Maize functional requirements drive the selection of rhizobacteria under long-term fertilization practices.

Rhizosphere microbiomes are pivotal for crop fitness, but the principles underlying microbial assembly during root-soil interactions across soils with different nutrient statuses remain elusive. We examined the microbiomes in the rhizosphere and bulk soils of maize plants grown under six long-term (≥ 29 yr) fertilization experiments in three soil types across middle temperate to subtropical zones. The assembly of rhizosphere microbial communities was primarily driven by deterministic processes. Plant selection interacted with soil types and fertilization regimes to shape the structure and function of rhizosphere microbiomes. Predictive functional profiling showed that, to adapt to nutrient-deficient conditions, maize recruited more rhizobacteria involved in nutrient availability from bulk soil, although these functions were performed by different species. Metagenomic analyses confirmed that the number of significantly enriched Kyoto Encyclopedia of Genes and Genomes Orthology functional categories in the rhizosphere microbial community was significantly higher without fertilization than with fertilization. Notably, some key genes involved in carbon, nitrogen, and phosphorus cycling and purine metabolism were dominantly enriched in the rhizosphere soil without fertilizer input. In conclusion, our results show that maize selects microbes at the root-soil interface based on microbial functional traits beneficial to its own performance, rather than selecting particular species.

Commissioning and clinical evaluation of a novel high-resolution quality assurance digital detector array for SRS and SBRT.

PURPOSE: We aimed to perform the commissioning and clinical evaluation of myQA SRS detector array for patient-specific quality assurance (PSQA) of stereotactic radiosurgery (SRS)/ stereotactic body radiotherapy (SBRT) plans. METHODS: To perform the commissioning of myQA SRS, its dose linearity, dose-rate dependence, angular dependence, and field-size dependence were investigated. Ten SBRT plans were selected for clinical evaluation: 1) Common clinical deviations based on the original SBRT plan (Plan0), including multileaf collimator (MLC) positioning deviation and treatment positioning deviation were introduced. 2) Compared the performance of the myQA SRS and a high-resolution EPID dosimetry system in PSQA measurement for the SBRT plans. Evaluation parameters include gamma passing rate (GPR) and distance-to-agreement (DTA) pass rate (DPR). RESULTS: The dose linearity, angle dependence, and field-size dependence of myQA SRS system exhibit excellent performance. The myQA SRS is highly sensitive in the detection of MLC deviations. The GPR of (3%/1 mm) decreases from 90.4% of the original plan to 72.7%/62.9% with an MLC outward/inward deviation of 3 mm. Additionally, when the setup error deviates by 1 mm in the X, Y, and Z directions with the GPR of (3%/1 mm) decreasing by an average of -20.9%, -25.7%, and -24.7%, respectively, and DPR (1 mm) decreasing by an average of -33.7%, -32.9%, and -29.8%. Additionally, the myQA SRS has a slightly higher GPR than EPID for PSQA, However, the difference is not statistically significant with the GPR of (3%/1 mm) of (average 90.4%% vs. 90.1%, p = 0.414). CONCLUSION: Dosimetry characteristics of the myQA SRS device meets the accuracy and sensitivity requirement of PSQA for SRS/SBRT treatment. The dose rate dependence should be adequately calibrated before its application and a more stringent GPR (3%/1 mm) evaluation criterion is suggested when it is used for SRS/SBRT QA.

Neuroprotective Effect of miR-483-5p Against Cardiac Arrest-Induced Mitochondrial Dysfunction Mediated Through the TNFSF8/AMPK/JNK Signaling Pathway.

Substantial morbidity and mortality are associated with postcardiac arrest brain injury (PCABI). MicroRNAs(miRNAs) are essential regulators of neuronal metabolism processes and have been shown to contribute to alleviated neurological injury after cardiac arrest. In this study, we identified miRNAs related to the prognosis of patients with neurological dysfunction after cardiopulmonary resuscitation based on data obtained from the Gene Expression Omnibus (GEO) database. Then, we explored the effects of miR-483-5p on mitochondrial biogenesis, mitochondrial-dependent apoptosis, and oxidative stress levels after ischemia‒reperfusion injury in vitro and in vivo. MiR-483-5p was downregulated in PC12 cells and hippocampal samples compared with that in normal group cells and hippocampi. Overexpression of miR-483-5p increased the viability of PC12 cells after ischemia‒reperfusion injury and reduced the proportion of dead cells. A western blot analysis showed that miR-483-5p increased the protein expression of PCG-1, NRF1, and TFAM and reduced the protein expression of Bax and cleaved caspase 3, inhibiting the release of cytochrome c from mitochondria and alleviating oxidative stress injury by inhibiting the production of ROS and reducing MDA activity. We confirmed that miR-483-5p targeted TNFSF8 to regulate the AMPK/JNK pathway, thereby playing a neuroprotective role after cardiopulmonary resuscitation. Hence, this study provides further insights into strategies for inhibiting neurological impairment after cardiopulmonary resuscitation and suggests a potential therapeutic target for PCABI.

