Objective:To explore the dosimetric advantages of 3D printed individualized molds in assisting postoperative three-dimensional brachytherapy (3D BT) for endometrial cancer.Methods:The 3D BT plans of 21 postoperative patients with early-stage endometrial cancer at the First Affiliated Hospital of Ningbo University were retrospectively selected as the individualized mold group (the mold group). On this basis, virtual single-channel cylindrical applicator plans that employed a 3D inverse simulated annealing algorithm were designed for all the patients using the Beijing Colins Planning System (the single-channel group). Comparisons were made between the two groups of plans regarding the minimum doses exposed to 90%, 98%, and 100% of target area ( D90, D98, and D100), conformity index (CI), homogeneity index (HI), and overdose index (OI), as well as the maximum doses exposed to 0.01, 1, 2, and 5 cm 3organs at risk (bladder, rectum, small intestine, and urethra) ( D0.01 cm 3, D1 cm 3, D2 cm 3, and D5 cm 3). Results:Both groups met clinical requirements. For doses to target volumes, there was no significant difference in D90, D98, and D100 between both groups, with the mold group demonstrating superior CI and HI but lower OI compared to the single-channel group ( t = -3.21, -5.99, 6.25, P < 0.05). Concerning the doses exposed to organs at risk, the mold group displayed significantly reduced D1 cm 3, D2 cm 3, and D5 cm 3 for the bladder, rectum, and urethra compared to the single-channel group ( t = 3.18, 3.21, 3.77, 7.97, 8.92, 10.92, 2.54, 3.46, 4.28, P < 0.05). There was no significant difference in the doses exposed to the small intestine between both groups ( P > 0.05) due to the large distance from the small intestine to the target volumes. Conclusions:3D printed individualized molds exhibit advantages in terms of the homogeneity and conformity indices of target volumes in postoperative three-dimensional brachytherapy for endometrial cancer, accompanied by low doses exposed to the bladder, rectum, and urethra, thereby holding the potential for broader application.

Objective:To identify the dosimetric and radiobiological differences of three radiotherapy techniques of whole breast irradiation with simultaneous integrated boost (WBI-SIB) following breast-conserving surgery for early breast cancer (EBC).Methods:The data of 20 patients with early left-sided breast cancer who received radiotherapy following breast-conserving surgery were retrospectively analyzed. Three radiotherapy techniques, namely hybrid intensity-modulated radiotherapy (HIMRT), intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT), were redesigned with the same prescription dose and target conditions. Then, doses to target volume (TV) and organs at risk (OAR), along with the normal tissue complication probability (NTCP) and secondary cancer risk (SCR) for specific organs, were compared.Results:Compared to HIMRT and IMRT, VMAT led to significant decreases in various dosimetric indices of the affected lung and heart and increases in the Dmean doses to the healthy lung and healthy breast and V5 Gy doses to the healthy breast, with the differences being significantly different ( P < 0.05). The average NTCP values of cardiac death, radiation pneumonitis, and pulmonary fibrosis induced by VMAT were 0.41%, 1.62%, and 23.59%, respectively, significantly lower than those caused by other two techniques ( P < 0.05). No statistical differences were found in 10 dosimetric indices of OAR between IMRT and HIMRT, while the NTCP analysis suggested that the risks of cardiac death ( t = 2.70, P < 0.05) and pulmonary fibrosis ( t =4.11, P < 0.05) induced by IMRT were slightly lower than those caused by HIMRT. In addition, the excess absolute risk (EAR) to the healthy lung posed by VMAT was 1.65 and 1.83 times those induced by HIMRT and IMRT, respectively ( z = -3.92, t = -6.43, P < 0.05). In contrast, the EAR to the healthy breast induced by VMAT was 2.79 and 2.65 times those posed by HIMRT and IMRT, respectively ( z = -3.21, -3.70, P < 0.05). Conclusions:Among three intensive-modulated radiotherapy techniques of WBI-SIB for EBC, VMAT provides the optimal protection for the heart and affected lung but leads to the highest SCR to the healthy lung and breast. When VMAT is employed for young EBC patients or those with normal cardiopulmonary function, special attention should be paid to reducing low-dose irradiations to the healthy breast and thereby minimizing SCR. In contrast, VMAT might be more favorable for patients with pronounced cardiopulmonary risks or aged patients.

