MIB2 functions in oocyte meiosis by modulating chromatin configuration.

Chromatin configuration serves as a principal indicator of GV (germinal vesicle)-stage oocyte quality. However, the underlying mechanisms governing the chromatin configuration transition from NSN (non-surrounded nucleolus) to SN (surrounded nucleolus) remain unclear. In this study, by conducting a quantitative proteomic analysis, we identified an increased expression of the MIB2 (MIB E3 ubiquitin protein ligase 2) protein in SN oocytes. Specific depletion of MIB2 in SN oocytes not only leads to severe disruption of the meiotic apparatus and a higher incidence of aneuploidy, but also adversely affects meiotic maturation and early embryo development. Notably, overexpression of MIB2 in NSN oocytes facilitates the chromatin configuration transition. Meantime, we observed that forced expression of MIB2 in NSN oocytes significantly mitigates spindle/chromosome disorganization and aneuploidy. In summary, our results suggest that chromatin configuration transition regulated by MIB2 is crucial for oocyte to acquire the developmental competence.

Proteomic Profiling Reveals the Molecular Control of Oocyte Maturation.

Meiotic maturation is an intricate and precisely regulated process orchestrated by various pathways and numerous proteins. However, little is known about the proteome landscape during oocytes maturation. Here, we obtained the temporal proteomic profiles of mouse oocytes during in vivo maturation. We successfully quantified 4694 proteins from 4500 oocytes in three key stages (germinal vesicle, germinal vesicle breakdown, and metaphase II). In particular, we discovered the novel proteomic features during oocyte maturation, such as the active Skp1-Cullin-Fbox pathway and an increase in mRNA decay-related proteins. Using functional approaches, we further identified the key factors controlling the histone acetylation state in oocytes and the vital proteins modulating meiotic cell cycle. Taken together, our data serve as a broad resource on the dynamics occurring in oocyte proteome and provide important knowledge to better understand the molecular mechanisms during germ cell development.

The prognostic value of tumour-infiltrating lymphocytes, programmed cell death protein-1 and programmed cell death ligand-1 in Stage I-III triple-negative breast cancer.

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) represent a robust biological prognostic biomarker in triple-negative breast cancer (TNBC); however, the contribution of different subsets of immune cells is unclear. We investigated the prognostic value of immune markers, including stromal TILs (sTILs), CD8+T and FOPX3+T cells, PD-1 and PD-L1 in non-metastatic TNBC. METHODS: In total, 259 patients with Stage I-III TNBC were reviewed. The density of sTILs along with the presence of total (t), stromal (s), and intratumoral (i) CD8+T cells and FOPX3+T cells were evaluated by haematoxylin and eosin and immunohistochemical staining. Immunohistochemical staining of PD-1, PD-L1 was also conducted. RESULTS: All immune markers were positively correlated with each other (P < 0.05). In the multivariate analysis, sTILs (P = 0.046), tCD8+T cells (P = 0.024), iCD8+T cells (P = 0.050) and PD-1 (P = 0.039) were identified as independent prognostic factors for disease-free survival (DFS). Further analysis showed that tCD8+T cells (P = 0.026), iCD8+T cells (P = 0.017) and PD-1 (P = 0.037) increased the prognostic value for DFS beyond that of the classic clinicopathological factors and sTILs. CONCLUSIONS: In addition to sTILs, inclusion of tCD8+T, iCD8+T cells, or PD-1 may further refine the prognostic model for non-metastatic TNBC beyond that including classical factors alone.

Antimony Isotope Fractionation Revealed from EXAFS during Adsorption on Fe (Oxyhydr)oxides.

