Construction of a nomogram risk prediction model for prolonged mechanical ventilation in patients following surgery for acute type A aortic dissection.

Background: This study aims to analyze the risk factors associated with prolonged mechanical ventilation (PMV) in patients following surgical treatment for acute type A aortic dissection (ATAAD). The objectives include constructing a predictive model for risk assessment and validating its predictive efficacy. Methods: A total of 452 patients diagnosed with ATAAD and undergoing surgical procedures at a tertiary hospital in Nanjing between January 2021 and April 2023 were selected using a convenience sampling method. Patients were categorized into two groups: PMV group (n = 132) and non-PMV group (n = 320) based on the occurrence of prolonged mechanical ventilation (PMV), and their clinical data were compared. The data were randomly divided into a modeling set and a validation set in a 7:3 ratio. Risk factors for PMV were identified in the modeling group using logistic regression analysis. A risk prediction model was constructed using R 4.1.3 software, visualized via a column chart. Receiver Operating Characteristic (ROC) curves were generated using the validation set to assess model differentiation. Calibration curves were plotted to evaluate accuracy and consistency, and Decision Curve Analysis (DCA) was applied to evaluate clinical utility. Results: The logistic regression analysis identified age, body mass index, preoperative white blood cell count, preoperative creatinine, preoperative cerebral hypoperfusion, and cardiopulmonary bypass time as significant risk factors for postoperative PMV in patients with ATAAD. The area under the curve (AUC) for the validation set ROC curve was 0.856, 95% confidence interval (0.805-0.907), indicating good discrimination. Calibration curves revealed strong alignment with the ideal curve, and the Hosmer-Lemeshow goodness-of-fit test indicated a well-fitted model (P = 0.892). The DCA curve demonstrated a high net benefit value, highlighting the model's strong clinical utility. Conclusions: The risk prediction model developed in this study for PMV in patients undergoing surgery for ATAAD exhibits robust predictive performance. It provides valuable insights for healthcare practitioners in predicting the likelihood of PMV and devising timely and personalized intervention strategies.

Past dynamics and future prediction of the impacts of land use cover change and climate change on landscape ecological risk across the Mongolian plateau.

Land use/land cover (LULC) change and climate change are interconnected factors that affect the ecological environment. However, there is a lack of quantification of the impacts of LULC change and climate change on landscape ecological risk under different shared socioeconomic pathways and representative concentration pathways (SSP-RCP) on the Mongolian Plateau (MP). To fill this knowledge gap and understand the current and future challenges facing the MP's land ecological system, we conducted an evaluation and prediction of the effects of LULC change and climate change on landscape ecological risk using the landscape loss index model and random forest method, considering eight SSP-RCP coupling scenarios. Firstly, we selected MCD12Q1 as the optimal LULC product for studying landscape changes on the MP, comparing it with four other LULC products. We analyzed the diverging patterns of LULC change over the past two decades and observed significant differences between Mongolia and Inner Mongolia. The latter experienced more intense and extensive LULC change during this period, despite similar climate changes. Secondly, we assessed changes in landscape ecological risk and identified the main drivers of these changes over the past two decades using a landscape index model and random forest method. The highest-risk zone has gradually expanded, with a 30% increase compared to 2001. Lastly, we investigated different characteristics of LULC change under different scenarios by examining future LULC products simulated by the FLUS model. We also simulated the dynamics of landscape ecological risks under these scenarios and proposed an adaptive development strategy to promote sustainable development in the MP. In terms of the impact of climate change on landscape ecological risk, we found that under the same SSP scenario, increasing RCP emission concentrations significantly increased the areas with high landscape ecological risk while decreasing areas with low risk. By integrating quantitative assessments and scenario-based modeling, our study provides valuable insights for informing sustainable land management and policy decisions in the region.

Diverse ALS mutations and cross-and multiple-resistance to ALS and EPSPS inhibitors in flucarbazone­sodium-resistant Bromus japonicus populations from Hebei province, China.

