Identification of non-small cell lung cancer with chronic obstructive pulmonary disease using clinical symptoms and routine examination: a retrospective study.

Background: Patients with non-small cell lung cancer (NSCLC) and patients with NSCLC combined with chronic obstructive pulmonary disease (COPD) have similar physiological conditions in early stages, and the latter have shorter survival times and higher mortality rates. The purpose of this study was to develop and compare machine learning models to identify future diagnoses of COPD combined with NSCLC patients based on the patient's disease and routine clinical data. Methods: Data were obtained from 237 patients with COPD combined with NSCLC as well as NSCLC admitted to Ningxia Hui Autonomous Region People's Hospital from October 2013 to July 2022. Six machine learning algorithms (K-nearest neighbor, logistic regression, eXtreme gradient boosting, support vector machine, naïve Bayes, and artificial neural network) were used to develop prediction models for NSCLC combined with COPD. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, F1 score, Mathews correlation coefficient (MCC), Kappa, area under the receiver operating characteristic curve (AUROC)and area under the precision-recall curve (AUPRC) were used as performance indicators to evaluate the performance of the models. Results: 135 patients with NSCLC combined with COPD, 102 patients with NSCLC were included in the study. The results showed that pulmonary function and emphysema were important risk factors and that the support vector machine-based identification model showed optimal performance with accuracy:0.946, recall:0.940, specificity:0.955, precision:0.972, npv:0.920, F1 score:0.954, MCC:0.893, Kappa:0.888, AUROC:0.975, AUPRC:0.987. Conclusion: The use of machine learning tools combining clinical symptoms and routine examination data features is suitable for identifying the risk of concurrent NSCLC in COPD patients.

[Ecological Risk and Migration Patterns of Heavy Metals in Soil and Crops in the Lead-Zinc Mining Area in Guizhou, China].

An accumulation of heavy metals in soil poses a risk to the ecological environment and human health. In this study, the concentrations of heavy metals in soil and crops were examined in a lead-zinc mining area in Guizhou Province, China. The distribution and sources of heavy metals were analyzed using GIS spatial mapping. The potential ecological risks of heavy metals were assessed using the potential ecological risk index (RI), and the human health risk assessment method recommended by the United States Environmental Protection Agency (USEPA) was used to quantify the health risk of residents exposed to heavy metals in the soil around lead-zinc mines. According to the results, the average of concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in the soil were 58, 7.9, 175, 64, 0.461, 65, 1539, and 2513 mg·kg-1, respectively, which were significantly higher than the background values in Guizhou Province. It was found that the As, Cd, Cu, Hg, Pb, and Zn concentrations were extremely irregular in the soil and that the concentrations decreased significantly with the distance to the smelters, which were greatly disturbed by human activities. Comprehensive evaluation of soil heavy metals using the potential ecological risk index revealed that the risks of soil heavy metals were pole-strength and strong levels, and Cd constituted the primary ecological risk factor. A total of 22% and 10% of the corn samples contained Pb and As above the heavy metal pollution thresholds in the national food safety standards. According to human health risk assessments, heavy metals in the soil present potential non-carcinogenic risks to adults or children, and pose a potential carcinogenic risk to children. Soil pH was an important controlling factor affecting the bioavailability, migration, and accumulation of Cd in soil-crop systems. This study provides data and theoretical support for the prevention and control of soil pollution in lead-zine mining areas.

Discovery of anthraquinones as DPP-IV inhibitors: Structure-activity relationships and inhibitory mechanism.

