Stem moisture content prediction model for Larix olgensis based on beta regression.

To investigate the longitudinal variation patterns of sapwood, heartwood, bark and stem moisture content along the trunk of artificial Larix olgensis, we constructed mixed effect models of moisture content based on beta regression by combining the effects of sampling plot and sample trees. We used two sampling schemes to calibrate the model, without limiting the relative height (Scheme Ⅰ) and with a limiting height of less than 2 m (Scheme II). The results showed that sapwood and stem moisture content increased gradually along the trunk, heartwood moisture content decreased slightly and then increased along the trunk, and bark moisture content increased along the trunk and then levelled off before increasing. Relative height, height to crown base, stand area at breast height per hectare, age, and stand dominant height were main factors driving moisture content of L. olgensis. Scheme Ⅰ showed the stable prediction accuracy when randomly sampling moisture content measurements from 2-3 discs to calibrate the model, with the mean absolute percentage error (MAPE) of up to 7.2% for stem moisture content (randomly selected 2 discs), and the MAPE of up to 7.4%, 10.5% and 10.5% for sapwood, heartwood and bark moisture content (randomly selected 3 discs), respectively. Scheme Ⅱ was appropriate when sampling moisture content measurements from discs of 1.3 and 2 m height and the MAPE of sapwood, heartwood, bark and stem moisture content reached 7.8%, 11.0%, 10.4% and 7.1%, respectively. The prediction accuracies of all mixed effect beta regression models were better than the base model. The two-level mixed effect beta regression models, considering both plot effect and tree effect, would be suitable for predicting moisture content of each part of L. olgensis well.

Treatment Options for Distal Rectal Cancer in the Era of Organ Preservation.

OPINION STATEMENT: The introduction of total mesorectal excision into the radical surgery of rectal cancer has significantly improved the oncological outcome with longer survival and lower local recurrence. Traditional treatment modalities of distal rectal cancer, relying on radical surgery, while effective, take their own set of risks, including surgical complications, potential damage to the anus, and surrounding structure owing to the pursuit of thorough resection. The progress of operating methods as well as the integration of systemic therapies and radiotherapy into the peri-operative period, particularly the exciting clinical complete response of patients after neoadjuvant treatment, have paved the way for organ preservation strategy. The non-inferiority oncological outcome of "watch and wait" compared with radical surgery underscores the potential of organ preservation not only to control local recurrence but also to reduce the need for treatments followed by structure destruction, hopefully improving the long-term quality of life. Radical radiotherapy provides another treatment option for patients unwilling or unable to undergo surgery. Organ preservation points out the direction of treatment for distal rectal cancer, while additional researches are needed to answer remaining questions about its optimal use.

Height-diameter model of broad-leaved mixed forest based on species classification in Maoershan, Northeast China.

The complex stand structure and high species diversity of natural forests pose great challenges for analyzing stand growth and formulating reasonable plans for forest management. The height-diameter relationship is of great significance for predicting stand growth and formulating forest management measures. Based on survey data of 48 broad-leaved mixed forest plots in Maoershan, we classified 23 tree species into four groups based on species structure, growth characteristics and bionomics. We established a generalized model including stand, tree competition, species mixing and species diversity variables by reparameterization method, and a two-level mixed effect model of plot and tree species group. We tested the prediction ability of the model by leave-one-out cross-validation method. The results showed that the Ratkowsky (1990) model was the optimal basic model. The introduction of dominant height, basal area of trees larger than the object tree, basal area proportion of each species, and Shannon index could better explain the height-diameter relationship of broad-leaved mixed forest in Maoershan. The introduction of the mixed effect model of plot and tree species group could significantly improve the prediction accuracy of the model, with a Ra2 of 0.83. Under the same gradient of environmental factors, intolerant tree species exhibited higher tree heights than shade-tolerant tree species. In this study, we used the constructed tree height-diameter model to analyze the effects of species mixing and tree functional traits on tree height, which provided a theoretical basis for accurately predicting height of different tree species and analyzing the growth relationships in broadleaved mixed forests.

