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Human cytochromes P450 1A1 (CYP1A1) and P450 1B1 (CYP1B1) catalyze the metabolic activation of a number of procarcinogens and the hydroxylation of 17β-estradiol (E2) at the C-2 and C-4 positions, respectively. The aromatic hydrocarbon receptor (AhR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a marked effect on estrogen metabolism in MCF-7 breast-tumor cells by induction of these two enzymes. To investigate whether induction of CYP1A1 and CYP1B1 by AhR agonists and the associated increase in E2 metabolism are common to all breast epithelial cells and breast-tumor cells, we determined the effects of TCDD on E2 metabolism, and CYP1A1 and CYP1B1 mRNA levels in a series of non-tumor-derived breast epithelial (184A1 and MCF-10A) and breast-tumor (MCF-7, T-47D, ZR-75-1, BT-20, MDA-MB-157, MDA-MB-231 and MDA-MB-436) cell lines. In 184A1 cells, which did not express detectable estrogen receptor (ER) αmRNA, CYP1A1 mRNA and activity were induced by TCDD, and enhanced E2 metabolism in TCDD-treated cells was predominantly E2 2-hydroxylation. In MCF-10A, MCF-7, T-47D, ZR-75-1 and BT-20 cells, which expressed varying levels of ERα mRNA, both CYP1A1 and CYP1B1 mRNA levels and rates of both E2 2- and 4-hydroxylation were highly elevated following exposure to TCDD. In MDA-MB-157, MDA-MB-231 and MDA-MB-436 cells, which did not express detectable ERα mRNA and generally displayed fibroblastic or mesenchymal rather than epithelial morphology, CYP1B1 induction was favored, and the rate of E2 4-hydroxylation exceeded that of 2-hydroxylation in TCDD-treated cells. These results show that breast epithelial cells and tumor cells vary widely with regard to AhR-mediated CYP1A1 and CYP1B1 induction, suggesting that factors in addition to the AhR regulate CYP1A1 and CYP1B1 gene expression. In these cell lines, significant CYP1A1 inducibility was restricted to cultures dismaying epithelial morphology, whereas CYP1B1 inducibility was observed in cells of both epithelial and mesenchymal morphology. [ABSTRACT FROM PUBLISHER]