Multiomics reveals an essential role of long-distance translocation in regulating plant cadmium resistance and grain accumulation in allohexaploid wheat (Triticum aestivum).

Cadmium (Cd) is a highly toxic heavy metal that readily enters cereals, such as wheat, via the roots and is translocated to the shoots and grains, thereby posing high risks to human health. However, the vast and complex genome of allohexaploid wheat makes it challenging to understand Cd resistance and accumulation. In this study, a Cd-resistant cultivar of wheat, 'ZM1860', and a Cd-sensitive cultivar, 'ZM32', selected from a panel of 442 accessions, exhibited significantly different plant resistance and grain accumulation. We performed an integrated comparative analysis of the morpho-physiological traits, ionomic and phytohormone profiles, genomic variations, transcriptomic landscapes, and gene functionality in order to identify the mechanisms underlying these differences. Under Cd toxicity, 'ZM1860' outperformed 'ZM32', which showed more severe leaf chlorosis, poorer root architecture, higher accumulation of reactive oxygen species, and disordered phytohormone homeostasis. Ionomics showed that 'ZM32' had a higher root-to-shoot translocation coefficient of Cd and accumulated more Cd in the grains than 'ZM1860'. Whole-genome re-sequencing (WGS) and transcriptome sequencing identified numerous DNA variants and differentially expressed genes involved in abiotic stress responses and ion transport between the two genotypes. Combined ionomics, transcriptomics, and functional gene analysis identified the plasma membrane-localized heavy metal ATPase TaHMA2b-7A as a crucial Cd exporter regulating long-distance Cd translocation in wheat. WGS- and PCR-based analysis of sequence polymorphisms revealed a 25-bp InDel site in the promoter region of TaHMA2b-7A, and this was probably responsible for the differential expression. Our multiomics approach thus enabled the identification of a core transporter involved in long-distance Cd translocation in wheat, and it may provide an elite genetic resource for improving plant Cd resistance and reducing grain Cd accumulation in wheat and other cereal crops.

RhoA/ROCK pathway mediates the effect of oestrogen on regulating epithelial-mesenchymal transition and proliferation in endometriosis.

Endometriosis is a benign gynaecological disease appearing with pelvic pain, rising dysmenorrhoea and infertility seriously impacting on 10% of reproductive-age females. This research attempts to demonstrate the function and molecular mechanism of RhoA/ROCK pathway on epithelial-mesenchymal transition (EMT) and proliferation in endometriosis. The expression of Rho family was abnormally changed in endometriotic lesions; in particular, RhoA and ROCK1/2 were significantly elevated. Overexpression of RhoA in human eutopic endometrial epithelial cells (eutopic EECs) enhanced the cell mobility, epithelial-mesenchymal transition (EMT) and proliferation, and RhoA knockdown exhibited the opposite function. Oestrogen up-regulated the RhoA activity and expression of RhoA and ROCK1/2. RhoA overexpression reinforced the effect of oestrogen on promoting EMT and proliferation, and RhoA knockdown impaired the effect of oestrogen. oestrogen receptor α (ERα) was involved with the regulation of oestrogen on EMT and proliferation and up-regulated RhoA activity and expression of RhoA and ROCK1/2. The function of ERα was modulated by the change in RhoA expression. Furthermore, phosphorylated ERK that was enhanced by oestrogen and ERα promoted the protein expression of RhoA/ROCK pathway. Endometriosis mouse model revealed that oestrogen enhanced the size and weight of endometriotic lesions. The expression of RhoA and phosphorylated ERK in mouse endometriotic lesions was significantly elevated by oestrogen. We conclude that abnormal activated RhoA/ROCK pathway in endometriosis is responsible for the function of oestrogen/ERα/ERK signalling, which promoted EMT and proliferation and resulted in the development of endometriosis.

Establishment of an immortalized stromal cell line derived from human Endometriotic lesion.