Japanese brome (Bromus japonicus) has become one of the main weeds in wheat fields in Hebei province of China and causes a large decrease of wheat production. A total of 44 putative resistant and 2 susceptible Japanese brome populations were collected in the 2021/2022 crop season from Hebei province of China to determine resistance levels to flucarbazone­sodium and to investigate the diversity of acetolactate synthase (ALS) mutations, as well as to confirm the cross-and multiple-resistance levels to ALS and EPSPS (5-enolpyruvate shikimate-3-phosphate synthetase) inhibitors. Whole plant bioassay results showed that 15 out of 44 populations tested or 34% were resistant to flucarbazone­sodium. The resistance indices of Japanese brome to flucarbazone­sodium ranged from 43 to 1977. The resistant populations were mainly distributed in Baoding and Shijiazhuang districts, and there was only one resistant population in Langfang district. Resistant Japanese brome had diverse ALS mutations, including Pro-197-Ser, -Thr, -Arg and Asp-376-Glu. The incidence of Pro-197-Ser mutation was the highest at 68%. Application of the CYP450 inhibitor malathion suggested that CYP450 was involved in metabolic resistance in a population without an ALS mutation. The population with Pro-197-Thr mutation evolved weak cross-resistance to mesosulfuron-methyl and pyroxsulam, and it is in the process of evolving multiple-resistance to glyphosate.

Spatiotemporal patterns and driving factors of gross primary productivity over the Mongolian Plateau steppe in the past 20 years.

The Eurasian steppe is the largest temperate grassland in the world. The grassland of the Mongolian Plateau (MP) represents an important part of the Eurasian steppe with high climatic sensitivity. Gross primary productivity (GPP) is a key indicator of the grassland's production, status and dynamic on the MP. In this study, we calibrated and evaluated the grassland-specific light use efficiency model (GRASS-LUE) against the observed GPP collected from nine eddy covariance flux sites on the MP, and compared the performance with other four GPP products (MOD17, VPM, GLASS and GOSIF). GRASS-LUE with higher R2 (0.91) and lower root mean square error (RMSE = 0.99 gC m-2 day-1) showed a better performance compared to the four GPP products in terms of model accuracy and dynamic consistency, especially in typical and desert steppe. The parameters of the GRASS-LUE are more suitable for water-limited grassland could be the reason for its outstanding performance in typical and desert steppe. Mean grassland GPP derived from GRASS-LUE was higher in the east and lower in the west of the MP. Grassland GPP was on average 205 gC m-2 over the MP between 2001 and 2020 with mean annual total GPP of 322 TgC yr-1. 30 % of the MP steppe showed a significant GPP increase. Growing season precipitation is the main factor affecting GPP of the MP steppe across regions. Anthropogenic factors (livestock density and population density) had greater effect on GPP than growing season temperature in pastoral counties in IM that take grazing as one of main industries. These findings can inform the status and trend of the productivity of MP steppe and help government and scientific research institutions to understand the drivers for spatial pattern of grassland GPP on the MP.

Recognition memory deficits detected through eye-tracking in well-controlled children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Children with self-limited epilepsy characterized by centrotemporal spikes (SeLECTS) exhibit cognitive deficits in memory during the active phase, but there is currently a lack of studies and techniques to assess their memory development after well-controlled seizures. In this study, we employed eye-tracking techniques to investigate visual memory and its association with clinical factors and global intellectual ability, aiming to identify potential risk factors by examining encoding and recognition processes. METHODS: A total of 26 recruited patients diagnosed with SeLECTS who had been seizure-free for at least 2 years, along with 24 control subjects, underwent Wechsler cognitive assessment and an eye-movement-based memory task while video-electroencephalographic (EEG) data were recorded. Fixation and pupil data related to eye movements were utilized to detect distinct memory processes and subsequently to compare the cognitive performance of patients exhibiting different regression patterns on EEG. RESULTS: The findings revealed persistent impairments in visual memory among children with SeLECTS after being well controlled, primarily observed in the recognition stage rather than the encoding phase. Furthermore, the age at onset, frequency of seizures, and interictal epileptiform discharges exhibited significant correlations with eye movement data. SIGNIFICANCE: Children with SeLECTS exhibit persistent recognition memory impairment after being well controlled for the disease. Controlling the frequency of seizures and reducing prolonged epileptiform activity may improve memory cognitive development. The application of the eye-tracking technique may provide novel insights into exploring memory cognition as well as underlying mechanisms associated with pediatric epilepsy.

Pregnancy-related knowledge in women with epilepsy in childbearing age: A pilot questionnaire survey from China.

