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Summary: To guide individualized intensity-modulated radiotherapy (IMRT), we developed and prospectively validated a multiview radiomics risk model for predicting radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma. And simulated radiotherapy plans with same dose-volume-histogram (DVH) but different dose distributions were redesigned to explore the clinical application of the multiview radiomics risk model. The radiomics and dosiomics were built based on selected radiomics and dosiomics features from planning computed tomography and dose distribution, respectively. The multiview radiomics risk model that integrated radiomics, dosiomics, DVH parameters, and clinical factors had better performance than traditional normal tissue complication probability models. And multiview radiomics risk model could identify differences of patient hypothyroidism-free survival that cannot be stratified by traditional models. Besides, two redesigned simulated plans further verified the clinical application and advantage of the multiview radiomics risk model. The multiview radiomics risk model was a promising method to predict radiation-induced hypothyroidism and guide individualized IMRT.

Summary: Background: MRI is the routine examination to surveil the recurrence of nasopharyngeal carcinoma, but it has relatively lower sensitivity than PET/CT. We aimed to find if artificial intelligence (AI) could be competent pre-inspector for MRI radiologists and whether AI-aided MRI could perform better or even equal to PET/CT. Methods: This multicenter study enrolled 6916 patients from five hospitals between September 2009 and October 2020. A 2.5D convolutional neural network diagnostic model and a nnU-Net contouring model were developed in the training and test cohorts and used to independently predict and visualize the recurrence of patients in the internal and external validation cohorts. We evaluated the area under the ROC curve (AUC) of AI and compared AI with MRI and PET/CT in sensitivity and specificity using the McNemar test. The prospective cohort was randomized into the AI and non-AI groups, and their sensitivity and specificity were compared using the Chi-square test. Findings: The AI model achieved AUCs of 0.92 and 0.88 in the internal and external validation cohorts, corresponding to the sensitivity of 79.5% and 74.3% and specificity of 91.0% and 92.8%. It had comparable sensitivity to MRI (e.g., 74.3% vs. 74.7%, P = 0.89) but lower sensitivity than PET/CT (77.9% vs. 92.0%, P

Abstract Background The aim of this work was to determine whether patients with intermediate-risk head and neck squamous cell carcinoma (HNSCC) can benefit from postoperative chemoradiotherapy (POCRT). Methods Patients without extracapsular extension (ECE) or positive margins (PMs) who received POCRT or postoperative radiotherapy (PORT) at our center were retrospectively (December 2009 to October 2018) included for analysis, in particular, using a propensity score-matching method. Results After matching, 264 patients were enrolled, including 142 (41.2%) patients with pT3-4, 136 (38.3%) patients with pN2-3, 68 (21.1%) patients with perineural invasion, and 45 (12.8%) patients with lymphatic/vascular space invasion. With a median follow-up of 52 months, 3-year overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) rates were 72.4%, 79.3%, 83.5% and 62.5%, respectively. pN2-3 was an independent risk factor for OS (p

Summary: Deficits in astrocyte function contribute to major depressive disorder (MDD) and suicide, but the therapeutic effect of directly reactivating astrocytes for depression remains unclear. Here, specific gains and losses of astrocytic cell functions in the medial prefrontal cortex (mPFC) bidirectionally regulate depression-like symptoms. Remarkably, recombinant human Thrombospondin-1 (rhTSP1), an astrocyte-secreted protein, exerted rapidly antidepressant-like actions through tyrosine hydroxylase (Th)/dopamine (DA)/dopamine D2 receptors (D2Rs) pathways, but not dopamine D1 receptors (D1Rs), which was dependent on SH3 and multiple ankyrin repeat domains 3 (Shank3) in the mPFC. TSP1 in the mPFC might have potential as a target for treating clinical depression.

Summary: Background: Radiotherapy is the mainstay of treatment for nasopharyngeal carcinoma. Radiation-induced temporal lobe injury (TLI) can regress or resolve in the early phase, but it is irreversible at a later stage. However, no study has proposed a risk-based follow-up schedule for its early detection. Planning evaluation is difficult when dose-volume histogram (DVH) parameters are similar and optimization is terminated. Methods: This multicenter retrospective study included 6065 patients between 2014 and 2018. A 3D ResNet-based deep learning model was developed in training and validation cohorts and independently tested using concordance index in internal and external test cohorts. Accordingly, the patients were stratified into risk groups, and the model-predicted risks were used to develop risk-based follow-up schedules. The schedule was compared with the Radiation Therapy Oncology Group (RTOG) recommendation (every 3 months during the first 2 years and every 6 months in 3–5 years). Additionally, the model was used to evaluate plans with similar DVH parameters. Findings: Our model achieved concordance indexes of 0.831, 0.818, and 0.804, respectively, which outperformed conventional prediction models (all P