BACKGROUND: Endometriosis is a benign gynecological disease with obviously feature of estrogen-dependence and inflammatory response. The applications of primary endometriotic stromal cells in research of endometriosis are restricted for short life span, dedifferentiation of hormone and cytokine responsiveness. The objective of this study was to establish and characterize immortalized human endometriotic stromal cells (ihESCs). METHODS: The endometriotic samples were from a patient with ovarian endometriosis and the primary endometriotic stromal cells were isolated from the endometriotic tissues. The primary cells were infected by lentivirus to establish telomerase reverse transcriptase (hTERT)-induced immortalized cells. Quantification of mRNA and proteins was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western Blot. CCK-8 assay and EdU labeling assay were assigned to assess the growth of ihESCs. Karyotype assay was performed to detect the chromosomes of ihESCs. Colony formation assay and nude mouse tumorigenicity assay were used to evaluate colony-formation and tumorigenesis abilities. RESULTS: ihESCs continuously overexpressed hTERT via infection of lentivirus and significant extended the life span reaching 31 passages. The morphology, proliferation and karyotype of ihESCs remained unchanged. The expression of epithelial-mesenchymal transition (EMT) markers, estrogen-metabolizing proteins and estrogen/progesterone receptors (ERs and PRs) were unaltered. Furthermore, the treatment of estrogen increased the proliferation and EMT of ihESCs. Lipopolysaccharides (LPS) and IL-1ß remarkably induced inflammatory response. The clonogenesis ability of ihESCs was consistent with primary cells, which were much lower than Ishikawa cells. In addition, nude mouse tumorigenicity assay demonstrated that ihESCs were unable to trigger tumor formation. CONCLUSION: This study established and characterized an immortalized endometriotic stromal cell line that exhibited longer life span and kept the cellular morphology and physiological function as the primary cells. The immortalized cells remained normal feedback to estrogen and inflammatory response. Moreover, the immortalized cells were not available with tumorigenic ability. Therefore, ihESCs would be serviceable as in vitro cell tool to investigate the pathogenesis of endometriosis.

Deep Learning for Automated Contouring of Primary Tumor Volumes by MRI for Nasopharyngeal Carcinoma.

Background Nasopharyngeal carcinoma (NPC) may be cured with radiation therapy. Tumor proximity to critical structures demands accuracy in tumor delineation to avoid toxicities from radiation therapy; however, tumor target contouring for head and neck radiation therapy is labor intensive and highly variable among radiation oncologists. Purpose To construct and validate an artificial intelligence (AI) contouring tool to automate primary gross tumor volume (GTV) contouring in patients with NPC. Materials and Methods In this retrospective study, MRI data sets covering the nasopharynx from 1021 patients (median age, 47 years; 751 male, 270 female) with NPC between September 2016 and September 2017 were collected and divided into training, validation, and testing cohorts of 715, 103, and 203 patients, respectively. GTV contours were delineated for 1021 patients and were defined by consensus of two experts. A three-dimensional convolutional neural network was applied to 818 training and validation MRI data sets to construct the AI tool, which was tested in 203 independent MRI data sets. Next, the AI tool was compared against eight qualified radiation oncologists in a multicenter evaluation by using a random sample of 20 test MRI examinations. The Wilcoxon matched-pairs signed rank test was used to compare the difference of Dice similarity coefficient (DSC) of pre- versus post-AI assistance. Results The AI-generated contours demonstrated a high level of accuracy when compared with ground truth contours at testing in 203 patients (DSC, 0.79; 2.0-mm difference in average surface distance). In multicenter evaluation, AI assistance improved contouring accuracy (five of eight oncologists had a higher median DSC after AI assistance; average median DSC, 0.74 vs 0.78; P < .001), reduced intra- and interobserver variation (by 36.4% and 54.5%, respectively), and reduced contouring time (by 39.4%). Conclusion The AI contouring tool improved primary gross tumor contouring accuracy of nasopharyngeal carcinoma, which could have a positive impact on tumor control and patient survival. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Chang in this issue.

Long-term manure amendments and chemical fertilizers enhanced soil organic carbon sequestration in a wheat (Triticum aestivum L.)-maize (Zea mays L.) rotation system.

