Search

Aim: To assess the association between established clinicopathological variables and the 21-gene recurrence score (RS) stratification of invasive lobular carcinoma (ILC) of the breast. Materials & methods: We identified 9030 ILC patients from the Surveillance, Epidemiology and End Results database. Results: Older age, higher grade tumor and progesterone receptor (PR)-negative disease were independent predictors of high-risk RS stratification. Among patients with PR-positive tumors, 3, 6 and 15% with well-differentiated (G1), moderately-differentiated (G2) and poorly and/or undifferentiated (G3) disease were in the high-risk cohort, respectively. In patients with PR-negative tumors: 16, 24 and 41% of patients with G1, G2 and G3 disease were in the high-risk cohort, respectively. Conclusion: The 21-gene RS testing may not be necessary for patients with PR+/G1–2 ILC.

Introduction Diabetes is closely related with depression. Gardenia fructus antidepressant formula (GFAF) is a Chinese herbal medicine that may be beneficial for depression in diabetic patients. This study aimed to evaluate the efficacy and safety of GFAF for depression in diabetes patients. Methods Randomized controlled trials (RCTs) were included. The patients were diagnosed as having diabetes mellitus with depression. The experimental interventions included GFAF alone or combined with another active treatment. The control interventions included no treatment, placebo or another active treatment. The primary outcome was reduction in the Hamilton Depression Scale (HAMD) scores. Secondary outcomes included reduction in the Self-rating Depression Scale (SDS) scores, response rate, adverse events, etc. PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan fang database and Chinese Science and Technology Periodicals database (VIP) were searched from inception to May 2019 for potentially eligible studies. The meta-analysis was performed using RevMan 5.3 software. Results We identified 12 eligible RCTs including 822 diabetes patients with depression. Results of meta-analysis showed that the HAMD score was significantly reduced following GFAF treatment compared with no antidepressant treatment (SMD: −2.53, 95% CI: −4.80 to −0.27, P = 0.03). Another meta-analysis indicated that patients taking GFAF alone had lower HAMD scores compared with selective serotonin reuptake inhibitors (SSRI) treatment alone (SMD: −0.62, 95% CI: −1.07 to −0.18, P = 0.006). The HAMD scores in the GFAF plus SSRI treatment group were significantly decreased compared with the SSRI treatment group (SMD: −0.37, 95% CI: −0.69 to −0.06, P = 0.02). The same pattern of change was identified with the SDS scores. Conclusion GFAF may be considered an alternative treatment for depression in patients with diabetes. However, more large-scale and well-designed RCTs are warranted.

The recently developed preoperative systemic inflammation response index (SIRI) was reported as a useful biomarker that could predict survival in certain types of malignant tumors. However, the prognostic value of preoperative SIRI in postmenopausal breast cancer remains unclear. This study aimed to explore the relationship between SIRI and survival in postmenopausal patients with breast cancer. A total of 390 postmenopausal patients with breast cancer who underwent a mastectomy at Sun Yat-sen University Cancer Center were retrospectively studied. SIRI was based on peripheral neutrophil, monocyte, and lymphocyte counts, calculated as: neutrophil count × monocyte count/lymphocyte count. The best cut-off value for SIRI was determined using receiver operating characteristic curve analysis. Patients were divided into 2 groups:Low SIRI0.54 and high SIRI0.54. High SIRI was significantly related to progesterone receptor status. Kaplan-Meier survival analysis showed that T stage, N stage, clinical stage, carcinoembryonic antigen, estrogen receptor, progesterone receptor, endocrinotherapy, and SIRI were significantly correlated with overall survival (OS). Multivariate analysis showed that SIRI could also independently predict OS. Preoperative SIRI may be a reliable predictor of OS in postmenopausal patients with operable breast cancer to provide personalized prognostication and to assist in the formulation of a clinical treatment strategy.

Esophageal squamous cell carcinoma (ESCC) is a prevalent aggressive malignant tumor with poor prognosis. Investigations into the molecular changes that occur as a result of the disease, as well as identification of novel biomarkers for its diagnosis and prognosis, are urgently required. Long non-coding RNAs (lncRNAs) have been reported to play a critical role in tumor progression. The present study performed data mining analyses for ESCC via an integrated study of accumulated datasets and identification of the differentially expressed lncRNAs from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The identified intersection of differentially expressed genes (lncRNAs, miRNAs and mRNAs) in ESCC tissues between the GEO and TCGA datasets was investigated. Based on these intersected lncRNAs, the present study constructed a competitive endogenous RNA (ceRNA) network of lncRNAs in ESCC. A total of 81 intersection lncRNAs were identified; 67 of these were included in the ceRNA network. Functional analyses revealed that these 67 key lncRNAs primarily dominated cellular biological processes. The present study then analyzed the associations between the expression levels of these 67 key lncRNAs and the clinicopathological characteristics of the ESCC patients, as well as their survival time using TCGA. The results revealed that 31 of these lncRNAs were associated with tumor grade, tumor-node-metastasis (TNM) stage and lymphatic metastasis status (P

Introduction: It is still controversial whether post-mastectomy radiotherapy (PMRT) is necessary for women with T1-2 N1mic ER-positive HER2-negative breast cancer. The 21-gene recurrence score (RS) assay has been validated in T1-2 N1 breast cancer to be prognostic of locoregional recurrence (LRR) and overall survival (OS). This study aims to evaluate the predict value of 21-gene recurrence score assay for the benefit of PMRT in T1-2 N1mic ER-positive HER2-negative breast cancer.Methods: A population-based cohort study was performed on women with T1-2 N1mic ER-positive HER2-negative breast cancer who underwent mastectomy and were evaluated using the 21-gene RS in the Surveillance, Epidemiology, and End Results (SEER) registry between 2004 and 2015. Clinical characteristics as well as OS and breast cancer-specific survival (BCSS) were compared between patients with and without PMRT in patients with a Low-, Intermediate-, and High-RS. Multivariate COX regression analysis was performed to investigate if the 21-gene RS assay could predict benefit of PMRT in this group of breast cancer patients.Results: A total of 1571 patients met the criteria of our study and were enrolled, including 970 patients in the Low-Risk group (score 30). In the High-Risk group, there were more patients with age ≥50 (87.0 vs. 64.3%, P = 0.040) and received chemotherapy with a borderline significance (91.3 vs. 72.9%, P = 0.066) in the PMRT subgroup than in the no PMRT subgroup. In all three groups, OS was comparable between the PMRT subgroup and the no PMRT subgroup. Furthermore, multivariate analysis did not show any OS benefit for PMRT based on the 21-gene recurrence score.Conclusion: This study showed that the 21-gene RS assay was not able to predict the benefit of PMRT for OS in women with T1-2 N1mic ER-positive HER2-negative breast cancer. However, further prospective larger sample-size trials are warranted to determine if a benefit exists.

Orofacial pain is characterized by its easy spread to adjacent areas, thus presenting with primary hyperalgesia (hypersensitivity at the site of injury) and secondary hyperalgesia (extraterritorial hypersensitivity outside the injured zone). However, the mechanisms behind the secondary hyperalgesia are poorly understood. In the present study, we used a mouse model of partial transection of the infraorbital nerve (pT-ION) to study whether calcium channel subunit α2δ1 (Cavα2δ1) and its downstream signaling contributes to the development of secondary hyperalgesia in the orofacial area. pT-ION caused primary (V2 skin) and secondary (V3 skin) hyperalgesia, which was reversed by the Cavα2δ1 antagonist gabapentin and by the expression of Cavα2δ1-targeting interfering RNA in trigeminal ganglion (TG)-V3 neurons. pT-ION induced increased expression of PKC and TRPA1, which was reversed by Cavα2δ1-targeting interfering RNA, and PKC inhibition reversed the upregulation of TRPA1 and gap junction (GJ) proteins induced by pT-ION. Cavα2δ1 overexpression in TG-V2 neurons induced the upregulation of PKC, TRPA1, and the GJ proteins in the TG and trigeminal subnucleus caudalis and induced hypersensitivity in the V3 skin area, which was reversed by TRPA1, GJ, or PKC blockade. Thus, we conclude that Cavα2δ1 contributes to the development of secondary hyperalgesia through its downstream PKC-TRPA1/GJ signaling pathways. PERSPECTIVE: This study demonstrates that the activation of Cavα2δ1 and the downstream PKC-TRPA1/GJ signaling pathway contributes greatly to trigeminal nerve injury-induced secondary mechanical and cold hyperalgesia. This suggests that inhibitors of Cavα2δ1, TRPA1, or GJs might be effective treatments for nerve injury-induced spreading of orofacial pain.

