Experimental and modeling investigation of dual-source iron release in water-solid-gas interaction of abandoned coal mine drainage.

After mine closure and flooding, abandoned iron-prone devices and equipment (e.g., steel bolts and ground support meshes) and iron-bearing minerals (e.g., pyrite) form a dual-source iron pollution system in mine groundwater. Dual-source iron contributes to the water-solid-gas interaction in abandoned coal mines and the release of iron at different periods after mine closure, posing environmental risks in groundwater and discharging acid mine drainage, which contains large amounts of iron. In this study, a series of hydrochemical experiments were conducted to simulate the iron release process of the dual-source system, and electrochemical experiments were carried out to reveal the reaction mechanism, characterize the dual-source iron pollution release mode and quantify the release rate ratio. PHREEQC package was used to simulate the long-term hydrogeochemistry reactions of the water-solid-gas interaction to determine the key factors and suitable conditions that inhibit dual-source iron release. The results show that the dual-source system of iron-bearing minerals (pyrite) and steel bolts promote iron release from each other. The resulting calculated annual iron release indicated that the overall iron release rate ratio is: dual-source > bolt > pyrite, indicating that mine water would remain acidic for a long time due to the continuous release of iron from the system. Numerical modeling results show that maintaining the environment temperature below 25 °C and the pH above 3.5 is an effective way to reduce the iron release rate.

Combined effects of hydrothermally-altered feldspar and water regime on cadmium minimization in rice.

The accumulation of cadmium (Cd) in grains and edible parts of crops poses a risk to human health. Because rice is the staple food of more than half of the world population, reducing Cd uptake by rice is critical for food safety. HydroPotash (HYP), an innovative potassium fertilizer produced with a hydrothermal process, has the characteristics of immobilizing heavy metals and potential use for remediating Cd-contaminated soils. The objective of this study was to evaluate the HYP as a soil amendment to immobilize Cd in acidic soils and to reduce the accumulation of Cd in rice tissues. The experiment was performed in a greenhouse with a Cecil sandy loam soil (pH 5.3 and spiked with 3 mg Cd kg-1) under either flooding conditions (water level at 4 cm above the soil surface) or at field capacity. Two hydrothermal materials (HYP-1 and HYP-2) were compared with K-feldspar + Ca(OH)2 (the raw material used for producing HYP), Ca(OH)2, zeolite, and a control (without amendment). After 30 days of soil incubation, HydroPotashs, the raw material, and Ca(OH)2 increased both soil solution pH and electrical conductivity. These materials also decreased soluble Cd concentration (up to 99.7%) compared with the control (p < 0.05). After 145 days, regardless of the materials applied, plant growth was favored (up to 35.8%) under the flooded regime. HydroPotash-1 was more effective for increasing dry biomass compared with other amendments under both water regimes. HydroPotashs reduced extractable Cd in soil, Cd content in plant biomass at tillering and maturing stage, and were efficient in minimizing Cd accumulation in rice grains.

Management of medically inoperable and tyrosine kinase inhibitor-naïve early-stage lung adenocarcinoma with epidermal growth factor receptor mutations: a retrospective multi-institutional analysis.

BACKGROUND: The clinical value of combined local radiation and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) for medically inoperable and TKI-naïve early-stage lung adenocarcinoma patients with EGFR mutations has not yet been determined. In this study, we aimed to pool multi-institutional data to compare the therapeutic effect of EGFR-TKI treatment alone and combined radiation and TKI treatment on the survival outcomes in this patient subgroup. METHODS: A total of 132 cases of medically inoperable stage I to III EGFR mutant lung adenocarcinoma were retrospectively reviewed based on data from 5 centers. Among these patients, 65 received combined radiation and EGFR-TKI therapy (R + TKI) (49.2%), while 67 received EGFR-TKI (50.8%) treatment alone. All patients were followed until death. RESULTS: For the R + TKI group, the median overall survival (OS) after primary therapy was 42.6 months, while that of the TKI alone group was 29.4 months (log-rank p < 0.001). In terms of progression-free survival (PFS), the median PFS in these two treatment groups was 24 months and 14.7 months respectively (log-rank p < 0.001). Multivariate analysis showed that R + TKI was independently associated with improved OS (adjusted HR 0.420; 95% CI 0.287 to 0.614; p < 0.001) and PFS (adjusted HR 0.420; 95% CI 0.291 to 0.605; p < 0.001) compared to TKI alone. Subgroup analysis confirmed the significant OS benefits in stage III patients and RFS benefits in stage II/III patients. CONCLUSIONS: Upfront radiation to primary sites with subsequent TKI treatment is a feasible option for patients with medically inoperable EGFR-mutant non-small-cell lung carcinoma (NSCLC) during first-line EGFR-TKI treatment, with significantly improved PFS and OS compared with those yielded by TKI treatment alone.