A lack of knowledge about antimony (Sb) isotope fractionation mechanisms in key geochemical processes has limited its environmental applications as a tracer. Naturally widespread iron (Fe) (oxyhydr)oxides play a key role in Sb migration due to strong adsorption, but the behavior and mechanisms of Sb isotopic fractionation on Fe (oxyhydr)oxides are still unclear. Here, we investigate the adsorption mechanisms of Sb on ferrihydrite (Fh), goethite (Goe), and hematite (Hem) using extended X-ray absorption fine structure (EXAFS) and show that inner-sphere complexation of Sb species with Fe (oxyhydr)oxides occurs independent of pH and surface coverage. Lighter Sb isotopes are preferentially enriched on Fe (oxyhydr)oxides due to isotopic equilibrium fractionation, with neither surface coverage nor pH influencing the degree of fractionation (Δ123Sbaqueous-adsorbed). Limited Fe atoms are present in the second shell of Hem and Goe, resulting in weaker surface complexes and leading to greater Sb isotopic fractionation than with Fh (Δ123Sbaqueous-adsorbed of 0.49 ± 0.004, 1.12 ± 0.006, and 1.14 ± 0.05‰ for Fh, Hem, and Goe, respectively). These results improve the understanding of the mechanism of Sb adsorption by Fe (oxyhydr)oxides and further clarify the Sb isotope fractionation mechanism, providing an essential basis for future application of Sb isotopes in source and process tracing.

Using Mercury Stable Isotopes to Quantify Bidirectional Water-Atmosphere Hg(0) Exchange Fluxes and Explore Controlling Factors.

In this study, exchange fluxes and Hg isotope fractionation during water-atmosphere Hg(0) exchange were investigated at three lakes in China. Water-atmosphere exchange was overall characterized by net Hg(0) emissions, with lake-specific mean exchange fluxes ranging from 0.9 to 1.8 ng m-2 h-1, which produced negative δ202Hg (mean: -1.61 to -0.03‰) and Δ199Hg (-0.34 to -0.16‰) values. Emission-controlled experiments conducted using Hg-free air over the water surface at Hongfeng lake (HFL) showed negative δ202Hg and Δ199Hg in Hg(0) emitted from water, and similar values were observed between daytime (mean δ202Hg: -0.95‰, Δ199Hg: -0.25‰) and nighttime (δ202Hg: -1.00‰, Δ199Hg: -0.26‰). Results of the Hg isotope suggest that Hg(0) emission from water is mainly controlled by photochemical Hg(0) production in water. Deposition-controlled experiments at HFL showed that heavier Hg(0) isotopes (mean ε202Hg: -0.38‰) preferentially deposited to water, likely indicating an important role of aqueous Hg(0) oxidation played during the deposition process. A Δ200Hg mixing model showed that lake-specific mean emission fluxes from water surfaces were 2.1-4.1 ng m-2 h-1 and deposition fluxes to water surfaces were 1.2-2.3 ng m-2 h-1 at the three lakes. Results from the this study indicate that atmospheric Hg(0) deposition to water surfaces indeed plays an important role in Hg cycling between atmosphere and water bodies.

Distribution, Source Identification, and Output flux of Barium in Surface Waters in the Sanjiangyuan Region and Qilian Mountain Region of Tibetan Plateau.

Water safety concerning Barium (Ba) has become a public issue worldwide. As the "Asian water tower", Tibetan Plateau is the birthplace of many rivers. However, the distribution, source, and output flux of Ba are largely unknown. In this study, surface water samples were collected from different catchments in the Sanjiangyuan Region (SJY) and the Qilian Mountain Region (QLM) in Tibetan Plateau. The concentration of Ba was determined by inductively coupled plasma optical emission spectroscopy, the source of Ba was discussed by a Gibbs diagram, and the output flux of Ba was estimated using the observation data from different hydrological stations. The results showed that the Ba concentrations were less than 160 µg/L, which is much lower than the guideline value of 700 µg/L for surface waters. The main sources of Ba were rock weathering and evaporation concentration. The total Ba output flux from SJY and QLM to downstream waters was 1,240 t/yr, which accounts for about 0.01% of the global freshwater Ba output flux to the ocean. The Ba production rate in Tibetan Plateau was comparable with that in the Arctic rivers. Under the scenario of global warming, water safety issues concerning Ba will be more serious since the output flux of Ba to downstream waters will be increased by intensified rock weathering, evaporation concentration, glacial retreat, and permafrost thawing. This study reveals the Ba flux and production rate in Tibetan Plateau, which will provide important information for evaluating the environmental impact of global warming on public health.

Dissociation of Mercuric Oxides Drives Anomalous Isotope Fractionation during Net Photo-oxidation of Mercury Vapor in Air.