Dipeptidyl peptidase IV (DPP-IV) is an integrated type II transmembrane protein that reduces endogenous insulin contents and increases plasma glucose levels by hydrolyzing glucagon-like peptide-1 (GLP-1). Inhibition of DPP-IV regulates and maintains glucose homeostasis, making it an attractive drug target for the treatment of diabetes II. Natural compounds have tremendous potential to regulate glucose metabolism. In this study, we examined the DPP-IV inhibitory activity of a series of natural anthraquinones and synthetic structural analogues on DPP-IV using fluorescence-based biochemical assays. The inhibitory efficiency differed among anthraquinone compounds with different structures. Alizarin (7), aloe emodin (11), emodin (13) emerged the outstanding inhibitory potential for DPP-IV with IC50 values lower than 5 µM. To clarifying the inhibitory mechanism, inhibitory kinetics were performed, which showed that alizarin red S (8) and 13 were effective non-competitive inhibitors of DPP-IV, while alizarin complexone (9), rhein (12), and anthraquinone-2-carboxylic acid (23) were mixed inhibitors. Emodin was determined as inhibitor with the strongest DPP-IV-binding affinity determined via molecular docking. Structure-activity relationship (SAR) demonstrated that hydroxyl group at C-1 and C-8 sites and hydroxyl, hydroxymethyl or carboxyl group at the C-2 or C-3 site were very essential for DPP-IV inhibition, replacement of hydroxyl group with amino group at C-1 could led to an increase of the inhibitory potential. Further fluorescence imaging showed that both compounds 7 and 13 significantly inhibited DPP-IV activity in RTPEC cells. Overall, the results indicated that anthraquinones would be a natural functional ingredient for inhibiting DPP-IV and provided new ideas for searching and developing potential antidiabetic compounds.

Inhibition of miR-4640-5p alleviates pulmonary hypertension in chronic obstructive pulmonary disease patients by regulating nitric oxide synthase 1.

BACKGROUND: Pulmonary hypertension (PH) is a devastating disease characterized by vasoconstriction and vascular remodeling, leading to right ventricular failure and death. PH is a common complication of chronic obstructive pulmonary disease (COPD). Accumulating evidence demonstrate that microRNAs participate in the pathobiology of PH in COPD patients. In this study, we aimed to evaluate the expression and function of microRNA-4640-5p (miR-4640-5p) in PH. METHODS: The mRNA and protein levels were determined by quantitative polymerase chain reaction (qPCR) and western blot, separately. Functional assays and western blot were performed to determine the effects of miR-4640-5p and NOS1 on cell growth, migration. Besides, the dual-luciferase reporter assays were used to validate miR-4640-5p and NOS1 interactions. RESULTS: We found that miR-4640-5p expression was significantly higher in the lung tissues of COPD-PH patients than in the healthy controls while higher expression of miR-4640-5p was correlated with more severe COPD-PH. By using pulmonary artery smooth muscle cell (PASMC) in in vitro assays, we demonstrated that inhibition of miR-4640-5p suppressed cell proliferation and migration of PASMC via regulating mTOR/S6 signaling. Bioinformatics analysis and validation experiments revealed that nitric oxide synthase 1 (NOS1) was a direct downstream target of miR-4640-5p. Overexpression of NOS1 partially antagonized the effect of miR-4640-5p in regulating PASMC cell proliferation and migration. In addition, our findings suggested that miR-4640-5p/NOS1 axis regulated mitochondrial dynamics in PASMCs. Furthermore, in the hypoxia-induced PH rat model, inhibition of miR-4640-5p ameliorated PH with reduced right ventricular systolic pressure and Fulton index. CONCLUSIONS: miR-4640-5p regulates PH via targeting NOS1, which provides a potential diagnostic biomarker and therapeutic target for COPD-PH patients.

[Sources Identification, Ecological Risk Assessment, and Controlling Factors of Potentially Toxic Elements in Typical Lead-Zinc Mine Area, Guizhou Province, Southwest China].