Inhibition of MEG3 ameliorates cardiomyocyte apoptosis and autophagy by regulating the expression of miRNA-129-5p in a mouse model of heart failure.

The long non-coding RNA, maternally expressed gene 3 (MEG3), are involved in myocardial fibrosis and compensatory hypertrophy, but its role on cardiomyocyte apoptosis and autophagy in heart failure (HF) remains unclear. The aim of this study was to investigate the effect of MEG3 on cardiomyocyte apoptosis and autophagy and the underlying mechanism. A mouse model of HF was established by subcutaneous injection of isoproterenol (ISO) for 14 days, and an in vitro oxidative stress injury model was replicated with H2O2 for 6 h. SiRNA-MEG3 was administered in mice and in vitro cardiomyocytes to knock down MEG3 expression. Our results showed that cardiac silencing of MEG3 can significantly ameliorate ISO-induced cardiac dysfunction, hypertrophy, oxidative stress, apoptosis, excessive autophagy and fibrosis induced by ISO. In addition, inhibition of MEG3 attenuated H2O2-induced cardiomyocyte oxidative stress, apoptosis and autophagy in vitro. Downregulation of MEG3 significantly inhibited excessive cardiomyocyte apoptosis and autophagy induced by ISO and H2O2 through miRNA-129-5p/ATG14/Akt signaling pathways, and reduced H2O2-induced cardiomyocyte apoptosis by inhibiting autophagy. In conclusion, inhibition of MEG3 ameliorates the maladaptive cardiac remodeling induced by ISO, probably by targeting the miRNA-129-5p/ATG14/Akt signaling pathway and may provide a tool for pharmaceutical intervention.

Cardioprotective role of A-cycloglycosylated derivative of Rubiadin in diabetic cardiomyopathy in rats.

Diabetic cardiomyopathy (DCM) is a kind of idiopathic heart disease, which is one of the main complications of diabetes and seriously threatens the life of diabetic patients. Rubiadin, an anthraquinone compound extracted from the stems and roots of rubiaceae, has been widely discussed for its anti-diabetes, anti-oxidation and other pharmacological effects. However, Rubiadin can cause drug-induced liver injury. Therefore, A-cycloglycosylated derivative of Rubiadin (ACDR) was obtained by modifying its structure. The purpose of this study was to investigate the effect of ACDR on DCM cardiac injury and its mechanism. The DCM animal model was established by streptozotocin, and the success of DCM was verified by blood glucose level, echocardiographic evidence of impaired myocardial functions along with enhanced myocardial fibrosis. We performed liver function tests, morphological staining of the heart and tests for oxidative stress to evaluate cardiac functional and structural changes. Finally, the expression of Na+/H+ exchanger (NHE1) protein was analyzed by immunohistochemistry and western bolt, and the expression of hairy/enhancer-of-split related with YRPW motif 1 (Hey1) and P-p38 protein was detected by immunofluorescence chemistry and western blotting. The results showed that ACDR can improve cardiac dysfunction, reduce myocardial injury, reduce oxidative stress, and protect the liver in DCM rats. Interestingly, all variations were countered by LiCl. Our study suggests that, along with controlling hyperglycemia, ACDR may improve DCM by reducing NHE1 expression, further inhibiting P-p38 activity and increasing Hey1 expression to reduce oxidative stress.

Discovery of a CSF-1R inhibitor and PET tracer for imaging of microglia and macrophages in the brain.