Introduction: We conducted a non-inferiority analysis using real-world data to compare the survival outcomes of stage T1-2N2-3 (tumor size ≤5 cm and four or more node metastases) breast cancer after breast-conserving surgery (BCS) and mastectomy (MAST).Methods: The study included patients with stage T1-2N2-3 invasive breast carcinoma from the Surveillance, Epidemiology, and End Results program, who underwent BCS or MAST between 2004 and 2012, along with both radiotherapy and chemotherapy. The statistical analyses used included the chi-squared test, multivariate Cox proportional hazards models, and propensity score matching (PSM).Results: The study population comprised 13,263 patients, including 4,787 (36.1%) and 8,476 (63.9%) patients who were treated with BCS and MAST, respectively. Patients with younger age and advanced stage were more likely to have received MAST. The probability of receiving MAST increased over the years, while the probability of BCS decreased (p < 0.001). The 5-year breast cancer-specific survival (BCSS) was 86.1% in the BCS cohort compared to 83.1% in the MAST cohort (p < 0.001). Surgical procedure was an independent prognostic factor for BCSS. Patients who received MAST had worse BCSS than those treated with BCS (hazard ratio = 1.179, 95% confidence interval = 1.087–1.278, p < 0.001). These results remained significant after stratification by age, tumor grade, T stage, N stage as well as marital status. Similar results were obtained after PSM.Conclusions: BCS resulted in noninferior outcome than MAST in patients with T1-2/N2-3 invasive breast carcinoma. BCS may therefore be an optimal treatment option when both treatment options are feasible and appropriate.

The control of chemo-, regio-, diastereo-, and enantioselectivity is a central theme in organic synthesis. The capability to obtain the full set of stereoisomers of a molecule would significantly enhance the efficiency for the synthesis of natural product analogues and creation of chiral compound libraries for drug discovery. Despite the tremendous progress achieved in the field of asymmetric synthesis in the past decades, the precise control of both relative and absolute configurations in catalyst-controlled reactions that create multiple stereocenters remains a significant synthetic challenge. We report here the development of a catalyst-controlled hydroboration with hitherto unattainable selectivity. The Rh-catalyzed hydroboration of α, β-unsaturated carbonyl compounds with pinacolborane proceeds with high levels of regio-, diastereo-, and enantioselectivities to provide a hydroboration product with two vicinal stereocenters. Through the appropriate choice of substrate geometry ( E or Z) and ligand enantiomer ( S or R), all the possible diastereoisomers are readily accessible. The boron-containing products underwent many stereospecific transformations, thus providing a strategy for collective stereodivergent synthesis of diverse valuable chiral building blocks.

Current sample processing (SP) methods for tacrolimus (FK506) immunoassays are mainly based on extraction of drug by organic solvent and divalent metal ions. Although these methods are effective for drug extraction and interference elimination, they suffer from drawbacks including inconvenience for operation, difficulties for automation and potential measurement bias. To overcome these limitations, this study describes a new SP reagent for blood cell lysis and protein denaturation. A TRFIA (time-resolved fluorescence immunoassay) was developed by using this SP reagent for whole blood FK506 quantification. Results show that blood samples could be turned into homogeneous solution after being treated by this SP reagent, and so could be directly applied to immunoassays without centrifugation. The analytical sensitivity of the FK506-TRFIA was 0.57 ng/mL, the within-run and between-run coefficient of variations (CVs) were both less than 10%. The FK506 values of 126 samples obtained by FK506-TRFIA correlated excellently with that obtained by ABBOTT FK506-CMIA (R2 = 0.982). Comparison studies also show that the FK506-TRFIA was highly resistant to endogenous interferences. These results suggest that the present SP method is a more promising chose for FK506 immunoassay, and in the meantime, its simplicity makes the whole-process immunoassay automation more feasible by obviating the necessary for centrifugation.

Introduction: To assess the role of the 21-gene recurrence score (RS) assay on decision-making of postoperative radiotherapy (RT) following breast-conserving surgery (BCS) in elderly women with early-stage breast cancer. Methods: The 21-gene RS for elderly (≥65 years) women with stage T1–2N0M0 estrogen receptor-positive breast cancer who underwent BCS from 2004 to 2015 was obtained from the Surveillance, Epidemiology, and End Results program. We estimated the association of 21-gene RS and adjuvant RT related to breast cancer-specific survival (BCSS) using propensity score matching (PSM). Results: We identified 18,456 patients, of which 15,326 (83.0%) received postoperative RT. Of identified patients, 58.9%, 34.0%, and 7.1% of patients had a low-, intermediate-, and high-risk RS, respectively. Receipt of postoperative RT was not related to the year of diagnosis according to the 21-gene RS groups. Multivariate analysis suggested that receipt of postoperative RT was an independent predictor of better BCSS before (hazard ratio [HR] 0.587, 95% confidence interval [CI] 0.426–0.809, P = 0.001) and after (HR 0.613, 95%CI 0.390–0.963, P = 0.034) PSM. However, subgroups analyses indicated that receipt of postoperative RT was related to better BCSS in women with intermediate-risk RS before (HR 0.467, 95%CI 0.283–0.772, P = 0.003) and after (HR 0.389, 95%CI 0.179–0.846, P = 0.017) PSM, but not in women with low- and high-risk RS groups before and after PSM. Conclusions: Although causation cannot be implied, adjuvant RT in elderly women was associated with a greater effect size in patients with an intermediate-risk RS.

Aim: To determine the effect of the 21-gene recurrence score (RS) on outcome and chemotherapy decision in breast invasive lobular carcinoma (ILC). Materials & methods: We included 6467 patients with early stage and estrogen receptor–positive ILC from the Surveillance, epidemiology, and end results database. Results: A total of 9.1, 31.4, and 70.1% of patients with low-, intermediate-, and high-risk RS groups received chemotherapy, respectively. A higher RS was independently associated with poor breast cancer-specific survival, and receipt of chemotherapy was not related to better breast cancer-specific survival in low-, intermediate-, or high-risk RS groups. Conclusion: The 21-gene RS could impact chemotherapy decision making in early-stage ILC. However, adjuvant chemotherapy does not appear to improve outcome in high-risk RS cohort.