Carbonatite and basalt are widely distributed in southwest China, and potentially toxic elements (PTEs) are associated with the naturally high background properties. It is important to carry out ecological risk assessments and identify potential sources of PTEs. A total of 3180 soil samples (0-20 cm) were collected in Hezhang county, a typical high background area of PTEs with the parent lithology of carbonatite and basalt. Samples were obtained from 18 large lead-zinc mines, which belong to a multi-ecological risk superimposed area with high ecological risk. The concentration of PTEs (Cd, Cr, As, Hg, Pb, Cu, Zn, and Ni) in the topsoil were analyzed, and statistical analysis (SA), geographic information system (GIS), enrichment factor (EF), potential ecological risk index (RI), and positive matrix factorization (PMF) methods were used to assess the ecological risk and quantify sources of PTEs. The mean values of PTEs concentrations in topsoil were 24.55, 2.25, 176.40, 89.60, 0.19, 64.20, 102.00, and 257.00 mg·kg-1 for As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn, respectively, which were remarkably higher than the average background value (ABV) of soils in Guizhou Province. The average concentrations of Cd, Cr, Cu, Ni, Pb, and Zn exceeded the screening values specified for the soil contamination risk in agricultural land (GB 15618-2018) by 7.50, 1.18, 1.79, 1.07, 1.40, and 1.29 times, respectively. The EF showed that Cd had a large area of moderate pollution; Pb, Zn, and Cu had a small area of slight pollution; the EFs values of Hg, Cr, Ni, and As were near the baseline value (EF≈1), and contaminations were slight or nonexistent. The PMF indicated that there were five sources, namely pyrite mines, lead-zinc mines, natural sources of basalt and carbonatite, and agricultural activities; the risk contribution ratios were 5.25%, 27.37%, 28.94%, 17.91%, and 20.53%, respectively. The most toxic coefficients of Hg and Cd were mainly natural sources, with contribution ratios of 86.3% and 72.7%, respectively. The soil samples in the mining areas expectedly contained high ratios of Zn/Cd and Pb/Cd, which confirmed that PTEs in the soil were mainly derived from the smelting wastes. The contents of metal oxides such as Fe, Mn, and Si were the influencing factors of PTEs enrichment. On the contrary, soil samples exhibited much lower Zn/Cd and Pb/Cd ratios in non-mining areas, indicating that the main origin of these metals in soil was the smelting flue gas dusts and geological background.

Cinnabar protects serum-nutrient starvation induced apoptosis by improving intracellular oxidative stress and inhibiting the expression of CHOP and PERK.

Cinnabar has been used for treatment of various disorders for thousands of years. The medical use of cinnabar, however, has been controversial because of its heavy metal mercury content. A large quantity of studies indicate that the toxicity of cinnabar is far below other inorganic or organic mercury-containing compounds. Yet, the underlying molecular basis has remained unresolved. Here, we investigated the beneficial effects of cinnabar on serum-nutrient starvation-elicited cell injury. Our findings showed that treatment of human renal proximal tubular cells (HK-2) with 4 nM cinnabar effectively inhibited nutrient deprivation induced apoptosis, reduced intracellular reactive oxygen species generation and increased GSH content, which was contrary to the exacerbated apoptotic cell death and oxidative stress in cells treated with HgCl2 at equal mercury concentration. In addition, cinnabar exerted robust antioxidative and antiapoptotic effects in cells under dual challenges of nutrient deprivation and treatment of H2O2. The protein expression levels of both CHOP and PERK were remarkably down-regulated in the cells treated with cinnabar compared to the control cells or cells treated with HgCl2. Overall, our data indicates that cinnabar at low concentration exerts anti-oxidative stress and anti-apoptosis effects by inhibiting the expression of the endoplasmic reticulum stress pathway proteins CHOP and PERK.

[Migration, Transformation Characteristics, and Ecological Risk Evaluation of Heavy Metal Fractions in Cultivated Soil Profiles in a Typical Carbonate-Covered Area].