BACKGROUND: The carbon sequestration potential is affected by cropping system and management practices, but soil organic carbon (SOC) sequestration potential under fertilizations remains unclear in north China. This study examined SOC change, total C input to soil and, via integration of these estimates over years, carbon sequestration efficiency (CSE, the ratio of SOC change over C input) under no fertilization (control), chemical nitrogen fertilizer alone (N) or combined with phosphorus and potassium fertilizers (NP, NK, PK and NPK), or chemical fertilizers combined with low or high (1.5×) manure input (NPKM and 1.5NPKM). RESULTS: Results showed that, as compared with the initial condition, SOC content increased by 0.03, 0.06, 0.05, 0.09, 0.16, 0.26, 0.47 and 0.68 Mg C ha-1 year-1 under control, N, NK, PK, NP, NPK, NPKM and 1.5NPKM treatments respectively. Correspondingly, the C inputs of wheat and maize were 1.24, 1.34, 1.55, 1.33, 2.72, 2.96, 2.97 and 3.15 Mg ha-1 year-1 respectively. The long-term fertilization-induced CSE showed that about 11% of the gross C input was transformed into SOC pool. CONCLUSION: Overall, this study demonstrated that decade-long manure input combined with chemical fertilizers can maintain high crop yield and lead to SOC sequestration in north China. © 2016 Society of Chemical Industry.

Normal Tissue Complication Probability Model for Radiation-induced Temporal Lobe Injury after Intensity-modulated Radiation Therapy for Nasopharyngeal Carcinoma.

PURPOSE: To identify predictors for the development of temporal lobe injury (TLI) after intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma. MATERIALS AND METHODS: Data in 351 patients with nasopharyngeal carcinoma treated with IMRT were reviewed retrospectively according to institutional ethics committee approval. Clinical factors associated with TLI were analyzed. Dose-volume histograms for 550 evaluable temporal lobes were analyzed, and the predictive value of therapy-associated and patient-associated factors for the occurrence of TLI was evaluated. Survival curves were depicted by using the Kaplan-Meier method and compared by using the log-rank test. Logistic regression analysis was used for multivariate analyses. RESULTS: Median follow-up was 76 months (range, 6-100 months). Twenty-nine of 351 patients (8.3%) developed TLI; 21 patients had unilateral TLI, and eight had bilateral TLI. Median latency from IMRT until first TLI was 33 months (range, 12-83 months) among patients with TLI. The actuarial TLI-free survival rates were 94.4% and 91.3% at 3 and 5 years after radiation therapy, respectively. Logistic regression analysis demonstrated that dose delivered to a 1-cm(3) volume of the temporal lobe (D1cc) was the only independent predictor for TLI. The biologically equivalent tolerance doses at 2 Gy for a 5% and 50% probability of developing TLI were 62.83-Gy equivalents (95% confidence interval: 59.68, 65.97) and 77.58-Gy equivalents (95% confidence interval: 74.85, 80.32), respectively. CONCLUSION: D1cc is predictive for radiation-induced TLI, suggesting that delivery of a high dose of radiation to a small volume of the temporal lobe is unsafe. A D1cc of 62.83 Gy by using a correction formula for varying fraction size may be the dose tolerance of the temporal lobe.

Risk factors and prediction-score model for distant metastasis in nasopharyngeal carcinoma treated with intensity-modulated radiotherapy.

The objective of this study is to identify the risk factors and construct a prediction-score model for distant metastasis (DM) in nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). A total of 520 nonmetastatic NPC patients were analysed retrospectively. The independent risk factors for DM were tested by multivariate Cox regression analysis. The prediction-score model was established according to the regression coefficient. The median follow-up was 88.4 months. The 5-year DM rate was 15.1%. N2-3, primary tumour volume of nasopharynx (GTVnx) >24.56 cm(3), haemoglobin change after treatment (ΔHGB) >25.8 g/L, albumin-globulin ratio (AGR) ≤1.34, pretreatment neutrophil-lymphocyte ratio (NLR) >2.81 and pretreatment serum lactate dehydrogenase (LDH) >245 U/L were significantly adverse independent predictive factors for DM. Three subgroups were defined based on the prediction-score model: low risk (0-2), intermediate risk (3-4) and high risk (5-8). The 5-year DM rates were 4.6, 21.8 and 50.8%, respectively (P < 0.001). The areas under the curve for DM in the prediction-score model and the UICC/AJCC staging system seventh edition were 0.748 and 0.627, respectively (P < 0.001). The scoring model is useful in evaluating the risk of DM in IMRT-treated NPC patients and guiding future therapeutic trials. Further prospective study is needed.

Effect of total dose and fraction size on survival of patients with locally recurrent nasopharyngeal carcinoma treated with intensity-modulated radiotherapy: a phase 2, single-center, randomized controlled trial.