Background: The clinical value of 21-gene recurrence score (RS) in various breast cancer histologic subtypes is not well established. Aims: To assess the distribution and outcomes of the 21-gene RS among various T1-T2N0 estrogen receptor-positive breast cancer histologic subtypes. Methods: Using the Surveillance, Epidemiology and End Results database, we investigated the distribution and outcomes of the 21-gene RS among various breast cancer histologic subtypes between 2004 and 2015. The histologic subtypes with 200 or more cases were further analyzed. Results: We identified 83,665 patients including eight histologic subtypes. The most common subtype was invasive ductal carcinoma not otherwise specified (IDC NOS) (77.9%), followed by lobular carcinoma NOS, mixed infiltrating duct and lobular carcinoma (IDC-L), mucinous adenocarcinoma, tubular adenocarcinoma, micropapillary ductal carcinoma, cribriform carcinoma NOS, and intraductal papillary adenocarcinoma with invasion with 10.8, 7.7, 2.1, 0.6, 0.3, 0.2, and 0.2%, respectively. The 5-years breast cancer specific survival (BCSS) was 98.8, 98.8, 98.9, 99.6, 100, 100, 100, and 100%, respectively (P = 0.011). Patients with IDC NOS (8.9%), micropapillary ductal carcinoma (8.8%), and intraductal papillary adenocarcinoma with invasion (8.2%) had significantly higher percentage of high-risk RS compared to other histologic subtypes (1.0–3.8%) (P < 0.001). The mean RS was higher in IDC NOS, lobular carcinoma NOS, and IDC-L compared to other subtypes. In multivariate analysis, 21-gene RS was the independent prognostic factor in patients with IDC NOS (P < 0.001), lobular carcinoma NOS (P < 0.001), and IDC-L (P < 0.001), patients with a higher RS was associated with poor BCSS. Conclusion: Our results demonstrate that there is a significant difference in distribution of 21-gene RS in T1-T2N0 estrogen receptor-positive breast cancer with different histologic subtypes. Long-term studies with larger series are needed to confirm the role of the 21-gene RS array in prognosis assessment and chemotherapy decision-making in special histologic subtypes with favorable prognosis.

Introduction: To examined survival outcome by histological subtypes in de novo stage IV epithelial ovarian cancer (EOC).Methods: Between 2004 and 2015, patients with stage IV EOC were included using the Surveillance, Epidemiology, and End Results program. The effects of histological subtypes on overall survival (OS) were assessed using Kaplan–Meier and multivariable Cox regression analyses.Results: We identified 5,953 patients including 5,351 (89.9%), 249 (4.2%), 145 (2.4%), and 208 (3.4%) patients with high-grade serous, endometrioid, mucinous, and clear cell subtypes, respectively. The 5-year OS rates were 28.1, 38.6, 14.2, and 18.8% in patients with high-grade serous, endometrioid, mucinous, and 18.8% clear cell subtypes, respectively, (p < 0.001). Multivariate analyses indicated that histological subtype was an independent predictor of OS. Using the high-grade serous subtype as a reference, OS was comparable for the endometrioid subtype (hazard ratio (HR) 0.915, 95% confidence interval) (CI 0.772–1.085, p = 0.305), but significantly lower for mucinous (HR 3.292, 95% CI 2.701–4.011, p < 0.001) and clear cell subtypes (HR 1.820, 95% CI 1.546–2.141, p < 0.001). Patients with no residual tumor had better OS in the high-grade serous and endometrioid subtypes compared to patients with residual tumors. However, the residual tumor size was not a prognostic factor for OS in mucinous and clear cell carcinoma.Conclusions: Our study suggest a markedly mortality rate in patients with stage IV mucinous and clear cell carcinoma, but better survival in patients with high-grade serous and endometrioid subtypes. Aggressive radical surgery to leave no residual disease would improve survival for high-grade serous and endometrioid carcinoma. More studies are needed to assess the value of aggressive radical surgery in patients with mucinous and clear cell subtypes.

Natural astaxanthin mainly derives from a microalgae producer

Carbon policies differentiated according to regional disparities have been recognized and recommended. However, the air quality co-benefits of differentiated policies remain unclear. Here we combine a multi-regional dynamic computable general equilibrium (CGE) model and an extend response surface model (ERSM) to investigate the impact of nationally uniform and subnationally differentiated carbon pricing policies on fine particulate matter (PM2.5) concentrations in China. All policies examined lead to the same accumulated national CO2 emissions (2020–2050), with the 2030 emissions attaining China's national abatement target. We find that, when subnational policies differentiated according to provincial PM2.5 concentrations are implemented, the higher-than-average carbon price over more polluted provinces results in twice as much reduction in CO2 and air pollutant emissions in 2050 as the national policy. As a result, the subnational policies cause larger PM2.5 concentration reductions in these provinces (9%–18%) than the national policy (7%–11%). Also, the subnational policies eliminate high PM2.5 exposure of over 45 μg/m3 which 12% people suffer from under the national policy. The subnational policies substantially reduce regional disparity in PM2.5 pollution and hence improve environmental equity. The results suggest that subnationally differentiated carbon policies are a promising instrument to mitigate severe pollution and promote environmental equity.

In view of deep water and soft soil foundation, a new type of breakwater with cylindrical jacket and pile foundations is proposed. According to the hydrological and geological conditions of Tianjin Port, the stability and bearing capacity of breakwater are numerically simulated by ABAQUS software. The results show that when the pile is an elastic model, the failure of soil is the main cause of structural instability. In the limit state, the structure is unstable in rotation in addition to arc sliding, and its turning point is below the bottom of the cylindrical jacket and deviates from the structural axis near the front-pile side. When the pile is a damage plastic model, the loss of bearing capacity is the cause of structural instability. The safety coefficient is greater than 1, but it is obviously smaller than the one of elastic model. The research results provide a reference for structural design and stability study of the breakwater with cylindrical jacket and pile foundations.

Two novel silver-based metal − organic frameworks (MOFs) have been successfully designed and synthesized by coordination assembly of tri(pyridin-4-yl)amine (TPA) and Ag(I) salts with different anions (SiF62− vs. CH3SO3−). Both MOFs show excellent physicochemical stability and superior electrochemical activity. It is the first time to implement Ag(I)-MOFs to fabricate high-efficient aptasensors to detect ultra-trace penicillin by electrochemical method. Remarkably, the Ag2SiF6-MOF-based biosensor shows ultra-high selectivity toward penicillin in the presence of other antibiotic interferences, which also exhibits the lowest detection limit of 0.849 pg mL−1 among all reported sensing materials, in the concentration range from 0.001 to 0.5 ng mL−1. Moreover, the fabricated aptasensor with good repeatability and high stability can effectively monitor penicillin in real milk sample. Interestingly, the isostructrual nature of two MOFs firstly illustrates the critical role of anion in constructing MOFs-based aptasensors. This work establishes a promising approach to design and modulate MOFs-based aptasensors for rapid and convenient detection of ultra-trace targets.

Niflumic acid (NFA) is a novel gap junction (GJ) inhibitor. The aim of the present study was to investigate the effect of NFA on GJ communication and the expression of connexin (Cx) in vascular smooth muscle cells (VSMCs) of mesenteric arterioles of spontaneously hypertensive rats (SHR). Whole-cell patch clamp recording demonstrated that NFA at 1×10–4 M significantly inhibited the inward current and its effect was reversible. The time for charging and discharging of cell membrane capacitance (Cinput) reduced from 9.73 to 0.48 ms (P

Using the logarithmic mean Divisia index (LMDI) method, we decomposed the factors that affect carbon emissions at a multi-regional level. Based on a comparative analysis of the regional contributions to carbon emissions in China from 1995 to 2012, we found that economic growth is a major factor that increases carbon emissions. Excluding Hainan, Guangxi, Ningxia, and Xinjiang, the energy intensity effects of other provinces and municipalities inhibited carbon emissions clearly. The energy structure effect in Beijing and Shanghai inhibited carbon emissions most obviously, whereas the energy structure effect in Xinjiang promoted carbon emissions to the greatest extent. The energy structure effect in most regions had little influence on carbon emissions. The output proportion effect enhances carbon emissions on the whole, which indicates China's regional economic development is not coordinated from the perspective of carbon emission reductions. Overall, Shandong, Inner Mongolia, and Hebei made the biggest contributions to national carbon emissions. Policy implications in terms of our study results are discussed.