Objective: To provide a comprehensive assessment of various fractionation schemes in radiation therapy for breast cancer, with a focus on side effects, cosmesis, quality of life, risks of recurrence, and survival outcomes., Design: Systematic review and meta-analysis., Data Sources: Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (from inception to 23 October 2023)., Study Selection: Included studies were randomised controlled trials focusing on conventional fractionation (CF; daily fractions of 1.8-2 Gy, reaching a total dose of 50-50.4 Gy over 5-6 weeks), moderate hypofractionation (MHF; fraction sizes of 2.65-3.3 Gy for 13-16 fractions over 3-5 weeks), and/or ultra-hypofractionation (UHF; schedule of only 5 fractions)., Data Extraction: Two independent investigators screened studies and extracted data. Risk of bias and quality of evidence were assessed using the Cochrane Collaboration's tool and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach, respectively., Data Synthesis: Pooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity was analysed using Cochran's Q test and I 2 statistic. Network meta-analysis was used to integrate all available evidence., Main Outcome Measures: The pre-specified primary outcome was grade ≥2 acute radiation dermatitis and late radiation therapy related side effects; secondary outcomes included cosmesis, quality of life, recurrence, and survival metrics., Results: From 1754 studies, 59 articles representing 35 trials (20 237 patients) were assessed; 21.6% of outcomes showed low risk of bias, whereas 78.4% had some concerns or high risk, particularly in outcome measurement (47.4%). The RR for grade ≥2 acute radiation dermatitis for MHF compared with CF was 0.54 (95% CI 0.49 to 0.61; P<0.001) and 0.68 (0.49 to 0.93; P=0.02) following breast conserving therapy and mastectomy, respectively. Hyperpigmentation and grade ≥2 breast shrinkage were less frequent after MHF than after CF, with RRs of 0.77 (0.62 to 0.95; P=0.02) and 0.92 (0.85 to 0.99; P=0.03), respectively, in the combined breast conserving therapy and mastectomy population. However, in the breast conserving therapy only trials, these differences in hyperpigmentation (RR 0.79, 0.60 to 1.03; P=0.08) and breast shrinkage (0.94, 0.83 to 1.07; P=0.35) were not statistically significant. The RR for grade ≥2 acute radiation dermatitis for UHF compared with MHF was 0.85 (0.47 to 1.55; P=0.60) for breast conserving therapy and mastectomy patients combined. MHF was associated with improved cosmesis and quality of life compared with CF, whereas data on UHF were less conclusive. Survival and recurrence outcomes were similar between UHF, MHF, and CF., Conclusions: MHF shows improved safety profile, cosmesis, and quality of life compared with CF while maintaining equivalent oncological outcomes. Fewer randomised controlled trials have compared UHF with other fractionation schedules, but its safety and oncological effectiveness seem to be similar with short term follow-up. Given the advantages of reduced treatment time, enhanced convenience for patients, and potential cost effectiveness, MHF and UHF should be considered as preferred options over CF in appropriate clinical settings, with further research needed to solidify these findings., Systematic Review Registration: PROSPERO CRD42023460249., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; IC has received consulting fees from Pfizer, Novartis, Eli Lilly, Seagen, Gilead, Astra Zeneca, Daiichi Sankyo, and Menarini StemLine and is a clinical board member of the European Society for Radiotherapy and Oncology (unpaid); JQC has received funding from the Canadian Institutes of Health Research and honorariums from Roche, Pfizer, Novartis, AstraZeneca, Well Doc Alberta, Merck, La Roche-Posay, Knight, Seagen, Oncology Education, and Gilead; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Foot dystonia occurs in patients with Parkinson's disease (PD) and leads to pain, malformation, and difficulty with walking. Botulinum toxin injections may be effective for foot dystonia, but the extent of improvement and effects on motor function are unclear., Methods: In this study, we performed botulinum toxin injections for foot dystonia in 25 patients with PD. At 3 weeks and 3 months post-infection, we assessed changes in plantar pressure distribution utilizing the Pressure Plate system; dystonia using the Modified Ashworth Spasm score; pain using the visual analog scale (VAS) score; and lower extremity function using the Calf-raise Senior (CRS) test, Timed Up and Go (TUG) test, and gait parameters (eg, stride length, step length)., Results: We found improved Modified Ashworth Spasm score (p < 0.01) and VAS score (p < 0.01) post-injection. CRS test score (3 weeks, p = 0.006; 3 months, p = 0.068), stride length (3 weeks, p = 0.012; 3 months, p = 0.715), and step length (3 weeks, p = 0.011; 3 months, p = 0.803) also improved. Plantar pressure distribution improved after botulinum toxin injection (metatarsal 1, 3 weeks, p = 0.031; 3 months, p = 0.144; metatarsal 2, 3 weeks, p = 0.049; 3 months, p = 0.065; metatarsal 3, 3 weeks, p = 0.002; 3 months, p = 0.017; metatarsal 4, 3 weeks, p = 0.017; 3 months, p = 0.144; medial heel, 3 weeks, p = 0.01; 3 months, p = 0.395; lateral heel, 3 weeks, p = 0.035; 3 months, p = 0.109)., Conclusion: Botulinum toxin injection for foot dystonia in patients with PD can reduce spasms and pain and normalize plantar pressure distribution, which improves balance and lower extremity function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The small intestine is known to play a crucial role in the development and remission of diabetes mellitus (DM). However, the exact mechanism by which mid-small intestinal bypass improves glucose metabolism in diabetic rats is not fully understood., Aim: To elucidate the mechanisms by which mid-small intestinal bypass improves glucose metabolism., Methods: Streptozotocin (STZ) was used to induce DM in Sprague-Dawley (SD) rats at a dose of 60 mg/kg. The rats were then randomly divided into two groups: The mid-small intestine bypass (MSIB) group and the sham group (underwent switch laparotomy). Following a 6-wk recovery period post-surgery, the rats underwent various assessments, including metabolic parameter testing, analysis of liver glycogen levels, measurement of key gluconeogenic enzyme activity, characterization of the gut microbiota composition, evaluation of hormone levels, determination of bile acid concentrations, and assessment of the expression of the intestinal receptors Takeda G protein-coupled receptor 5 and farnesoid X receptor., Results: The MSIB group of rats demonstrated improved glucose metabolism and lipid metabolism, along with increased hepatic glycogen content. Furthermore, there was a decrease in the expression of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 and glucose-6-phosphatase. Importantly, the MSIB group exhibited a substantial increase in the abundances of intestinal Lactobacillus , Clostridium symbiosum , Ruminococcus gnavus , and Bilophila . Moreover, higher levels of secondary bile acids, such as intestinal lithocholic acid, were observed in this group. Remarkably, the changes in the gut microbiota showed a significant correlation with the expression of key gluconeogenic enzymes and glucagon-like peptide 1 (GLP-1) at 6 wk postoperatively, highlighting their potential role in glucose regulation. These findings highlight the beneficial effects of mid-small intestine bypass on glucose metabolism and the associated modulation of the gut microbiota., Conclusion: The findings of this study demonstrate that the introduction of postoperative intestinal Clostridium symbiosum in the mid-small intestine contributes to the enhancement of glucose metabolism in nonobese diabetic rats. This improvement is attributed to the increased inhibition of hepatic gluconeogenesis mediated by GLP-1, resulting in a favorable modulation of glucose homeostasis., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Different metabolic/bariatric surgery approaches vary in their effect on weight loss and glucose levels, although the underlying mechanism is unclear. Studies have demonstrated that the gut microbiota might be an important mechanism of improved metabolism after metabolic/bariatric surgery., Aim: To investigate the relationship between the improvement in metabolic disturbances and the changes in gut microbiota after gastric or intestinal bypass., Methods: We performed sleeve gastrectomy (SG), distal small intestine bypass (DSIB) or sham surgery in nonobese rats with diabetes induced by 60 mg/kg streptozotocin (STZ-DM)., Results: The group comparisons revealed that both SG and DSIB induced a reduction in body weight and significant improvements in glucose and lipid metabolism in the STZ-DM rats. Furthermore, DSIB exhibited a stronger glucose-lowering and lipid-reducing effect on STZ-DM rats than SG. 16S ribosomal RNA gene sequencing revealed the gut abundance of some Lactobacillus spp. increased in both the SG and DSIB groups after surgery. However, the DSIB group exhibited a more pronounced increase in the gut abundance of Lactobacillus spp. compared to the SG group, with more Lactobacillus spp. types increased in the gut., Conclusion: The gut abundance of Lactobacillus was significantly correlated with the improvement in glycolipid metabolism and the change in serum fibroblast growth factor 21 levels., Competing Interests: Conflict-of-interest statement: All authors declare that there are no potential conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Depression is one of the common non-motor symptoms of Parkinson's disease (PD). In the clinic, botulinum neurotoxin A (BoNT/A) has been used to treat depression. In this study, we investigated the mechanisms underlying the anti-depressive effect of BoNT/A in a PD mouse model. Mice were administered reserpine (3 μg/mL in the drinking water) for 10 weeks. From the 10 th week, BoNT/A (10 U·kg -1 ·d -1 ) was injected into the cheek for 3 consecutive days. We showed that chronic administration of reserpine produced the behavioral phenotypes of depression and neurochemical changes in the substantia nigra pars compacta (SNpc) and striatum. BoNT/A treatment significantly ameliorated the depressive-like behaviors, but did not improve TH activity in SNpc of reserpine-treated mice. We demonstrated that BoNT/A treatment reversed reserpine-induced complement and microglia activation in the hippocampal CA1 region. Furthermore, BoNT/A treatment significantly attenuated the microglial engulfment of presynaptic synapses, thus ameliorating the apparent synapse and spine loss in the hippocampus in the reserpine-treated mice. Moreover, BoNT/A treatment suppressed microglia-mediated expression of pro-inflammatory cytokines TNF-α and IL-1β in reserpine-treated mice. In addition, we showed that BoNT/A (0.1 U/mL) ameliorated reserpine-induced complement and microglia activation in mouse BV2 microglial cells in vitro. We conclude that BoNT/A ameliorates depressive-like behavior in a reserpine-induced PD mouse model through reversing the synapse loss mediated by classical complement induced-microglial engulfment as well as alleviating microglia-mediated proinflammatory responses. BoNT/A ameliorates depressive-like behavior, and reverses synapse loss mediated by classical complement pathway-initiated microglia engulfment as well as alleviates microglia-mediated proinflammatory response in the reserpine-induced Parkinson's disease mouse model., (© 2023. The Author(s).)

Recent evidence suggests that cyclin-dependent kinase 4/6 (CDK4/6) inhibitors significantly improve progression-free survival and overall survival among metastatic breast cancer patients. However, given the effects on cell cycle arrest, there is potential for CDK4/6 inhibitors and radiotherapy (RT) to work synergistically, enhancing the effect and toxicities of RT. A comprehensive review of the literature on the combination of RT and CDK4/6 inhibitors was performed with 19 eligible studies included in the final analysis. A total of 373 patients who received radiotherapy combined with CDK4/6 inhibitors were evaluated across 9 retrospective studies, 4 case reports, 3 case series, and 3 letters to the editor. The CDK4/6 inhibitor used, RT target, and RT technique were assessed in terms of toxicities. This literature review demonstrates generally limited toxicities with the combination of CDK4/6 inhibitors and palliative radiotherapy to metastatic breast cancer patients. The current evidence is nonetheless limited, and further results of ongoing prospective clinical trials will help clarify whether these treatments can be safely combined.

4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is one of the most promising herbicide targets for the development of agricultural chemicals owing to its unique mechanism of action in plants. We previously reported on the co-crystal structure of Arabidopsis thaliana ( At ) HPPD complexed with methylbenquitrione ( MBQ ), an inhibitor of HPPD that we previously discovered. Based on this crystal structure, and in an attempt to discover even more effective HPPD-inhibiting herbicides, we designed a family of triketone-quinazoline-2,4-dione derivatives featuring a phenylalkyl group through increasing the interaction between the substituent at the R 1 position and the amino acid residues at the active site entrance of At HPPD. Among the derivatives, 6-(2-hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-1,5-dimethyl-3-(1-phenylethyl)quinazoline-2,4(1H,3H)-dione ( 23 ) was identified as a promising compound. The co-crystal structure of compound 23 with At HPPD revealed that hydrophobic interactions with Phe392 and Met335, and effective blocking of the conformational deflection of Gln293, as compared with that of the lead compound MBQ , afforded a molecular basis for structural modification. 3-(1-(3-Fluorophenyl)ethyl)-6-(2-hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-1,5-dimethylquinazoline-2,4(1H,3H)-dione ( 31 ) was confirmed to be the best subnanomolar-range At HPPD inhibitor (IC 50 = 39 nM), making it approximately seven times more potent than MBQ . In addition, the greenhouse experiment showed favorable herbicidal potency for compound 23 with a broad spectrum and acceptable crop selectivity against cotton at the dosage of 30-120 g ai/ha. Thus, compound 23 possessed a promising prospect as a novel HPPD-inhibiting herbicide candidate for cotton fields.