BACKGROUND: The optimal model of total dose and fraction size for patients with locally recurrent nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) remains unclear. The authors designed a randomized phase 2 clinical trial to investigate the efficacy of 2 different models, with the objective of determining an optimal model. METHODS: Between January 2003 and December 2007, a total of 117 patients with locally recurrent nonmetastatic nasopharyngeal carcinoma were randomized to 2 different models of total dose and fraction size: group A (59 patients) received 60 gray in 27 fractions and group B (58 patients) received 68 gray in 34 fractions. Both groups received 5 daily fractions per week. All patients received IMRT alone. RESULTS: The median follow-up was 25.0 months. The 5-year overall survival in group A was higher than that in group B (44.2% vs 30.3%; P =.06), and the local failure-free survival in group A was slightly lower than that in group B (63.7% vs 71.0%; P =.41). Severe late complications were the main cause of death. The incidences of mucosal necrosis and massive hemorrhage in patients in group B were significantly higher than those among patients in group A at 50.8% versus 28.8% (P =.02) and 31.0% versus 18.6% (P =.12), respectively. Tumor volume (P<.01) and model of total dose and fraction size (P =.03) were found to be significant factors for mucosal necrosis and massive hemorrhage. CONCLUSIONS: Appropriately decreasing the total dose and increasing the fraction size can achieve local control similar to that achieved with a higher dose after IMRT; furthermore, it can improve overall survival by significantly reducing the incidence of severe late complications including mucosal necrosis and massive hemorrhage.

Temporal lobe injury after re-irradiation of locally recurrent nasopharyngeal carcinoma using intensity modulated radiotherapy: clinical characteristics and prognostic factors.

Temporal lobe injury (TLI) is a debilitating complication after radiotherapy for nasopharyngeal carcinoma (NPC), especially in patients who suffer treatment relapses and receive re-irradiation. We explored the clinical characteristics and prognostic factors of TLI in locally recurrent NPC (rNPC) patients after re-irradiation using intensity modulated radiotherapy (IMRT). A total of 454 temporal lobes (TLs) from 227 locally rNPC patients were reviewed. The clinical characteristics of TLI were analyzed. In the two radiotherapy courses, the equivalent dose in 2 Gy per fraction (EQD2) for the TLs was recalculated to facilitate comparison of the individual data. The median follow-up time was 31 (range, 3-127) months. After re-irradiation using IMRT, 31.3 % (71/227) of patients developed TLI. The median latency of TLI was 15 (range, 4-100) months. Univariate and multivariate analysis showed that the interval time (IT) between the two courses of radiotherapy and the summation of the maximum doses of the two radiotherapy courses (EQD2 - ∑max) were independent factors influencing TLI. The 5-year incidence of TLI for an IT ≤26 or >26 months was 35.9 and 53.7 % respectively (p = 0.024). The median maximum doses delivered to the injured TLs were significantly higher than was the case for the uninjured TLs after two courses of radiotherapy (135.3 and 129.8 Gy, respectively: p < 0.001). The incidence of TLI with an EQD2 - ∑max < 125 Gy was <5 %, and with an EQD2 - ∑max <145 Gy it was <50 %. A treatment mode limiting EQD2 - ∑max <125 Gy with a >2-year interval was found to be relatively safe.

Identifying early urinary metabolic changes with long-term environmental exposure to cadmium by mass-spectrometry-based metabolomics.

Cadmium (Cd) is a common environmental pollutant, and urinary Cd (UCd) is generally used as a marker of exposure; however, our understanding on the related urinary metabolic changes caused by Cd exposure is still not clear. In this study, we applied a mass-spectrometry-based metabolomic approach to assess the urinary metabolic changes in human with long-term environmental Cd exposure, aimed to identify early biomarkers to assess Cd nephrotoxicity. Urine samples from 94 female never smokers aged 44-70 with UCd in the range of 0.20-68.67 µg/L were analyzed by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-ToF-MS) and gas chromatography-mass spectrometry (GC-MS). It was found that metabolites related to amino acid metabolism (L-glutamine, L-cystine, L-tyrosine, N-methyl-L-histidine, L-histidinol, taurine, phenylacetylglutamine, hippurate, and pyroglutamic acid), galactose metabolism (D-galactose and myo-inositol), purine metabolism (xanthine, urea, and deoxyadenosine monophosphate), creatine pathway (creatine and creatinine), and steroid hormone biosynthesis (17-α-hydroxyprogesterone, tetrahydrocortisone, estrone, and corticosterone) were significantly higher among those with a UCd level higher than 5 µg/L. Moreover, we noticed that the level of N-methyl-L-histidine had already started to elevate among individuals with a UCd concentration of ≥2 µg/L. The overall findings illustrate that metabolomics offer a useful approach for revealing metabolic changes as a result of Cd exposure.