Abstract Purpose We aimed to develop and prospectively validate a risk score model to guide individualized concurrent chemoradiotherapy (CCRT) for patients with stage II nasopharyngeal carcinoma (NPC) in intensity‐modulated radiotherapy (IMRT) era. Materials and Methods In total, 1220 patients who received CCRT or IMRT alone were enrolled in this study, including a training cohort (n = 719), a validation cohort (n = 307), and a prospective test cohort (n = 194). Patients were stratified into different risk groups by a risk score model based on independent prognostic factors, which were developed in the training cohort. Survival rates were compared by the log‐rank test. The validation and prospective test cohorts were used for validation. Results Total tumor volume, Epstein–Barr virus DNA, and lactate dehydrogenase were independent risk factors for failure‐free survival (FFS, all p

Abstract Background AK098656 may be an adverse factor for coronary heart disease (CHD), especially in patients with hypertension. This study aimed to analyze the effect of AK098656 on CHD and CHD with various complications. Methods A total of 117 CHD patients and 27 healthy control subjects were enrolled in the study. Plasma AK098656 expression was determined using the quantitative real-time polymerase chain reaction. Student’s t-test was used to compare AK098656 expression levels in different groups. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to quantify the discrimination ability between CHD patients and health controls and between CHD and CHD + complications patients. The relationship between AK098656 and coronary stenosis was analyzed using Spearman’s correlation. Results AK098656 expression was remarkably higher in CHD patients than in healthy controls (P = 0.03). The ROC curve revealed an effective predictive AK098656 expression value for CHD risk, with an AUC of 0.656 (95% CI 0.501–0.809). Moreover, AK098656 expression was increased in CHD + complications patients compared to CHD patients alone (P = 0.005), especially in patients with hypertension (CHD + hHTN, P = 0.030). The ROC curve revealed a predictive AK098656 prognostic value for discriminating between CHD and CHD + hHTN patients, with an AUC of 0.666 (95% CI 0.528–0.805). There was no significant difference in AK098656 expression in CHD patients with diabetes mellitus compared to CHD patients alone. In addition, AK098656 expression in CHD patients was positively correlated with stenosis severity (R = 0.261, P = 0.006). Conclusion AK098656 expression was significantly increased in patients with CHD, especially those with hypertension, and its expression level was positively correlated with the degree of coronary stenosis. This implied that AK098656 may be a risk factor for CHD and can potentially be applied in clinical diagnosis or provide a novel target for treatment.

A stable narrow range of extracellular calcium concentration in the blood is essential for life. The calcium-sensing receptor (CaSR), a member of the G protein-coupled receptors family, is required to adjust the set point of blood extracellular calcium concentration, thus regulate parathyroid hormone (PTH) secretion and renal calcium excretion. Loss or gain function of CaSR mutations may result in either hyper- or hypocalcaemia. The CaSR activating mutations increase its sensitivity to extracellular ionized calcium (Ca2+). As consequence, PTH synthesis and secretion are suppressed continuously at normal ionized calcium concentrations. Patients display hypocalcaemia, hyperphosphatemia and lower levels of PTH. Urinary calcium excretion is increased due to the decreased circulating inappropriately PTH level and the activation of the renal tubular CaSR. Therefore, CaSR becomes a good potential clinical therapeutic target for hypoparathyroidism treatment. In order to define new drugs and improve medical management of hypoparathyroidism patients, this study attempts to identify new CaSR variants and analyse in detail the functional change of these CaSR variants, thus better understand the molecular mechanism involved. The study is based on collected hypoparathyroidism patients in our clinical site. In the study we enrolled in 10 patients, obtained all their clinical results and DNA results from seven patients. Our results indicated that the effect of serum intact PTH level correlated to change of serum Ca2+ and phosphate level. The CaSR carrying newly identified DNA variants displayed strong phosphorylation of phospholipase C and mitogen-activated protein kinases. Although the size of clinical cases need to be accumulated, current cases have showed a tendency that the identified multiple DNA variants in CaSR gene revealed an effect on the diagnostic criterion of the hypocalcaemic syndrome. It is undeniable that our research has certain limitations. So far, we tested several DNA variants at the same time, further functional examination for individual DNA variant would largely help to be better understand the mechanisms of CaSR regulation on extracellular calcium concentration.

