Concurrent and longitudinal associations of dissatisfaction with height and weight, body mass index with sleep disturbance among adolescents in China.

Sleep disturbance in adolescents is a significant global public health issue that can result in various physical and mental disorders. Height and weight dissatisfaction, as subjective perceptions of body shape, are common in adolescence and may affect individuals' sleep situations. However, the association of them is unclear. This study aimed to examine the cross-sectional and longitudinal associations among height dissatisfaction, weight dissatisfaction, body mass index (BMI), and sleep disturbance in adolescents. A total of 27,260 participants completed measures of sleep disturbance, height and weight satisfaction, and BMI. The cross-sectional and longitudinal effects of height satisfaction, weight satisfaction, and BMI as well as their changes in sleep disturbance over time were tested. Height satisfaction (ps < 0.001) and weight satisfaction (ps < 0.001) were negatively associated with concurrent sleep disturbance after adjusting for socio-demographic covariates and previous sleep disturbance. Height satisfaction (ps < 0.001) and weight satisfaction (ps < 0.001) at T1 as well as their increases (ps < 0.001) over 6 months predicted decreases in sleep disturbance over time. The cross-sectional and longitudinal associations between BMI and sleep disturbance were not significant (ps > 0.42). Moreover, height dissatisfaction (ORs = 1.06 to 1.34) and weight dissatisfaction (ORs = 1.21 to 1.36) were risk factors for concurrent and long-term sleep disturbance while adjusting socio-demographic covariates and previous sleep disturbance. Greater attention to subjective perception of height satisfaction and weight satisfaction, instead of BMI is needed.

Gut Prevotellaceae-GABAergic septohippocampal pathway mediates spatial memory impairment in high-fat diet-fed ovariectomized mice.

Clarifying the risk factors and mechanisms that contribute to the onset of cognitive impairment following estrogen depletion is essential for improving the quality of life of older females. In the current study, using behavioral tests, 16S rDNA sequencing, in vivo and in vitro electrophysiology, optogenetics and chemogenetics, we found that high-fat diet (HFD)-accelerated impairment of hippocampus-dependent memory, gut microbiota, and hippocampal theta rhythmogenesis in ovariectomized (OVX) mice and fecal microbiota transplantation rescued these phenomena. The identification of fasting-activated medial septal neurons showed that PV+ GABAergic neurons in the medial septal area (MSA) respond to gut sensory signals. Optogenetic activation of septohippocampal PV+ GABAergic fibers (but not cholinergic fibers) significantly rescued hippocampal theta rhythmogenesis and spatial memory in HFD-fed OVX mice. Resistant starch supplementation (RSHFD) rectified the gut Prevotellaceae and considerably alleviated reduced septal gut-responsive neurons, decreased hippocampal theta rhythm, and impaired hippocampus-dependent memory in HFD-fed OVX mice. Furthermore, chemogenetic inhibition of septal PV+ GABAergic neurons reversed the neuroprotective effects of resistant starch supplementation. These findings highlight the notable gut-sensory nature of medial septal PV+ GABAergic neurons. A HFD accelerates estrogen deficiency-induced cognitive impairment by disrupting the gut Prevotellaceae-septo-hippocampal pathway. This study contributes to a better understanding of the precise gut-brain control of cognition and cognitive impairment in postmenopausal females.

Intravenous Patient-Controlled Analgesia Versus Oral Opioid to Maintain Analgesia for Severe Cancer Pain: A Randomized Phase II Trial.