In China, high heavy metal concentrations in cultivated soil are mainly distributed in carbonate-covered areas. The migration and transformation of heavy metals in such soils are influenced by interactions between natural processes and human activities. This study examined the profiles of nine paddy soils, derived from carbonate rocks in Guangxi. The Cd, As, Zn, Cr, Cu, Hg, Ni, and Pb contents we determined, and soil properties such as pH, Corg content, and fractions of Cd, As, Zn, and Cr were tested. Based on the above data, we assessed the vertical distribution of heavy metal fractions, as well as the ecological risks and factors affecting the migration ability of heavy metals, under the influence of human activities and natural soil formation. The results show that compared with the carbonate rocks in Guangxi, the soil profile of the study area is significantly enriched with all eight heavy metals. Among them, Cd, As, Zn, and Cr exceeded China's agricultural land (paddy field) pollution risk screening values, and Cd and As partially exceed the risk intervention values. All fractions of Cd in the soil profiles are widely distributed. The proportion of water-soluble and ion-exchange Cd fractions with high ecological risk decreased significantly from the surface to greater depths in the soil profile. As, Zn, and Cr in the soil profile were mainly in residual states, and the proportion of water-soluble and ion-exchange fractions did not change considerably with increasing depth. The evaluation results of RAC and RSP show that Cd pollution risk in the study area is relatively high, whereas As, Zn, and Cr are generally pollution-free or risk-free. In naturally developed soil in the study area, the clay mineral content and degree of soil development have significant effects on Cd migration, whereas in the cultivated layer affected by human activities, the soil pH and organic matter content are the main controlling factors. The migration ability of soil As is mainly related to soil organic matter, Fe2O3 content, and soil development degree, but organic matter has an obviously enhanced effect in the tillage layer. The main controlling factor of Zn and Cr migration in soil is pH, and the effects are more intense under the disturbance of human activities.

[Factors Affecting the Translocation and Accumulation of Cadmium in a Soil-Crop System in a Typical Karst Area of Guangxi Province, China].

To understand the main factors influencing the translocation and accumulation of cadmium (Cd) in soil-crop systems in typical karst areas, 68 sets of paddy soil and rice grain samples were collected in Guangxi Province. These were used to analyze Cd concentrations and soil properties (pH, organic matter (OM) content, oxide content, and texture). Spearman's correlation coefficients and principal component analysis (PCA) were used to examine the effects of soil properties on Cd concentrations and identify the main influencing factors. The studied soils were highly enriched in iron oxide (TFe2O3), aluminum oxide (Al2O3), and manganese oxide (MnO) compared to background levels, with average concentrations of 20.2%, 19.0%, and 0.2%, respectively. However, the soils are relatively depleted in silica (SiO2), with an average concentration of 41.0%. The soils are strongly weathered and leached in study area, giving rise to rich occurrences of Fe-Mn nodules. The concentrations of TFe2O3 and MnO in the study soils were significantly correlated with soil Cd, rice seed Cd, and the Cd bioconcentration factor (BCF). The PCA analysis further showed that TFe2O3 and MnO in soils were the main factors affecting the migration and enrichment of Cd while soil pH, OM, and Al2O3 had less of an influence. Furthermore, SiO2 and soil texture indirectly affected the migration and enrichment of Cd. It is suggested that the Fe-Mn nodules effectively adsorb and immobilize Cd in the study area soils, acting as a heavy metal scavenger that reduced the biological accessibility of Cd.

[Ecological Risk Assessment of Heavy Metals at Township Scale in the High Background of Heavy Metals, Southwestern, China].