The atmosphere is the primary medium for long-distance transport and transformation of elemental mercury (Hg), a potent neurotoxin. The recent discovery of mass-independent fractionation (MIF) of even-mass Hg isotopes (even-MIF, measured as Δ200Hg and Δ204Hg) in the atmosphere is surprising and can potentially serve as a powerful tracer in understanding Hg biogeochemistry. Far-ultraviolet (UVC) light-induced gas-phase reactions have been suspected as a likely cause for even-MIF, yet the mechanism remains unknown. Here, we present the first experimental evidence of large-scale even-MIF caused by UVC-induced (wavelength: 254 nm) Hg oxidation in synthetic air at the pressure (46-88 kPa) and temperature (233-298 K) resembling those of the lower atmosphere. We observe negatively correlated Δ200Hg and Δ204Hg signatures with values as low as -50‰ and as high as 550‰, respectively, in the remaining atomic Hg pool. The magnitude of even-MIF signatures decreases with decreasing pressure with the Δ200Hg/Δ204Hg ratio being similar to that observed in global precipitation. This even-MIF can be explained by photodissociation of mercuric oxides that are photochemically formed in the UVC-irradiated Hg-O2 system. We propose that similar processes occurring in the atmosphere, where mercuric oxide species serve as intermediates, are responsible for the observed even-MIF in the environment.

Concentrations, leachability, and health risks of mercury in green tea from major production areas in China.

Green tea has many health benefits and is the most consumed type in China. However, the heavy metals and contaminants in tea can also pose a great risk to human health. In this study, mercury (Hg) concentration in green tea collected from 11 provinces in China was examined. The leaching characteristics of Hg during brewing and the associated exposure to drinkers were also evaluated. Results indicated a low potential of Hg accumulation in green tea. The Hg content of green tea from Wanshan District, Guizhou Province-which has the largest Hg mine in China and is severely contaminated by Hg-could be limited by controlling the harvest time of tea leaves. The average Hg content of green tea from 43 tea production sites in China was only 6.3 ± 6.4 µg/kg dry weight. The brewing experiments of green tea showed that the leaching ratio of Hg was 22.61 ± 7.58% for 40 min of a single brew, and increased to 32.83 ± 12.37% after four rounds (3 min/ round) of brewing. The leaching of Hg from tea leaves was significantly affected by leaching time, temperature, and solid-liquid ratio but not by water hardness. The risk of Hg exposure from green tea intake was found to be very low, with an average hazard quotient (HQ) value of only 1.82 ± 1.85% for a single brew in 40 min and 2.64 ± 2.68% after four rounds of brewing. However, in some highly contaminated areas, with HQ values as high as 43.12 ± 2.41%, green tea intake may still pose a high risk of Hg exposure, and this risk should not be ignored.

Mass flow, enrichment and potential environmental impacts of mercury in a preheater-precalciner cement plant using multiple mining and industrial wastes.

Cement plants (CPs) are one of the most important anthropogenic sources of mercury (Hg) emissions in China. Over 1000 cement production lines operate in China and use various raw materials; however, little data on Hg emissions is recorded on site. This study investigated a CP in Guizhou Province that uses multiple mining and industrial wastes as part of the circular economy policy. Among the various raw materials, carbide slag had the highest Hg content (2.6 mg/kg) and contributed half of the Hg input. High Hg concentration (27 mg/kg) in the kiln tail dust and a strong Hg enrichment factor (39) was found, which was determined as the ratio of total Hg accumulated within the clinker production process to the daily Hg input from raw materials and fuel. The clinker had negligible Hg (0.001 mg/kg), while the Hg in cement products (0.04 mg/kg) mostly came from additives and retarders. The estimated atmospheric emission factor of Hg from this CP was 161.5 mg Hg/t clinker, which was much higher than those of other CPs in Guizhou that employ low-Hg raw materials. A five-step sequential extraction experiment with kiln tail dust indicates that Hg mainly existed in fraction of F4 (73-96% of the total Hg, possibly as Hg2Cl2) and that some samples had high proportions of water-soluble Hg (up to 21% of the total), which may be easily released into surrounding water bodies and pose high environmental risks. Using low-Hg raw (or alternative raw) materials and conducting proper disposal of kiln tail dust will reduce the environmental risk of Hg from CPs.

Understanding the excretion rates of methylmercury and inorganic mercury from human body via hair and fingernails.