Colony stimulating factor 1 receptor (CSF-1R) is a kinase expressed on macrophages and microglia in the brain. It has been recognized as a potential drug and imaging target in treatment of neuroinflammatory diseases and glioblastoma. Despite several attempts, no validated CSF-1R PET tracer is currently available. The aim of this work was to develop a brain permeable CSF-1R PET tracer for non-invasive imaging of CSF-1R in vivo. Based on fragments of two potent and selective CSF-1R inhibitors, novel hybrid molecules were designed and synthesized. Affinity for human recombinant CSF-1R and selectivity over c-KIT and PDGFR-ß was determined using a FRET based in vitro assay. Radiosynthesis was performed by fully automated [11C]CH3I methylation of the corresponding des-methyl precursor. PET imaging was performed at baseline, efflux transporter blocking and CSF-1R blocking conditions. Moreover, tracer distribution and blood and plasma radiometabolites were determined following injection in healthy mice. The most promising CSF-1R inhibitor, compound 4, showed high selectivity and high affinity for CSF-1R (IC50: 12 ± 3 nM) and no affinity for kinase family members c-KIT and PDGFR-beta. [11C]4 was obtained in good yield (15 ± 0.2 % decay corrected yield, (2.0 ± 0.26 GBq at end of synthesis) and excellent purity. The compound demonstrated high brain penetration and good metabolic stability (>2 %ID/g at 60 min post injection and 79 ± 8 % intact [11C]4 in brain at 60 min post injection) and no strong efflux transporter substrate behavior. Blocking CSF-1R prior to imaging with [11C]4 resulted in significant decrease in brain uptake. In conclusion, [11C]4 shows good potential as a novel PET tracer for imaging of CSF-1R in the CNS and future experiments in relevant animal models are warranted.

Multi-Objective Optimization of the Basic and Regenerative ORC Integrated with Working Fluid Selection.

A multi-objective optimization based on the non-dominated sorting genetic algorithm (NSGA-II) is carried out in the present work for the basic organic Rankine cycle (BORC) and regenerative ORC (RORC) systems. The selection of working fluids is integrated into multi-objective optimization by parameterizing the pure working fluids into a two-dimensional array. Two sets of decision indicators, exergy efficiency vs. thermal efficiency and exergy efficiency vs. levelized energy cost (LEC), are adopted and examined. Five decision variables including the turbine inlet temperature, vapor superheat degree, the evaporator and condenser pinch temperature differences, and the mass fraction of the mixture are optimized. It is found that the turbine inlet temperature is the most effective factor for both the BORC and RORC systems. Compared to the reverse variation of exergy efficiency and thermal efficiency, only a weak conflict exists between the exergy efficiency and LEC which tends to make the binary objective optimization be a single objective optimization. The RORC provides higher thermal efficiency than BORC at the same exergy efficiency while the LEC of RORC also becomes higher because the bare module cost of buying one more heat exchange is higher than the cost reduction due to the reduced heat transfer area. Under the heat source temperature of 423.15 K, the final obtained exergy and thermal efficiencies are 45.6% and 16.6% for BORC, and 38.6% and 20.7% for RORC, respectively.

[Effects of mixing proportions on carbon storage and allocation in mixed plantation of Larix olgensis and Fraxinus mandshurica]. / æ··äº¤æ¯”ä¾‹å¯¹é•¿ç™½è½å¶æ¾å’Œæ°´æ›²æŸ³æ··äº¤æž—ç¢³å‚¨é‡åŠå ¶åˆ†é æ ¼å±€çš„å½±å“.

In this study, four types of mixed Larix olgensis and Fraxinus mandshurica plantations were selected according to the rows-mixing proportions (type Ⅰ: 5:3, type Ⅱ: 6:4, type Ⅲ: 5:5, type Ⅳ: 1:1). The see-mingly unrelated biomass models of L. olgensis and F. mandshurica were developed for obtaining biomass values, and the difference and composition of carbon storage in each forest layer and ecosystem were analyzed. The results showed that carbon storage of arbor layer in different stand types was 39.86-50.12 t·hm-2, the carbon storage of arbor layer inⅠ, Ⅱ and Ⅳ was significantly higher than that in type Ⅲ. The carbon storage of understory was 0.10-0.30 t·hm-2, with that in type Ⅱ being significantly higher than other types. Carbon storage of litter layer was 4.43-6.96 t·hm-2, with type Ⅱ and Ⅲ being significantly higher than those of the other types. In the soil layer, carbon storage was 34.97-54.66 t·hm-2. The carbon storage of soil layer in type Ⅱ was significantly greater than those in the other types. At the whole ecosystem level, carbon storage of type Ⅰ-Ⅳ was 90.43, 108.27, 85.83 and 89.92 t·hm-2, respectively. Type Ⅱ had significantly greater carbon storage than the other types. The arbor layer and soil layer were the major carbon pools in the ecosystem, which accounted for 43.3%-55.7% and 38.7%-50.5% of the total, respectively. Our results suggested that mixing by six rows of L. olgensis and four rows of F. mandshurica was better for future planting.