The Stimulatory Effects of Nanochitin Whisker on Carbon and Nitrogen Metabolism and on the Enhancement of Grain Yield and Crude Protein of Winter Wheat.

Nanochitin whisker (NC) with a cationic nature could enhance plant photosynthesis, grain yield, and quality of wheat, but have not been systematically studied. This study was designed to investigate the stimulatory effects of NC on dry matter (DM) and nitrogen (N) accumulation and translocation, and on the metabolism of carbon (C) and N in later growth stages of winter wheat to reveal the enhancement mechanism of grain yield and crude protein concentration. Different parts of NC-treated plants from pot grown experiments were collected at the pre- and post-anthesis stages. The accumulation, translocation, and contributions of DM and N from pre-anthesis vegetation organs to grains, as well as key metabolic enzyme activities, including sucrose phosphate synthase (SPS) and phosphoenolpyruvate carboxylase (PEPC), were examined. The results showed that, at an application rate of 6 mg·kg-1 of NC in the soil, the accumulation of DM and N were significantly enhanced by 16.2% and 38.8% in pre-anthesis, and by 15.4% and 30.0% in post-anthesis, respectively. Translocation of N and DM in the post-anthesis periods were enhanced by 38.4% and 50.9%, respectively. NC could also stimulate enzyme activities, and increased 39.8% and 57.1% in flag leaves, and by 36.0% and 58.8% in spikes, respectively, at anthesis. SPS and PEPC increased by 28.2% and 45.1% in flag leaves, and by 42.2% and 56.5% in spikes, respectively, at 15 days after anthesis. The results indicated that the NC promoted N metabolism more than C metabolism, and resulted in the enhancement of grain yield by 27.56% and of crude protein concentration in grain by 13.26%, respectively.

MiR-29a/b/c regulate human circadian gene hPER1 expression by targeting its 3'UTR.

Several essential biological progresses in mammals are regulated by circadian rhythms. Though the molecular mechanisms of oscillating these circadian rhythms have been uncovered, the specific functions of the circadian genes are not very clear. It has been reported that knocking down circadian genes by microRNA is a useful strategy to explore the function of the circadian rhythms. In this study, through a forward bioinformatics screening approach, we identified miR-29a/b/c as potent inhibitors for the human circadian gene hPER1. We further found that miR-29a/b/c could directly target hPER1 3'untranslated region (UTR) and down-regulate hPER1 at both mRNA and protein expression levels in human A549 cells. Thus, our findings suggested that the expression of hPER1 is regulated by miR-29a/b/c, which may also provide a new clue for the function of hPER1.

Extreme precipitation accelerates nitrate leaching in the intensive agricultural region with thick unsaturated zones.