PURPOSE: We aim to understand the knowledge of and attitudes toward pregnancy issues among women with epilepsy (WWE) and their caregivers and analyze the answers from the questionnaire to expose topics that require educational activities; thus, WWE experiences pregnancy better. METHODS: WWE at their childbearing age and/or their caregivers who entered the Fourth Affiliated Hospital of Zhejiang University for treatment of their condition were invited to fill out a questionnaire between March 1 and November 31, 2022. RESULTS: A combined total of 205 WWE and 142 caregivers completed the questionnaires. Among the surveyed WWE, a majority (63.74%) reported experiencing at least one miscarriage or induced abortion. However, a significant proportion (84.62%) of these WWE were still able to successfully give birth to at least one child. Furthermore, the offspring of these WWE showed no significant differences compared to the offspring of women without epilepsy, as reported by 93.51% of the participants. The participants' knowledge regarding the impact of epilepsy on pregnancy was found to be comparable, with average scores of 7.74 and 7.84, respectively. The participants exhibited a limited comprehension of antiseizure medications (ASMs)-related knowledge, specifically pertaining to ASMs adjustment during pregnancy (17.56% vs. 16.90%) and offspring outcomes (30.24% vs. 26.06%). Statistical analysis revealed significant correlations between the overall score and education level (p < .001), as well as epilepsy duration (p = .008). Regarding the source of knowledge, participants acknowledged primarily relying on neurologists, who remained their preferred choice for consultation. CONCLUSION: In our study, the understanding of pregnancy-related knowledge did not differ from WWE and their caregivers, both are far from satisfactory in certain areas. It is urgent for WWE and their caregivers to improve their pregnancy-related knowledge of epilepsy. As their primary access is from knowledgeable health care professionals like neurologists, well-trained neurologists in epilepsy management during pregnancy are in need.

Spatial and temporal patterns of above- and below- ground biomass over the Tibet Plateau grasslands and their sensitivity to climate change.

The sensitivity of grassland above- (AGB, gC m-2) and below-ground biomass (BGB, gC m-2) to climate has been shown to be significant on the Tibetan Plateau, however, the spatial patterns and sensitivity of biomass with altitudinal change needs to be quantitated. In this study, large data sets of AGB and BGB during the peak growth season, and the corresponding geographical and climate conditions in the grasslands of the Tibetan Plateau between 2001 and 2020 were analyzed, and modelled using a Cubist regression trees algorithm. The mean values for AGB and BGB were 61.3 and 1304.3 gC m-2, respectively, for the whole region over the two decades. There was a significant change in spatial AGB of 64.8 % on the Plateau (P < 0.05, with areas where AGB increased being twice as large as areas where AGB decreased), while BGB did not change significantly in majority the of the region (≥ 90.1 %, P > 0.05). In general, the areas where AGB showed positive partial correlations with precipitation were larger than the areas where AGB had positive correlations with temperature (P < 0.05). However, these trends varied depending on the climatic conditions: in the wetter regions, temperature had a greater effect on the size of the areas with positive AGB responses than precipitation (P < 0.05), while precipitation had a greater effect on the size of areas with positive BGB changes than temperature (P < 0.05). In the drier areas, however, precipitation affected the AGB response significantly compared to temperature (P < 0.05), while temperature influenced the BGB response greater than precipitation (P < 0.05). The response and sensitivity of grassland biomass to temperature and precipitation varied according to the altitude of the Plateau: the response and sensitivity were stronger and more sensitive at medium altitudes, and weak at the higher or lower altitudes. Likely, this phenomenon was resulted from the natural selection of plants to maintain the efficient use of resources during un-favourable and stressed conditions for maximum plant development and growth. These findings will help assess the ecological consequences of global climate change for the grasslands of the Tibetan Plateau, particularly in those regions with highly variable altitudes.

Trp-574-Leu mutation and metabolic resistance by cytochrome P450 gene conferred high resistance to ALS-inhibiting herbicides in Descurainia sophia.

