv.Conclusions TLDs have the capability to measure not only accumulated dose but also dose equivalent from a single therapy According to ICRP 118 publication and as estimated in the present study,the number of therapy should be not more than 17 every year.OSLDs only give the accumulated dose,the accuracy of which needs to be studied in low-dose measurement.