BACKGROUND: Optimal analgesic maintenance for severe cancer pain is unknown. This study evaluated the efficacy and safety of intravenous patient-controlled analgesia (IPCA) with continuous infusion plus rescue dose or bolus-only dose versus conventional oral extended-release morphine as a background dose with normal-release morphine as a rescue dose to maintain analgesia in patients with severe cancer pain after successful opioid titration. METHODS: Patients with persistent severe cancer pain (≥7 at rest on the 11-point numeric rating scale [NRS]) were randomly assigned to 1 of 3 treatment arms: (A1) IPCA hydromorphone with bolus-only dose where dosage was 10% to 20% of the total equianalgesic over the previous 24 hours (TEOP24H) administered as needed, (A2) IPCA hydromorphone with continuous infusion where dose per hour was the TEOP24H divided by 24 and bolus dosage for breakthrough pain was 10% to 20% of the TEOP24H, and (B) oral extended-release morphine based on TEOP24H/2 × 75% (because of incomplete cross-tolerance) every 12 hours plus normal-release morphine based on TEOP24H × 10% to 20% for breakthrough pain. After randomization, patients underwent IPCA hydromorphone titration for 24 hours to achieve pain control before beginning their assigned treatment. The primary endpoint was NRS over days 1 to 3. RESULTS: A total of 95 patients from 9 oncology study sites underwent randomization: 30 into arm A1, 32 into arm A2, and 33 into arm B. Arm B produced a significantly higher NRS over days 1 to 3 compared with arm A1 or A2 (P<.001). Daily NRS from day 1 to day 6 and patient satisfaction scores on day 3 and day 6 were worse in arm B. Median equivalent-morphine consumption increase was significantly lower in A1 (P=.024) among the 3 arms. No severe adverse event occurred in any arm. CONCLUSIONS: Compared with oral morphine maintenance, IPCA hydromorphone for analgesia maintenance improves control of severe cancer pain after successful titration. Furthermore, IPCA hydromorphone without continuous infusion may consume less opioid.

Subgroup analysis by prior anti-VEGF or anti-EGFR target therapy in FRESCO, a randomized, double-blind, Phase III trial.

Background: FRESCO study demonstrated efficacy and safety of fruquintinib in metastatic colorectal cancer patients. Impact of prior targeted therapy (PTT) on efficacy and safety of fruquintinib was evaluated. Materials & methods: In this subgroup analysis of FRESCO trial, patients were divided into PTT and non-PTT subgroups, and efficacy and safety of fruquintinib were assessed, respectively. Results: In non-PTT subgroup, fruquintinib significantly prolonged overall survival (OS) and progression-free survival (PFS) of patients compared with placebo. In PTT subgroup, the median OS and PFS of patients in fruquintinib arm was significantly higher than those in placebo. Treatment-emergent adverse events (TEAEs) rates were similar in both subgroups. Conclusion: Fruquintinib demonstrated clinically meaningful improvement in OS, PFS, objective response rate, and disease control rate with manageable TEAEs in both subgroups. Clinical trial registration: NCT02314819 (ClinicalTrials.gov).

Lay abstract In this analysis of the FRESCO trial, we evaluated the efficacy and safety of fruquintinib in two different groups of patients (subgroups) with metastatic colorectal cancer - patients who received prior targeted therapy (PTT) and patients who did not (non-PTT). Of the 278 patients treated with fruquintinib, 111 patients received PTT. Patients treated with fruquintinib had longer overall survival and it took longer for their disease to worsen in both PTT and non-PTT subgroups compared with placebo. Patients in both subgroups treated with fruquintinib showed measurable reduction in their tumor size and disease control with similar side effects in patients of both the subgroups. These results suggest that fruquintinib is safe and effective in patients with metastatic colorectal cancer in both subgroups.

Technical note: Atlas-based Auto-segmentation of masticatory muscles for head and neck cancer radiotherapy.

PURPOSE: The study aimed to use quantitative geometric and dosimetric metrics to assess the accuracy of atlas-based auto-segmentation of masticatory muscles (MMs) compared to manual drawn contours for head and neck cancer (HNC) radiotherapy (RT). MATERIALS AND METHODS: Fifty-eight patients with HNC treated with RT were analyzed. Paired MMs (masseter, temporalis, and medial and lateral pterygoids) were manually delineated on planning computed tomography (CT) images for all patients. Twenty-nine patients were used to generate the MM atlas. Using this atlas, automatic segmentation of the MMs was performed for the remaining 29 patients without manual correction. Auto-segmentation accuracy for MMs was compared using dice similarity coefficients (DSCs), Hausdorff distance (HD), HD95, and variation in the center of mass (∆COM). The dosimetric impact on MMs was calculated (∆dose) using dosimetric parameters (D99%, D95%, D50%, and D1%), and compared with the geometric indices to test correlation. RESULTS: DSCmean ranges from 0.79 ± 0.04 to 0.85 ± 0.04, HDmean from 0.43 ± 0.08 to 0.82 ± 0.26 cm, HD95mean from 0.32 ± 0.08 to 0.42 ± 0.16 cm, and ∆COMmean from 0.18 ± 0.11 to 0.33 ± 0.23 cm. The mean MM volume difference was < 15%. The correlation coefficient (r) of geometric and dosimetric indices for the four MMs ranges between -0.456 and 0.300. CONCLUSIONS: Atlas-based auto-segmentation for masticatory muscles provides geometrically accurate contours compared to manual drawn contours. Dose obtained from those auto-segmented contours is comparable to that from manual drawn contours. Atlas-based auto-segmentation strategy for MM in HN radiotherapy is readily availalbe for clinical implementation.

Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial.

Importance: Patients with metastatic colorectal cancer (CRC) have limited effective and tolerable treatment options. Objective: To evaluate the efficacy and safety of oral fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, as third-line or later therapy in patients with metastatic CRC. Design, Setting, and Participants: FRESCO (Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients) was a randomized, double-blind, placebo-controlled, multicenter (28 hospitals in China), phase 3 clinical trial. From December 2014 to May 2016, screening took place among 519 patients aged 18 to 75 years who had metastatic CRC that progressed after at least 2 lines of chemotherapy but had not received VEGFR inhibitor therapy; 416 met the eligibility criteria and were stratified by prior anti-VEGF therapy and K-ras status. The final date of follow-up was January 17, 2017. Interventions: Patients were randomized in a 2:1 ratio to receive either fruquintinib, 5 mg (n = 278) or placebo (n = 138) orally, once daily for 21 days, followed by 7 days off in 28-day cycles, until disease progression, intolerable toxicity, or study withdrawal. Main Outcomes and Measures: The primary end point was overall survival. Key secondary efficacy endpoints were progression-free survival (time from randomization to disease progression or death), objective response rate (confirmed complete or partial response), and disease control rate (complete or partial response, or stable disease recorded ≥8 weeks postrandomization). Duration of response was also assessed. Safety outcomes included treatment-emergent adverse events. Results: Of the 416 randomized patients (mean age, 54.6 years; 161 [38.7%] women), 404 (97.1%) completed the trial. Median overall survival was significantly prolonged with fruquintinib compared with placebo (9.3 months [95% CI, 8.2-10.5] vs 6.6 months [95% CI, 5.9-8.1]); hazard ratio (HR) for death, 0.65 (95% CI, 0.51-0.83; P < .001). Median progression-free survival was also significantly increased with fruquintinib (3.7 months [95% CI, 3.7-4.6] vs 1.8 months [95% CI, 1.8-1.8] months); HR for progression or death, 0.26 (95% CI, 0.21 to 0.34; P < .001). Grades 3 and 4 treatment-emergent adverse events occurred in 61.2% (170) of patients who received fruquintinib and 19.7% (27) who received placebo. Serious adverse events were reported by 15.5% (43) of patients in the fruquintinib group and 5.8% (8) in the placebo group, with 14.4% (40) of fruquintinib-treated and 5.1% (7) of placebo-treated patients requiring hospitalization. Conclusions and Relevance: Among Chinese patients with metastatic CRC who had tumor progression following at least 2 prior chemotherapy regimens, oral fruquintinib compared with placebo resulted in a statistically significant increase in overall survival. Further research is needed to assess efficacy outside of China. Trial Registration: ClinicalTrials.gov Identifier: NCT02314819.

Controlled self-assembly and photovoltaic characteristics of porphyrin derivatives on a silicon surface at solid-liquid interfaces.

Two meso-tetraphenylporphyrin (H2TPP) derivatives with different central metal ions, namely ZnTPP, CuTPP, were synthesized, and characterized by a series of spectroscopic methods. Their self-assembly behaviors in mixed solvents without surfactant were systematically investigated. The morphology of the thus produced nanoarchitectures could be efficiently controlled. Nanoslices can be manufactured when a volume of cyclohexane is involved, octahedrons can be produced when a mixed solvent of chloroform and isopropanol is employed, while four-leaf clover-shaped structures can be produced with a large volume of methanol injected. The nanostructures have been characterized by electronic absorption, scanning electron microscopy (SEM) and photoelectric conversion techniques. The internal structures of the nanostructures are well described by XRD. The nanostructures exhibit a power conversion under illumination intensity of 2.3 mW cm(-2). The present result appears to represent an effort toward controlling the morphology of self-assembled nanostructures of porphyrin derivatives via synthesis through introduction of metal-ligand and solvent interaction. Nevertheless, the fundamental study will be helpful to understand photoinduced energy/charge transport in an organic interface and this might also serve as promising building blocks for nanoscale power sources for potential application in solar energy technologies and organic electronics and optoelectronics.