We numerically simulate Schrodinger-like paraxial wave equation of a four-waveguide system. The coherent tunneling by adiabatic passage in a four-waveguide optical coupler is analyzed by borrowing the dressed state theory of coherent atom system. We discuss the optical coupling mechanism and coupling efficiency of light energy in both intuitive and counterintuitive tunneling schemes and analyze the threshold condition from adiabatic to non-adiabatic regimes in intuitive scheme. The results show that this coupler can be used as power splitter under certain conditions.

LPIN1 is a Mg(2+)-dependent phosphatidic acid phosphatase. Variation in chicken LPIN1 exon 6 and its flanking regions were identified and three indel variants in 6 breeds and their associations with performance traits were studied. Seven variants were detected from 6 breeds, which contained a synonymous tri-allelic variant (c.924A/T/C) and three indels. The exon 6 variants detected from chicken breeds were conserved among bird species. The indel variation frequency presented clear differences among breeds. Two coding indels (c.1014-1018del3 and c.1125-1138del12) were multiples of three nucleotides and maintained the open reading frames of LPIN1 proteins. However, they were predicted to result in the clear change of the RNA secondary structure of chicken LPIN1 exon 6 and LPIN1 protein conformation. The association analysis showed that c.871-15-22del6 variation had a significant effect on body weight at hatch (BW0) and 2 weeks (BW2); c. 1014-1018del3 variation had a significant effect on BW4, BW6, caecum length and gizzard weight (GW) traits; c.1125-1138del12 variation had a significant effect on BW12, shank length at 4 weeks (SL4), carcass weight, lactate dehydrogenase traits (LDH), glucose (GLU) and albumin (ALB) traits. The genotype combination for c.1014-1018del3 and c.1125-1138del12 also presented significant effects on SL4, SL8, GW, leg muscle weight, ALB, GLU and LDH. The study demonstrated that chicken LPIN1 has an important effect on body, carcass and organ weight, serum LDH, GLU and ALB level.

Carbon policies are important not only for mitigating global climate change, but also for controlling local and regional air pollution. The large regional disparities in economic development and air pollution across China calls for regionally differentiated policies. Previous studies have not systematically investigated the environmental impacts of regional carbon policies in China covering different spatial scales. This study constructs a multi-regional dynamic computable general equilibrium (CGE) model covering 30 provinces of China to assess the impacts of national and subnational carbon polices on CO2 emissions and co-emitted air pollutants from 2020 to 2050. We consider one national carbon policy which aims to achieve China's 2030 national CO2 abatement target, as well as three regional policies with the same policy stringency as the national one but only applied to eastern China (EP), the Jiangsu-Shanghai-Zhejiang area (JSZP), and the Beijing-Tianjin-Hebei area (BTHP), respectively. We find that regional policies (EP, JSZP, and BTHP) are as effective in reducing CO2 emissions in their targeted regions as the national policy. However, they lead to an increase in CO2 emissions in untargeted regions (the so-called "emissions leakage"). The CO2 leakage rates, which depend on the policy spatial coverage, are 4%, 13%, and 65% for EP, JSZP, and BTHP, respectively, in 2050. Compared with CO2, changes in air pollutant emissions, including sulfur dioxide (SO2), nitrogen oxides (NOx), volatile organic compounds (VOC), and fine particulate matter (PM2.5), exhibit a similar pattern under all policy scenarios, but the magnitude of change is significantly smaller. Transportation, thermal power, and some energy intensive industries are the three largest contributors to CO2 and air pollutant emission reductions. Our results suggest that regional carbon policy is effective in reducing CO2 and air pollutant emissions in the targeted regions, and extending the spatial coverage or increasing policy stringency can largely inhibit emissions leakage.

Safflower honey is a unique type of monofloral honey collected from the nectar of Carthamus tinctorius L. in the Apis mellifera colonies of northwestern China. Scant information is available regarding its chemical composition and biological activities. Here, for the first time, we investigated this honey&rsquo, s chemical composition and evaluated its in vitro antioxidant and anti-inflammatory activities. Basic physicochemical parameters of the safflower honey samples in comparison to established quality standards suggested that safflower honeys presented a good level of quality. The in vitro antioxidant tests showed that extract from Carthamus tinctorius L. honey (ECH) effectively scavenged DPPH and ABTS+ free radicals. In lipopolysaccharides (LPS) activated murine macrophages inflammatory model, ECH treatment to the cells inhibited the release of nitric oxide and down-regulated the expressions of inflammatory-relating genes (iNOS, IL-1&beta, TNF-&alpha, and MCP-1). The expressions of the antioxidant genes TXNRD, HO-1, and NQO-1, were significantly boosted in a concentration-dependent manner. ECH decreased the phosphorylation of I&kappa, B&alpha, and inhibited the nuclear entry of the NF-&kappa, B-p65 protein, in LPS-stimulated Raw 264.7 cells, accompany with the increased expressions of Nrf-2 and HO-1, suggesting that ECH achieved the anti-inflammatory effects by inhibiting NF-&kappa, B signal transduction and boosting the antioxidant system via activating Nrf-2/HO-1 signaling. These results, taken together, indicated that safflower honey has great potential into developing as a high-quality agriproduct.

Nowadays, the requirement for achieving dynamic radiative cooling is more and more intense, so a cooling system is proposed and developed to meet the demand in this paper. This cooling system is composed of a filter and a periodic trapezoidal VO2-Ge multilayer absorber (VGMA). The filter on the top enables the VGMA to reflect most of the solar irradiation at daytime and the absorptance or emittance of the VGMA is very different in the spectrum band of 8-13 μm for insulating and metallic VO2 due to the phase transition characteristic of VO2. With this cooling system, close-to-zero absorptance in the range of 0.3-2.5 μm and high (low) absorptance from 8 to 13 μm are achieved for metallic (insulating) VO2. Based on changing the temperature and absorptivity or emissivity simultaneously, radiative heat can be transferred dynamically to the outer space. When VO2 is in the insulating phase, the absorption mechanism of the absorber is magnetic resonance and surface plasmon polariton resonance, and broadband high absorptivity is achieved by exciting slowlight waveguide mode at broadband wavelengths when VO2 is in metallic phase. The spectral absorptance characteristics of the absorber in the two phase states are investigated as a function of the layer number and the incident angle of the electromagnetic waves. The results show that the absorber designed is insensitive to the incident angle. Moreover, the net cooling power of the VGMA of metallic VO2 is instantly 4 times more than that of insulating VO2 once the phase change temperature is reached. This work will be beneficial to the advancement of dynamic radiative cooling.

Anaerobically digested waste sludge contains very high concentrations of ammonium and phosphate that are difficult to be purified using traditional processes. Mixotrophic culture of microalgae is a potential way to achieve ammonium and phosphate removal, while harvesting considerable biomass for biodiesel production. In this study, four typical volatile organic acids that could be potentially produced from sludge fermentation were tested for algal mixotrophic culture in anaerobically digested waste sludge. The results showed that the addition of propionate and isovaleric acid had no significant improvement on biomass production, and even inhibited algal growth at low concentration. Fortunately, the addition of acetic and n-butyric acid (initial C/N = 10) increased biomass production by1.9–2.4 times compared to the blank culture. Higher biomass production increased ammonium and orthophosphate removal to 88.3–97.1% and 80.4–93.0%, respectively. Moreover, the optimal addition of volatile organic acids enhanced lipids production by 3.9–6.3 times, while achieving higher saturation degree in biodiesels. The results suggest that adding these optimal volatile organic acids is suitable to enhance nutrients recycling and algal biodiesel production from anaerobically digested waste sludge.

A catalytic macrolactonization through oxidative cyclization of alkynyl alcohol by synergistic transition-metal and Lewis-acid catalysis was developed. Because the alkynyl alcohol substrates involved in this method are different from the seco acids that are used in conventional macrolactonization methods, the current method provides a strategically distinct entry to macrolactones. In addition to the operational simplicity, this macrolactonization protocol proceeds at relatively high concentration, precluding the need for high dilution or slow addition procedures.