Nitrate accumulation in the soil profile in the intensive agricultural region has been widely concerned in the world. However, the changes in nitrate accumulation characteristics caused by climate change, such as extremely high precipitation, are not well quantified, particularly for the regions with thick unsaturated zones. Here, we resampled the soil profiles taken in normal year (2020) after extreme precipitation year (2021) (>800 cm) in three regions in the southern Loess Plateau (LP) with three different water managements including rainfed orchards (n = 10), well-irrigated orchards (n = 4) and canal-irrigated orchards (n = 8). The accumulation amounts, peak depths, and accumulation depths of nitrate soil profiles of the different regions of two years were compared. The results showed that average nitrate accumulation in normal year at the rainfed region (800-cm depth), well-irrigated region (800-cm depth) and canal-irrigated region (1400-cm depth) were 5995 kg N ha-1, 9765 kg N ha-1, and 19,608 kg N ha-1, respectively. Compared with 2020, extreme precipitation in 2021 led to 56-91% reductions (2060-3702 kg N ha-1) in nitrate accumulation in 0-200 cm soil layer, and average nitrate leaching into the aquifer was >1390 kg N ha-1 in the canal-irrigated region. Average migration depths of nitrate peak in rainfed, well-irrigated and canal-irrigated regions were 92 cm, 115 cm, and 188 cm, respectively; as for nitrate accumulation depths, they were 10 cm, 80 cm and 108 cm, respectively. Vertically, the dried soil layer and paleosol layer (high clay content) in the canal-irrigated region significantly hindered nitrate deep migration caused by the extreme precipitation. The result highlights that extreme precipitation significantly accelerated nitrate leaching in the deep soil profiles, and future vulnerability and risk assessment studies must account for the impacts of extreme precipitation on nitrate leaching.

Cancer department nurses' attitudes and practices in response to the sexual issues of pelvic radiation patients: a survey in Sichuan, China.

Our aim was to investigate cancer department nurses' attitudes and practices in response to pelvic radiation patients' sexual issues in Sichuan, China. A self-made questionnaire survey was conducted with 150 registered nurses of six hospitals in China. Nurses were asked about their experiences regarding consultation about sexual issues and attitudes toward the sex-related statements of pelvic radiation patients. We analyzed the correlation factors for the attitudes about dealing with patients' sexual issues by using the χ(2)-test. Of the survey sample, 128 nurses (85.33%) responded. Of the respondents, 46.88% had been consulted about sexual issues by patients or families. In addition, 87.5% of the nurses believed that 'reliable information on sexual in pelvic radiotherapy is lacking', and 77.34% reported having 'an interest in undertaking education of knowledge about pelvic radiation patients' sexual issues'; yet only 4.69% had completed professional sexual education about pelvic radiation patients. The hospital type and bed number as well as nurse age and seniority also affected the responses. This study shows that discussing sexuality is still repressed in the patient-nurse relationship, and most nurses' in Chinese cancer departments lack knowledge about pelvic radiation patients' sexual problems.

Dynamic Release Characteristics and Kinetics of a Persulfate Sustained-Release Material.

Sustained-release materials are increasingly being used in the delivery of oxidants for in situ chemical oxidation (ISCO) for groundwater remediation. Successful implementation of sustained-release materials depends on a clear understanding of the mechanism and kinetics of sustained release. In this research, a columnar sustained-release material (PS@PW) was prepared with paraffin wax and sodium persulfate (PS), and column experiments were performed to investigate the impacts of the PS@PW diameter and PS/PW mass ratio on PS release. The results demonstrated that a reduction in diameter led to an increase in both the rate and proportion of PS release, as well as a diminished lifespan of release. The release process followed the second-order kinetics, and the release rate constant was positively correlated with the PS@PW diameter. A matrix boundary diffusion model was utilized to determine the PS@PW diffusion coefficient of the PS release process, and the release lifespan of a material with a length of 500 mm and a diameter of 80 mm was predicted to be more than 280 days. In general, this research provided a better understanding of the release characteristics and kinetics of persulfate from a sustained-release system and could lead to the development of columnar PS@PW as a practical oxidant for in situ chemical oxidation of contaminated aquifers.

[Determination of bisphenols in sediment by accelerated solvent extraction and solid-phase extraction purification coupled with ultra performance liquid chromatography-tandem mass spectrometry].