Descurainia sophia (flixweed) is a troublesome weed in winter wheat fields in North China. Resistant D. sophia populations with different acetolactate synthetase (ALS) mutations have been reported in recent years. In addition, metabolic resistance to ALS-inhibiting herbicides has also been identified. In this study, we collected and purified two resistant D. sophia populations (R1 and R2), which were collected from winter wheat fields where tribenuron-methyl provided no control of D. sophia at 30 g a.i. ha-1. Whole plant bioassay and ALS activity assay results showed the R1 and R2 populations had evolved high-level resistance to tribenuron-methyl and florasulam and cross-resistance to imazethapyr and pyrithiobac­sodium. The two ALS genes were cloned from the leaves of R1 and R2 populations, ALS1 (2004 bp) and ALS2 (1998 bp). A mutation of Trp 574 to Leu in ALS1 was present in both R1 and R2. ALS1 and ALS2 were cloned from R1 and R2 populations respectively and transferred into Arabidopsis thaliana. Homozygous T3 transgenic seedlings with ALS1 of R1 or R2 were resistant to ALS-inhibiting herbicides and the resistant levels were the same. Transgenic seedlings with ALS2 from R1 or R2 were susceptible to ALS-inhibiting herbicides. Treatment with cytochrome P450 inhibitor malathion decreased the resistant levels to tribenuron-methyl in R1 and R2. RNA-Seq was used to identify target cytochrome P450 genes possibly involved in resistance to ALS-inhibiting herbicides. There were five up-regulated differentially expressed cytochrome P450 genes: CYP72A15, CYP83B1, CYP81D8, CYP72A13 and CYP71A12. Among of them, CYP72A15 had the highest expression level in R1 and R2 populations. The R1 and R2 populations of D. sophia have evolved resistance to ALS-inhibiting herbicides due to Trp 574 Leu mutation in ALS1 and possibly other mechanisms. The resistant function of CYP72A15 needs further research.

Unveiling the nexus of postoperative fever and delirium in cardiac surgery: identifying predictors for enhanced patient care.

Background: Postoperative delirium (POD) is a significant complication observed in cardiac surgery patients, characterized by acute cognitive decline, fluctuating mental status, consciousness impairment, and confusion. Despite its impact, POD often goes undiagnosed. Postoperative fever, a common occurrence after cardiac surgery, has not been comprehensively studied in relation to delirium. This study aims to identify perioperative period factors associated with POD in patients undergoing cardiopulmonary bypass, with the potential for implementing preventive interventions. Methods: In a prospective observational study conducted between February 2023 and April 2023 at the Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, a total of 232 patients who underwent cardiac surgery were enrolled. POD assessment utilized the Confusion Assessment Method for the ICU (CAM-ICU), while high fever was defined as a bladder temperature exceeding 39°C. Statistical analysis included univariate and multivariate analyses, logistic regression, nomogram development, and internal validation. Result: The overall incidence of postoperative delirium was found to be 12.1%. Multivariate analysis revealed that postoperative lactate levels [odds ratio (OR) = 1.787], maximum temperature (OR = 11.290), and cardiopulmonary bypass time (OR = 1.015) were independent predictors of POD. A predictive nomogram for POD was developed based on these three factors, demonstrating good discrimination and calibration. The prediction model exhibited a C-statistic value of 0.852 (95% CI, 0.763-0.941), demonstrating excellent discriminatory power. Sensitivity and specificity, based on the area under the receiver operating characteristic (AUROC) curve, were 91.2% and 67.9%, respectively. Conclusion: This study underscores the high prevalence of POD in cardiac surgery patients and identifies postoperative lactate levels, cardiopulmonary bypass duration, and postoperative fever as independent predictors of delirium. The association between postoperative fever and POD warrants further investigation. These findings have implications for implementing preventive strategies in high-risk patients, aiming to mitigate postoperative complications and improve patient outcomes.

Loss of Feedback Regulation between FAM3B and Androgen Receptor Driving Prostate Cancer Progression.

BACKGROUND: Although the TMPRSS2-ERG fusion occurs frequently in prostate cancer (PC), its impact on clinical outcomes remains controversial. Roughly half of TMPRSS2-ERG fusions occur through intrachromosomal deletion of interstitial genes and the remainder via insertional chromosomal rearrangements. Because PCs with deletion-derived TMPRSS2-ERG fusions are more aggressive than those with insertional fusions, we investigated the impact of interstitial gene loss on PC progression. METHODS: We conducted an unbiased analysis of transcriptome data from large collections of PC samples and employed diverse in vitro and in vivo models combined with genetic approaches to characterize the interstitial gene loss that imposes the most significant impact on clinical outcome. RESULTS: This analysis identified FAM3B as the top-ranked interstitial gene whose loss is associated with a poor prognosis. The association between FAM3B loss and poor clinical outcome extended to fusion-negative PCs where FAM3B downregulation occurred through epigenetic imprinting. Importantly, FAM3B loss drives disease progression in PC. FAM3B acts as an intermediator of a self-governing androgen receptor (AR) feedback loop. Specifically, AR upregulates FAM3B expression by binding to an intronic enhancer to induce an enhancer-RNA and facilitate enhancer-promoter looping. FAM3B, in turn, attenuates AR signaling. CONCLUSION: Loss of FAM3B in PC, whether through the TMPRSS2-ERG translocation or epigenetic imprinting, causes an exit from this autoregulatory loop to unleash AR activity and PC progression.These findings establish FAM3B loss as a new driver of PC progression and support the utility of FAM3B loss as a biomarker to better define aggressive PC.