Purpose: Our purpose was to investigate radiation therapy (RT) toxicity when given with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) compared with RT alone., Methods and Materials: We conducted a retrospective cohort study of patients with hormonal receptor-positive and human epidermal growth factor-2 negative metastatic breast cancer treated with RT at 4 cancer centers in Alberta, Canada, between 2016 and 2020. Toxicity in patients treated with RT within 30 days of initiating to discontinuing CDK4/6i (RT + CDK4/6i) was compared with toxicity of RT in CDK4/6i-naïve patients (RT alone). The primary outcome was acute grade (G) 2 or higher, nonhematological toxicity within 30 days of RT. We also explored toxicity based on the timing of RT (prior, concurrent, post) in relation to CDK4/6i. Propensity score matching was applied to create comparable cohorts. A generalized linear mixed model was used to evaluate factors associated with acute toxicity., Results: One hundred thirty-two patients (220 RT sites) in the RT + CDK4/6i and 53 patients (93 RT sites) in RT alone were eligible. The rate of acute G2 or higher nonhematological toxicity was 11.5% versus 7%, respectively (P = .439), and acute G3 or higher nonhematological toxicity was 3.7% versus 0%, respectively (P = .151). Acute toxicity in RT + CDK4/6i group was mainly observed when RT was given concurrently (67%), with most of the G3 toxicity recorded. After propensity score matching, the association of acute toxicity with RT + CDK4/6i versus RT alone was not significant on multivariable analysis (odds ratio, 3.13; 95% confidence interval, 0.74-13.2; P = .121)., Conclusions: We did not observe a significant association between CDK4/6i use and acute G2 or higher nonhematological toxicity in women with metastatic breast cancer receiving palliative RT. Given the findings of G3 toxicity, caution is advised whenever CDK4/6i is given concurrently with RT., (Copyright © 2022 Elsevier Inc. All rights reserved.)

While cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including palbociclib, combined with endocrine therapy (ET), are becoming the standard-of-care for hormone receptor-positive/human epidermal growth factor receptor 2‒negative metastatic breast cancer, further mechanistic insights are needed to maximize benefit from the treatment regimen. Herein, we conducted a systematic comparative analysis of gene expression/progression-free survival relationship from two phase 3 trials (PALOMA-2 [first-line] and PALOMA-3 [≥second-line]). In the ET-only arm, there was no inter-therapy line correlation. However, adding palbociclib resulted in concordant biomarkers independent of initial ET responsiveness, with shared sensitivity genes enriched in estrogen response and resistance genes over-represented by mTORC1 signaling and G2/M checkpoint. Biomarker patterns from the combination arm resembled patterns observed in ET in advanced treatment-naive patients, especially patients likely to be endocrine-responsive. Our findings suggest palbociclib may recondition endocrine-resistant tumors to ET, and may guide optimal therapeutic sequencing by partnering CDK4/6 inhibitors with different ETs. Pfizer (NCT01740427; NCT01942135)., (© 2022. The Author(s).)

Locoregional management of breast cancer is founded on evidence generated over a vast time period, much longer than the career span of many practicing physicians. Oncologists rely on specific patient and tumour characteristics to recommend modern-day treatments. However, some of this information may not have been available during prior periods in which the evidence was generated. For example, the comprehensive Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analyses published in the 2000s typically included older trials accruing patients between the 1960s and 1980s. This raises some uncertainty about whether conclusions from studies conducted in prior eras are as relevant or applicable to modern-day patients and treatments. Reviewing the chronological order and details of the evidence can be beneficial to understanding these nuances. This review discusses the evolution of locoregional management through some key clinical trials. We aim to highlight the time period in which the evidence was generated and emphasize the 10-year outcomes for the comparability of results. Evidence supporting surgical management of the breast and axilla, as well as details of radiotherapy are discussed briefly for all stages of breast cancer.

Cancer is the leading cause of mortality in Canada. Undergraduate medical education therefore must ensure adequate oncology education for all physicians and inspire some to make oncology their career specialty, in an effort to ensure public care needs are met in the future. Medical student-led oncology interest groups (OIGs) are a subset of specialty interest groups that supplement formal didactic and clinical learning to increase exposure to oncology and access to mentors. We conducted a survey of OIG leaders to ascertain their goals, activities, barriers, future directions, and perceptions about employment prospects. OIG leaders from 12/17 Canadian medical schools responded. Medical oncology was the most represented specialty in OIGs. Half of OIGs had faculty mentors. Self-reported goals were to increase exposure to oncology disciplines (n = 12), assist students with career selection (n = 11) and finding mentors (n = 7), and enhance oncology education (n = 10). OIGs held on average 5 events per year (range 1-12). Reported barriers were finding time to plan events, declining student interest over academic year, and limited funding. Many OIGs showed interest in more standardized resources about oncology disciplines (n = 9), access to presentations (n = 10), more funding (n = 7), and collaboration (n = 7). Employment in many oncology specialties was perceived poorly, and the most important career selection considerations were ease of employment, practice location, and partner/family preference. Our survey highlights common goals, barriers, and perceptions in OIG medical student leaders across Canada and provides guidance for future interventions., (© 2020. American Association for Cancer Education.)

Breast cancer patients receiving adjuvant chemotherapy are at increased risk of acute care use. The incidence of emergency department (ED) visits and hospitalizations (H) have been characterized in other provinces but never in Alberta. We conducted a retrospective population-based cohort study using administrative data of women with stage I-III breast cancer receiving adjuvant chemotherapy. Rates of ED and H use in the 180 days following chemotherapy initiation were determined, and logistic regression was performed to identify risk factors. We found that 47% of women receiving adjuvant chemotherapy experienced ED or H, which compared favourably to other provinces. However, Alberta had the highest rate of febrile neutropenia-related ED visits, and among the highest chemotherapy-related ED visits. The incidence of acute care use increased over time, and there were significant institutional differences despite operating under a single provincial healthcare system. Our study demonstrates the need for systematic measurement and the importance of quality improvement programs to address this gap.