Comparison of splinting immobilization and K-wire fixation in children with type II phalange neck fracture.

To compare outcomes of type II phalangeal neck fractures in children who received closed reduction followed by splinting immobilization or by K-wire fixation. Furthermore, we analyzed the remodeling potential of residual deformities and the relationship between age and outcomes. Patients in Children's Hospital of Fudan University, Xiamen Hospital were included in the study from October 2015 to October 2018. We compared outcomes between the conservation group and operation group. Remodeling of residual deformities was calculated on a series of anteroposterior and lateral radiography. The correlation between age and outcomes was analyzed using Spearman's rank correlation coefficient. Forty patients (25 males) were enrolled. Nineteen patients had subtype IIa, 19 subtype IIb, and two subtype IIc fractures. Left hands were affected more than right hands, and small finger and proximal phalanx were more frequently involved. There were no significant differences between conservation group and operation group among excellent, good, and fair outcomes. And the outcomes were not significantly different between the IIa and IIb subtypes. An average sagittal remodeling rate was 88.5%, and coronal remodeling rate was 56.71%, respectively, in 13 patients with residual deformities. There was a significant correlation between age and final outcomes. Closed reduction and stable splint fixation may be an effective and economical initial treatment option. Fracture subtype does not seem to be a key factor for choosing treatment options. The fractured phalangeal neck had remodeling potential whether on sagittal or coronal plane. Younger age might be a predictor of better outcomes in children with type II phalanx neck fractures.

Radiation-induced temporal lobe injury after intensity modulated radiotherapy in nasopharyngeal carcinoma patients: a dose-volume-outcome analysis.

BACKGROUND: To identify the radiation volume effect and significant dosimetric parameters for temporal lobe injury (TLI) and determine the radiation dose tolerance of the temporal lobe (TL) in nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT). METHODS: Twenty NPC patients with magnetic resonance imaging (MRI)-diagnosed unilateral TLI were reviewed. Dose-volume data was retrospectively analyzed. RESULTS: Paired samples t-tests showed all dosimetric parameters significantly correlated with TLI, except the TL volume (TLV) and V75 (the TLV that received ≥75 Gy, P = 0.73 and 0.22, respectively). Receiver operating characteristic (ROC) curves showed V10 and V20 (P = 0.552 and 0.11, respectively) were the only non-significant predictors from V10 to V70 for TLI. D(0.5cc) (dose to 0.5 ml of the TLV) was an independent predictor for TLI (P < 0.001) in multivariate analysis; the area under the ROC curve for D(0.5cc) was 0.843 (P < 0.001), and the cutoff point 69 Gy was deemed as the radiation dose limit. The distribution of high dose 'hot spot' regions and the location of TLI were consistent. CONCLUSIONS: A D0.5cc of 69 Gy may be the dose tolerance of the TL. The risk of TLI was highly dependent on high dose 'hot spots' in the TL; physicians should be cautious of such 'hot spots' in the TL during IMRT treatment plan optimization, review and approval.

Long-term outcomes in lean and non-lean NAFLD patients: a systematic review and meta-analysis.

BACKGROUND: Although nonalcoholic fatty liver disease (NAFLD) commonly occurs in overweight or obese individuals, it is increasingly being identified in the lean population. The association between lean and an increased risk of all-cause mortality among patients with NAFLD remains controversial. We aimed to perform a systematic review and meta-analysis of the literature to evaluate this association and compare the long-term outcomes of lean NAFLD patients and non-lean NAFLD patients. METHODS: For this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang, and Chinese Biomedical Literature Database (CBM) from inception to October 15, 2021, for relevant original research articles without any language restrictions. Our primary outcome was to compare the all-cause mortality in lean NAFLD patients and non-lean NAFLD patients by qualitative synthesis. Relative risks (RRs) and corresponding 95% confidential intervals (CIs) were pooled with a random effect model. Heterogeneity was evaluated using I-squared (I²) statistics while publication bias was determined using Egger's tests. Subgroup and sensitivity analyses were performed. As for secondary outcomes, we estimated total, cardiovascular, and liver-related mortality, as well as the incidence of diabetes, hypertension, cirrhosis, and cancer in lean and non-lean individuals with NAFLD by quantitative synthesis. Person-years of follow-up were used as the denominator to estimate the mortality and incidence. RESULTS: We identified 12 studies (n = 26,329), 7 of which (n = 7924) were used to evaluate the risk of all-cause mortality between lean and non-lean NAFLD patients. Lean patients with NAFLD were found to be at an elevated risk of death compared to non-lean patients (RR = 1.39, 95% CI 1.08-1.82, heterogeneity: I² = 43%). Among the lean NAFLD population, all-cause mortality was 13.3 (95% CI: 6.7-26.1) per 1000 person-years, 3.6 (95% CI: 1.0-11.7) for liver-related mortality, and 7.7 (95% CI: 6.4-9.2) for cardiovascular-related mortality. The incidence of new-onset diabetes was 13.7 (95% CI 8·2-22.7) per 1000 person-years, new-onset hypertension was 56.1 (95% CI: 40.2-77.9), cirrhosis was 2.3 (95% CI: 1.0-5.0), and cancer was 25.7 (95% CI: 20.3-32.4). CONCLUSIONS: Lean patients with NAFLD had a higher risk of all-cause death than non-lean patients. Body mass index (BMI) should not be used as a criterion to determine whether further observation and therapy of patients with NAFLD are warranted.