Effective biomarkers are necessary to better understand the human mercury (Hg) exposure levels. However, mismatched biomarker sampling method causes extra uncertainty in assessing the risk of Hg exposure. To compare the differences between hair and fingernail, and further understand the excretion rates of methylmercury (MeHg) and inorganic mercury (IHg) via hair and fingernails, the total mercury (THg), MeHg, and IHg concentrations in paired hair and fingernail samples were investigated through paired samples collected from two typical mining areas, Wanshan mercury mine area (WMMA) and Hezhang zinc smelting area (HZSA). The positive correlation in THg, MeHg, and IHg concentrations (p <0.01) between hair and fingernail samples indicated that those two biomarkers can be corrected in application of assessing human Hg exposure. Compared to fingernails, the hair was suggested to be a more sensitive biomarker as the concentration of THg, MeHg and IHg were 2 ∼ 4 times higher than those in fingernails. Furthermore, the amounts of THg, MeHg, and IHg excreted via hair were 70 ∼ 226 times higher than that excreted via fingernails, and the hair plays a more important role than fingernails in the excretion of Hg from human bodies. Present study therefore provides some new insights to better understand the fate of human assimilated Hg.

Chemistry and Isotope Fractionation of Divalent Mercury during Aqueous Reduction Mediated by Selected Oxygenated Organic Ligands.

We have investigated the chemistry and Hg isotope fractionation during the aqueous reduction of HgII by oxalic acid, p-quinone, quinol, and anthraquinone-2,6-disulfonate (AQDS), a derivate of anthraquinone (AQ) that is found in secondary organic aerosols (SOA) and building blocks of natural organic matter (NOM). Each reaction was examined for the effects of light, pH, and dissolved O2. Using an excess of ligand, UVB photolysis of HgII was seen to follow pseudo-first-order kinetics, with the highest rate of ∼10-3 s-1 observed for AQDS and oxalic acid. Mass-dependent fractionation (MDF) occurs by the normal kinetic isotope effect (KIE). Only the oxalate ion, rather than oxalic acid, is photoreactive when present in HgC2O4, which decomposes via two separate pathways distinguishable by isotope anomalies. Upon UVB photolysis, only the reduction mediated by AQDS results in a large odd number mass-independent fractionation (odd-MIF) signified by enrichment of odd isotopes in the reactant. Consistent with the rate, MDF, and odd-MIF reported for fulvic acid, our AQDS result confirms previous assumptions that quinones control HgII reduction in NOM-rich waters. Given the magnitude of odd-MIF triggered via a radical pair mechanism and the significant rate in the presence of air, reduction of HgII by photoproducts of AQDS may help explain the positive odd-MIF observed in ambient aerosols depleted of HgII.

Role of AMP-activated protein kinase during postovulatory aging of mouse oocytes†.

Studies suggested that postovulatory oocyte aging might be prevented by maintaining a high maturation-promoting factor (MPF) activity. Whether AMP-activated protein kinase (AMPK) plays any role in postovulatory oocyte aging is unknown. Furthermore, while activation of AMPK stimulates meiotic resumption in mouse oocytes, it inhibits meiotic resumption in pig and bovine oocytes. Thus, the species difference in AMPK regulation of oocyte MPF activities is worth in-depth studies. This study showed that AMPK activation with metformin or 5-aminoimidazole- 4-carboxamide- 1-beta-d- ribofuranoside and inactivation with compound C significantly increased and decreased, respectively, the activation susceptibility (AS) and other aging parameters in aging mouse oocytes. While AMPK activity increased, MPF activity and cyclic adenosine monophosphate (cAMP) decreased significantly with time post ovulation. In vitro activation and inactivation of AMPK significantly decreased and increased the MPF activity, respectively. MPF upregulation with MG132 or downregulation with roscovitine completely abolished the effects of AMPK activation or inactivation on AS of aging oocytes, respectively. AMPK facilitated oocyte aging with increased reactive oxygen species (ROS) and cytoplasmic calcium. Furthermore, treatment with Ca2+/calmodulin-dependent protein kinase (CaMK) inhibitors significantly decreased AS and AMPK activation. Taken together, the results suggested that AMPK facilitated oocyte aging through inhibiting MPF activities, and postovulatory oocyte aging activated AMPK with decreased cAMP by activating CaMKs via increasing ROS and cytoplasmic calcium.