Background: Cognitive impairment has been identified as a core feature of depression. Serum triglycerides (TG), gonadal hormone and sex difference were shown to influence cognitive performance. The purpose of this study was to investigate the associations among serum TG, gonadal hormone, sex difference and cognitive performance in patients with major depressive disorders (MDD)., Methods: The enrolled 183 patients (male/female = 80/103) meeting DSM-IV criteria for MDD were divided into high TG group (patients-HTG) and normal TG group (patients-NTG) according to TG level. Serum TG, estradiol (E2) and testosterone (T) levels were measured by the glycerokinase peroxidase-peroxidase and chemiluminescence methods. Cognition was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The study was conducted between August 2016 and January 2020., Results: In female, patients-HTG had lower immediate memory, language, attention, delayed memory and RBANS total scores than patients-NTG after adjusting for covariates. There were significant differences in serum E2 and T levels between patients-HTG and patients-NTG in female after controlling for covariates. In female patients-HTG, serum E2 level was positively associated with immediate memory, delayed memory and RBANS total scores, and serum T level was positively related to immediate memory, language and RBANS total scores. These findings were not seen in male patients., Conclusions: Our data suggested that patients-HTG exhibited poorer cognitive function compared with patients-NTG in female. Moreover, the decline in serum gonadal hormone level might contribute to the high TG development of female MDD, and was further implicated in their cognitive decline., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: To understand the association between various treatments and survival for older women with higher-risk breast cancer when controlling for patient and tumor factors., Materials and Methods: We conducted a retrospective, population-based study. Women aged 80 years or older and diagnosed between 2004 and 2017 with non-metastatic, higher-risk breast cancer were identified form the provincial cancer registry in Alberta, Canada. Higher-risk was defined as any of following: T3/4, node positive, human epidermal factor receptor-2 (Her2) positive or triple negative disease. Treatments were surgery, radiotherapy and systemic therapy (hormonal therapy, and/or chemotherapy and/or trastuzumab) or a combination of the previous. Cox regression models were used to examine the association between treatments and breast cancer specific survival (BCSS) and overall survival (OS)., Results: 1369 patients were included. The median age was 84 years. 332 (24%) of women had T3-T4 tumors, 792 (58%) had nodal involvement, 130 (10%) had Her2 positive tumors, 124 (9%) had triple negative tumors. After a median follow-up of 35 months, 29.5% of patients died of breast cancer whereas 34.2% died from other causes. Patients had a lower adjusted hazard for BCSS if they had surgery (hazard ratio [HR] = 0.37 95% confidence interval [CI]: 0.27, 0.51), or systemic therapy (HR = 0.75, 95%CI: 0.58, 0.98). Patients had an increased probability of breast cancer death in the first 5 years after diagnosis compared to death from other causes., Conclusions: Surgery and systemic therapy were associated with longer BCSS and OS. This suggests that maximizing treatments might benefit higher-risk patients., Competing Interests: Declarations of competing interest LB has received an honorarium from Genentech and travel support from Elekta. Other authors, none., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cognitive and sensory deficits were considered a core feature of major depressive disorder (MDD). However, few studies investigated stereopsis integrity in patients with MDD. Thus, the objectives of this study investigated stereopsis integrity and its correlations with cognitive function and depressive symptom in patients with MDD. 90 patients with MDD and 116 healthy controls (HCs) were enrolled in this study. Their stereoacuity was evaluated using the Titmus Stereopsis Test as well as assessing their cognitive function and depressive symptom by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Hamilton Depression Scale (HAMD). Log seconds of arc was significantly higher in patients than HCs (1.92 ± 0.41 versus 1.67 ± 0.16, t = 5.35, p < 0.0001). The percentage of patients with correct stereopsis detection was markedly declined in 400 (z = 3.06, p = 0.002), 200 (z = 3.84, p < 0.001), 140 (z = 4.73, p < 0.001), 100 (z = 4.58, p < 0.001), 80 (z = 5.06, p < 0.001), 60 (z = 4.72, p < 0.001), 50 (z = 4.24, p < 0.001), and 40 (z = 4.85, p < 0.001) seconds of arc compared with HCs. Log seconds of arc was significantly correlated with the RBANS total score (r = -0.38, p < 0.0001), subscores of attention (r = -0.49, p < 0.0001) and language (r = -0.33, p = 0.001) rather than HAMD score (r = 0.03, p = 0.78) in MDD patients. In addition, log seconds of arc was significantly related to the RBANS total score (r = -0.58, p < 0.0001) and language score (r = -0.45, p = 0.006) rather than attention score (r = -0.30, p = 0.07) in HCs. Further stepwise multivariate regression analyses showed the negative correlation of log seconds of arc with attention score (β = -0.80, t = -3.95, p < 0.0001) rather than HAMD score (β = -0.008, t = -0.09, p = 0.93) in MDD patients. However, there was no relationship between log seconds of arc and attention score in HCs (β = 1.52, t = 1.19, p = 0.24). Our results identified the marked deficits of stereopsis in MDD patients that were tightly correlated with their attention functioning rather than depressive symptom., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P >0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P <0.001), smaller maximum tumor diameter ( t =3.969, P <0.001), less number of metastatic lymph nodes ( t =1.343, P <0.001), lower ratio of vessel invasion (χ(2)=11.897, P =0.001) and nerve invasion (χ(2)=12.338, P <0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P =0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P =0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P <0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P <0.05); patients over 45 years of age ( P <0.05) and with normal body mass ( P <0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly ( P <0.05); patients with signet ring cell carcinoma benefited little ( P >0.05); tumors in the gastric body and gastric antrum benefited more significantly ( P <0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

Two triphenylamine chalcone derivatives 1 and 2 were synthesized through the Vilsmeier-Haack reaction and Claisen-Schmidt condensation reaction. Through ultraviolet absorption spectroscopy and fluorescence emission spectroscopy experiments, it was confirmed that these two compounds exhibited good aggregation-induced emission (AIE) behavior in ethanol/water mixtures. The solvent effect test showed with the increase of the orientation polarizability of the solvent, the Stokes shift in the solvent of compound 1 and compound 2 shows a linear change trend. Through solid state fluorescence test and universal density function theory (DFT), the existence of π-π stacking interaction in the solid state of the compound has been studied, resulting in weak fluorescence emission. pH has no effect on the fluorescence intensity of the aggregate state of excited state intramolecular proton transfer (ESIPT) molecules in an acidic environment, but greatly weakens its fluorescence intensity in an alkaline environment. Cyclic voltammetry (CV) test shows that compound 1 was more prone to oxidation reaction than compound 2. The results of thermal stability test show that the thermal stability of compound 1 was better than that of compound 2, indicating that triphenylamine chalcone derivatives can improve the thermal stability of compounds by increasing the number of branches.

Two novel monoterpenoid indole alkaloids (MIAs), gelsechizines A-B (1-2), along with four known ones (3-6) were isolated from the fruits of Gelsemium elegans. Compound 1 features a new carbon skeleton with two additional carbon atoms forming a 4-methylpyridine unit. Their structures with absolute configurations were elucidated by NMR, MS, X-ray diffraction and electronic circular dichroism (ECD) calculations. Compounds 1-3 showed significant anti-inflammatory effects in vivo and in vitro, which may be related to the inhibition of the trecruitment of neutrophils and macrophages as well as the secretion of TNF-α and IL-6. Preliminary structure-activity relationship analysis revealed that the β-N-acrylate moiety plays an important role in the anti-inflammatory effect., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Myrcauones A-D (1-4), four new phloroglucinol-terpene adducts were isolated from the leaves of Myrciaria cauliflora. Their structures with absolute configurations were elucidated by combination of spectroscopic analysis, single crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compound 1 was a rearranged isobutylphloroglucinol-pinene adduct featuring an unusual 2,3,4,4a,10,11-hexahydro-1H-3,11a-methanodibenzo[b,f]oxepin backbone. Compound 4 showed moderate antibacterial activity against Gram-positive bacteria including multiresistant strains.