Detecting the Research Trends and Hot Spots in External Irradiation Therapy for Rectal Cancer.

Purpose: The aim of this study is to visualize and analyze the research hot pots in radiation therapy for rectal cancer and provide researchers with a clear and visual reference for subsequent studies. Methods: The literature scientometric analysis about "external beam radiation therapy (EBRT) for rectal cancer" was made through the WoSCC (2010 to 2019). And the data was visualized and analyzed by the Microsoft Office Excel (2019) and CiteSpace (V. 5.7.R1). Results: 4,263 relevant articles were downloaded. The number of published articles per year has been increasing (2010-2020). The United States published the highest number of articles. The UK has the strongest partnerships with other countries/regions. Leiden University has the highest number of published articles and University Texas MD Anderson Cancer Center has extensive collaborations with other academic institutions. The number of articles published in the Diseases of the Colon Rectum is the most, and the Journal of Clinical Oncology is the most cited. 27 articles became the strongest burst citations lasting until 2020. In recent years, a lot of research has been done on "watch and wait", "short-course radiotherapy", "MRI", "neoadjuvant radiotherapy, "MRI in rectal cancer", "chemotherapy regimen improvement", "adding adjuvant chemotherapy", and so on. Conclusion: The current research hot pots may be the "watch and wait", "short-course radiotherapy", "MRI", "neoadjuvant chemoradiotherapy", "MRI in rectal cancer", "chemotherapy regimen improvement", and "adding adjuvant chemotherapy".

Comprehensive profiling of 1015 patients' exomes reveals genomic-clinical associations in colorectal cancer.

The genetic basis of colorectal cancer (CRC) and its clinical associations remain poorly understood due to limited samples or targeted genes in current studies. Here, we perform ultradeep whole-exome sequencing on 1015 patients with CRC as part of the ChangKang Project. We identify 46 high-confident significantly mutated genes, 8 of which mutate in 14.9% of patients: LYST, DAPK1, CR2, KIF16B, NPIPB15, SYTL2, ZNF91, and KIAA0586. With an unsupervised clustering algorithm, we propose a subtyping strategy that classisfies CRC patients into four genomic subtypes with distinct clinical characteristics, including hypermutated, chromosome instability with high risk, chromosome instability with low risk, and genome stability. Analysis of immunogenicity uncover the association of immunogenicity reduction with genomic subtypes and poor prognosis in CRC. Moreover, we find that mitochondrial DNA copy number is an independent factor for predicting the survival outcome of CRCs. Overall, our results provide CRC-related molecular features for clinical practice and a valuable resource for translational research.

Efficient saccharification of wheat straw pretreated by solid particle-assisted ball milling with waste washing liquor recycling.

Wheat straw was pretreated using ball milling (BM) promoted by solid particles (NaOH, NaCl, citric acid). NaOH showed the best synergistic interaction effect, due to the breakage of ß-1,4-glycosidic bonds among cellulose molecules by the alkali solid particles induced by BM. NaOH-BM pretreatment decreased the straw crystallinity from 46% to 21.4% and its average particle size from 398.3 to 50.6 µm in 1 h. After 4 h milling, the reducing-end concentration of cellulose increased by 3.8 times from 12.5 to 60.2 µM, with glucose yield increased by 2.1 times from 26.6% to 82.4% for 72 h enzymatic hydrolysis at cellulase loading of 15 FPU/g dry substrate. The pretreatment washing liquor was recycled for the re-treatment of partially pretreated biomass at 121 °C for 30 min, resulting in 99.4% glucose yield by enzymatic hydrolysis. BM assisted with alkali particles was an effective approach for improving biomass enzymatic saccharification.