Galectin-3 is associated with the functional outcome and mortality in stroke patients: A systematic review and meta-analysis.

Introduction: There is still a lack of sensitive predictive tools for stroke outcomes. High galectin-3 concentration is associated with an increased risk of stroke. This study investigated the relationship between blood galectin-3 levels and stroke prognosis. Methods: The PubMed, EMBASE, and Cochrane Library databases were searched as of May 2021. Data from eligible studies on the relationship between galectin-3 and stroke prognosis were extracted for the meta-analysis. Results: The outcomes included the modified Rankin Scale (mRS), mortality rate, and prognostic accuracy of galectin-3 on mRS after stroke. Odds ratio (OR) and 95% CI were used to assess the association between galectin-3 and the prognostic outcomes. Subgroup analysis based on the study design was performed to evaluate the correlation of galectin-3 with mRS and mortality. A random-effects model was adopted for this meta-analysis. A total of 5 studies involving 3607 stroke patients were included. Higher serum galectin-3 level was associated with mRS (OR [95% CI]: 2.02 [1.08, 3.77]) and mortality (OR [95% CI]: 2.17 [1.17, 4.02]) after stroke. Subgroup analysis revealed a similar relationship between galectin-3 and mRS for both prospective and retrospective studies. There were no associations between galectin-3 level and mortality rate in prospective studies. Galectin-3 had a good predictive ability on mRS after stroke (AUC: 0.88, 95% CI:0.85, 0.91). Conclusion: Elevated blood galectin-3 levels were associated with prognostic outcomes after stroke, including functional outcome mRS and mortality rate. Moreover, galectin-3 had a good predictive ability for the prognosis of stroke.

Efficacy of concurrent chemoradiotherapy alone for loco-regionally advanced nasopharyngeal carcinoma: long-term follow-up analysis.

BACKGROUND: To analysis the clinical outcomes of concurrent chemoradiotherapy (CCRT) alone based on 10-year results for loco-regionally advanced nasopharyngeal carcinoma (LANPC), so as to provide evidence for individualized treatment strategy and designing appropriate clinical trial for different risk LANPC patients. METHODS: Consecutive patients with stage III-IVa (AJCC/UICC 8th) were enrolled in this study. All patients received radical intensity-modulated radiotherapy (IMRT) and concurrent cisplatin chemotherapy (CDDP). The hazard ratios (HRs) of death risk in patients with T3N0 was used as baseline, relative HRs were calculated by a Cox proportional hazard model to classify different death risk patients. Survival curves for the time-to-event endpoints were analyzed by the Kaplan-Meier method and compared using the log-rank test. All statistical tests were conducted at a two-sided level of significance of 0.05. RESULTS: A total of 456 eligible patients were included. With 12-year median follow-up, 10-year overall survival (OS) was 76%. 10-year loco-regionally failure-free survival (LR-FFS), distant failure-free survival (D-FFS) and failure-free survival (FFS) were 72%, 73% and 70%, respectively. Based on the relative hazard ratios (HRs) of death risk, LANPC patients were classified into 3 subgroups, low-risk group (T1-2N2 and T3N0-1) contained 244 patients with HR < 2; medium-risk group (T3N2 and T4N0-1) contained 140 patients with HR of 2 - 5; high-risk group (T4N2 and T1-4N3) contained 72 patients with HR > 5. The 10-year OS for patients in low-, medium-, and high-risk group were 86%, 71% and 52%, respectively. Significantly differences of OS rates were found between each of the two groups (low-risk group vs. medium-risk group, P < 0.001; low-risk group vs. high-risk group, P < 0.001; and medium-risk group vs. high-risk group, P = 0.002, respectively). Grade 3-4 late toxicities included deafness/otitis (9%), xerostomia (4%), temporal lobe injury (5%), cranial neuropathy (4%), peripheral neuropathy (2%), soft tissue damage (2%) and trismus (1%). CONCLUSIONS: Our classification criteria demonstrated that significant heterogeneity in death risk among TN substages for LANPC patients. IMRT plus CDDP alone maybe suitable for low-risk LANPC (T1-2N2 or T3N0-1), but not for medium- and high-risk patients. These prognostic groupings provide a practicable anatomic foundation to guide individualized treatment and select optimal targeting in the future clinical trials.