This study focused on the role of methionine (MET) in the autophagy of gastric cancer stem cells (GCSCs) and aims to elaborate its regulatory mechanism. In the present study, the GCSCs were isolated from human gastric cancer cell lines using an anti-CD44 antibody, and then cultured in MET + homocysteine (HCY) - or MET - HCY + medium. In MET + HCY - treated GCSCs, autophagy was suppressed, the methylation and phosphorylation of RAB37 were elevated, and miR-200b expression was down-regulated. Lentiviral vector (LV-) carrying methionine-γ lyase (an enzyme that could specifically lyse MET; Metase) promoted autophagy, reduced the methylation and phosphorylation of RAB37, and up-regulated miR-200b expression in MET + HCY - -treated GCSCs. Then, we found that miR-200b suppressed the expression of protein kinase C α (PKCα), a protein that could inactivate RAB37 through promoting its phosphorylation. LV-Metase down-regulated RAB37 phosphorylation via miR-200b/PKCα, thus promoting the RAB37-mediated autophagy and suppressing cell viability in MET + HCY - treated GCSCs. Finally, the in vivo study proved that LV-Metase treatment inhibited tumor growth through up-regulating RAB37 expression. In conclusion, MET suppressed RAB37 expression via enhancing its methylation and suppressed RAB37 activity via miR-200b/PKCα axis, thus repressing RAB37-mediated autophagy in GCSCs. The supplementation of Metase lysed MET, thus inducing the autophagy of GCSCs and inhibiting tumor growth.

One new sesquiterpene (α-iso-cubebenol acetate, 8 ), together with 9 known compounds (1-7, 9, 10) were isolated from the stems of Schisandra chinensis (Turcz.) Baill. by repeated silica gel column chromatography. Based on the results of MS, NMR spectra and comparing with literature data, the six dibenzocyclooctadiene lignans were identified as schizandrin A to C (1-3), schizandrin (4), schisantherin A (5) and gomisin J (6), the two sesquiterpenes were identified as α-iso-cubebenol (7) and α-iso-cubebenol acetate (8), while the two triterpenic acids were identified as ganwuweizic acid (9) and kadsuric acid (10). The antifeedant activity of the 10 compounds against Tribolium castaneum adults was tested. Gomisin J (6) exhibited activity at 1500 ppm concentration with 40.3% antifeeding index percentages. As for the dibenzocyclooctene lignans (compounds 1-3 , 6 ), the number of methylenedioxies and the position of hydroxyl groups were the main factors to affect their antifeedant activities.

Whether an unplanned pregnancy should be terminated during follow-up of a hydatidiform mole is controversial. We report a patient who had an unplanned pregnancy with a hydatidiform mole at 2 months after uterine curettage when the human chorionic gonadotropin level had decreased to a negative value. Hydatidiform mole was confirmed by histopathology. Uterine curettage was performed twice and regular follow-ups were performed after surgery. The patient achieved a full-term pregnancy. The Apgar score of the newborn was 10 at 1, 5, and 10 minutes, and the newborn had no malformations. We conclude that the pregnancy outcome might be good in an unplanned pregnancy when the human chorionic gonadotropin level is negative.

Background: In this study, we investigated the effects of prior influenza exposure on vaccine-elicited humor immune responses to circulating influenza variants., Method: We randomly selected 360 participants in previous clinical trials stratified by age. Blood samples were collected and tested by hemagglutination-inhibition tests during the 2015-2016 influenza seasons in China. The antigenic map was plotted and antigenic distance was calculated., Results: Subjects with H1-priming had higher cross-reactive antibodies titers against A/JiangsuTinghu/11019/2015(H3N2) compared with subjects with B-priming did ( P adjusted  = .038). Subjects with H1-priming also had higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015(H3N2) than subjects with both H1 and B priming ( P adjusted  = .036). Nevertheless, subjects with no H1 and B-priming had higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015(H3N2) than subjects with both H1 and B priming ( P adjusted = .012). Antigenic distance was well matched with serological results. Moeover, age-specific differences in human postvaccination responses against the identical circulating strain was noted. In addition, children had the most cross-reactive response to both H3N2 and B-yamagata subtypes., Conclusions: Our results suggest that prior exposure to H1 or B influenza virus may influence cross-reactivity of H3-specific postvaccination responses and consequently could influence the vaccine effectiveness. Our findings also support that there are age-specific differences in human postvaccination responses., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

In order to develop more environmentally benignant insecticides, the Ligusticum pteridophyllum Franch. rhizomes essential oil and supercritical fluid (SFE-CO 2 ) extract were obtained by two published techniques, hydrodistillation and SFE-CO 2 . The chemical components of this two tested samples were identified by using gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detector (GC-FID). Repellent activity and contact toxicity of the obtained samples and myristicin against the adults of Tribolium castaneum (Coleoptera: Tenebrionidae), Lasioderma serricorne (Coleoptera: Anobiidae), and Liposcelis bostrychophila (Psocoptera: Liposcelididae) were compared. Nineteen components were identified in the SFE-CO 2 extract. Twelve components were identified in the L. pteridophyllum rhizomes essential oil. SFE-CO 2 extract exhibited higher contact toxicity against T. castaneum, L. serricorne, and L. bostrychophila (LD 50  = 69.60 μg/adult, 14.58 μg/adult, and 1.69 μg/cm 2 , respectively) than that of L. pteridophyllum rhizomes essential oil (LD 50  = 87.99 μg/adult, 89.82 μg/adult, and 7.87 μg/cm 2 , respectively). Besides, myristicin (LD 50  = 36.46 μg/adult) showed superior contact toxicity against T. castaneum than that of the L. pteridophyllum rhizomes essential oil and SFE-CO 2 extract. It possessed potentially practical significance to develop L. pteridophyllum rhizomes into plant pesticide or repellent agent for these stored insect controls. Graphical abstract .

Objective: Percutaneous transluminal balloon angioplasty (PTA) is recommended as the first choice to treat stenosis of Brescia-Cimino arteriovenous fistulas (B-C AVFs). The ability to predict which B-C AVFs are at risk for recurrent stenosis post-PTA would allow closer monitoring of patients, and possibly result in surgical intervention rather than repeat PTA. The purpose of this study was to identify predictive factors of primary patency after PTA in B-C AVFs., Methods: Patients diagnosed with B-C AVF primary stenosis and treated by PTA between November 2013 and March 2018 were included in the study. Patient and stenotic lesion characteristics and PTA procedure factors were included in the analysis. The Kaplan-Meier method was used to analyze the primary patency rate. Cox proportional hazard regression analysis was used to identify factors predictive of decreased primary patency., Results: 74 patients (35 males, 39 females) with a mean age of 61.68 ± 11.44 years (range, 36-84 years) were included in the study. The mean B-C AVF age was 16.34 ± 12.93 months (range, 2-84 months), and the median primary patency time was 7.79 ± 0.48 months. Cox proportional hazard regression analysis revealed stenosis location at the inflow artery [hazard ratio (HR)=3.83, 95% confidence interval (CI): 1.46-10.09] or anastomosis (HR = 1.90, 95% CI: 1.09-3.32), dilation >2 times during PTA (HR = 2.30, 95% CI: 1.22-4.34), and residual stenosis >30% (HR = 2.42, 95% CI: 1.26-4.63) were significantly associated with decreased patency., Conclusion: In conclusion, the primary patency rate of PTA for B-C AVF dysfunction is reduced by dilation >2 times, residual stenosis >30%, and stenosis located at the inflow artery or anastomosis. These results may help in tailoring surveillance programs, multiple PTA, or a proximal re-anastomosis surgery in patients with AVF dysfunction., Advances in Knowledge: A number of studies have been conducted to examine the predictors of primary patency after PTA, however, no definitive conclusions have been reached. Our study revealed that stenosis location at the inflow artery or anastomosis, dilation >2 times during PTA, and residual stenosis >30% were the predictors of primary patency after PTA, which may help in tailoring surveillance programs, multiple PTA, or a proximal re-anastomosis surgery in patients with arteriovenous fistulas dysfunction.