Bazi Bushen capsule attenuates cardiac systolic injury via SIRT3/SOD2 pathway in high-fat diet-fed ovariectomized mice.

Background: Bazi Bushen capsule (BZBS) is a Chinese herbal compound that is clinically used to treat fatigue and forgetfulness. However, it is still unclear whether and how BZBS affects heart function decline in menopausal women. This study aimed to examine the effect of BZBS on cardiac function in a high-fat diet-fed ovariectomy (HFD-fed OVX) mouse model and elucidate the underlying mechanism of this effect. Methods: The experimental animals were divided into five groups: sham group, HFD-fed OVX group, and BZBS (0.7, 1.4, 2.8 g/kg) intervention groups. Senescence ß-galactosidase staining and echocardiography were used to evaluate cardiac function. SwissTargetPrediction, KEGG and GO enrichment analyses were used to screen the underlying mechanism of BZBS. The morphological and functional changes in cardiac mitochondria and the underlying molecular mechanism were assessed by transmission electron microscopy, western blotting and biochemical assays. STRING database was used to analysis protein-protein interaction (PPI) network. Molecular docking studies were employed to predict the interactions of specific BZBS compounds with their protein targets. Results: BZBS treatment ameliorated cardiac senescence and cardiac systole injury in HFD-fed OVX mice. GO and KEGG analyses revealed that the 530 targets of the 14 main components of BZBS were enriched mainly in the oxidative stress-associated pathway, which was confirmed by the finding that BZBS treatment prevented abnormal morphological changes and oxidative stress damage to cardiac mitochondria in HFD-fed OVX mice. Furthermore, the STRING database showed that the targets of BZBS were broadly related to the Sirtuins family. And BZBS upregulated the SIRT3 and elevated the activity of SOD2 in the hearts of HFD-fed OVX mice, which was also verified in vitro. Additionally, we revealed that imperatorin and osthole from the BZBS upregulated the expression of SIRT3 by directly docking with the transcription factors HDAC1, HDAC2, and BRD4, which regulate the expression of SIRT3. Conclusion: This research shows that the antioxidative effect and cardioprotective role of BZBS on HFD-fed OVX mice involves an increase in the activity of the SIRT3/SOD2 pathway, and the imperatorin and osthole of BZBS may play central roles in this process.

Prediction of genetic polymorphisms of DNA repair genes XRCC1 and XRCC3 in the survival of colorectal cancer receiving chemotherapy in the Chinese population.

BACKGROUND/AIMS: We aimed to detect the distribution of DNA repair genes XRCC1 and XRCC3 genotypes in the survival of colorectal cancer patients receiving chemotherapy in the Chinese population. METHODOLOGY: The prospective study was conducted with 432 cases treated with 5-FU and oxaliplatin as first-line chemotherapy. All the patients were followed-up from May 2006 to May 2011 and 168 patients died during follow-up. XRCC1 and XRCC3 genotype polymorphisms were based upon the PCR-CTPP method. RESULTS: It was shown that the XRCC1 Arg399Gln and XRCC3 Thr241Met gene polymorphisms were associated with increased death risk of colorectal cancer. Individuals carrying XRCC1 Gln/Gln, Thr/Met and Met/Met genotypes positively associated with 2.78-, 2.86- and 3.0-fold death risk of colorectal cancer. Moreover, the combination of XRCC1 399Gln allele and XRCC3 241Met allele showed a significantly strong association with death risk of colorectal cancer (OR=3.46, 95%CI=1.65- 5.48). CONCLUSIONS: This study is first to report that the XRCC1 and XRCC3 gene polymorphisms are useful as a surrogate marker of clinical outcome in colorectal cancer with 5-FU/oxaliplatin combination chemotherapy in the Chinese population.

ANTXR1 as a potential prognostic biomarker for hepatitis B virus-related hepatocellular carcinoma identified by a weighted gene correlation network analysis.