Early numerical rating scale and Oswestry disability index in postmenopausal osteoporosis treated with denosumab / 中华骨科杂志

Objective:To compare the numerical rating scales (NRS) and Oswestry disability index (ODI) of denosumab in Chinese postmenopausal osteoporosis patients after 3 months, and analyze the early adverse reactions to provide reference for clinical diagnosis and treatment.Methods:Using a prospective study method, 260 patients with postmenopausal osteoporosis who were outpatients and inpatients in the Second Affiliated Hospital of Soochow University from September 2020 to October 2021 were selected, and general information, including age, height, weight, bone mineral density, history of fragility fractures, and use of anti-osteoporosis drugs. All subjects received denosumab 60 mg subcutaneously, and were given calcium and vitamin D at the same time. Pain was scored by NRS before treatment and 3 months after treatment, and functional improvement was assessed by ODI.Results:After 3 months of denosumab treatment in postmenopausal women with osteoporosis, among patients with different age groups, different degrees of osteoporosis, history of fragility fractures, and history of use of anti-osteoporosis drugs, NRS score and ODI score were lower than those before treatment, and the difference was statistically significant ( P<0.05). In addition, in patients with a history of fragility fractures (mainly vertebral fractures), the NRS scores and the ODI score decreased more significantly, and the difference was statistically significant ( P<0.05); the NRS score and ODI score decreased more significantly in patients with severe osteoporosis than in patients with osteoporosis, and the difference was statistically significant ( P<0.05); the BMD value of lumbar spine was negatively correlated with the reduction of NRS score before and after treatment ( P=0.042). In this study, 260 patients had musculoskeletal pain in 6 (2.3%), fatigue in 5 (1.9%), rash in 4 (1.5%), urinary tract infection in 2 (0.7%), and dizziness in 2 (0.7%), 2 case of fever (0.7%), 1 case of hypocalcemia (0.4%), a total of 22 cases of adverse reactions were reported, and the overall adverse reaction rate was 8.5%. Conclusion:Denosumab can improve pain symptoms and functional disability early in the clinical application of Chinese postmenopausal women with osteoporosis, and the incidence of adverse reactions is low. Especially for postmenopausal female osteoporosis patients with severe osteoporosis, low lumbar spine bone density, and a history of fragility fractures (mainly vertebral fractures), the application effect is more significant.

Risk of developing second malignant neoplasms in patients with neuroblastoma: a population study of the US SEER database.

BACKGROUND: Neuroblastoma is a common extracranial malignant tumor in children. Its main treatment modality is a combination of chemotherapy, radiotherapy, and surgery. Given the advances in chemotherapy regimens and the widespread use of bone marrow transplantation over the decades, there has been improvement in treatment efficacy, which has led to prolonged patient survival. Accordingly, long-term complications have become a growing concern among physicians and patients. This study aimed to analyze the survival rate of patients with neuroblastoma and the risk factors for developing second malignant neoplasms (SMNs). METHODS: The SEER 18 Regs (1973-2015) and SEER 9 Regs (1973-2015) data of the surveillance, epidemiology, and end results (SEER) database of the US National Cancer Institute were adopted for survival and SMN analysis. RESULTS: The 5-, 10-, and 20-year overall survival rates of patients with neuroblastoma were 67%, 65%, and 62%, respectively. Among 38 patients with neuroblastoma who presented with SMNs, those with abdomen as the primary site accounted for the majority (63.2%), followed by those with thorax (26.3%) and other sites (10.5%). SMNs occurred more commonly in non-specific neuroblastoma (incidence: 0.87%) than ganglioneuroblastoma (incidence: 0.3%). Compared with the general population, the risk of SMN is significantly higher (SIR = 4.36). The risk of developing SMNs was significantly higher in the digestive system (SIR = 7.29), bones and joints (SIR = 12.91), urinary system (SIR = 23.48), brain and other nervous systems (SIR = 5.70), and endocrine system (SIR = 5.84). Multivariate analysis revealed that the year of diagnosis (OR = 2.138, 95% CI = 1.634-2.797, p < 0.001) was the only independent risk factor for developing SMNs. CONCLUSION: This study identifies the risk factor for developing SMNs in patients with neuroblastoma, which could facilitate individualized screening for high-risk patients, to allow early diagnosis and treatment of SMNs.