Effectiveness of seasonal influenza vaccines varies greatly during the different flu seasons. Although the WHO assesses and updates influenza vaccine strains every year, the effectiveness of vaccine is sometimes not good. This review explores the various factors that influencing influenza vaccine effects in order to improve the effectiveness of influenza vaccines and provide a scientific basis for influenza vaccination. The results reveal that the degree of matching between epidemic strains and vaccine strains, pre-exposure (natural infection, vaccination), age, and immune status could all affect the vaccine effectiveness.

Guanine-rich DNA sequences can spontaneously fold into four-stranded structures called G-quadruplexes (G4s). G4s have been identified extensively in the promoter regions of several proto-oncogenes, including c-myc, as well as telomeres. G4s have attracted an increasing amount of attention in the field of nanotechnology because of their use as versatile building blocks of DNA-based nanostructures. In this study, we report the self-assembly of c-myc G-quadruplex DNA controlled by a pair of chiral ruthenium(ii) complexes coordinated by 2-(4-phenyacetylenephenyl)-1H-imidazo[4,5f][1,10]phenanthroline (PBEPIP), Λ-[Ru(bpy) 2 (PBEPIP)](ClO 4 ) 2 (Λ-RM0627, bpy = bipyridine) and Δ-[Ru(bpy) 2 (PBEPIP)](ClO 4 ) 2 (Δ-RM0627). Λ-RM0627 could promote the high-order self-assembly of c-myc G-quadruplex DNA into a nanowire structure, whereas Δ-RM0627 could induce DNA condensation into G-quadruplex aggregates. Moreover, in vitro studies on human liver carcinoma HepG2 cells showed that the nanowire of c-myc G-quadruplex DNA promoted by Λ-RM0627 could be localized in the nuclei of cells, whereas the nanoparticle of c-myc G-quadruplex DNA generated by Δ-RM0627 was taken up and localized in the cytoplasm. This study provides examples of the enantioselective self-assembly of G4 DNA molecules controlled by chiral ruthenium(ii) complexes and suggests the potential applications of assembled nanostructures as non-viral DNA vectors for gene therapy.

Multiple primary malignant tumors (MPMTs) refer to two or more primary malignant neoplasms that simultaneously or successively occur in one or more organs in the same individual. Cervical sarcoma concomitant with endometrial carcinoma is rare. A 46-year-old woman was admitted because of increased menstrual volume for 4 years and irregular vaginal bleeding with discharge for 6 months. The diagnosis of endometrial carcinoma at stage II was made on the basis of results of ultrasound, pelvic magnetic resonance imaging, and hysteroscopic curettage. Extensive total abdominal hysterectomy + bilateral adnexectomy + bilateral ovarian arteriovenous high ligation + pelvic adhesion separation + pelvic lymphadenectomy +abdominal aortic lymphadenectomy via the abdomen were performed. Postoperative diagnosis of cervical sarcomas with endometrial carcinoma in stage IIIC1 was made according to the results of pathology and immunohistochemistry. Six cycles of cisplatin-epirubicin-isocyclophosphamide treatment were provided after the operation. Most clinical manifestations of cervical sarcomas are abnormal vaginal bleeding. Use of preoperative imaging and hysteroscopy is difficult for diagnosing cervical sarcomas, and postoperative pathological examinations and immunohistochemical diagnosis are mainly used instead. The possibility of MPMTs should be considered for endometrial carcinoma, especially if the cervical lesion is larger than that of the uterine cavity.

In this work, the feasibility of using flattening filter free (FFF) beams in volumetric modulated arc therapy (VMAT) total body irradiation (TBI) treatment planning to decrease protracted beam-on times for these treatments was investigated. In addition, a methodology was developed to generate standardized VMAT TBI treatment plans based on patient physical dimensions to eliminate plan optimization time. A planning study cohort of 47 TBI patients previously treated with optimized VMAT ARC 6 MV beams was retrospectively examined. These patients were sorted into six categories depending on height and anteroposterior (AP) width at the umbilicus. Using Varian Eclipse, clinical 40 cm × 10 cm open field arcs were substituted with 6 MV FFF. Mid-plane lateral dose profiles in conjunction with relative arc output factors (RAOF) yielded how far a given multileaf collimator (MLC) leaf must move in order to achieve a mid-plane 100% isodose for a specific control point. Linear interpolation gave the dynamic MLC aperture for the entire arc for each patient AP width category, which was subsequently applied through Python scripting. All FFF VMAT TBI plans were then evaluated by two radiation oncologists and deemed clinically acceptable. The FFF and clinical VMAT TBI plans had similar Body-5 mm D98% distributions, but overall the FFF plans had statistically significantly increased or broader Body-5 mm D2% and mean lung dose distributions. These differences are not considered clinically significant. Median beam-on times for the FFF and clinical VMAT TBI plans were 11.07 and 18.06 min, respectively, and planning time for the FFF VMAT TBI plans was reduced by 34.1 min. In conclusion, use of FFF beams in VMAT TBI treatment planning resulted in dose homogeneity similar to our current VMAT TBI technique. Clinical dosimetric criteria were achieved for a majority of patients while planning and calculated beam-on times were reduced, offering the possibility of improved patient experience., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

There are many limitations in evaluating vaccine efficacy by comparing the incidence of clinical endpoint events (such as morbidity, bacterial colonization) between the vaccine group and the control group. Therefore, the researchers put forward the concept of Surrogate of protection to predict vaccine protection with immunological indicators. In 2012, WHO put forward the immunological substitution endpoint of pneumococcal vaccine, using 0. 35 μg/ml as the protective antibody level of pneumococcal vaccine. But subsequent studies have found that using this threshold to assess all vaccine serotypes may not be accurate.

Metabolites are the final products of cellular regulation processes, their level is the ultimate response of biological systems to environmental and genetic changes. Therefore, the identification of key metabolites is required for the diagnosis and therapy of diseases. In this study, atherosclerosis-related gene expression profile information was extracted from ArrayExpress database (GEOD-57691), and analyzed with limma package. Furthermore, we constructed an intricate multi-omics network involved in genes, phenotypes, metabolites and their associations. To identify the prioritization of atherosclerosis-related metabolites, the relation score of each metabolite in the composite network was computed with the random walk with restart (RWR) method. The top 50 metabolites and top 100 genes were chosen based on the score in the weighted composite network. Consequently, several key metabolites that were ranked in the top 5 of relation score or degree greater than 70 were confirmed. Particularly, metabolites Tretinoin and Estraderm not only have high relation scores, but also contain more degrees. Moreover, we obtained 24 co-expression genes that may be regarded as the targets of atherosclerosis therapy. Therefore, identification of metabolite prioritizations by the composite network integrated the information of genes, phenotypes and metabolites may be available to diagnose atherosclerosis, and can provide the potential therapeutic strategies for atherosclerosis.