Glucocorticoids impair oocyte competence and trigger apoptosis of ovarian cells via activating the TNF-α system.

Mechanisms by which female stress and particularly glucocorticoids impair oocyte competence are largely unclear. Although one study demonstrated that glucocorticoids triggered apoptosis in ovarian cells and oocytes by activating the FasL/Fas system, other studies suggested that they might induce apoptosis through activating other signaling pathways as well. In this study, both in vivo and in vitro experiments were conducted to test the hypothesis that glucocorticoids might trigger apoptosis in oocytes and ovarian cells through activating the TNF-α system. The results showed that cortisol injection of female mice (1.) impaired oocyte developmental potential and mitochondrial membrane potential with increased oxidative stress; (2.) induced apoptosis in mural granulosa cells (MGCs) with increased oxidative stress in the ovary; and (3.) activated the TNF-α system in both ovaries and oocytes. Culture with corticosterone induced apoptosis and activated the TNF-α system in MGCs. Knockdown or knockout of TNF-α significantly ameliorated the pro-apoptotic effects of glucocorticoids on oocytes and MGCs. However, culture with corticosterone downregulated TNF-α expression significantly in oviductal epithelial cells. Together, the results demonstrated that glucocorticoids impaired oocyte competence and triggered apoptosis in ovarian cells through activating the TNF-α system and that the effect of glucocorticoids on TNF-α expression might vary between cell types.

Effectiveness of the AJCC 8th edition staging system for selecting patients with T1-2N1 breast cancer for post-mastectomy radiotherapy: a joint analysis of 1986 patients from two institutions.

BACKGROUND: The role of post-mastectomy radiotherapy (PMRT) in the treatment of patients with T1-2N1 breast cancer is controversial. This study's purpose was to evaluate the risk of recurrence of T1-2N1 breast cancer and the efficacy of PMRT in low-, medium- and high-risk groups of patients. METHODS: Post-mastectomy patients with T1-2N1 breast cancer were restaged according to the American Joint Committee on Cancer Staging Manual, 8th edition (AJCC 8th ed.) staging system. Recurrence scores were generated using prognostic factors identified for loco-regional recurrence and distant metastasis in patients without PMRT, and three risk groups were identified. Rates of loco-regional recurrence and distant metastasis were calculated with a competing risk model and compared using Gray's test. Disease-free survival and overall survival were calculated using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards regression model was used for the multivariate analysis. RESULTS: Data from 1986 patients (1521without PMRT; 465 with PMRT) were analyzed. Patients without PMRT were stratified into low-, intermediate- and high-risk groups by age, tumor location, AJCC 8th ed. stage, number of positive nodes and lympho-vascular invasion. The 5-year loco-regional recurrence rate and distant metastasis rates for the three risk groups were significant at 2.5, 5.4 and 16.2% (p <  0.001) respectively, and 4.9, 8.4 and 18.6% (p <  0.001) respectively. In the high-risk group, loco-regional recurrence (p <  0.001), and distant metastasis (p = 0.044) were significantly reduced, and disease free survival (p = 0.004), and overall survival (p = 0.029) were significantly improved after PMRT. In the low- and intermediate-risk groups, PMRT had no significant effect on loco-regional recurrence (p = 0.268), distant metastasis (p = 0.252), disease free survival (p = 0.608) or overall survival (p = 0.986). CONCLUSION: Our results showed no benefits of PMRT in the low-risk group, and thus, omitting PMRT radiotherapy in this population could be considered.

Risk stratification for prediction of locoregional recurrence in patients with pathologic T1-2N0 breast cancer after mastectomy.