BACKGROUND: With high incidence and mortality rates, hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide. Chronic hepatitis B virus (HBV) infection is a leading cause of HCC, especially for Asians and blacks. However, the molecular mechanisms underlying HBV-related HCC are unclear. This study sought to identify novel prognostic biomarkers and explore the potential pathogenesis of HBV-related HCC. METHODS: The gene expression profiles and corresponding clinical information of HCC from The Cancer Genome Atlas Liver Hepatocellular Carcinoma data set were analyzed by a weighted gene co-expression network analysis. Correlations between the co-expression modules and clinical traits were calculated. Next, key modules associated with HBV infection were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted for the genes in the key modules. The hub genes were identified based on the protein-protein interaction (PPI) network via the Cytoscape. Finally, an overall survival (OS) analysis was performed. RESULTS: The two modules (i.e., the brown and yellow modules) most relevant to HBV infection were constructed. A functional enrichment analysis revealed that the genes in the two modules were mainly enriched in HCC-related pathways, such as the phosphatidylinositol-3-kinase and protein kinase B signaling pathway, focal adhesion, human papillomavirus infection, the Rap1 signaling pathway, and the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway. Ten hub genes [i.e., COL3A1, ANTXR1, COL14A1, THBS2, ADAMTS2, AEBP1, PRELP, EMILIN1, DCN and PODN] in the brown module, and 10 hub genes [i.e., USP34, SEC24C, ZNF770, STAG1, TSTD2, PKD1P6, CCNK, GFT2I, NT5C2 and SMG6] in the yellow module were identified. Among the hub genes, ANTXR1 (Anthrax-toxin receptor 1) was significantly correlated with HBV-related HCC patients' OS. CONCLUSIONS: ANTXR1 represents a potential therapeutic target for HBV-related HCC. This study offers novel insights into the molecular mechanisms of HBV-induced tumorigenesis, which needs to be further validated by basic experiments and large-scale cohort studies.

Subgroup Analysis by Liver Metastasis in the FRESCO Trial Comparing Fruquintinib versus Placebo Plus Best Supportive Care in Chinese Patients with Metastatic Colorectal Cancer.

OBJECTIVE: The aim of the present subgroup analysis of the FRESCO trial is to determine the efficacy and hepatotoxicity of fruquintinib in Chinese patients with metastatic CRC with liver metastasis (CRLM) who were receiving third-line or posterior-line therapy. METHODS: Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Hazard ratio (HR) was estimated through Cox proportional hazards model. Hepatotoxicity was coded using the standardized MedDRA queries of hepatic failure, fibrosis, cirrhosis, and other liver injury-related conditions and graded using the Common Terminology Criteria Adverse Events grades. The efficacy of fruquintinib in patients with CRLM was evaluated in various subgroups. RESULTS: A total of 287 (69.0%) patients with metastatic CRC had liver metastasis (LM, fruquintinib: 185 and placebo: 102). Median OS in patients with CRLM was significantly prolonged with fruquintinib compared with placebo (8.61 months vs 5.98 months; HR=0.59, 95% CI, 0.45-0.77, P<0.001). In patients with CRLM, the incremental median PFS for patients in the fruquintinib-treated group was significantly higher than in the placebo group (median PFS: 3.71 vs.1.84 months; HR=0.22, 95% CI: 0.17-0.30; P<0.001). Compared with placebo, significant improvements in OS were observed with fruquintinib in LM patients regardless of lung metastasis, prior target therapy, and K-RAS status. In patients with CRLM, treatment-emergent hepatotoxicities of any grade occurred in 7 (3.8%) patients in the fruquintinib group vs 2 (2.0%) in the placebo group. CONCLUSION: Fruquintinib demonstrated a statistically significant increase in OS and PFS as compared with placebo in Chinese patients with CRLM. The hepatotoxicity of fruquintinib was less reported, and comparable with placebo in patients with CRLM. CLINICALTRIALSGOV IDENTIFIER: NCT02314819.

Wogonoside inhibits inflammatory cytokine production in lipopolysaccharide-stimulated macrophage by suppressing the activation of the JNK/c-Jun signaling pathway.