OBJECTIVE To elucidate the mechanisms responsible for the inhibitory effects of limonene on the proliferation of non-small cell lung cancer(NSCLC) by non-targeted metabolomics and additional approaches. METHODS The CCK-8 assay was utilized to evaluate the inhibitory effects of limonene on NSCLC A549 cell viability and to ascertain the IC50. In vitro experiments, encompassing colony formation, flow cytometry, iron content assessment, and mitochondrial staining, were conducted to assess the anti-lung cancer and iron-induced cell death effects of limonene. Metabolomic analysis was employed to identify potential pathways influenced by limonene, and Western blotting was carried out to validate pivotal proteins within these pathways. RESULTS In comparison to the control group, the limonene-treated group demonstrated a significant, dose-dependent reduction in A549 cell proliferation and colony formation. Optical microscopy revealed cellular detachment and pronounced changes in cellular morphology following exposure to limonene. Limonene induced apoptosis in A549 cells and arrested them in the G0-G1 phase of the cell cycle. Confocal microscopy unveiled diminished mitochondrial fluorescence and an augmented intracellular iron content, indicative of the classical phenomenon of ferroptosis. Metabolomic investigations unveiled divergent metabolic pathways, including glutathione(GSH) metabolism, arginine biosynthesis, D-glutamine and D-glutamate metabolism, as well as cysteine and methionine metabolism, with many of them intricately linked to intracellular GSH synthesis. Western blotting experiments underscored a marked reduction in the levels of SLC40A1, SLC7A11(xCT), and GPX4 proteins within the cells post-limonene treatment. CONCLUSION Limonene may induce ferroptosis in lung cancer cells by reducing GSH synthesis and increasing Fe2+ levels.

[This corrects the article DOI: 10.1016/j.apsb.2022.07.023.].

Objective To establish an HPLC-based method for the determination of α-obscurine,ferulic acid,hydroxysafflower yellow A,benzoylneaconitine,benzoylaconitine,periplosin,4-methoxysalicylsalicylate,kaempferol and oleanolic acid simultaneously in Shujin Tongluo Black Plaster.Methods HPLC method was used to determine the 9 components in Shujin Tongluo Black Plaster simultaneously.The 70%methanol extracts were analyzed using Waters SunFire C18 chromatography column(4.6 mm×250 mm,5 μm),in mobile phase containing acetonitrile-0.2%phosphoric acid solution for gradient elution with volume flow rate of 1.0 mL/min;column temperature was set at 25℃;detection wavelength was set at 230 nm.Results The 9 components had good linear relationship in their respective ranges(r≥0.999 7).The average recoveries were between 98.06%-100.56%and RSD was between 0.48%-2.56%,respectively.Conclusion The method has the advantage of repeatability,simple and fast,and can be used as the quality control of Shujin Tongluo Black Plaster.

Objective: To analyze the trend and characteristics of school tuberculosis epidemic in Shijiazhuang from 2011 to 2020, and to provide reference for school tuberculosis prevention and control. Methods: Descriptive methods were used to analyze the epidemiological characteristics of tuberculosis among students and the epidemic situation of tuberculosis in schools in Shijiazhuang from 2011 to 2020. The χ 2 test and χ 2 trend test were used to analyze the characteristics and trend of school tuberculosis. Results: A total of 4 896 cases of tuberculosis were registered among students in Shijiazhuang from 2011 to 2020. The average annual registered incidence rate of students was 24.69/100 000, and the difference in incidence rate was statistically significant ( χ 2=318.50, P <0.01) the overall registered incidence rate of tuberculosis among students in the past 10 years was on the rise ( χ 2 trend =87.79, P <0.01). Among the student cases, male accounted for 53.89%, female accounted for 46.11%. The age group of students aged >18 and above accounted for the largest proportion(50.35%), followed by the age group aged 16-18( 35.80 %). Most students cases occurred in April and September-November, with September the highest(12.03%). A total of 22 clustered outbreaks (174 cases) and the aggregate epidemic accounted for 3.55% of the total number of students with tuberculosis. Conclusion The prevention and control of tuberculosis epidemic in schools in Shijiazhuang should not be underestimated, and strengthen the supervision, management, publicity and education of students in key age groups to avoid clusters of outbreaks.