Bisphenols are endocrine disruptors that are characterized with bioaccumulation, persistence, and estrogenic activity. Even low contents of bisphenols can exert adverse effects on human health and the ecological environment. Herein, a method combining accelerated solvent extraction and solid-phase extraction purification with ultra performance liquid chromatography-tandem mass spectrometry was developed for the accurate detection of bisphenol A (BPA), bisphenol B (BPB), bisphenol F (BPF), bisphenol S (BPS), bisphenol Z (BPZ), bisphenol AF (BPAF), and bisphenol AP (BPAP) in sediments. The mass spectrometric parameters of the seven bisphenols were optimized, and the response values, separation effects, and chromatographic peak shapes of the target compounds were compared under three different mobile phase conditions. The sediment samples were pretreated by accelerated solvent extraction, and orthogonal tests were used to optimize the extraction solvent, extraction temperature, and cycle number. The results showed that the use of 0.05% (v/v) ammonia and acetonitrile as the mobile phase for gradient elution could rapidly separate the seven bisphenols on an Acquity UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm). The gradient program was as follows: 0-2 min, 60%A; 2-6 min, 60%A-40%A; 6-6.5 min, 40%A; 6.5-7 min, 40%A-60%A; 7-8 min, 60%A. Orthogonal experiments indicated that the optimal extraction conditions were as follows: extraction solvent of acetonitrile, extraction temperature of 100 ℃, and cycle number of three. The seven bisphenols showed good linearity in the range of 1.0-200 µg/L, with correlation coefficients (r2) greater than 0.999, and the limits of detection were 0.01-0.3 ng/g. The recoveries for the seven bisphenols ranged from 74.9% to 102.8% at three spiking levels (2.0, 10, 20 ng/g), with relative standard deviations ranging from 6.2% to 10.3%. The established method was applied to detect the seven bisphenols in sediment samples collected from Luoma Lake and its inflow rivers. BPA, BPB, BPF, BPS, and BPAF were detected in the sediments of the lake, and BPA, BPF, and BPS were detected in the sediments of its inflow rivers. The detection frequency of BPA and BPF was 100%, and the contents of these bisphenols in the sediment were 11.9-38.0 ng/g and 11.0-27.3 ng/g, respectively. The developed method is simple, rapid with high accuracy and precision, and is suitable for the determination of the seven bisphenols in sediment.

Efficient degradation of phenanthrene by biochar-supported nano zero-valent iron activated persulfate: performance evaluation and mechanism insights.

Biochar-supported nano zero-valent iron (BC@nZVI) is a novel and efficient non-homogeneous activator for persulfate (PS). This study aimed to identify the primary pathways, the degradation mechanism and the performance of phenanthrene (PHE) with PS activated by BC@nZVI (BC@nZVI/PS). BC@nZVI as an activator for PS was prepared by liquid phase reduction method. BC@nZVI was characterized using scanning electron microscopy, transmission electron microscopy, X-ray diffractometer and Fourier transform infrared spectroscopy. The effects of the iron-carbon mass ratio and BC@nZVI dosage were investigated, and a pseudo-first-order kinetic model was used to evaluate the PHE degradation. The results showed that BC supported nZVI and inhibited the agglomeration of nZVI, improving PS's activation efficiency. The optimal iron-carbon mass ratio was determined to be 1:4, accompanied by a dosage of 0.6 g/L of BC@nZVI. During PS activation, nZVI was transformed to Fe2+ and Fe3+, with the majority being Fe3+. The reducibility of nZVI in BC@nZVI enabled the reduction of Fe3+ to Fe2+ to activate PS. Radical quenching and electron paramagnetic resonance (EPR) revealed that the oxidative radicals in the BC@nZVI/PS system were mainly SO4-· and ·OH, where SO4-· was the primary free radical under acidic and neutral conditions and ·OH in alkaline conditions. Additionally, BC@nZVI adsorption had a limited role in PHE removal. This study can provide mechanism insights of PHE degradation in water with BC@nZVI activation of the Na2S2O8 system.

Randomized Trial of First-Line Tyrosine Kinase Inhibitor With or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated Non-Small Cell Lung Cancer.

BACKGROUND: Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether these findings translate to epidermal growth factor receptor (EGFR)-mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual. METHODS: Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided. RESULTS: A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial. CONCLUSIONS: As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.

A construction strategy for conservative adaptive Kriging surrogate model with application in the optimal design of contaminated groundwater extraction-treatment.