Grazing-induced cattle behaviour modulates the secondary production in a Eurasian steppe ecosystem.

Livestock-grassland interactions are among the most important relationships in grazed grassland ecosystems, where herbivores play a crucial role in plant community and ecosystem functions. However, previous studies primarily have focused on the responses of grasslands to grazing, with few focussing on the effects of livestock behaviour that in turn would influence livestock intake and primary and secondary productivity. Through a 2-year grazing intensity experiment with cattle in Eurasian steppe ecosystem, global positioning system (GPS) collars were used to monitor animal movements, where animal locations were recorded at 10-min intervals during the growing season. We used a random forest model and the K-means method to classify animal behaviour and quantified the spatiotemporal movements of the animals. Grazing intensity appeared to be the predominant driver for cattle behaviour. Foraging time, distance travelled, and utilization area ratio (UAR) all increased with grazing intensity. The distance travelled was positively correlated with foraging time, yielding a decreased daily liveweight gain (LWG) except at light grazing. Cattle UAR showed a seasonal pattern and reached the maximum value in August. In addition, the canopy height, above-ground biomass, carbon content, crude protein, and energy content of plants all affected cattle behaviour. Grazing intensity and the resulting change in above-ground biomass and forage quality jointly determined the spatiotemporal characteristics of livestock behaviour. Increased grazing intensity limited forage resources and promoted intraspecific competition of livestock, which induced longer travelling distance and foraging time, and more even spatial distribution when seeking habitat, which ultimately led to a reduction in LWG. In contrast, under light grazing where there were sufficient forage resources, livestock exhibited higher LWG with less foraging time, shorter travelling distance, and more specialized habitat occupation. These findings support the Optimal Foraging Theory and the Ideal Free Distribution model, which may have important implications for grassland ecosystem management and sustainability.

A mechanochemical model of the forward/backward movement of motor protein kinesin-1.

Kinesin-1 is an ATP-driven, two-headed motor protein that transports intracellular cargoes (loads) along microtubules. The movement of kinesin-1 has generally been modeled according to its correlation with ATP cleavage (forward movement), synthesis (backward movement), or unproductive cleavage (futile consumption). Based on recent experimental observations, we formulate a mechanochemical model for this movement in which the forward/backward/futile cycle can be realized through multiple biochemical pathways. Our results show that the backward motion of kinesin-1 occurs mainly through backward sliding along the microtubule and is usually also coupled with ATP hydrolysis. We also found that with a low external load, about 80% of ATP is wasted (futile consumption) by kinesin-1. Furthermore, at high ATP concentrations or under high external loads, both heads of kinesin-1 are always in the ATP- or ADP ⋅ Pi-binding state and tightly bound to the microtubule, while at low ATP concentrations and low loads, kinesin-1 is mainly in the one-head-bound state. Unless the external load is near the stall force, the motion of kinesin-1 is almost deterministic.

Spatial patterns and driving factors of aboveground and belowground biomass over the eastern Eurasian steppe.

The Eurasian steppe is the largest steppe region in the world and is an important part of the global grassland ecosystem. The eastern Eurasian steppe has favorable hydrothermal conditions and has the highest productivity and the richest biodiversity. Located in the arid and semi-arid region, the eastern Eurasian steppe has experienced large-scale grassland degradation due to dramatic climate change and intensive human activities during the past 20 years. Hence, accurate estimation of aboveground biomass (AGB, gC m-2) and belowground biomass (BGB, gC m-2) is necessary. In this study, plenty of AGB and BGB in-situ measurements were collected among dominated grassland types during summer in 2013 and 2016-2018 in the eastern Eurasian steppe. Vegetation indices from the Moderate Resolution Imaging Spectroradiometer (MODIS), Digital Elevation Model (DEM) and climate variables were chosen as independent variables to establish predictive models for AGB and BGB with random forest (RF). Both AGB (R2 = 0.47, MAE = 21.06 gC m-2, and RMSE = 27.52 gC m-2) and BGB (R2 = 0.44, MAE = 173.02 gC m-2, and RMSE = 244.20 gC m-2) models showed acceptable accuracy. Then the RF models were applied to generate spatially explicit AGB and BGB estimates for the study area over the last two decades (2000-2018). Both AGB and BGB showed higher values in the Greater Khingan Mountains and decreased gradually to the east and west sides. The mean values for AGB and BGB were 62.16 gC m-2 and 531.35 gC m-2, respectively. The climatic factors were much more important in controlling biomass than anthropogenic drivers, and shortage of water and raising temperature were the main limiting factor of AGB and BGB, respectively, in the peak growth season. These findings provide scientific data for the scientific management of animal husbandry and can contribute to the sustainable development of grassland ecology in the eastern Eurasian steppe.