Wen-Wen Zhang,1,* San-Gang Wu,2,* Yi-Hong Ling,3 Jia-Yuan Sun,1 Zhi-Qing Long,1 Xin Hua,1 Yong Dong,4 Feng-Yan Li,1 Zhen-Yu He,1 Huan-Xin Lin1 1Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 2Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China; 3Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 4Department of Radiation Oncology, the Third People’s Hospital of Dongguan, Dongguan, Guangdong, People’s Republic of China *These authors contributed equally to this work Introduction: We aimed to evaluate the clinicopathologic characteristics and clinical outcomes of the mixed type versus the pure type of tubular carcinoma (TC) of the breast in a retrospective cohort study. Materials and methods: Patients were categorized into the following three groups: patients with pure TC of the breast (the PTC group), patients with TC and carcinoma in situ of the breast (the TC-CIS group), and patients with TC and other invasive carcinomas of the breast (the TC-IC group). We compared the clinicopathologic characteristics and treatment outcomes of the three groups. The primary end point of this study was breast cancer-specific survival (BCSS). Secondary end points included distant metastasis-free survival (DMFS) and locoregional recurrence (LRR). Results: A total of 68 patients were included in this study, including 31 patients in the PTC group, 12 in the TC-CIS group, and 25 in the TC-IC group. Our data showed that PTC and TC-CIS were more likely to be smaller in size (P=0.014) and had substantially less nodal involvement (P=0.019), compared with TC-IC. The median follow-up time was 64.3 months (range, 3.78–223.2 months) for all patients. No locoregional relapse was observed in any group during the follow-up period. The 10-year BCSS of the PTC, TC-CIS, and TC-IC groups was 100%, 100%, and 95.2%, respectively, and the 10-year DMFS was 92.3%, 100%, and 96.0%, respectively. There was no significant difference in terms of BCSS (P=0.53) or DMFS (P=0.84) between the three groups. Conclusion: This study indicates that both the pure type and mixed type of TC of the breast show very low LRR and distant metastasis rate and have excellent survival. The TC-IC group is likely to show good prognosis similar to the PTC group. Further clinical trials with larger sample sizes as well as molecular and genetic studies are warranted. Keywords: pure type of tubular carcinoma, mixed type of tubular carcinoma, clinicopathologic characteristics, clinical outcomes

There are increasing concerns regarding the impact of agrochemical pesticides on non-target organisms. Pesticides could cause honeybee abnormal development in response to neurotoxins such as neonicotinoid. However, knowledge of carbendazim, a widespread fungicide in beekeeping practice, influencing on honeybee (Apis mellifera L.) brain development is lacking. Large-scale transcriptome approaches were applied to determine the changes in global gene expression in the brains of newly emerged honeybees after carbendazim exposure during the larval stage. To further understand the effects of carbendazim on the brain development of honeybees, the functions of differentially expressed genes were compared between the treatment and control groups. We found that neuroregulatory genes were down-regulated after carbendazim exposure, which suggest the neurotoxic effects of this fungicide on honeybee nervous system. Carbendazim exposure also altered the expression of genes implicated in metabolism, transport, sensor, and hormone. Notably, larvae in the carbendazim-treated group observed longer time to shift into the dormant pupal state than the control group. Moreover, a low juvenile hormone and high ecdysone titers were found in the treatment group compared to control group. The data is the first report of neurotoxic effects on honeybee caused by carbendazim, and the sublethal carbendazim may disturb honeybee development and is a potential chemical threating the honeybee colonies.

BACKGROUND: We aimed to assess the prognostic value of the skeletal muscle index (SMI) and monocyte-to-lymphocyte ratio (MLR) in lymph node-positive breast cancer patients after mastectomy. METHODS: We enrolled female lymph node-positive breast cancer patients who had undergone mastectomy between January 2011 and December 2013 with lymph node metastasis. Skeletal muscle tissue was measured using computed tomography (CT), and the patients were grouped based on the receiver operating characteristic curves to obtain the cut-off point for SMI; similarly, the optimal cutoff point for the MLR was obtained. Survival analysis was chiefly performed to determine overall survival (OS) among the patients. RESULTS: The median age of the 97 included patients was 46 years (range, 27–73 years), whereas the median follow-up duration was 62.5 months. Of these patients, 71 exhibited low SMI and 66 exhibited high MLR. Kaplan-Meier curves indicated that low SMI (5-year OS, 97.2% vs. 84.6%; log-rank P=0.021) and low MLR (5-year OS, 98.5% vs. 83.9%; log-rank P=0.004) were associated with better OS. Moreover, patients with both high SMI and MLR (high SMLR) had significantly worse OS (5-year OS, 66.7% vs. 96.6%; log-rank P

Di(2-ethylhexyl) phthalate (DEHP) is an environmental pollutant that is widely used in medical and consumer products. An epidemiological study has suggested that a large daily intake of DEHP from phthalate-contaminated food may be a risk factor for liver dysfunction. Long-term exposure to DEHP is associated with liver disease and exacerbates the progression of chronic liver injury. However, the effect of DEHP on hepatic fibrosis is rarely studied. In the present study, we sought to determine the effect of DEHP on carbon tetrachloride (CCl4)-induced liver fibrosis, and to further examine the molecular mechanisms. We found that DEHP exposure remarkably promoted liver inflammation, necrosis and fibrosis, and increased expression of the protein associated with liver inflammation and fibrogenesis, including α-SMA, COL-Ⅰ, COL-Ⅲ, TGF-β1, P-Smad2, P-Smad3, P-p38 and P-p65. The similar trend was observed in the LX-2 cells. Furthermore, DEHP exposure induced oxidative stress and inflammatory cytokine production. Taken together, DEHP might play a fibrotic role in hepatic fibrosis rats and TGF-β1-stimulated LX-2 cells in vitro which was related to TGF-β1/Smad and p38MAPK/NF-κB signal pathway.

Purpose The study aimed to search and identify genes that were differentially expressed in breast cancer, and their roles in cancer growth and progression. Materials and methods The Gene Expression Omnibus (Oncomine) and The Cancer Genome Atlas databases (https://cancergenome.nih.gov/) were screened for genes that were expressed differentially in breast cancer and were closely related to a poor prognosis. Gene expressions were verified by quantitative real-time polymerase chain reaction, and genes were knocked down by a lentivirus-based system. Cell growth and motility were evaluated and in vivo nude mice were used to confirm the in vitro roles of genes. Markers of epithelial-to-mesenchymal transition and the associations of KIF11 with the classical cancer signaling pathways were detected by Western blot. Results A series of genes expressed differentially in patients with breast cancer. The prognosis associated with high KIF11 expression was poor, and the expression of KIF11 increased significantly in high stage and malignant tumor cells. Inhibiting KIF11 expression in lentivirus-suppressed cells revealed that KIF11 inhibition significantly reduced cell viability and colony formation, inhibited migration and invasion, but promoted apoptosis. The sizes and weights of KIF11-inhibited tumors in nude mice were significantly lower than in the negative controls. Western blot showed that E-cadherin in breast cancer was significantly upregulated in KIF-inhibited cells and tumor tissues, whereas N-cadherin and vimentin were significantly downregulated. BT549 and MDA231 cells with KIF11 knockdown exhibited decreased ERK, AMPK, AKT, and CREB phosphorylation. Conclusion KIF11 acts as a potential oncogene that regulates the development and progression of breast cancer.