Background. As one of the first steps in the pathology of cerebral ischemia, glutamate-induced excitotoxicity progresses too fast to be the target of postischemic intervention. However, ischemic preconditioning including electroacupuncture (EA) might elicit cerebral ischemic tolerance through ameliorating excitotoxicity. Objective. To investigate whether EA pretreatment based on TCM theory could elicit cerebral tolerance against ischemia/reperfusion (I/R) injury, and explore its potential excitotoxicity inhibition mechanism from regulating proapoptotic pathway of the NMDA subtype of glutamate receptor (GluN2B). Methods. The experimental procedure included 5 consecutive days of pretreatment stage and the subsequent modeling stage for one day. All rats were evenly randomized into three groups: sham MCAO/R, MCAO/R, and EA+MCAO/R. During pretreatment procedure, only rats in the EA+MCAO/R group received EA intervention on GV20, SP6, and PC6 once a day for 5 days. Model preparation for MCAO/R or sham MCAO/R started 2 hours after the last pretreatment. 24 hours after model preparation, the Garcia neurobehavioral scoring criteria was used for the evaluation of neurological deficits, TTC for the measurement of infarct volume, TUNEL staining for determination of neural cell apoptosis at hippocampal CA1 area, and WB and double immunofluorescence staining for expression and the cellular localization of GluN2B and m-calpain and p38 MAPK. Results. This EA pretreatment regime could improve neurofunction, decrease cerebral infarction volume, and reduce neuronal apoptosis 24 hours after cerebral I/R injury. And EA pretreatment might inhibit the excessive activation of GluN2B receptor, the GluN2B downstream proapoptotic mediator m-calpain, and the phosphorylation of its transcription factor p38 MAPK in the hippocampal neurons after cerebral I/R injury. Conclusion. The EA regime might induce tolerance against I/R injury partially through the regulation of the proapoptotic GluN2B/m-calpain/p38 MAPK pathway of glutamate.

In China, the sacrificial anode cathodic protection systems of many pipelines in service with asphalt coating have failed or are about to fail. If the sacrificial anode systems are replaced according to the original design, some pipelines could not be effectively protected. In this work, based on the surface resistivity change rule of the anticorrosive layer of on - site pipeline with time, the change of resistivity of the as - mentioned anticorrosive layer in the next 20 years was predicted. The change of protection distance of pipeline after 15 years of operation with time was estimated using simulation calculation, which provided a basis for the redesign of cathodic protection system. Results showed that the surface resistivity of anticorrosive layer of asphalt coating decreased with the prolonging of burried time, and the decreasing rate decreased gradually; the damage rate of anticorrosion coating increased with the prolonging of buried time, and the increase rate rised gradually. After 15 years of operation single group sacrificial anode protection system, the single - side protection distance of the pipeline was 50 m. And then with the continuous service of the pipeline, the single - side protection distance decreased significantly. After 20, 25, 30 and 35 years of operation, the single - side protection distance declined to 28.0, 19.0, 14.0 and 11.5 m, respectively. When the distance between the anode and the pipeline was in the range of 1～4 m, with the increase of such distance, the potential distribution on the pipeline became more and more uniform, and the protection distance increased. Furthermore, in the next 20～35 years, the replacement time of sacrificial anode system would have little impact on the anode life, which was estimated to be about 23 years.

Carbonic anhydrase (CA), an enzyme that catalyzes the interconversion of CO2 and HCO3−, has a critical role in inorganic carbon acquisition in many kingdoms, including animals, plants, and bacteria. In this study, the full-length cDNA of the CA gene from Porphyra yezoensis Ueda (denoted as PyCA) was cloned by using an expressed sequence tag (EST) and rapid amplification of cDNA ends (RACE). The nucleotide sequence of PyCA consists of 1,153 bp, including a 5′ untranslated region (UTR) of 177 bp, a 3′ UTR of 151 bp, and an open reading frame (ORF) of 825 bp that can be translated into a 274-amino-acid putative peptide with a molecular mass ( M) of 29.8 kDa and putative isoelectric point (pI) of 8.51. The predicted polypeptide has significant homology to the β-CA from bacteria and unicellular algae, such as Porphyridium purpureum. The mRNA in filamentous thalli, leafy thalli, and conchospores was examined, respectively, by real-time fluorescent quantitative PCR (qPCR), and the levels of PyCA are different at different stages of the life cycle. The lowest level of mRNA was observed in leafy thalli, and the level in filamentous thalli and in the conchospores was 4-fold higher and 10-fold higher, respectively. [ABSTRACT FROM AUTHOR]