Objective:Topredict the three-dimensional dose distribution of regions of interest (ROI) with brachytherapy for cervical cancer based on U-Net fully convolutional network, and evaluate the accuracy of prediction model.Methods:First, 100 cases of cervical cancer intracavity combined with interstitial implantation were selected as the entire research data set, and divided into the training set ( n=72), validation set ( n=8), and test set ( n=20). Then the U-Net was used to construct two models based on whether the uterine tandem and the implantation needles were included as the distinguishing factors. Finally, dose distribution of 20 cases in the test set were predicted using the trained model, and comparative analysis was performed. The performance of the model was jointly evaluated by , and the mean absolute deviation (MAD). Results:Compared with the model without the uterine tandem and the implantation needles, the of the rectum was increased by (16.83±1.82) cGy ( P<0.05), and the or of the other ROI were not different significantly (all P>0.05). The MAD of the high-risk clinical target volume, rectum, sigmoid, small bowel, and bladder was increased by (11.96±3.78) cGy, (11.43±0.54) cGy, (24.08±1.65) cGy, (17.04±7.17) cGy and (9.52±4.35) cGy, respectively (all P<0.05). The MAD of the intermediate-risk clinical target volume was decreased by (120.85±29.78) cGy ( P<0.05). The mean value of MAD for all ROI was decreased by (7.8±53) cGy ( P<0.05), which was closer to the actual plan. Conclusions:U-Net fully convolutional network can be used to predict three-dimensional dose distribution of patients with cervical cancer undergoing brachytherapy. Combining the uterine tube with the implantation needles as the input parameters yields more accurate predictions than a single use of the ROI structure as the input.

As a promising modality for cancer therapy, photodynamic therapy (PDT) still acquired limited success in clinical nowadays due to the extremely serious hypoxia and immunosuppression tumor microenvironment. To ameliorate such a situation, we rationally designed and prepared cascade two-stage re-oxygenation and immune re-sensitization BSA-MHI148@SRF nanoparticles via hydrophilic and hydrophobic self-assembly strategy by using near-infrared photodynamic dye MHI148 chemically modified bovine serum albumin (BSA-MHI148) and multi-kinase inhibitor Sorafenib (SRF) as a novel tumor oxygen and immune microenvironment regulation drug. Benefiting from the accumulation of SRF in tumors, BSA-MHI148@SRF nanoparticles dramatically enhanced the PDT efficacy by promoting cascade two-stage tumor re-oxygenation mechanisms: (i) SRF decreased tumor oxygen consumption via inhibiting mitochondria respiratory. (ii) SRF increased the oxygen supply via inducing tumor vessel normalization. Meanwhile, the immunosuppression micro-environment was also obviously reversed by two-stage immune re-sensitization as follows: (i) Enhanced immunogenic cell death (ICD) production amplified by BSA-MHI148@SRF induced reactive oxygen species (ROS) generation enhanced T cell infiltration and improve its tumor cell killing ability. (ii) BSA-MHI148@SRF amplified tumor vessel normalization by VEGF inhibition also obviously reversed the tumor immune-suppression microenvironment. Finally, the growth of solid tumors was significantly depressed by such well-designed BSA-MHI148@SRF nanoparticles, which could be potential for clinical cancer therapy.