Introduction: Distant metastasis remains the major cause of treatment failure in esophageal cancer, though there have been few large-scale studies of the patterns of distant metastasis in different histological types. We investigated the patterns of distant metastasis in esophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) using a population-based approach.Methods: Patients with de novo stage IV esophageal cancer at diagnosis were identified using the Surveillance, Epidemiology, and End Results database. Multivariable logistic regression was performed to identify potential risk factors for site-specific distant metastasis to the distant lymph nodes, bone, liver, brain, and lung at diagnosis.Results: We identified 1,470 patients with complete data for analysis including 1,096 (74.6%) patients with AC and 374 (25.4%) patients with SCC. A total of 2,243 sites of distant metastasis were observed, the liver was the most common site of distant metastasis (727, 32.4%), followed by the distant lymph nodes (637, 28.4%), lung (459, 20.5%), bone (344, 15.3%), and brain (76, 3.4%). Multivariable logistic regression showed that compared to patients with SCC, patients with AC were more likely to have metastasis to the brain (odds ratio [OR] 3.026, 95% confidence interval [CI] 1.441-6.357, p = 0.003) and liver (OR 1.848, 95% CI 1.394–2.451, p < 0.001), and less likely to have metastasis to the lung (OR 0.404, 95% CI 0.316–0.516, p < 0.001). Histological type had no effect on metastasis to the distant lymph nodes or bone.Conclusions: Patients with esophageal AC are more likely to present with liver and brain metastases, and less likely to present with lung metastasis than patients with esophageal SCC.

Summary: The proinflammatory cytokine interleukin-17 (IL-17) is implicated in pain regulation. However, the synaptic mechanisms by which IL-17 regulates pain transmission are unknown. Here, we report that glia-produced IL-17 suppresses inhibitory synaptic transmission in the spinal cord pain circuit and drives chemotherapy-induced neuropathic pain. We find that IL-17 not only enhances excitatory postsynaptic currents (EPSCs) but also suppresses inhibitory postsynaptic synaptic currents (IPSCs) and GABA-induced currents in lamina IIo somatostatin-expressing neurons in mouse spinal cord slices. IL-17 mainly expresses in spinal cord astrocytes, and its receptor IL-17R is detected in somatostatin-expressing neurons. Selective knockdown of IL-17R in spinal somatostatin-expressing interneurons reduces paclitaxel-induced hypersensitivity. Overexpression of IL-17 in spinal astrocytes is sufficient to induce mechanical allodynia in naive animals. In dorsal root ganglia, IL-17R expression in nociceptive sensory neurons is sufficient and required for inducing neuronal hyperexcitability after paclitaxel. Together, our data show that IL-17/IL-17R mediate neuron-glial interactions and neuronal hyperexcitability in chemotherapy-induced peripheral neuropathy. : Luo et al. find that glia-produced IL-17 regulates synaptic transmission and excitability of spinal SOM+ neurons and DRG small neurons by IL-17R in the DRG and spinal pain circuit. These results suggest that IL-17/IL-17R mediate neuron-glial interactions and drives chemotherapy-induced neuropathic pain. Keywords: interleukin-17, chemotherapy-induced peripheral neuropathy, excitatory postsynaptic currents (EPSCs), inhibitory postsynaptic synaptic currents (IPSCs), somatostatin-expressing neurons, Cre-recombinase-dependent adeno-associated virus (AAV), astrocytes, allodynia, spinal cord, neuron-glial interaction

Wen-Wen Zhang,1,* San-Gang Wu,2,* Jia-Yuan Sun,1 Feng-Yan Li,1 Zhen-Yu He1 1Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, People’s Republic of China; 2Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen 361003, People’s Republic of China *These authors contributed equally to this work Introduction: The timing of postmastectomy radiotherapy (PMRT) may influence locoregional recurrence and survival outcomes. In this study, we assessed the long-term survival effect of the interval between surgery and PMRT in locally advanced breast cancer treated with mastectomy and adjuvant chemotherapy.Methods: In this retrospective study, we included women with locally advanced breast cancer who underwent adjuvant chemotherapy and PMRT after mastectomy between 1999 and 2007. Based on the interval between surgery and PMRT, the patients were classified into three groups: Group 1 (≤4 vs >4 months), Group 2 (≤5 vs >5 months), and Group 3 (≤6 vs >6 months). Univariate and multivariate regression analyses were performed to determine the prognostic factors of survival outcomes.Results: A total of 340 women were included in this study, and the median follow-up duration was 79.8 months. The median surgery–PMRT interval was 5 months. The surgery–PMRT interval including Group 1, Group 2, and Group 3 was not significantly associated with locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival. In addition, in the subgroup analysis of the effect of surgery–PMRT interval on survival outcomes according to various clinicopathologic factors, the surgery–PMRT interval was also not associated with survival outcomes in different age groups, tumor stage, and breast cancer subtypes.Conclusion: Our findings suggest that the delay in the start of PMRT in locally advanced breast cancer does not increase the likelihood of locoregional recurrence, distant metastasis, and death. Keywords: breast carcinoma, surgery, time, irradiation, delay

San-Gang Wu,1,* Wen-Wen Zhang,2,* Jia-Yuan Sun,2 Qin Lin,1 Zhen-Yu He2 1Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen 361003, People’s Republic of China; 2Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, People’s Republic of China *These authors contributed equally to this work Objective: To compare the survival outcomes in locally advanced breast cancer (LABC) patients receiving post-mastectomy radiotherapy (PMRT) with and without immediate breast reconstruction. Methods: We used the Surveillance, Epidemiology, and End Results program to include LABC patients who were treated/not treated with immediate breast reconstruction followed by PMRT between 2003 and 2010. Statistical analysis was performed using the chi-squared test, Kaplan–Meier survival analysis, and Cox regression analysis. A 1:1 propensity score matching method was performed to decrease the selection bias. Results: We identified 1,732 patient-pairs that were completely matched. In the unmatched population, 8,198 and 1,802 patients received mastectomy only and immediate breast reconstruction, respectively. Patients who received immediate breast reconstruction had better breast cancer-specific survival (BCSS) (hazard ratio [HR] 0.880, 95% CI 0.783–0.989, P = 0.032) and overall survival (OS) (HR 0.846, 95% CI 0.758–0.943, P = 0.003) than patients who underwent mastectomy alone. However, in the matched population, there was comparable BCSS and OS between patients who received immediate breast reconstruction and mastectomy alone. Subset analysis in the matched population found that immediate breast reconstruction was associated with better BCSS (HR 0.750, 95% CI 0.614–0.917, P = 0.005) and OS (HR 0.779, 95% CI 0.644–0.942, P = 0.010) compared to patients aged

Aim: We explored the clinicopathologic characteristics, prognostic factors and outcomes in tubular carcinoma (TC) of the breast. Methods: We retrospectively assessed 8091 TC patients using the SEER database from 2000 to 2013. Results: Most patients were non-Hispanic white, well-differentiated disease, tumor size ≤2 cm, node-negative, nonmetastatic, hormone receptor-positive and HER2-negative status. The 10-year breast cancer-specific survival and overall survival were 98.1 and 82.0%, respectively. Multivariate analysis indicated that age, ethnicity, surgery procedures, radiotherapy and chemotherapy were independent predictors affecting survival outcomes. There was comparable breast cancer-specific survival between surgery and nonsurgery groups. Conclusion: The patients with TC has excellent survival outcomes, which may in part be due to the favorable tumor characteristics.