BACKGROUND: Mediated by innate immune cells, inflammation is an underlying presence in the pathogenesis of numerous pulmonary diseases. Macrophages play a critical role in mediating the initial response to infection in the lungs. When there is excessive activation of macrophages, hyper-production of inflammatory factors occurs, with inflammation as the ultimate result. Wogonoside, a bioactive flavonoid glycoside, has been reported to alleviate pulmonary inflammation. However, the mechanism underlying the anti-inflammatory effect of wogonoside has not yet been clarified. METHODS: The productions of nitric oxide (NO) and reactive oxygen species (ROS) were determined using a Griess reagent kit and a DAF-FM DA fluorescent probe, respectively. Moreover, the mRNA levels of inflammatory factors were quantified by qPCR, and the binding ability of c-Jun to promoters of inflammatory factors was performed by ChIP assay. Western blot was employed to detect the protein expression of inflammatory factors and signaling pathway. RESULTS: In this study, we found that pre-treatment with wogonoside dramatically suppressed lipopolysaccharide (LPS)-induced increase in the protein and mRNA levels of inflammatory factors in macrophages, such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-6. Furthermore, wogonoside profoundly reduced the increase in NO and ROS production and significantly blocked phosphorylation of JNK in LPS-stimulated macrophages. As revealed by Western blot and qPCR analysis, wogonoside mediated the JNK-dependent inhibitory effect. Compared with wogonoside alone, a combination of wogonoside and JNK inhibitor SP600125 provided no extra benefit in suppressing the protein expression and mRNA levels of inflammatory factors in LPS-stimulated macrophages. Additionally, ChIP analysis demonstrated wogonoside to remarkably reduce c-Jun enrichment in COX-2, iNOS, IL-1ß, TNF-α, and IL-6 promoters. CONCLUSIONS: Collectively, our findings showed that wogonoside notably suppresses LPS-stimulated production of inflammatory factors by repressing the activation of the JNK/c-Jun signaling pathway in macrophages. This suggests that wogonoside could serve as a promising therapeutic agent for pulmonary diseases related to macrophage inflammation.

MRI Radiomics for Prediction of Tumor Response and Downstaging in Rectal Cancer Patients after Preoperative Chemoradiation.

PURPOSE: This study aimed to investigate radiomic features extracted from magnetic resonance imaging (MRI) scans performed before and after neoadjuvant chemoradiotherapy (nCRT) in predicting response of locally advanced rectal cancer (LARC). METHODS AND MATERIALS: Thirty-nine patients who underwent nCRT for LARC were included, with 294 radiomic features extracted from MRI that was performed before (pre-CRT) and 6 to 8 weeks after completing nCRT (post-CRT). Based on tumor regression grade (TRG), 26 patients were classified as having a histopathologic good response (GR; TRG 0-1) and 13 as non-GR (TRG 2-3). Tumor downstaging (T-downstaging) occurred in 25 patients. Univariate analyses were performed to assess potential radiomic and delta-radiomic predictors for TRG in pathologic complete response (pCR) versus non-pCR, GR versus non-GR, and T-downstaging. The support vector machine-based multivariate model was used to select the best predictors for TRG and T-downstaging. RESULTS: We identified 13 predictive features for pCR versus non-pCR, 14 for GR versus non-GR, and 16 for T-downstaging. Pre-CRT gray-level run length matrix nonuniformity, pre-CRT neighborhood intensity difference matrix (NIDM) texture strength, and post-CRT NIDM busyness predicted all 3 treatment responses. The best predictor for GR versus non-GR was pre-CRT global minimum combined with clinical N stage in the multivariate analysis. The best predictor for T-downstaging was the combination of pre-CRT gray-level co-occurrence matrix correlation, NIDM-texture strength, and gray-level co-occurrence matrix variance. The pre-CRT, post-CRT, and delta radiomic-based models had no significant difference in predicting all 3 responses. CONCLUSIONS: Pre-CRT MRI, post-CRT MRI, and delta radiomic-based models have the potential to predict tumor response after nCRT in LARC. These data, if validated in larger cohorts, can provide important predictive information to aid in clinical decision making.

Effect and Safety of Radiation Therapy Boost to Extramesorectal Lymph Nodes in Rectal Cancer.

PURPOSE: In rectal cancer, the presence of extramesorectal/lateral pelvic lymph node (LPN) is associated with higher risk of locoregional and distant recurrences. LPNs are not typically resected during a standard total mesorectal excision (TME) procedure, and the optimal management for these patients is controversial. We assessed the safety and efficacy of adding a radiation therapy boost to clinically positive LPN during neoadjuvant chemoradiation therapy for rectal cancer. METHODS AND MATERIALS: We analyzed nonmetastatic, lymph node positive rectal adenocarcinoma patients treated with neoadjuvant chemoradiation therapy followed by TME between May 2011 and February 2018. Patients without LPN involvement received external beam radiation therapy (45 Gy in 25 fractions) to the primary tumor and regional draining lymph node basins followed by a boost (5.4 Gy in 3 fractions) to gross disease. Patients with clinically positive LPN that would not be removed during TME received an additional boost (up to a total dose between 54.0 and 59.4 Gy) to the involved LPNs. We compared locoregional control, overall survival, progression-free survival, and treatment-related toxicity between these 2 groups. RESULTS: Fifty-three patients were included in this analysis with median follow-up of 30.6 months for the LPN- group (n = 41) and 19.9 months for the LPN+ group (n = 12). There was no difference in 3-year overall survival (90.04% vs 83.33%, P = .890) and progression-free survival (80.12% vs 80.21%, P = .529) between the 2 groups. We did not observe any LPN recurrences. There were no differences in rates of acute grade 3+ or chronic toxicities. CONCLUSIONS: Despite the well-documented negative prognostic effect of LPN metastasis, we observed promising outcomes for LPN+ patients treated with an additional radiation boost. Our results suggest that radiation therapy boost to clinically involved, unresected LPN is an effective treatment approach with limited toxicity. Additional studies are needed to optimize treatment strategies for this unique patient subset.