When the simulation-optimization model to optimize the groundwater extraction-treatment schemes is used, the construction of a surrogate model for the numerical simulation model has become an effective means to overcome the large calculation load of repeatedly calling the numerical model. However, there are still some problems in using the surrogate model, such as large training sample size, low accuracy, and poor optimization results. In this paper, a conservative adaptive Kriging surrogate model (CAKSM) was proposed by coupling the Kriging surrogate model, optimal solution adaptive sampling method (OSAS), and conservative prediction idea. Firstly, an initial Kriging surrogate model (IKSM) was built for the numerical simulation model of groundwater flow and solute transport. Then, the IKSM was coupled with the optimization model to construct the adaptive Kriging surrogate model (AKSM) by using OSAS. A safety margin was added to the AKSM to build the CAKSM. Finally, the simulation-optimization models based on IKSM, AKSM, and CAKSM were solved by the genetic algorithm, respectively. The results showed that the IKSM could well substitute for the simulation model. The AKSM significantly improved the approximation degree between the surrogate model and the simulation model at the optimal solution by supplementing a small number of new samples. CAKSM could effectively constrain the pollutant mass concentrations within the controlled value, improving the reliability of the optimization scheme. The optimal extraction wells based on different surrogate models were all well 5, well 6, and well 9. They were concentrated in the middle and lower reaches of the contaminated plume's central axis. The sequence for the remediation effects by different surrogate models from high to low was as follows: CAKSM, AKSM, and IKSM. The risk rate of the optimal remediation scheme from the hydraulic conductivity random fields was as high as 12.12%, and the risks were mainly located upstream of the pollution plume's central axis.

Occurrence, distribution, and risk assessment of bisphenol analogues in Luoma Lake and its inflow rivers in Jiangsu Province, China.

Bisphenol analogs (BPs) are widely used in industrial and commercial products and have been detected in surface water, sediment, sewage, and sludge. The presence of BPs in the natural environment poses threats to the aquatic ecosystem and human health. The concentration, distribution, seasonal variation, and risk assessment of BPA and BPA structural analogs including BPB, BPF, BPS, BPZ, BPAF, and BPAP in surface water and sediment during dry season and flood season in Luoma Lake and its inflow rivers in Jiangsu Province, China, were investigated in this study. The detection frequency of BPA and BPF was 100%. Although the use of BPA is restricted, BPA is still the dominant BPs in surface water and sediment. The concentration of BPs in surface water during flood season was higher than that in dry season. The concentrations of BPs in Fangting River, Zhongyun River, and Bulao River were higher than those in Luoma Lake. The average concentrations of BPs in surface water were in the order of BPA > BPF> BPS> BPB > BPZ > BPAF> BPAP. Compared with other studies, the concentration of BPs in Luoma Lake was moderate. There is no significant spatial distribution and difference in seasonal variation of BPs concentration in sediment (p > 0.05). Compared with other studies, the contamination of BPs in sediment of Luoma Lake was relatively low. Risk quotient (RQ) was used to evaluate the ecological risk of BPs in water environment, and the 17ß estradiol equivalent (EEQ) method was used to estimate the estrogenic activity of BPs. The risk assessment showed no high ecological risk (RQ < 1.0) and estrogenic risk (EEQ < 1.0 ng/L) in dry season and flood season. The estimated RQ and EEQt indicated that the ecological and human health impacts were negligible in the short term.

Degradation Characteristics of Carbon Tetrachloride by Granular Sponge Zero Valent Iron.

Granular sponge zero valent iron (ZVI) was employed to degrade carbon tetrachloride (CCl4). The effects of acidic washing, initial solution pH, and ZVI dosage on CCl4 degradation were investigated. Results showed that CCl4 was effectively removed by ZVI and approximately 75% of CCl4 was transformed into chloroform through hydrogenolysis. The rate of chloroform transformation was slower compared to that of CCl4, resulting in chloroform accumulation. CCl4 degradation was a pseudo first-order process. The observed pseudo first-order reaction rate constant (kobs) for CCl4 and chloroform were 0.1139 and 0.0109 h-1, respectively, with a ZVI dosage of 20 g/L and an initial CCl4 concentration of 20 mg/L. Surface acidic washing had a negligible effect on CCl4 degradation with ZVI. The kobs for CCl4 degradation increased linearly with increasing ZVI dosage and the optimal dosage of ZVI was 20 g/L based on the surface area-normalized rate constants. The negative relationship between kobs and the solution pH indicated that the degradation of CCl4 by ZVI performed better under weakly acidic conditions.