Great attention has been paid to accelerate the start-up period and enhance floc properties and structural stability in activated sludge reactors with the aid of inorganic chemical agents such as calcium ion. The laboratory-scale sequencing batch reactors (SBRs) were operated continuously for 35 days to investigate the effect of calcium ion (Ca

Interleukin-33 (IL-33) and its receptor ST2 contribute to spinal glial activation and chronic pain. A recent study showed that peripheral IL-33 plays a pivotal role in the pathogenesis of chronic itch induced by poison ivy. However, how IL-33/ST2 signaling in the spinal cord potentially mediates chronic itch remains elusive. Here, we determined that St2-/- substantially reduced scratching behaviors in 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis (ACD) as well as acetone and diethylether followed by water-induced dry skin in mice. Intrathecal administration of the neutralizing anti-ST2 or anti-IL-33 antibody remarkably decreased the scratching response in DNFB-induced ACD mice. Expression of spinal IL-33 and ST2 significantly increased in ACD mice, as evidenced by increased mRNA and protein levels. Immunofluorescence and in situ hybridization demonstrated that increased expression of spinal IL-33 was predominant in oligodendrocytes and astrocytes, whereas ST2 was mainly expressed in astrocytes. Further studies showed that in ACD mice, the activation of astrocytes and increased phosphorylation of signal transducer and activator of transcription 3 (STAT3) were markedly attenuated by St2-/- . Intrathecal injection of Janus Kinase 2 Inhibitor AG490 significantly alleviated scratching behaviors in ACD mice. rIL-33 pretreatment exacerbated gastrin-releasing peptide (GRP)-evoked scratching behaviors. This increased gastrin-releasing peptide receptor (GRPR) expression was abolished by St2-/- . Tnf-α upregulation was suppressed by St2-/- . Our results indicate that the spinal IL-33/ST2 signaling pathway contributes to chronic itch via astrocytic JAK2-STAT3 cascade activation, promoting TNF-α release to regulate the GRP/GRPR signaling-related itch response. Thus, these findings provide a potential therapeutic option for treating chronic pruritus.

The benzophenone-3,3′-disulfonyl-4,4′-dicarboxylic acid (H4–BODSDC) ligand and compounds, {(H3O)[Ln(BODSDC)(H2O)2]}n (Ln = Tb(1), Eu(2), and Gd(3)), were synthesized and structurally characterized. The lanthanide centers are bridged by the carboxylate groups of BODSDC4– ligands to give a one-dimensional (1D) chain. The 1D chains are connected by the BODSDC4– ligands to yield a three-dimensional (3D) structure featuring 1D channels. The lanthanide ions are efficiently sensitized by the BODSDC4– ligand with an appropriate triplet excited state to generate characteristic Tb(III) and Eu(III) emissions in Tb(1) and Eu(2), respectively. Thus the binary compound, {(H3O)[Tb0.93Eu0.07(BODSDC)(H2O)2]}n (abbreviated as Tb0.93Eu0.07-BODSDC), was achieved for use as a ratiometric temperature sensor. The ratio values of Tb(III) emission at 544 nm (ITb) and Eu(III) emission at 616 nm (IEu) for Tb0.93Eu0.07-BODSDC linearly vary with temperature over a wide range, which indicates that the Tb0.93Eu0.07-BODSDC is a thermome...

Aim: We investigated the value of the number of positive lymph nodes (PLNs) and lymph node ratio (LNR) on survival of vulvar cancer patients. Methods: A total of 2332 patients with vulvar squamous cell carcinoma were included from the SEER program. Results: In multivariate analysis, the number of PLNs and LNR were independent prognostic indictors of survival outcomes, a higher number of PLNs and a higher LNR had poorer survival outcomes. An LNR >0.2 was associated with poor survival outcomes according to the number of PLNs. Conclusion: The LNR has prognostic value related to the number of PLNs and may allow a more accurate determination of the lymph node status of vulvar cancer patients.

Acupoint catgut embedding (ACE) is a widely used traditional Chinese medicine method to manage various diseases, including chronic inflammatory pain. We sought to assess the possible analgesic effects of ACE in comparison with electroacupuncture (EA) and to study the analgesic mechanisms of ACE in a rat model of inflammatory pain induced by injection of complete Freund's adjuvant (CFA) into the hind paw of rats. The von Frey, radiant heat, and gait analysis tests were performed to evaluate the analgesic effects of ACE and EA, and Western blot and immunohistochemistry assays were carried out to determine the molecular mechanisms of ACE. ACE treatments were administered every 4 days or every week with different acupoints (ipsilateral, contralateral, or bilateral ST36 and GB30 acupoints). The most effective ACE strategy for attenuating the nocifensive response induced by CFA injection was performing ACE once a week at ipsilateral ST36 in combination with GB30. EA treatment every other day at ipsilateral ST36 and GB30 showed comparable analgesic effects. ACE inhibited the increased activation of the GluN1 subunit of the N-methyl-d-aspartate receptor and the subsequent Ca2+-dependent signals (CaMKII, ERK, and CREB) that take place in response to CFA. The effects of ACE were similar to intrathecal injection of vilazodone (a serotonin 1A receptor [5-HT1AR] agonist) and were blocked by WAY-100635 (a 5-HT1AR antagonist). In summary, we show that ACE attenuates CFA-induced inflammatory pain in rats by activating spinal 5-HT1AR and by inhibiting the phosphorylation of GluN1, thus, inhibiting the activation of Ca2+-dependent signaling cascades. PERSPECTIVE: This article presents the novel evidence concerning the spinal 5-HT1AR activation-related molecular signaling of ACE analgesia in a rat model of CFA-induced inflammatory pain. This work may help clinicians to verify the effectiveness of ACE analgesia and to better understand the underlying mechanism.

To assess the effects of different habitat conditions on the genetic diversity of Apis cerana cerana, 2400 individual workers from 120 colonies in four localities of South Anhui mountainous area were analyzed using microsatellite DNA loci. Results showed that in the tea tree monoculture, the number of alleles, average expected heterozygosity and polymorphism information content showed no significant difference with those in the natural forest. The number of alleles and polymorphic information content in domesticated population were significantly different from those in the wild population. The average expected heterozygosity was not significantly different between those two populations. The number of alleles, the average expected heterozygous and polymorphic information content were significantly different from those in the wild for samples collected in 2006. There was significant genetic differentiation among populations, with an average differential coefficient of 0.32. Our results indicated that the cultivation of tea plantation in South Anhui would not affect the genetic structure and conservation of bees.为了评估不同栖息条件对中华蜜蜂(简称中蜂)种群遗传多样性的影响,本研究运用微卫星标记的方法,对皖南山区4个不同采样点120个中华蜜蜂群体的2400只工蜂样本进行了分析.结果表明: 与天然林野生中蜂群相比,单一茶树种植结构下,皖南中蜂群的等位基因数、平均期望杂合度和多态信息含量的差异均不显著;人工驯养中蜂群的等位基因数、多态信息含量差异显著,平均期望杂合度差异不显著;2006年采集的野生中蜂群与天然林野生中蜂群的等位基因数、平均期望杂合度和多态信息含量均差异显著.各种群间存在极显著的遗传分化,平均分化系数为0.32.说明皖南地区茶树单一化种植不会影响中蜂的遗传结构与资源保护.

IntroductionTo investigate the effect of the number of removed lymph nodes (RLNs) on outcomes in patients with node-positive vulvar squamous cell carcinoma (SCC).MethodsThis population-based retrospective study included vulvar SCC patients recorded on the surveillance, epidemiology, and end results database, who received surgery and lymphadenectomy. Cox regression proportional hazards were used for multivariate analysis. The number of RLNs was examined as a 4-level categorical variable based on quartiles.ResultsIn total, 703 patients were identified. Patients with a higher RLN count had a significantly higher number of positive lymph nodes. The 3-year cause-specific survival (CSS) rates were 48.9, 65.9, 73.1, and 67.3% in patients with 1–6, 7–10, 11–16, and 17–45 RLNs, respectively (p 6 RLNs.ConclusionThe removal of more than six lymph nodes improves vulvar SCC outcomes in patients with node-positive disease.