New data of Nazeris Fauvel from the Dayao Mountains, Guangxi, China (Coleoptera, Staphylinidae, Paederinae).

Three new species of Nazeris Fauvel, 1873 from the Dayao Mountains, Guangxi, China, are described and illustrated: N. shengtangus Ma, Miao Hu, sp. n., N. songi Ma, Miao Hu, sp. n., and N. curvilaminatus Ma, Miao Hu, sp. n. An identification key to the Nazeris species in Guangxi, and a map showing their distribution are provided.

Second Malignant Neoplasms in Patients With Rhabdomyosarcoma.

OBJECTIVE: Rhabdomyosarcoma (RMS) is a rare malignant tumor. The main treatment modality is comprehensive with chemotherapy, radiotherapy, and surgery. With the advancement in recent decades, patient survival has been prolonged, and long-term complications are attracting increasing attention among both physicians and patients. This study aimed to present the survival of patients with RMS and analyze the risk factors for the development of a second malignant neoplasm (SMN). METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program 18 registry database from 1973 to 2015 of the National Cancer Institute of the United States was used for the survival analyses, and the SEER 9 for the SMN analysis. RESULTS: The 5-, 10-, and 20-year overall survival rates of the patients with RMS were 45%, 43%, and 33%, respectively. The risk of SMN was significantly higher in patients with RMS compared to the general population (SIR=1.95, 95% CI: 1.44 - 2.57, p < 0.001). The risk of developing SMN was increased in multiple locations, including the bones and joints (SIR = 35.25) soft tissues including the heart (SIR = 22.5), breasts (SIR = 2.10), male genital organs (SIR = 118.14), urinary system (SIR = 2.36), brain (SIR = 9.21), and all nervous system organs (SIR = 8.59). The multivariate analysis indicated that RMS in the limbs and earlier diagnosis time were independent risk factors for the development of SMN. Patients with head and neck (OR = 0.546, 95% CI: 0.313 - 0.952, p = 0.033) and trunk RMS (OR = 0.322, 95% CI: 0.184 - 0.564. p < 0.001) and a later diagnosis time were less likely to develop SMN (OR = 0.496, 95% CI: 0.421 - 0.585, p < 0.001). CONCLUSION: This study describes the risk factors associated with the development of SMN in patients with RMS, which is helpful for the personalized screening of high-risk patients with RMS.

Modeling and scheduling for remanufacturing systems with disassembly, reprocessing, and reassembly considering total energy consumption.

As one of the mainstream development directions of remanufacturing industry, remanufacturing system scheduling has become a hot research topic recently. This study regards a scheduling problem for remanufacturing systems where end-of-life (EOL) products are firstly disassembled into their constituent components, and next these components are reprocessed to like-new states. At last, the reprocessed components are reassembled into new remanufactured products. Among various system configurations, we investigate a scheduling problem for the one with parallel disassembly workstations, several parallel flow-shop-type reprocessing lines and parallel reassembly workstations for the objective of minimize total energy consumption. To address this problem, a mathematical model is established and an improved genetic algorithm (IMGA) is proposed to solve it due to the problem complexity. The proposed IMGA adopts a hybrid initialization method to improve the solution quality and diversity at the beginning. Crossover operation and mutation operation are specially designed subject to the characteristics of the optimization problem. Besides, an elite strategy is combined to gain a faster convergence speed. Numerical experiments are conducted and the results verify the effectiveness of the scheduling model and proposed algorithm. The work can assist production managers in better planning a scheduling scheme for remanufacturing systems.