Rapid Degradation of Carbon Tetrachloride by Microscale Ag/Fe Bimetallic Particles.

Cost-effective zero valent iron (ZVI)-based bimetallic particles are a novel and promising technology for contaminant removal. The objective of this study was to evaluate the effectiveness of CCl4 removal from aqueous solution using microscale Ag/Fe bimetallic particles which were prepared by depositing Ag on millimeter-scale sponge ZVI particles. Kinetics of CCl4 degradation, the effect of Ag loading, the Ag/Fe dosage, initial solution pH, and humic acid on degradation efficiency were investigated. Ag deposited on ZVI promoted the CCl4 degradation efficiency and rate. The CCl4 degradation resulted from the indirect catalytic reduction of absorbed atomic hydrogen and the direct reduction on the ZVI surface. The CCl4 degradation by Ag/Fe particles was divided into slow reaction stage and accelerated reaction stage, and both stages were in accordance with the pseudo-first-order reaction kinetics. The degradation rate of CCl4 in the accelerated reaction stage was 2.29-5.57-fold faster than that in the slow reaction stage. The maximum degradation efficiency was obtained for 0.2 wt.% Ag loading. The degradation efficiency increased with increasing Ag/Fe dosage. The optimal pH for CCl4 degradation by Ag/Fe was about 6. The presence of humic acid had an adverse effect on CCl4 removal.

Box Experiment Study of Thermally Enhanced SVE for Benzene.

In order to describe the changes of soil temperature field, air flow field and remediation situation with time during the process of thermally enhanced SVE (soil vapor extraction), a remediation experiment of benzene contaminated soil with single extraction pipe was carried out in a box device. The results showed that the whole temperature of the system was raised to 80 °C in 4 h. 43% of benzene were removed in the first 2% of the extraction time. After 24 h, the repair efficiency was close to 100%. The device can efficiently remove benzene from soil. By continuously monitoring the parameters in the operation process of the system, the spatial distribution of temperature and soil gas pollutant concentration with time was plotted. It showed the benzene concentration distribution in the soil gas was more consistent with the temperature distribution before the start of ventilation, and the concentration of benzene in the soil gas dropped rapidly after ventilation, while the temperature distribution was almost unaffected. In the treatment of soil with a benzene content of 17.8 mg∙kg-1, when the soil gas benzene concentration is the highest at 180 min, the peak value is 11,200 mg∙m-3, and the average concentration is 7629.4 mg∙m-3.

Alterations in Immune Response Profile of Tumor-Draining Lymph Nodes after High-Intensity Focused Ultrasound Ablation of Breast Cancer Patients.

Previous studies have revealed that high-intensity focused ultrasound (HIFU) ablation can trigger an antitumor immune response. The aim of this study was to investigate immune response in tumor-draining lymph nodes (TDLNs) after HIFU treatment. Forty-eight female patients with biopsy-confirmed breast cancer were divided into a control group and an HIFU group. In the control group, 25 patients underwent modified radical mastectomy, but 23 patients in the HIFU group received HIFU ablation of primary cancer, followed by the same operation. Using HE and immunohistochemical staining, the immunologic reactivity pattern and immune cell profile were assessed in paraffin-embedded axillary lymph nodes (ALNs) in all patients. The results showed that ALNs presented more evident immune reactions in the HIFU group than in the control group (100% vs. 64%). Among the ALNs, 78.3% had mixed cellular and humoral immune response, whereas 36% in the control group showed cellular immune response. The numbers of CD3+, CD4+, NK cell, and activated CTLs with Fas ligand+, granzyme+ and perforin+ expression were significantly higher in the ALNs in the HIFU group. It was concluded that HIFU could stimulate potent immune response and significantly increase T cell, activated CTLs and NK cell populations in the TDLNs of breast cancer.

A retrospective study comparing D1 limited lymph node dissection and D2 extended lymph node dissection for N3 gastric cancer.