A pair of enantiomeric triketone-phloroglucinol hybrids, (+)- and (-)-myrtuspirone A (1), featuring an unprecedented 3-isopropyl-3 H-spiro[benzofuran-2,1'-cyclohexane] backbone, were isolated from the leaves of Myrtus communis. The absolute configuration of each enantiomer of 1 was determined by X-ray diffraction and chemical calculations. Furthermore, the gram-scale total syntheses of (±)-1 and (-)-1 were conducted in four steps using a Michael- N-iodosuccinimide (NIS)-mediated (3 + 2)-annulation reaction. Both (+)- and (-)-1 exhibited antibacterial activities against Gram-positive bacteria including multidrug-resistant strains.

In this work, the essential oils (EO) were extracted from seven typical Chinese herbs, and their repellent and contact toxicities against Tribolium castaneum adults (red flour beetles) were evaluated. The experimental results showed that the above EOs presented the various levels of repellent and contact toxicities. The EOs extracted from A. lancea and A argyi of the Compositae (Asteraceae) family presented obvious repellent effects (Repellency Percentage > 90% at 3.15 nL/cm 2 after 4 h exposure) and strong contact toxicity with LD 50 values of 5.78 and 3.09 μg/adult respectively. Based on literature researches and screening results, the EO from A. lancea was analyzed by GC-MS and chosen for further identification of bioactive components. Altogether 59 chemical components were identified and 17 of them were recognized as sesquiterpene compounds, accounting for 57.8% of the total weight of the EO. From the identified sesquiterpenes, three individual compounds (β-eudesmol, hinesol, valencene) were selected for the laboratory bioassays of the toxicity against red flour beetles. It was found that all the three compounds expressed some repellent effects. Although β-eudesmol (31.2%) and hinesol (5.1%) were identified as main constituents and had been considered to be symbolic characteristics of high medicinal value, valencene (0.3%) showed strong repellent property which could be comparable to that of DEET (N, N‑diethyl‑3‑methylbenzamide), a powerful commercial pesticides, and it had best toxicity with LD 50 values of 3.25 (μg/adult) in the contact test. This work may provide toxicity evidence of seven common herbs against red flour beetles, add the information for the development and comprehensive utilization of A. lancea, and will contribute to the application of grain preservation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Combining radiosensitizers with ionizing radiation (IR) is an effective strategy to increase the radiation therapeutic effect for hepatocellular carcinoma (HCC) patients. A phenanthroline derivative, 2-phenyl-imidazo [4, 5 f] [1, 10] phenanthroline (L02), had been synthesized. This study investigated the radiosensitization and mechanisms of L02 combined with IR against HCC. The radiosensitization of L02 combined with IR was evaluated by the sensitivity enhancement ratio (SER) and the isobolographic analysis. The toxicity of L02 and cisplatin were compared by the zebrafish model. The cell cycle and apoptosis were examined by flow cytometry. DNA damage was measured by comet assay and the expressions of apoptosis related proteins were analyzed by western blotting. L02 was effective in sensitizing HCC to IR. The SERs in HepG2 and BEL7402 were 1.41 and 1.28, respectively. The sensitization of L02 was comparable with cisplatin. L02 treatment with IR had synergistic anti-tumor effect. L02 enhanced the percentage of IR induced apoptosis cells. L02 increased comet tail in comet assay when combined with IR. L02 sensitized HCC to IR by the activation of P53 signaling, the decrease in Bcl-2, up-regulation of cytochrome c and the subsequent activation of caspase-3. L02 sensitizes HCC to IR, mostly likely by inhibiting cell proliferation, inducing DNA damage and mitochondria-dependent apoptosis. L02 may be a novel radiosensitizer for HCC., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Treatment options for patients with cavernous transformation of portal vein (CTPV) are limited. This study aimed to evaluate the feasibility, efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) to prevent recurrent esophageal variceal bleeding in patients with CTPV., Methods: We retrospectively analyzed 67 consecutive patients undergone TIPS from January 2011 to December 2016. All patients were diagnosed with CTPV. The indication for TIPS was a previous episode of variceal bleeding. The data on recurrent bleeding, stent patency, hepatic encephalopathy and survival were retrieved and analyzed., Results: TIPS procedure was successfully performed in 56 out of 67 (83.6%) patients with CTPV. TIPS was performed via a transjugular approach alone (n = 15), a combined transjugular/transhepatic approach (n = 33) and a combined transjugular/transsplenic approach (n = 8). Mean portosystemic pressure gradient (PSG) decreased from 28.09 ± 7.28 mmHg to 17.53 ± 6.12 mmHg after TIPS (P < 0.01). The probability of the remaining free recurrent variceal bleeding was 87.0%. The probability of TIPS patency reached 81.5%. Hepatic encephalopathy occurrence was 27.8%, and survival rate was 88.9% until the end of follow-up. Four out of 11 patients who failed TIPS died, and 4 had recurrent bleeding., Conclusions: TIPS should be considered a safe and feasible alternative therapy to prevent recurrent esophageal variceal bleeding in patients with CTPV, and to achieve clinical improvement., (Copyright © 2018. Published by Elsevier B.V.)

Genes play an important role in the immune system response, and different gene loci may result in different vaccine immune response rates. This review focuses on the correlation between gene polymorphisms and vaccine immune response in order to investigate the influence of gene polymorphisms on the immune response to vaccines. It discusses the effect of an individual's immune response after vaccination at genetic level and provides a scientific basis for individualized immune development strategies. It reveals that human leukocyte antigen genes, various cytokines and their receptor genes, and Toll-like receptor genes all affect the vaccine immune response.

In this work, the essential oil (EO) was extracted from the fruits of Evodia lenticellata, and the fumigant toxicity, contact toxicity and repellency against three stored-product insect species were evaluated for the obtained EO and several of its chemical components. The target insects were the adults of Tribolium castaneum (Coleoptera: Tenebrionidae), Lasioderma serricorne (Coleoptera: Anobiidae) and Liposcelis bostrychophila (Psocoptera: Liposcelididae). The EO was obtained with hydrodistillation and its chemical components were analyzed with the gas chromatography-mass spectrometry (GC-MS). Twenty-seven compounds, accounting for 83.1% of the total amount of the oil, were identified from the EO sample. The main compounds included linalool (12.0%), β-pinene (11.5%), 3-carene (9.6%), caryophyllene oxide (8.7%) and β-caryophyllene (7.9%). Among them, the amounts of monoterpenes and sesquiterpenes were as high as 52.7% and 22.7% to the total amount of EO respectively. The results of bioactivity test showed that the EO and its testing compounds had interspecific toxicity and repellent activity. So that, it might be expected that the EO extracted from the fruits of E. lenticellata could be developed to a new type of eco-friendly natural insecticide or repellent for the control of stored-product insects., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The development of Ru(ii) complexes as luminescent probes has attracted increasing attention in recent decades. In this study, the nanosized polymers of two Ru(ii) complexes [Ru(phen) 2 (dppz)](ClO 4 ) 2 (1, phen = 1,10-phenanthrolin; dppz = dipyrido[3,2- a :2',3'- c ]phenazine) and [Ru(phen) 2 (Br-dppz)](ClO 4 ) 2 (2, Br-dppz = 11-bromodipyrido[3,2- a :2',3'- c ]phenazine) with oligonucleotides were prepared and investigated as potential tumor-imaging probes. The formation of the nanosized polymers, which had an average width of 125-438 nm and an average height of 3-6 nm, for 1 and 2@oligonucleotides were observed through atomic force microscopy. The emission spectra indicated that the luminescence of 1 and 2 markedly increased after binding to oligonucleotides and double-strand DNA (calf thymus DNA), respectively. Moreover, further studies indicated that 1@oligonucleotides and 2@oligonucleotides can easily enter into tumor cells and selectively highlight the tumor area in the zebrafish bear xenograft tumor (MDA-MB-231). In summary, this study demonstrated that 1@oligonucleotides and 2@oligonucleotides could be developed as potential tumor-imaging luminescent probes for clinical diagnosis and therapy., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