Radiotherapy for Vaginal Recurrences of Cervical Cancer in Patients After Prior Surgery: Analysis of Effect and Prognostic Factors.

OBJECTIVE: The role of salvage radiotherapy (RT) in the treatment for vaginal recurrence of cervical cancer in patients after prior surgery remains controversial. The aim of this study was to evaluate the efficacy and toxicity of salvage RT and explore prognostic factors associated with the survival after recurrence. METHODS: Patients with cervical cancer, treated for vaginal recurrences at Peking Union Medical College Hospital between July 2011 and November 2019, were identified. All the patients underwent prior surgery for primary tumor and received salvage RT including external beam radiotherapy (EBRT), brachytherapy (BT), or both. The irradiation field and dose depended on the conditions of patients. Recurrence patterns were classified into four categories according to the site of recurrence. Prognostic factors on the overall survival (OS), progression-free survival (PFS), and local control (LC) were analyzed, and late toxicity was evaluated. RESULTS: A total of 141 patients were included in the analysis, with a median follow-up time of 40.8 months. The estimated 5-year OS, PFS, and LC rates were 81%, 75%, and 87%, respectively. In multivariate analysis, endovaginal recurrence and no irradiation history were favorable prognostic factors associated with OS (all p < 0.05), PFS (all p < 0.05), and LC (all p < 0.05). The area under the receiver operating characteristic (ROC) curve (AUC) of the recurrence pattern is larger than the stage of primary tumor (0.734 vs. 0.670). CONCLUSIONS: RT was an effective treatment with tolerable toxicity for vaginal recurrences of cervical cancer in patients with prior surgery. Recurrence pattern and irradiation history were important prognostic factors.

The Impact of Different Simulation Modalities on Target Volume Delineation in Breast-Conserving Radiotherapy.

PURPOSE: In the management of breast-conserving radiotherapy, computed tomography (CT) simulation is now commonly used to identify tumor bed while has difficulties defining precisely. We aimed to evaluate the impact of magnetic resonance (MR) and CT simulation on defining the postoperative tumor bed for breast-conserving radiotherapy in patients without the aid of surgical clips. METHODS: From August 2018 to March 2019, twenty patients with T1-2N0M0 breast cancer at our institution were enrolled. All the patients underwent breast-conserving surgery without implantation of surgical clips and were prepared to receive radiotherapy. CT and MR images were acquired on the same day for each patient. Three radiation oncologists independently assigned cavity visualization score (CVS) and delineated the tumor bed based on first the CT then the MR images. Interobserver variability was assessed by volumes, generalized conformity index (CIgen) and the distance between the centers of mass (dCOM). Differences in mean values for parameters were tested by paired t-test or one-way analysis of variance, as appropriate. RESULTS: First, the mean volumes of tumor bed derived from MR were 22%, 27% and 21% smaller than those based on CT images for each observer. In addition, the mean CIgen was significantly superior, and dCOM was smaller for MR than for CT images (CIgen: 0.59 vs 0.52, P= 0.008; dCOM: 1.30 cm vs 1.39 cm, P= 0.095). Moreover, the mean CVS was 3.23±1.34 and 2.43±0.92 for MR and CT images, respectively (P= 0.035). Last, a positive association was observed between the CVS and CIgen for both modalities (P< 0.01). CONCLUSION: Compared to CT, MR can improve the visualization of changes in the postoperative tumor bed. In addition, MR can yield a more precise definition of the tumor bed and improve the consistency of tumor bed contouring in patients without surgical clips.

BLZ945 derivatives for PET imaging of colony stimulating factor-1 receptors in the brain.