sLex expression in invasive micropapillary breast carcinoma is associated with poor prognosis and can be combined with MUC1/EMA as a supplementary diagnostic indicator.

OBJECTIVE: Mucin 1 (MUC1/EMA) and sialyl Lewis X (sLex) indicate polarity reversal in invasive micropapillary carcinoma (IMPC). The purpose of this study was to evaluate the expression of MUC1/EMA and sLex and to assess their diagnostic and prognostic value in patients with IMPC. METHODS: The expression of sLex and MUC1/EMA in 100 patients with IMPC and a control group of 89 patients with invasive ductal carcinoma not otherwise specified (IDC-NOS) were analyzed with IHC. Fresh tumor tissues were collected from patients with IMPC or IDC-NOS for primary culture and immunofluorescence analysis. RESULTS: The rate of nodal metastasis was higher in patients with IMPC than those with IDC-NOS, and IMPC cells tended to express more sLex and MUC1/EMA in the cytomembranes (the stroma-facing surfaces of the micropapillary clusters) than IDC-NOS cells. In IMPC, high cytomembrane expression of sLex, but not MUC1/EMA, indicated poor prognosis. In addition, among the 100 patients with IMPC, 10 patients had sLex+/EMA- expression patterns, and 8 patients had sLex-/EMA+ expression patterns. The primary IMPC cells were suspended, non-adherent tumor cell clusters, whereas the primary IDC cells were adherent tumor cells. Immunofluorescence analysis showed that MUC1/EMA and sLex were co-expressed on the cytomembranes in IMPC cell clusters and in the cytoplasm in IDC-NOS cells. CONCLUSIONS: sLex can be used as a prognostic indicator and can be combined with MUC1/EMA as a complementary diagnostic indicator to avoid missed IMPC diagnosis.

Residues of organochlorine pesticides (OCPs) and polycyclic aromatic hydrocarbons (PAHs) in waters of the Ili-Balkhash Basin, arid Central Asia: Concentrations and risk assessment.

Release and transport of contaminants in watersheds can have adverse effects on aquatic organisms and human health. Little attention, however, has been paid to chemical contamination of aquatic environments in arid regions by persistent organic pollutants. We analyzed the concentrations and distributions of organochlorine pesticides (OCPs) and polycyclic aromatic hydrocarbons (PAHs) in waters of the Ili-Balkhash Basin, in arid central Asia. ΣOCP concentrations ranged from 4.02 to 122.80 ng L-1 and ΣPAH concentrations were between 7.58 and 70.98 ng L-1. On a global scale, OCP and PAH concentrations in waters of the Ili-Balkhash system were relatively low, with only a few exceptions, i.e., highest concentrations near cities and relatively high values in some headwater areas. Source identification revealed that the dichlorodiphenyltrichloroethanes (DDTs) may come from recent use, whereas endosulfans stem from historic applications. Lindane, a common insecticide, may be responsible for hexachlorocyclohexanes (HCHs). Low-molecular-weight PAHs, primarily originating from wood and coal combustion and petroleum-derived sources, were the primary components of PAHs in waters. Furthermore, the primary sources of PAHs at different sites were identified using a Positive Matrix Factorization model: 1) oil leakage (33.9%), 2) biomass burning (29.5%), 3) coal combustion (22.6%), and 4) petroleum-powered vehicles (14.1%). Agricultural, industrial and domestic activities are all potential pollution sources. Besides, contaminated headwater areas indicate that long-range transport has probably become a non-negligible mechanism for pollutant distribution. Risk assessment showed low to moderate toxicity for aquatic organisms, but no marked carcinogenic or non-carcinogenic risks for human health.

Validation of the 7-item Generalized Anxiety Disorder scale (GAD-7) as a screening tool for anxiety among pregnant Chinese women.