Safety Profile and Adverse Events of Special Interest for Fruquintinib in Chinese Patients with Previously Treated Metastatic Colorectal Cancer: Analysis of the Phase 3 FRESCO Trial.

INTRODUCTION: In FRESCO (Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients) trial, fruquintinib demonstrated a statistically significant and clinically meaningful overall survival benefit in Chinese patients with metastatic colorectal cancer (mCRC). However, its safety profile, including adverse events of special interest (AESIs) and treatment-emergent adverse events (TEAEs) by age, sex, and body mass index (BMI), is not well known. The present analysis evaluated the safety profile and AESIs for fruquintinib in the FRESCO trial. METHODS: In FRESCO, eligible Chinese patients were randomized (2:1) to receive fruquintinib (5 mg once daily for 3 weeks, followed by 1 week off in 28-day cycles) or placebo plus best supportive care. Treatment-related AESIs and time to first occurrence of AESIs were summarized. Treatment-related TEAEs by age, sex, and BMI were also summarized. RESULTS: A total of 266 patients (95.7%) in the fruquintinib group and 97 (70.8%) in the placebo group had at least one treatment-related TEAE; the mean relative dose intensity was 92% and 98%, respectively. In the fruquintinib group, the most common (in > 40% of patients) treatment-related AESIs were hypertension (55.4%), palmar-plantar erythrodysesthesia syndrome [known as hand-foot skin reaction (HFSR)] (49.3%), and proteinuria (42.1%). The most common treatment-related grade ≥ 3 AESIs (≥ 3% of patients) were hypertension (21.2%), HFSR (10.8%), and proteinuria (3.2%); the median time to onset of these events was 10, 21, and 20 days, respectively. Subgroup analysis by age, sex, and BMI revealed that the frequencies of treatment-related TEAEs were similar across all subgroups, and were consistent with the overall safety profile of fruquintinib. CONCLUSIONS: The most common treatment-related grade ≥ 3 AEs were hypertension, HFSR, and proteinuria. The treatment-related TEAE profile of fruquintinib in Chinese patents with mCRC was comparable among different subgroups and consistent with that reported in the overall population. TRIAL REGISTRATION: Clinical Trials identifier NCT02314819.

Quantification on Growing Mass of Solid Electrolyte Interphase and Deposited Mn(II) on the Silicon Anode of LiMn2O4 Full Lithium-Ion Cells.

Silicon is considered to be one of the most important high-energy density anode materials for next-generation lithium-ion batteries. A large number of experimental studies on silicon anode have achieved better results, and greatly promoted its practical application potentiality, but almost of them are only tested in metal lithium half batteries. There is still an unavoidable question for commercial applications: what is the performance of the full cell composed of a silicon anode and a manganese-based material cathode? In this paper, the growing solid electrolyte interphase (SEI) and deposited manganese ions of the silicon anode's surface of the spinel lithium manganese oxide LiMn2O4/silicon full cells are quantitatively studied during electrochemical cycling, and the SEI performances are tested by differential scanning calorimetry to find out the reason for the rapid decline of reversible capacity in the LiMn2O4/silicon system. The experimental results show that manganese ions can make SEI films rapidly grow on the silicon anode and make SEI films more brittle, which results in lower Coulombic efficiency and rapid decline in capacity of the silicon anode.

[Manufacture of high frequency direct current dental X-ray machine].