San-Gang Wu,1,* Wen-Wen Zhang,2,* Jia-Yuan Sun,2 Zhen-Yu He2 1Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China; 2Department of Radiation Oncology, Sun Yat-sen University Cancer Center, and State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: The prognostic implication of concomitant ductal carcinoma in situ (DCIS) in invasive ductal carcinoma (IDC) remains controversial. Our objective was to investigate whether concomitant DCIS affects survival outcomes in patients with IDC.Materials and methods: Patients with nonmetastatic breast cancer who underwent surgery in 2010–2014 were included from the Surveillance, Epidemiology, and End Results program. Statistical analyses were conducted using Χ2 test, linear-by-linear association, one-way analysis of variance, Kaplan–Meier method, Cox proportional hazards regression model, and propensity score matching (PSM).Results: A total of 61,745 patients were identified, including 44,630 (72.3%), 13,559 (22.0%), and 3,556 (5.7%) patients with no DCIS component reported (No-DCIS), DCIS

BACKGROUND AND OBJECTIVES To determine the survival benefits of additional adjuvant hysterectomy in the International Federation of Gynecology and Obstetrics (FIGO) stage I-II cervical adenocarcinoma patients treated with radiochemotherapy. METHODS Patients with FIGO stage I-II cervical adenocarcinoma were selected from the Surveillance, Epidemiology, and End Results 18 Regs research database. Propensity score matching (PSM) was used to balance patient baseline characteristics. Patient characteristics and outcomes were compared between the two groups. RESULTS A total of 530 patients were included, 389 (73.4%) underwent definitive radiochemotherapy and 141 (26.6%) underwent an additional adjuvant hysterectomy. The multivariate Cox analysis surgery was shown to be an independent predictor of survival. Before PSM, the hazard ratios for cause-specific survival and overall survival in the surgery group were 0.632 (P = 0.036) and 0.674 (P = 0.041), respectively. After PSM, the respective hazard ratios were 0.392 (P

Juan Zhou,1,* Wen-Wen Zhang,2,* Fang Peng,3 Jia-Yuan Sun,2 Zhen-Yu He,2 San-Gang Wu4 1Department of Obstetrics and Gynecology, the First Affiliated Hospital of Xiamen University, Xiamen 361003, People’s Republic of China; 2Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, People’s Republic of China; 3Department of Radiation Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, People’s Republic of China; 4Department of Radiation Oncology, Xiamen Cancer Hospital, the First Affiliated Hospital of Xiamen University, Xiamen 361003, People’s Republic of China *These authors contributed equally to this work Introduction: Although some circRNAs have been found to regulate the progression of malignancies, their functions and coupled molecular mechanisms are still unclear. In our study, we sought to assess the underlying molecular mechanisms of circRNAs in breast cancer and therefore explored the differentially expressed circRNAs and co-expression networks, followed by in vitro experiments. Materials and methods: High-throughput RNA sequencing was performed to obtain an unbiased profile of circRNA expression. CircRNA-miRNA-mRNA co-expression networks were predicted, and sequence analyses were carried out. The MTT, transwell migration and invasion assay was conducted in Michigan Cancer Foundation-7 cells that had been transfected with si-circRNA and si-negative control (si-NC). Results: A total of 152 circRNAs were differentially expressed in breast cancer tissues, among which 85 were upregulated and 67 downregulated. Out of these, hsa_circ_0011946 was selected and the subsequent bioinformatics analysis predicted that hsa_circ_0011946 sponging miR-26a/b directly targeted replication factor C subunit 3 (RFC3) and that its knockdown could inhibit RFC3 mRNA and protein expression. Furthermore, hsa_circ_0011946 loss-of-function significantly suppressed the migration and invasion of Michigan Cancer Foundation-7 cells. Conclusion: Together, these results indicate that hsa_circ_0011946 and RFC3 comprise a novel pathway involved in the progression of breast cancer. Keywords: hsa_circ_0011946, MCF-7, RFC, breast cancer, high-throughput sequencing

Introduction: To investigate the temporal trends of postoperative radiotherapy (RT) administration and the effects of omitting postoperative radiotherapy (RT) on breast cancer-specific survival (BCSS) in women aged ≥65 years with tubular carcinoma (TC) of the breast who received breast-conserving surgery (BCS). Methods: We included women aged ≥65 years with non-metastatic TC of the breast who underwent BCS between 2000 and 2013 using the Surveillance, Epidemiology and End Results database. Statistical analyses were performed using chi-square tests, Kaplan-Meier analyses, Cox proportional hazards models, and a 1:1 propensity score-matching (PSM). Results: Before PSM, a total of 1475 patients with tumor size ≤2cm, node-negative disease, and estrogen receptor positive disease were identified, including 927 (62.8%) underwent postoperative RT and 548 (37.2%) had postoperative omission of RT. The administration of postoperative RT steadily declined over the study period. Patients with younger age, larger tumor size, and other race/ethnicity were more likely to receive postoperative RT. The median follow-up duration was 85.0 months, the 5- and 10-year BCSS rates were 98.7% and 97.9%, respectively. The median BCSS was 161.9 and 165.0 months for patients with and without postoperative RT, respectively, and the corresponding 5-year BCSS rates were 98.5% and 98.8%, respectively (p = 0.134). Prognostic analysis indicated that postoperative RT was not associated with improved BCSS rates compared to RT omission (p = 0.134). After PSM, a total of 431 completely-matched pairs were generated. In the matched population, the 5-year BCSS rates were 98.6% and 98.4% in non-postoperative RT and postoperative RT groups, respectively (p = 0.858). The univariate analyses also confirmed that the administration of postoperative RT was not associated with better BCSS (p = 0.858). Conclusions: The incidence of breast cancer-related death is probably sufficiently low to avoid postoperative RT in women aged ≥65 years with TC of the breast after BCS.

G-protein-coupled receptors are considered to be cell-surface sensors of extracellular signals, thereby having a crucial role in signal transduction and being the most fruitful targets for drug discovery. G-protein-coupled receptor 151 (GPR151) was reported to be expressed specifically in the habenular area. Here we report the expression and the epigenetic regulation of GRP151 in the spinal cord after spinal nerve ligation (SNL) and the contribution of GPR151 to neuropathic pain in male mice. SNL dramatically increased GPR151 expression in spinal neurons.GPR151mutation or spinal inhibition by shRNA alleviated SNL-induced mechanical allodynia and heat hyperalgesia. Interestingly, the CpG island in theGPR151gene promoter region was demethylated, the expression of DNA methyltransferase 3b (DNMT3b) was decreased, and the binding of DNMT3b withGPR151promoter was reduced after SNL. Overexpression of DNMT3b in the spinal cord decreasedGPR151expression and attenuated SNL-induced neuropathic pain. Furthermore, Krüppel-like factor 5 (KLF5), a transcriptional factor of the KLF family, was upregulated in spinal neurons, and the binding affinity of KLF5 withGPR151promoter was increased after SNL. Inhibition of KLF5 reducedGPR151expression and attenuated SNL-induced pain hypersensitivity. Further mRNA microarray analysis revealed that mutation ofGPR151reduced the expression of a variety of pain-related genes in response to SNL, especially mitogen-activated protein kinase (MAPK) signaling pathway-associated genes. This study reveals that GPR151, increased by DNA demethylation and the enhanced interaction with KLF5, contributes to the maintenance of neuropathic pain via increasing MAPK pathway-related gene expression.SIGNIFICANCE STATEMENTG-protein-coupled receptors (GPCRs) are targets of various clinically approved drugs. Here we report that SNL increased GPR151 expression in the spinal cord, and mutation or inhibition of GPR151 alleviated SNL-induced neuropathic pain. In addition, SNL downregulated the expression of DNMT3b, which caused demethylation ofGPR151gene promoter, facilitated the binding of transcriptional factor KLF5 with theGPR151promoter, and further increased GPR151 expression in spinal neurons. The increased GPR151 may contribute to the pathogenesis of neuropathic pain via activating MAPK signaling and increasing pain-related gene expression. Our study reveals an epigenetic mechanism underlying GPR151 expression and suggests that targeting GPR151 may offer a new strategy for the treatment of neuropathic pain.