BACKGROUND: Anxiety is common during pregnancy. The 7-item Generalized Anxiety Disorder scale (GAD-7) is a self-rating scale for detecting anxiety and has been validated in various populations, but it has not been validated in pregnant Chinese women. The objective of this study was to validate the GAD-7 as a screening tool to detect anxiety during pregnancy among Chinese women. METHODS: The GAD-7 and the anxiety subscale of the Hospital Anxiety and Depression scale (HADS-A) were administered to 140 pregnant Chinese women to evaluate the Cronbach's alpha and the criterion-related validity. Additionally, a diagnostic study (n=170) was conducted by using the Mini International Neuropsychiatric Interview (MINI) as a gold standard to examine the screening performance of the GAD-7. We calculated the sensitivity, specificity, and area under the curve (AUC) by receiver operating characteristic (ROC) analysis. RESULTS: Cronbach's alpha for the GAD-7 was 0.84. The Pearson correlation coefficient between GAD-7 and HADS-A scores was 0.66 (P<0.01). At the maximum Youden Index of 0.53, the optimal cutoff score for the GAD-7 among pregnant women was 7, and an AUC of 0.83, a sensitivity of 96.8%, and a specificity of 56.1% were obtained. LIMITATION: The majority of the participants were in the first trimester, and thus, the findings cannot be generalized to all pregnant women. CONCLUSIONS: The GAD-7 is a suitable screening instrument for detecting antenatal anxiety in mainland China. Further validation is warranted in women in different trimesters of pregnancy.

Primary signet ring cell carcinoma of the breast: A rare entity with unique biological behavior-A clinical study based on pure signet ring cell carcinoma cohort.

BACKGROUND: Primary signet ring cell carcinoma (SRCC) of the breast is a rare entity, and only a few case reports of the pure SRCC cases could be found in English literatures. We summarized the clinicopathological characteristics of a relatively large cohort of pure breast SRCCs for the first time. METHODS: We reviewed the medical records of 23 cases of pure breast SRCC with a median follow-up time of 70 months. RESULTS: Three patients had bilateral primary breast cancer (BC) and two of them had bilateral pure SRCCs. 30 % of patients had the malignant tumor family history including two bilateral BC patients. Malignant calcification was observed in 35.3 % of mammography images. Multifocal lesions were microscopically found in 26.1 % of cases. 63.6 % of the cases had lymph node metastasis, 45.5 % were classified as Stage III, 69.6 % had high value of Ki-67 index, and 34.8 % were triple negative subtype. 19.0 % of patients had local recurrence, and 52.6 % had distant metastasis. Four in five patients with positive tumor family history and follow-up data had relapse of SRCC. The 5-year overall survival rate was 73.7 %, the 5-year relapse-free survival rate was 54.3 %, and the 5-year breast cancer specific survival rate was 78.3 %. CONCLUSION: Pure SRCC of the breast showed an aggressive behavior. Neoadjuvant chemotherapy could be considered, breast-conserving surgery should be prudently chosen, and axillary lymph node dissection may be necessary. The high rate of positive tumor family histories and high bilateral incidence, which showed an adverse effect on prognosis, indicate the unique genetic burden of SRCC.

ATM kinase regulates tumor immunoreactions in lymphocyte-predominant breast cancer through modulation of NKG2D ligand and TNF cytokines on tumor cells.

To explore impact of Ataxia telangiectasia mutated (ATM) kinase on immunoreactions in lymphocyte-predominant breast cancer (LPBC), particularly its role in triple negative breast cancer (TNBC), 194 cases of LPBC were identified with pertinent clinical information retrieved. The expressions of ATM, activated ATM (P-ATM), Fas ligand (FASL), tumor necrosis factor-related apoptosis-induced ligand (TRAIL), major histocompatibility complex class I chain-related protein A (MICA), CD8, and Forkhead box P3 (FOXP3) were assessed by immunohistochemically. We found that ATM expressed on tumor cells was correlated with upregulated expression of P-ATM and MICA (P < 0.05), down-regulated expression of FASL and TRAIL (P < 0.01), and decreased Ki-67 tumor labeling (P < 0.05). However, within the TNBC group, only a negative correlation with FASL expression was found (P = 0.001). ATM and MICA expressions were significantly down -regulated in TNBC (P < 0.01) compared to non-TNBC, while TRAIL was significantly upregulated (P < 0.01). Tregs were increased in TNBC (P < 0.05), with CD8 + TILs decreased (P < 0.01). Ki-67 index was higher in TNBC than in non-TNBC (P < 0.01). ATM may play an important role in immunoreaction of LPBC, probably through upregulation of MICA and down-regulation of FASL and TRAIL. The down-regulated ATM expression in TNBC might be responsible for impaired tumor immunoactivity, rapid tumor growth, and aggressive clinical course.