Heavy metals (HMs) are naturally occurring elements that have high natural background levels in the environment. Therefore, it is important to conduct ecological risk assessment and identify potential sources of HMs. In the past, studies were conducted at the regional scale. The accuracy of those studies could not meet the needs of spatial planning and natural resource management. Therefore, it is necessary to conduct ecological risk assessment at the township scale. In this study, 1092 soil samples (from 0-20 cm depth) were collected in the town of Reshui, an area with high background levels of soil HMs with the parent material of carbonatite, which is commonly found in Southwest China. The town of Reshui is a multi-ecological risk superimposed area where the ecological risk is high. In this study, concentrations of HMs (Cd, Cr, As, Hg, Pb, Cu, Zn, and Ni) in the topsoil were analyzed, and statistical analysis (SA), geographic information system (GIS) modeling, and positive matrix factorization (PMF) analysis were performed. The geoaccumulation index (Igeo) and potential ecological risk index (PERI) were applied for the ecological risk assessment and quantification of the sources of the soil HMs. The mean values of HM concentrations in the topsoil were 18.1, 1.18, 174.1, 202.2, 0.09, 71.1, 34.9, and 167.2 mg ·kg-1for As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn, respectively, which were considerably higher than the average background value (ABV) in soils in Yunnan Province except for As and Pb. The average concentrations of Cd, Cr, Cu, and Ni exceeded the screening values specified in the soil contamination risk in agricultural land (GB 15618-2018) by 5.82, 1.16, 4.04, and 1.02 times, respectively. The Igeo value shows that the major pollutant is Cu in the surface soil of the study area, followed by Cr, and Cd. Speciation analysis of HMs indicates that HMs (Cr, As, Pb, Cu, Zn, and Ni) mainly exist in the residual form, mostly from the geological background with low bioavailability. The potential effective components of Hg have higher levels, but the total amount of Hg and its pollution risk are lower. Cd has a high bioavailability ratio, is easy to enter the soil solution and be absorbed by crops, and is the HM with the highest pollution risk in the study area. The PERI shows that the proportions of low ecological risk, moderate risk, and high risk soil samples are 44.23%, 54.40%, and 1.37% of the total number of samples, respectively. Hg and Cd were the major sources of risk because of their high toxicity coefficient. The PMF analysis indicates that there are four major sources of HMs in the study area: human activity, natural sources, coal mining and traffic emissions, and agricultural sources with the risk contribution ratios of 9.29%, 53.67%, 11.23%, and 25.81%, respectively. The PMF analysis effectively quantified the ecological risk from these sources, providing a reference for further pollution control and prevention measures.

[Trace Metals Pollution and Health Risks for Planning Area Soils of 193 Chinese Cities].

Urban soils are more easily subjected to modification, especially by contamination because of various human activities, and the environmental problems caused by urban soil pollution have become more prominent. To systematically investigate concentration characteristics, pollution levels, and exposure risks of 13 trace metals in urban soils of planning areas for 193 cities above the prefectural level, located in 31 provinces (autonomous regions and municipalities) of China, levels of pollution in urban soil were evaluated using the geoaccumulation index and integrated pollution index of trace metals, and health risks of residents exposed to urban soils were quantified using the health risk assessment method recommended by the US Environmental Protection Agency (USEPA). The results show that the median concentrations of As, Be, Cd, Co, Cr, Cu, Hg, Ni, Pb, Se, Tl, V, and Zn in topsoils of urban planning areas were 9.25, 2.14, 0.174, 12.4, 68.4, 28.2, 0.095, 27.7, 31.1, 0.29, 0.61, 82.7, and 82.2 mg·kg-1, respectively. Compared with the corresponding urban soil background values, the concentrations of Cd, Hg, and Se changed significantly. The geoaccumulation index (Igeo) values showed that Hg in urban soils of the planning area was the most severe pollutant, followed by Se and Cd, which caused pollution levels of uncontaminated to moderately contaminated levels, while other trace metals were uncontaminated. The Nemerow IPI (IPIN) revealed that the soils in 22 urban planning areas were heavily polluted and 16 urban planning areas were moderately polluted; in addition, the most polluted city in China was Zhuzhou in the Hunan province. The results of health risk assessment indicate that the soils in the five urban planning areas-Chenzhou City, Huangshi City, Zhuzhou City, Xiangtan City, and Longyan City-posed potential non-carcinogenic risks to children, and the major factor triggering risks was ingestion of Pb. To understand the soil pollution status and distribution of contaminated land parcel, it is suggested to carry out detailed investigation in cities with integrated moderate to heavy pollution to establish the list of contaminated land parcel and implement pollution control and restoration.

[Bioavailability, Translocation, and Accumulation Characteristic of Heavy Metals in a Soil-Crop System from a Typical Carbonate Rock Area in Guangxi, China].