A real-time in vivo dosimetric verification method for high-dose rate intracavitary brachytherapy of nasopharyngeal carcinoma.

PURPOSE: A real-time in vivo dosimetric verification method using metal-oxide-semiconductor field effect transistor (MOSFET) dosimeters has been developed for patient dosimetry in high-dose rate (HDR) intracavitary brachytherapy of nasopharyngeal carcinoma (NPC). METHODS: The necessary calibration and correction factors for MOSFET measurements in (192)Iridium source were determined in a water phantom. With the detector placed inside a custom-made nasopharyngeal applicator, the actual dose delivered to the tumor was measured in vivo and compared to the calculated values using a commercial brachytherapy planning system. RESULTS: Five MOSFETs were independently calibrated with the HDR source, yielding calibration factors of 0.48 ± 0.007 cGy∕mV. The maximum sensitivity variation was no more than 7% in the clinically relevant distance range of 1-5 cm from the source. A total of 70 in vivo measurements in 11 NPC patients demonstrated good agreement with the treatment planning. The mean differences between the planned and the actually delivered dose within a single treatment fraction were -0.1% ± 3.8% and -0.1% ± 3.7%, respectively, for right and left side assessments. The maximum dose deviation was less than 8.5%. CONCLUSIONS: In vivo measurement using the real-time MOSFET dosimetry system is possible to evaluate the actual dose to the tumor received by the patient during a treatment fraction and thus can offer another line of security to detect and prevent large errors.

Radioprotective effect of X-ray abdominal FLASH irradiation: Adaptation to oxidative damage and inflammatory response may be benefiting factors.

BACKGROUND: Ultrahigh dose-rate irradiation (FLASH-IR) was reported to be efficient in tumor control while reducing normal tissue radiotoxicity. However, the mechanism of such phenomenon is still unclear. Besides, the FLASH experiments using high energy X-ray, the most common modality in clinical radiotherapy, are rarely reported. This study aims to investigate the radiobiological response using 6 MV X-ray FLASH-IR or conventional dose-rate IR (CONV-IR). METHODS: The superconducting linac of Chengdu THz Free Electron Laser (CTFEL) facility was used for FLASH-IR, a diamond radiation detector and a CeBr3 scintillation detector were used to monitor the time structure and dose rate of FLASH pulses. BALB/c nude mice received whole abdominal 6 MV X-ray FLASH-IR or CONV-IR, the prescribed dose was 15 Gy or 10 Gy and the delivered absolute dose was monitored with EBT3 films. The mice were either euthanized 24 h post-IR to evaluate acute tissue responses or followed up for 6 weeks to observe late-stage responses and survival probability. Complete blood count, histological analyses, and measurement of cytokine expression and redox status were performed. RESULTS: The mean dose rate of >150 Gy/s and instantaneous dose rate of >5.5 × 105  Gy/s was reached in FLASH-IR at the center of mice body. After 6 weeks' follow-up of mice that received 15 Gy IR, the FLASH group showed faster body weight recovery and higher survival probability than the CONV group. Histological analysis showed that FLASH-IR induced less acute intestinal damage than CONV-IR. Complete blood count and cytokine concentration measurement found that the inflammatory blood cell counts and pro-inflammatory cytokine concentrations were elevated at the acute stage after both FLASH-IR and CONV-IR. However, FLASH irradiated mice had significantly fewer inflammatory blood cells and diminished pro-inflammatory cytokine at the late stage. Moreover, higher reactive oxygen species (ROS) signal intensities but significantly reduced lipid peroxidation were found in the FLASH group than in the CONV group in the acute stage. CONCLUSIONS: The radioprotective effect of 6 MV X-ray FLASH-IR was observed. The differences in inflammatory responses and redox status between the two groups may be the factors responsible for reduced radiotoxicities following FLASH-IR. Further studies are required to thoroughly evaluate the impact of ROS on FLASH effect.