Increased number of intratumoral IL-17+ cells, a harbinger of the adverse prognosis of triple-negative breast cancer.

INTRODUCTION: Triple negative breast cancer (TNBC) is an aggressive cancer subtype and lack of effective targeted therapies. It has been recently reported that Interleukin 17 (IL-17), a family of cytokines secreted in tumor microenvironment, affects tumor progression through a variety of molecular pathways. Its role in TNBC is so far still poorly explored. MATERIALS AND METHODS: We employed immunohistochemistry to evaluate the distribution of IL-17+ cells in TNBC with no special type features (TNBC-NST), their association with tumor microangiogenesis, as well as their impact on prognosis of the patients. RESULTS: In comparison to medullary carcinoma with triple-negative molecular features (TNBC-MC), we found a significant increase in IL-17+ cell infiltrates in intratumoral stroma and extratumoral stroma of TNBC-NST. Similarly, stromal cells with co-expression of CD4 and IL-17 were noted in intratumoral and extratumoral stroma in both TNBC-NST and TNBC-MC. In addition, intratumoral IL-17+ cells were positively associated with tumor cell expression of vascular endothelial growth factor A (VEGFA) and with intratumoral tumor microvascular density (MVD). Multivariate analysis identified that intratumoral IL-17+ cells (P = 0.018), MVD (P = 0.039), and TNM stage (P = 0.002) were independent prognostic factors for predicting poor PFS. CONCLUSION: The study indicates that IL-17 is overexpressed in intratumoral stromal cells of TNBC-NST. The overexpression of IL-17 might engage in active tumor microangiogenesis through its signal transduction pathways resulting in increased tumor secretion of VEGFA, and then promote tumor progression. IL-17 might serve as a potential new target for individualized therapy to TNBC-NST patients by development of specific antibodies. Additional study is deemed to further explore the role of IL-17+ stromal cells in breast cancer.

[Hydrochemical and Isotopic Characteristics of the Lake Balkhash Catchment, Kazakhstan].

Lake Balkhash is one of the largest lakes in the world. It is located in arid Central Asia and receives major water from the Ili River, which is an international river flowing across China and Kazakhstan. Hydrochemical and isotopic measurements of waters can provide an improved understanding of hydrogeochemical processes and environmental characteristics, which is useful for water resource management in arid regions. In this study, δD, δ18 O, and major ions in water samples from the Lake Balkhash catchment were analyzed using an integration of mathematical statistics, Piper diagrams, Gibbs model, and principal component analysis (PCA). Water types and main mechanisms controlling the hydrochemistry presented a clear spatial heterogeneity. The chemical composition of lake waters was dominated by SO4-Na and Cl-Na type, whereas river waters were classified as a HCO3-Ca type. The chemical composition downstream of the Ili River evolved from HCO3-Ca to SO4-Na-Cl type. Gibbs model suggested that the main mechanisms controlling the lake water chemistry were evaporation-crystallization processes, and that major ions in the river water were affected by rock-weathering and evaporation processes. The main controlling factors of the water chemistry changed from the upstream to the downstream, and may have related to spatial differences whereby the upstream area experienced higher rainfall and snow melt, and the downstream area experienced relatively higher evaporation. PCA analysis showed that human activities also played an important role in the chemical composition of water sampled from the lake, middle and lower reaches of the Ili River, and other rivers. The isotopic compositions of the lake and river waters varied spatially. In the lake waters, positive isotopic ratios and negative deuterium-excess values indicated that evaporitic enrichment dominated the changes in the isotopic signature of the lake water. In river waters, isotope values located near the global meteoric water line (GMWL) and lower slopes of the regression lines (r=0.91, P<0.001 for Ili River, and r=0.63, P<0.001 for other rivers), were associated with a stronger influence of rainfall and weaker evaporation. Correlation analysis showed that there were significant relationships between isotope values and chemical parameters in the lake water, especially in the eastern area, thus suggesting that extensive evaporation led to simultaneous enrichment of isotopes and ions in the lake water.