Objective:To investigate the efficacy and safety of geritinib in the treatment of acute myeloid leukemia (AML) with FLT3 mutation.Methods:The clinical data of 5 AML patients with FLT3 mutation who were diagnosed in the University of Hong Kong-Shenzhen Hospital, Shenzhen People's Hospital, Shenzhen Second People's Hospital, Shenzhen University General Hospital from March 2020 to April 2021 were retrospectively analyzed. Relapsed patients concurrently received two- or three-drug chemotherapy combined with geritinib. Blood routine was checked once a week; liver function and renal function were checked once every 2 weeks during treatment. Bone marrow puncture was performed once every 1 to 3 months to monitor the bone marrow morphology, minimal residual disease (MRD) and FLT3 mutation expression levels. The efficacy, side effects, overall survival of these patients were analyzed after treatment with geritinib.Results:The white blood cell was increased in all the 5 patients at the initial diagnosis. FLT3 mutations analysis showed FLT3-internal tandem duplication (ITD) (3 cases) and FLT-3 tyrosine-kinase domain (TKD) (2 cases). Among 5 patients, 1 patient was relapse-free with maintenance therapy of oral geritinib after hematological stem cell transplantation (HSCT) for 60 days; among other 4 relapsed and refractory patients, 1 female patient after pregnancy relapsed after transplantation and then achieved complete remission followed by the maintenance therapy with geritinib after oral geritinib, 1 16-year-old patient achieved treatment outcome close to the complete remission after treatment with geritinib, 1 patient achieved complete remission after treatment with geritinib, and then underwent haplo-HSCT followed by the maintenance therapy with geritinib and the other 1 relapsed patient achieved complete remission after treatment with geritinib. After transplantation, 3 patients receiving maintenance treatment of geritinib did not relapse. The main side effects included anemia, decreased neutrophil count, rash, and increased aminotransferase. The median follow-up time of 5 patients was 15 months (6-20 months). All 5 cases survived until the last follow-up in November 2021 and 4 patients were disease-free.Conclusions:Relapsed and refractory AML patients with FLT3 mutation can achieve complete remission after treatment with geritinib and get a chance for transplantation. Geritinib may reduce the risk of recurrence after transplantation and improve survival rate. No serious side effects occur in geritinib treatment.

Objective:To investigate the relationship between plasma levels of complements before treatment and the clinicopathological feathers and prognoses of diffuse large B-cell lymphoma (DLBCL) patients treated with Rituximab (R)-CHOP or R-CHOP-like therapy.Methods:The clinicopathological data of 105 DLBCL patients treated in cancer Hospital of Chinese Academy of Medical Sciences from 2010 to 2016 were collected. The plasma samples from 105 DLBCL patients treated with R-CHOP or R-CHOP-like therapy and 80 healthy controls were used to detect 34 complement levels before treatment by utilizing antibody microarray. The relationship between plasma levels of complements and the clinicopathological feathers and prognosis of DLBCL patients were analyzed.Results:The signal values of C1QA and CR1L in patients with international prognostic index (IPI) scores of 3-5 were 1 261.43±138.9 and 2 214.69±98.58, respectively, higher than 950.79±80.19 and 984.67±121.79 in patients with IPI scores of 0~2 (both P<0.05). The levels of C1QA and CR1L in the non-complete response (CR) group were 1 165.43±98.56 and 2 263.13±145.63, respectively, higher than 914.70±100.77 and 1 821.34±84.68 in the CR group (both P<0.05). Cox regression analysis showed that elevated C1QA signal value was associated with poor progression-free survival (PFS) and poor overall survival (OS) (PFS: HR=2.063, 95% CI: 1.220-3.489, P=0.007; OS: HR=2.23, 95% CI: 1.036~4.798, P=0.040). After IPI correction by Cox multivariate model, the elevated C1QA signal value was still correlated with poor PFS ( HR=1.765, 95% CI 1.034~3.013, P=0.037). Conclusions:The baseline plasma levels of C1QA and CR1L are correlated with IPI scores and therapeutic effects of DLBCL patients treated with R-CHOP. The baseline plasma level of C1QA has a certain predictive value for the prognostic evaluation of DLBCL.