BACKGROUND: Previous studies have revealed that nearly 15-20% of selected high-risk T1-2N0 breast cancers developed LRR after mastectomy. This study is aim to indentify the risk factors of locoregional recurrence (LRR) in patients with pathologic T1-2N0 breast cancer after mastectomy in a real-world and distinguish individuals who warrant postmastectomy radiotherapy (PMRT). METHODS: Female patients treated from 1999 to 2014 in National Cancer Center of China were retrospectively reviewed. A competing risk model was developed to estimate the cumulative incidence of LRR with death treated as a competing event. RESULTS: A total of 4841 patients were eligible. All underwent mastectomy plus axillary nodes dissection or sentinel node biopsy without PMRT. With a median follow-up of 56.4 months (range, 1-222 months), the 5-year LRR rate was 3.9%.Besides treatment era, age ≤ 40 years old (p < 0.001, hazard ratio [HR] = 2.262), tumor located in inner quadrant (p < 0.001, HR = 2.236), T2 stage (p = 0.020, HR = 1.419), and negative expressions of estrogen receptor (ER) and progesterone receptor (PR) (p = 0.032, HR = 1.485), were patients-related independent risk factors for LRR. The 5-year LRR rates were 1.7, 3.5, and 15.0% for patients with zero, 1-2, and 3-4 risk factors (p < 0.001). CONCLUSIONS: Risk Stratification based on age, T stage, ER/PR status and tumor location can stratify patients with pT1-2 N0 breast cancer into subgroups with different risk of LRR. PMRT might be suggested for patients with 3-4 risk factors.

Radiotherapy plays an important role in improving the survival outcome in patients with T1-2N1M0 breast cancer - a joint analysis of 4262 real world cases from two institutions.

BACKGROUND: To compare the survival outcomes between breast-conserving surgery (BCS) and modified radical mastectomy (MRM), and to investigate the role of radiotherapy (RT) in patients with pT1-2N1M0 breast cancer. METHODS: A total of 4262 women with T1-2N1M0 breast cancer treated at two institutions were retrospectively reviewed. A total of 3858 patients underwent MRM, and 832 (21.6%) of them received postoperative RT (MRM + RT). A total of 404 patients received BCS plus postoperative RT (BCS + RT). All patients received axillary lymph node dissection, while 3.8% of them had upfront sentinel node biopsy. The association of survival outcomes with different surgical modalities (BCS vs. MRM) and the role of RT were evaluated using multivariable proportional hazards regression and confirmed by the propensity score-matching (PSM) method. RESULTS: At a median follow-up of 71 months (range of 6-230 months), the 5-year overall survival (OS) rates of the BCS and MRM groups were 96.5 and 92.7%, respectively (P = .001), and the corresponding 5-year disease-free-survival (DFS) and locoregional recurrence (LRR) rates were 92.9 and 84.0%, and 2.0 and 7.0% (P = .001), respectively (P < .001). Multivariate analysis revealed that RT was an independent prognostic factor for improved OS (P = .001) and DFS (P = .009), and decreased LRR (P < .001). However, surgery procedure was not independently associated with either OS (P = .495), DFS (P = .204), or LRR (P = .996), which was confirmed by PSM analysis. CONCLUSION: Postoperative radiotherapy rather than the surgery procedures was associated with superior survival outcomes in patients with T1-2N1M0 breast cancer.

Vegetable Houttuynia cordata Thunb. as an important human mercury exposure route in Kaiyang county, Guizhou province, SW China.

Consumption of mercury (Hg) contaminated vegetable is one important pathway of Hg expose to humans. In this study, Hg contents in a popular vegetable, Houttuynia cordata Thunb. (HCT), and its growing soils in Kaiyang county in Guizhou province of southwest China were investigated. Health risk related to Hg exposure through consumption of this vegetable was evaluated for the first time. Hg contents in HCT were found to be much higher in three towns in western Kaiyang county (42.3 ± 48.2 µg/kg, FW), where former Hg mines located, than that in other towns (7.6 ± 5.0 µg/kg, FW). Hg contents in HCT were also higher than in the other five vegetables (Chinese cabbage, Lettuce, Tomato, Carrot and White radish). Consumption of HCT may account for 37.4-61.1% of total vegetable Hg intake of local people in Kaiyang county. Hg concentration in HCT positively correlated with that in soil (r2 = 0.311, p < 0.01), especially, the labile Hg species (FC1, r2 = 0.796, p < 0.01) and the elemental Hg that is bound to the crystalline oxides (FC3, r2 = 0.711, p < 0.01), and negatively correlated with Hg that is bound to humic and fulvic complexes (FC2, - 0.304). Estimated daily intake (EDI) and target hazard quotient (THQ) results shown that Hg expose risk is much higher for children than adults, likely due to their different eating habits and the amount of snack intake.