This paper introduces five dental X-ray machines which are manufactured with IGBT to realize high frequency, real-time sampling and PWM to ensure the closed-loop control for tube current and Anodes's high voltage. These five machines also use microcomputer and combined X-ray tube for precise control. The sets don't have high voltage outside. The error of tube voltage is less than 1% and exposure time is less than 3%. The photos of pulp cavity and surrounding tissue can be seen clearly. These sets surely meet the requirements of perspective use in clinical.

Investigations on the driving forces of the fluorocarbon surfactant-assisted spontaneous imbibition using thermogravimetric analysis (TGA).

Spontaneous imbibition is crucial for the development of matrix-fractured petroleum reservoirs. To improve the ultimate oil recovery, it is essential to demonstrate the role of the surfactant solution on the imbibition process. In this study, spontaneous imbibition experiments were carried out using self-prepared oil sand that to investigate the dependence of oil recovery on the concentration of a fluorocarbon surfactant (FS-30). Emulsion and solubilization were assessed to identify the correlation between oil-water interface properties and spontaneous imbibition. Moreover, thermogravimetric analysis (TGA) was also applied to accurately determine the imbibition recovery and look into the influence of components of crude oil on spontaneous imbibition. The maximum ultimate oil recovery in this work was 70.8% using 0.3 wt% FS-30, when the oil-solid adhesion tension, the capillary pressure (P C) and solubilization factor (S F) attained extreme values of -3.7002 mN m-1, 4.8751 MPa and 242.7 mL g-1, respectively. It was found that the surface activator played a critical role in promoting the imbibition process through altering the contact angle and interfacial tension. A negative adhesive tension and a positive capillary pressure would accordingly be generated, which facilitated the departure of oil droplets from the rock surface. In addition, it was observed that a lower solubilization factor and higher emulsion stability could favour spontaneous imbibition. Finally, heavier components in oil sands were more prone to be displaced than lighter counterparts, especially when the surfactant concentration was relatively high. This study may shed light on the effect of surfactants on spontaneous imbibition and thus is of great significance in understanding the underlying mechanism of the imbibition process.

Association between XRCC1 single-nucleotide polymorphism and acute radiation reaction in patients with nasopharyngeal carcinoma: A cohort study.

To explore the association of the X-ray repair cross-complementing gene 1 (XRCC1) codon 399 single-nucleotide polymorphism (SNP) with acute radiation dermatitis and oral mucositis in nasopharyngeal carcinoma (NPC) patients treated by intensity-modulated radiation therapy (IMRT).Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the SNP of the XRCC1 codon 399 in 114 NPC patients before radiotherapy.The risk of patients with the Arg/Arg genotype suffering from acute radiation dermatitis Grade ≥2 was higher than the other 2 genotypes (P = .014, 95% CI: 1.182-4.582). No significant difference was observed in the degree of acute radiation oral mucositis injury among the patients with different genotypes (P = .449, 95% CI: 0.691-2.304). Multivariate analysis showed that N stage and genotype were significantly associated with acute radiation dermatitis of Grade ≥2 (OR = 3.221, P < .001, 95% CI: 1.669-6.216, OR = 2.860, P = .006, 95% CI: 1.354-6.043). T stage and smoking status were significantly associated with acute radiation oral mucositis with Grade ≥2 (OR = 2.508, P = .001, 95% CI: 1.427-4.408, OR = 6.355, P < .001, 95% CI: 2.533-15.841).The XRCC1 codon 399 genotype in NPC could be an important predicting factor in the risk of acute radiation dermatitis during IMRT.

Central neurocytoma.

Central neurocytomas (CN) are rare intraventricular tumors with prominent neuronal differentiation. CN commonly arise in the lateral ventricles of young adults who predominantly present with raised intracranial pressure. Few studies have described the clinical, pathological, and radiological features of these tumors, and those that have are typically single case reports. Herein, we report ten patients with CN with variable clinical and pathological features and discuss the management of these tumors. Nine tumors occupied the lateral ventricle and only one was located in the sellar region. On MRI, all 10 tumors showed heterogeneous hypo-or iso-intensity on T1-weighted and hyperintensity on T2-weighted MRI. Contrast enhancement varied greatly from very slight to intense. All patients were surgically treated by macroscopic total or subtotal removal. Postoperative radiotherapy was given to six patients (four of whom had undergone subtotal resection and two of whom had undergone total resection). The surgical and histopathological data of these patients were reviewed and analyzed. No recurrences were noted although we were unable to contact two patients for follow-up. A brief review of the literature concerning differential diagnosis and therapeutic aspects of these tumors is also presented.