This study uses 68 sets of paddy soil and rice grain samples collected from an area of carbonate rocks in Guangxi Province, China, to explore the ecological risks of heavy metals (As, Cd, Cr, Cu, Hg, Pb, Ni, and Zn) in soils from a high background area. We analyzed the concentrations of these heavy metals in soil and grain samples, and their chemical speciation in soil, and use these data to assess the associated ecological risks by means of statistics, a geo-accumulation index, bioconcentration factors (BCF), and correlation analysis. The arithmetic mean values of heavy metals concentrations in soil samples from the study area were (75.8±50.1), (1.91±1.02), (467.0±253.1), (48.5±9.8), (0.21±0.08), (76.2±28.1), (84.2±25.0), and (258.0±122.6) mg·kg-1 for As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn, respectively, which were remarkably higher than of those from other regions within Guangxi Province and China. In comparison to China's soil environmental quality standard risk screening values (GB 15618-2018), the over-standard rates of Cd, As, and Cr were 95.6%, 86.8%, and 69.1%, respectively. In comparison to risk intervention values, the over-standard rates of Cd, As, and Cr were 27.9%, 17.6%, and 5.9%, respectively. Speciation analysis on heavy metals indicated that As, Cr, Cu, Ni, Pb, and Zn were mainly found in a residual form, and accounted for>80% of the total concentrations, and had a low bioavailability. The bioactive components (F1+F2+F3) of Cd accounted for 21%, and the bioactivity of Cd was higher than other elements. The potential bioavailable components (F4+F5+F6) of Hg accounted for 44%, with low total concentrations, which are understood to have little potential ecological harm for crops. However, the over-standard rates of Pb, Cd, and Cr in rice grains were only 23.5%, 8.8%, and 2.9%, respectively. Correlation analysis showed that there was no significant correlation between the concentrations of heavy metals in soils and the corresponding rice grains. The mean BCFs of each heavy metal were <0.1, and the BCFs of Hg, Pb, As, Cr, and Ni were <0.05. Overall, we found relatively high concentrations, low activity, and low ecological risks for heavy metals in the study area. For high geological background materials such as carbonate rocks, factors such as metal speciation, biological activity, and crop over-standard rates should be taken into account along with the traditional use of the total amount of heavy metals in a soil as the evaluation standard when formulating pollution control policies.

[Spatial Interpolation Methods and Pollution Assessment of Heavy Metals of Soil in Typical Areas].

It is important to choose the best spatial interpolation method to reflect spatial distribution features and evaluate soil heavy metal pollution. The spatial distribution of arsenic (As) and cadmium (Cd) concentrations in top soil samples from Hubei Province were studied by four frequently-used spatial interpolation methods, including inverse distance weighted (IDW), radial basis function (RBF), local polynomial interpolation (LPI) and ordinary kriging (OK). The interpolation precision and effect of the spatial distribution of the four methods were compared with the results of cross validation and spatial distribution, and the pollution was assessed by the geoaccumulative index (Igeo) and indicator kriging (IK). The results showed that the four interpolation methods had small prediction errors, but that the interpolation effects were quite different. Among them, LPI had the most serious smoothing effect, followed by OK. The IDW and RBF best retained the extreme value information for element concentrations, and interpolation results were more detailed-and so to accurately understand the distribution of soil heavy metals, IDW or RBF methods were recommended. Taking the arithmetic mean of heavy metal concentrations in deep soil of Hubei Province as the background value, the evaluation result of geo-cumulative index pollution allowed exceedance percentages for As and Cd accounted for 5.5% and 99.0% respectively. The soils of the study areas were heavily contaminated with Cd. The pollution evaluation result from IK showed that high probability contaminated areas, with moderate-heavy contamination levels, were mainly located in the central part of the study area. The authors concluded that development of agriculture in the research area should include attention to Cd pollution and that soils there required the effective treatment and restoration of Cd levels.