Distribution patterns and sources of heavy metals in soils from an industry undeveloped city in Southern China.

The accumulations of heavy metals in urban soils are derived from natural parent materials and complex anthropogenic emission sources. This paper investigated metal contamination in urban soils at an industry undeveloped city (Haikou) in southern China, an ideal place to quantitatively assess the contribution of metals from different sources. The concentrations of most heavy metals in the urban soils of Haikou were much lower than their guideline values and that of those from other big cities in China. In contrast, the chemical speciation of metals in this study was similar to those from other cities. The spatial distributions of heavy metals and principal component analysis (PCA) revealed that basaltic parent materials, traffic emissions, and coal combustion were the main factors controlling the distribution of metals in the soils. The Pb isotope signatures of the Haikou soils were greatly different from those of the Beijing and Shanghai soils, but similar to those of the Guangzhou soils, suggesting the common sources of Pb in southern China cities. The results of ternary mixing model of Pb isotopes showed that the contributions of Pb from natural background, coal combustion and traffic emission sources were 5.3-82.4% (mean: 39.7 ± 21.1%), 0-85.7% (mean: 25.5 ± 24.6%), and 1.9-64% (mean: 34.8 ± 22.9%), respectively. This suggests that traffic emission is still the most important anthropogenic source of Pb in Haikou.

Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial.

BACKGROUND: To our knowledge, no randomised study has compared postmastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy in patients with breast cancer. This study aimed to determine whether a 3-week schedule of postmastectomy hypofractionated radiotherapy is as efficacious and safe as a 5-week schedule of conventional fractionated radiotherapy. METHODS: This randomised, non-inferiority, open-label, phase 3 study was done in a single academic hospital in China. Patients aged 18-75 years who had undergone mastectomy and had at least four positive axillary lymph nodes or primary tumour stage T3-4 disease were eligible to participate. Patients were randomly assigned (1:1) according to a computer-generated central randomisation schedule, without stratification, to receive chest wall and nodal irradiation at a dose of 50 Gy in 25 fractions over 5 weeks (conventional fractionated radiotherapy) or 43·5 Gy in 15 fractions over 3 weeks (hypofractionated radiotherapy). The modified intention-to-treat population (including all eligible patients who underwent randomisation but excluding those who were considered ineligible or withdrew consent after randomisation) was used in primary and safety analyses. The primary endpoint was 5-year locoregional recurrence, and a 5% margin was used to establish non-inferiority (equivalent to a hazard ratio <1·883). This trial is registered at ClinicalTrials.gov, number NCT00793962. FINDINGS: Between June 12, 2008, and June 16, 2016, 820 patients were enrolled and randomly assigned to the conventional fractionated radiotherapy group (n=414) or hypofractionated radiotherapy group (n=406). 409 participants in the conventional fractionated radiotherapy group and 401 participants in the hypofractionated radiotherapy group were included in the modified intention-to-treat analyses. At a median follow-up of 58·5 months (IQR 39·2-81·8), 60 (7%) patients had developed locoregional recurrence (31 patients in the hypofractionated radiotherapy group and 29 in the conventional fractionated radiotherapy group); the 5-year cumulative incidence of locoregional recurrence was 8·3% (90% CI 5·8-10·7) in the hypofractionated radiotherapy group and 8·1% (90% CI 5·4-10·6) in the conventional fractionated radiotherapy group (absolute difference 0·2%, 90% CI -3·0 to 2·6; hazard ratio 1·10, 90% CI 0·72 to 1·69; p<0·0001 for non-inferiority). There were no significant differences between the groups in acute and late toxicities, except that fewer patients in the hypofractionated radiotherapy group had grade 3 acute skin toxicity than in the conventional fractionated radiotherapy group (14 [3%] of 401 patients vs 32 [8%] of 409 patients; p<0·0001). INTERPRETATION: Postmastectomy hypofractionated radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with high-risk breast cancer. Hypofractionated radiotherapy could provide more convenient treatment and allow providers to treat more patients. FUNDING: National Key Projects of Research and Development of China; the Chinese Academy of Medical Science Innovation Fund for Medical Sciences; and Beijing Marathon of Hope, Cancer Foundation of China.