The extract from Cinnamomum cassia Presl bark was obtained with supercritical CO 2 fluid extraction (SFE). Chemical components of the SFE extract were characterized by GC-MS spectrometry. The repellency and contact toxicity of the SFE extract were evaluated against the adults of Tribolium castaneum and Lasioderma serricorne along with those of its two main compounds. The results of GC-MS analysis indicated that 33 volatile constituents were identified from the extract. The main components included trans-cinnamaldehyde (32.1%), 3,3-dimethylhexane (10.6%) and 2,4-di-tert-butylphenol (7.9%). Testing results showed that the SFE extract had potent contact toxicity against T. castaneum and L. serricorne with LD 50 values of 3.96 and 23.89 μg/adult, respectively. LD 50 values of trans-cinnamaldehyde against T. castaneum and L. serricorne were 5.78 and 3.24 μg/adult, respectively. Additionally, percentage repellency values of the SFE extract and trans-cinnamaldehyde against T. castaneum and L. serricorne were rather high (PR = 100% and PR > 90%, respectively) at 78.63 and 15.73 nL/cm 2 at 2 h post-exposure. 2,4-Di-tert-butylphenol showed some repellency against both beetle species. Considering its insecticidal and repellent effects, the SFE extract from C. cassia bark might be used in integrated pest management programs for T. castaneum and L. serricorne.

The essential oils (EOs) extracted from Evodia lenticellata Huang and Evodia rutaecarpa (Juss.) Benth. leaves are screened to evaluate their contact toxicity and repellency towards Tribolium castaneum (Coleoptera: Tenebrionidae), Lasioderma serricorne (Coleoptera: Anobiidae) and Liposcelis bostrychophila (Psocoptera: Liposcelididae) adults. The EOs are obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS). The principal components in the E. lenticellata EO are identified to be caryophyllene oxide (28.5%), β-caryophyllene (23.1%), β-elemene (14.5%), and β-cubebene (4.7%), while the main components of the E. rutaecarpa EO are α-pinene (39.4%), β-elemene (13.5%), α-ocimene (7.6%), and α-selinene (4.0%). These two kinds of EOs and their individual compounds all showed different levels of contact toxicity and repellent activity against three stored-product insects.

Callistrilones F - K (1 - 6), six new triketone-phloroglucinol-monoterpene hybrids were isolated from the twigs and leaves of Callistemon rigidus. Their structures with absolute configurations were established by a combination analysis of NMR spectra, X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 3 and 4 exhibited moderate inhibitory activities against herpes simplex virus (HSV-1) with IC 50 values of 10.00 ± 2.50 and 12.50 ± 1.30 μm, respectively., (© 2018 Wiley-VHCA AG, Zurich, Switzerland.)

Cadmium is one major pollutant that is highly toxic to animals and humans. The mechanism of cadmium toxicity on the female reproductive system, particularly oocyte maturation and fertility, remains to be clarified. In this study, we used a mouse model to investigate the effects of cadmium in the drinking water on the meiotic maturation of oocytes and subsequent embryonic development, and the underlying mechanisms associated with the impairment of oocyte maturation such as mitochondrial distribution and histone modifications. Our results show that cadmium exposure decreased the number of ovulated oocytes and impaired oocyte meiotic maturation rate both in vivo and in vitro. The embryonic development after fertilization was also impaired even when the potential hazards of cadmium on the spermatozoa or the genital tract have been excluded by fertilization and embryonic development in culture. Cadmium exposure disrupted meiotic spindle morphology and actin filament, which are responsible for successful chromosome segregation and the polar body extrusion during oocyte maturation and fertilization. ATP contents, which are required for proper meiotic spindle assembly in the oocyte, were decreased, consistent with altered mitochondrial distribution after cadmium exposure. Finally, cadmium exposure affected the levels of H3K9me2 and H4K12ac in the oocyte, which are closely associated with the acquisition of oocyte developmental competence and subsequent embryonic development. In conclusion, cadmium exposure in female mice impaired meiotic maturation of oocytes and subsequent embryonic development by affecting the cytoskeletal organization, mitochondrial function, and histone modifications.

Callisretones A (1) and B (2), two rearranged phloroglucinol-monoterpenoid adducts featuring an unprecedented isopropylcyclopenta[b]benzofuran backbone, together with their postulated biosynthetic precursors (3-9), were isolated from Callistemon rigidus. The previously assigned absolute configurations of viminalins H (7), L (8), and N (9) were revised and unequivocally established by X-ray diffraction data. A putative biosynthetic pathway toward callisretones A and B involving the rearrangement of the terpenoid motif is proposed. In addition, 1 and 2 showed inhibitory effects on nitric oxide production with IC 50 values of 15.3 ± 1.0 and 17.7 ± 1.1 μM, respectively.

Background : Stem cells isolated from peripheral blood of gastric adenocarcinoma patients have noninvasive advantages. However, at present, there is no simple and effective separation technique. Purpose : In this study, CD133+ cells were isolated from peripheral blood of patients with gastric adenocarcinoma by using specific immunomagnetic particles, and the immunology of subcultured cells was identified to evaluate whether the immune magnetic particle separation had any effect on the cells themselves. Methods : Immune magnetic particles, made by a specific technique, are used to sort out the cells whose membrane could express CD133 from peripheral blood of gastric adenocarcinoma patients. By observing the sorted cells within serum-free culturing, we compare the differences in morphology and proliferation ability between the collected cells and cells from a standard tumor cell line. At the same time, an immunofluorescence method is used to detect the expression of the CD133 antibody. Moreover, this study explores the inhibition effect on gastric adenocarcinoma stem cell growth when combining 5-fluorouracil and methionine enzymes. Results and Conclusions : The specific immunomagnetic particles have a small diameter and strong sorting characteristics. In the experiment, there were 20 patients with gastric adenocarcinoma. CD133+ cells were separated successfully from peripheral blood of 13 patients (65%), among which subcultured cells of 9 cases (69.2%) were found to express CD44+ antigens. The sorted cells grew vigorously with a variety of morphologies in non-inducing culture, while the cells induced by β transforming growth factor presented slow growth and uniform morphology. There was a significant difference ( P < 0.05) in cell proliferation between these two groups and the standard tumor cell line. In addition, 5-fluorouracil combined with methionine enzyme inhibited the growth of gastric adenocarcinoma stem cells significantly ( P < 0.05). Accordingly, the CD133+/CD44+ cells from peripheral blood of gastric adenocarcinoma patients, sorted by specific immune magnetic particles, had clear stem cell properties as determined by cell function and structure. This lays a foundation for gastric adenocarcinoma stem cell extraction, culture and further research on stem cell characteristics.