BACKGROUND: The kinase colony stimulating factor-1 receptor (CSF-1R) has recently been identified as a novel therapeutic target for decreasing tumor associated macrophages and microglia load in cancer treatment. In glioblastoma multiforme (GBM), a high-grade cancer in the brain with extremely poor prognosis, macrophages and microglia can make up to 50% of the total tumor mass. Currently, no non-invasive methods are available for measuring CSF-1R expression in vivo. The aim of this work is to develop a PET tracer for imaging of CSF-1R receptor expression in the brain for future GBM patient selection and treatment monitoring. METHODS: BLZ945 and a derivative that potentially allows for fluorine-18 labeling were synthesized and evaluated in vitro to determine their affinity towards CSF-1R. BLZ945 was radiolabeled with carbon-11 by N-methylation of des-methyl-BLZ945 using [11C]CH3I. Following administration to healthy mice, metabolic stability of [11C]BLZ945 in blood and brain and activity distribution were determined ex vivo. PET scanning was performed at baseline, efflux transporter blocking, and CSF-1R blocking conditions. Finally, [11C]BLZ945 binding was evaluated in vitro by autoradiography on mouse brain sections. RESULTS: BLZ945 was the most potent compound in our series with an IC50 value of 6.9 ± 1.4 nM. BLZ945 was radiolabeled with carbon-11 in 20.7 ± 1.1% decay corrected radiochemical yield in a 60 min synthesis procedure with a radiochemical purity of >95% and a molar activity of 153 ± 34 GBq·µmol-1. Ex vivo biodistribution showed moderate brain uptake and slow wash-out, in addition to slow blood clearance. The stability of BLZ945 in blood plasma and brain was >99% at 60 min post injection. PET scanning demonstrated BLZ945 to be a substrate for efflux transporters. High brain uptake was observed, which was shown to be mostly non-specific. In accordance, in vitro autoradiography on brain sections revealed high non-specific binding. CONCLUSIONS: [11C]BLZ945, a CSF-1R PET tracer, was synthesized in high yield and purity. The tracer has high potency for the target, however, future studies are warranted to address non-specific binding and tracer efflux before BLZ945 or derivatives could be translated into humans for brain imaging.

Study on the iron accumulation-induced bone loss and hematopoietic autophagy dysfunction / 中华内分泌代谢杂志

Objective:Iron accumulation is related to the occurrence of postmenopausal osteoporosis. Meanwhile, autophagy abnormality of bone marrow hematopoietic cells is observed in hip osteoporotic fracture. This study is performed to investigate correlation between iron accumulation induced bone loss and hematopoietic autophagy dysfunction to explore the new risk factor of osteoporosis.Methods:Male iron accumulation mice model was established by intraperitoneally injecting ferric ammonium citrate. Serum ferritin and osteogenic indicator P1NP were tested by ELISA. Bone mineral density was measured by micro-CT. Femur and tibia bone marrows were collected for hematopoietic stem and progenitor cells proportion and cell apoptosis analysis. Autolysosome formation was measured by image flow cytometry. We used conditional mouse model Atg7 flox/flox; Vav-Cre(Atg7 -/-) in which Atg7 had been genetically deleted in the hematopoietic system. Bone marrow hematopoietic stem and progenitor cells were collected for RNA sequence. micro-CT scan was conducted for Atg7 -/- femur. Results:Ferritin level of iron accumulation mice was significantly higher than control group( P<0.05). Iron accumulation inhibited P1NP and induced decreased bone mineral density( P<0.05). Iron accumulation bone marrow displayed enhanced hematopoietic stem and progenitor cells proportion( P<0.05), with more cell apoptosis( P<0.05). Hematopoietic autophagy was deteriorated in iron accumulation bone marrow. Transcriptomic profiling showed up-regulation of iron activity in Atg7 -/- mice, with increased iron homeostasis and iron membrane transporter genes, including Lcn2, Tfr2, Slc40a1(Fpn1), Steap3, and Cpox. micro-CT revealed severe bone loss and decreased bone mineral density in Atg7 -/- mice( P<0.05). Conclusion:Iron accumulation induced bone loss is related to inhibition of hematopoietic cells. Hematopoietic autophagy dysfunction is associated with bone loss.