BACKGROUND: In countries in East Asia, the typical treatment for curable gastric cancer is gastrectomy with D2 lymphadenectomy. However, whether D2 lymphadenectomy is beneficial for high-risk N3 node disease remains controversial. We conducted a multi-institution retrospective study on patients with high-risk, locally advanced gastric cancer. To compare the rates of disease-free survival (DFS) and overall survival (OS) between radical D2-type gastric resection and lymphadenectomy and the more limited D1 type resection and lymphadenectomy. METHODS: From July 2010 to June 2015, 74 patients out of 949 who underwent curative-intent R0 surgery were selected in pairs to compare the survival outcomes between those who underwent radical D2 type (n=37) vs. the more limited D1 type (n=37) gastric resection and lymphadenectomy. RESULTS: The median DFS was 9.72 and 7.81 months for the D2 and D1 types, respectively (P=0.746), and the OS was 16.39 and 15.85 months for the D2 and D1 types, respectively (P=0.937). CONCLUSIONS: No statistically significant differences in DFS and OS were noted between D1 and D2 procedures for those with N3 disease. Our results support the hypothesis that a novel multidisciplinary approach rather than a surgical approach alone is needed to improve the survival outcomes of high-risk patients with N3 gastric cancer.

CENPE expression is associated with its DNA methylation status in esophageal adenocarcinoma and independently predicts unfavorable overall survival.

Centrosome-associated protein E (CENPE) is a plus end-directed kinetochore motor protein, which plays a critical role in mitosis. In this in silico study, using data from the Cancer Genome Atlas-Esophageal Carcinoma (TCGA-ESCA), we analyzed the expression profile of CENPE mRNA in esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EA), its independent prognostic value and the potential mechanisms of its dysregulation in EA. Results showed that both ESCC and EA tissues had significantly elevated CENPE expression compared with their respective adjacent normal tissues. However, Kaplan-Meier survival curves showed that high CENPE was associated with unfavorable OS in EA. Univariate and multivariate analysis confirmed that CENPE expression was an independent indicator of unfavorable OS in EA patients, as a continuous variable (HR: 1.861, 95%CI: 1.235-2.806, p = 0.003) or as categorical variables (HR: 2.550, 95%CI: 1.294-5.025, p = 0.007). However, CENPE expression had no prognostic value in ESCC. Compared with the methylation status in normal samples, 3 CpG sites were hypomethylated (cg27388036, cg27443373, and cg24651824) in EA, among which two sites (cg27443373 and cg24651824) showed moderately negative correlation with CENPE expression. In addition, we also found that although heterozygous loss (-1) was frequent in EA (50/88, 56.8%), it was not necessarily associated with decreased CENPE expression compared with the copy neutral (0) cases. The methylation of the -1 group was significantly lower than that of the +1/0 group (p = 0.04). Based on these findings, we infer that CENPE upregulation in EA might serve as a valuable indicator of unfavorable OS. The methylation status of cg27443373 and cg24651824 might play a critical role in modulating CENPE expression.

Changes in circulating immunosuppressive cytokine levels of cancer patients after high intensity focused ultrasound treatment.

Immunosuppression in a patient with malignant tumor is a major obstacle in cancer treatment. In this study, we investigated changes in the circulating level of all measured immunosuppressive cytokines in patients with malignancy before and after high intensity focused ultrasound (HIFU) treatment. Fifteen patients with solid malignancy were enrolled in this study and an enzyme-linked immunoabsorbent assay (ELISA) method was used to measure serum level of vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), transforming growth factor-beta2 (TGF-beta2), interleukin 6 (IL-6) and interleukin 10 (IL-10), respectively before and 1 wk after HIFU treatment. Among them, seven patients had distant metastasis and the remaining eight had no metastasis. All patients received one-session HIFU treatment for primary cancer, including complete ablation in eight patients without metastasis, and partial ablation in seven patients with metastases. The results showed that serum immunosuppressive cytokine levels decreased after HIFU treatment, and there were significant decreases of VEGF, TGF-beta1, and TGF-beta2 before and after HIFU treatment. Compared with the values in the metastatic patients, serum levels of immunosuppressive cytokines were significantly lower in the nonmetastatic patients after HIFU treatment. It is concluded that HIFU can decrease tumor-secreted immunosuppressive cytokine production in addition to its direct tumor destruction. This change may lessen tumor-induced immunosuppression and renew antitumor immunity after HIFU in cancer patients.