Knockdown of PIK3R6 impedes the onset and advancement of clear cell renal cell carcinoma.

In this research, we investigated the role of PIK3R6, a regulatory subunit of PI3Kγ, known for its tumor-promoting properties, in clear cell renal cell carcinoma (CCRCC). Utilizing the UALCAN website, we found PIK3R6 upregulated in CCRCC, correlating with lower survival rates. We compared PIK3R6 expression in CCRCC tumor tissues and adjacent normal tissues using immunohistochemistry. Post RNA interference-induced knockdown of PIK3R6 in 786-O and ACHN cell lines, we performed CCK-8, colony formation, Edu staining, flow cytometry, wound healing, and transwell assays. Results showed that PIK3R6 silencing reduced cell proliferation, migration, and invasion, and induced G0/G1 phase arrest and apoptosis. Molecular analysis revealed decreased CDK4, Cyclin D1, N-cadherin, Vimentin, Bcl-2, p-PI3K and p-AKT, with increased cleaved caspase-3, Bax, and E-cadherin levels in CCRCC cells. Moreover, inhibiting PIK3R6 hindered tumor growth. These findings suggest a significant role for PIK3R6 in CCRCC cell proliferation and metastasis, presenting it as a potential therapeutic target.

Risk assessment and source analysis of heavy metals in soil around an asbestos mine in an arid plateau region, China.

Asbestos is widely used in construction, manufacturing, and other common industrial fields. Human activities such as mining, processing, and transportation can release heavy metals from asbestos into the surrounding soil environment, posing a health hazard to the mining area's environment and its surrounding residents. The purpose of the present study was to determine the extent of ecological and human health damage caused by asbestos pollution, as well as the primary contributors to the contamination, by examining a large asbestos mine and the surrounding soil in China. The level of heavy metal pollution in soil and sources were analyzed using methods such as the geo-accumulation index (Igeo), potential ecological risk index (RI), and positive matrix factorization (PMF) model. A Monte Carlo simulation-based health risk model was employed to assess the health risks of heavy metals in the study area's soil to human beings. The results showed that the concentrations of As, Pb, Cr, Cu, and Ni in the soil were 1.74, 0.13, 13.31, 0.33, and 33.37 times higher than the local soil background values, respectively. The Igeo assessment indicated significant accumulation effects for Ni, Cr, and As. The RI evaluation revealed extremely high comprehensive ecological risks (RI ≥ 444) in the vicinity of the waste residue heap and beneficiation area, with Ni exhibiting strong individual potential ecological risk (Eir ≥ 320). The soil health risk assessment demonstrated that As and Cr posed carcinogenic risks to adults, with mean carcinogenic indices (CR) of 1.56E - 05 and 4.14E - 06, respectively. As, Cr, and Cd posed carcinogenic risks to children, with mean CRs of 1.08E - 04, 1.61E - 05, and 2.68E - 06, respectively. Cr also posed certain non-carcinogenic risks to both adults and children. The PMF model identified asbestos contamination as the primary source of heavy metals in the soil surrounding the asbestos mining area, contributing to 79.0%. According to this study, it is recommended that management exercise oversight and regulation over the concentrations of Ni, Cr, Cd, and As in the soil adjacent to asbestos mines, establish a designated control zone to restrict population activities, and locate residential zones at a safe distance from the asbestos mine production zone.

Comprehensive distribution characteristics and factors affecting the migration of chromium in a typical chromium slag-contaminated site with a long history in China.

The contamination of abandoned chromium slag-contaminated sites poses serious threats to human health and the environment. Therefore, improving the understanding of their distribution characteristics and health risks by multiple information is necessary. This study explored the distribution, accumulation characteristic, and the role in the migration process of chromium. The results showed that the contents of total Cr and Cr (VI) ranged from 12.00 to 7400.00 mg/kg, and 0.25 to 2160.00 mg/kg, respectively. The average contents of both total Cr and Cr (VI) reached the highest value at the depth of 7-9 m, where the silt layer retaining total Cr and Cr (VI) was. The spatial distribution analysis revealed that the total contamination area percentages of total Cr and Cr (VI) reached 7.87% and 90.02% in the mixed fill layer, and reduced to 1.21% and 34.53% in the silty layer, and the same heavily polluted areas were located in the open chromium residue storage. Soil pH and moisture content were the major factors controlling the migration of total Cr and Cr(VI) in soils. Results of probabilistic health risk assessment revealed that carcinogenic risk was negligible for adults and children, and the sensitive analysis implied that the content of Cr(VI) was the predominant contributor to carcinogenic risk. The combination of chemical reduction and microbial remediation could be the feasible remediation strategy for soil Cr(VI) pollution. Overall, this study provides scientific information into the chromium post-remediation and pollution management for various similar chromium-contaminated sites.

An Analysis of the Spatial Characteristics and Transport Fluxes of BTEX in Soil and Atmospheric Phases at a Decommissioned Steel Mill Site in China with a Long History.

BTEX (benzene, toluene, ethylbenzene, and xylene), as characteristic pollutants in chemical plant sites, are widely present in the environment and pose a serious threat to the health and safety of nearby residents. Studying the spatial distribution characteristics and transport fluxes of BTEX in soil and air at contaminated sites and the health risks they pose to humans is of great significance for fine pollution control and environmental management. This study took a typical decommissioned steel plant as a case study. A total of 23 soil and air samples were collected from different locations to investigate the spatial distribution characteristics of BTEX in soil and air. The transport and fate of BTEX in soil and air were evaluated using the fugacity model, and finally, a human health risk assessment was conducted. The results indicate a relatively severe level of benzene pollution in both soil and air. The maximum exceedance factor of benzene in soil samples is 31.5, with the concentration exceedance depth at 1.5 m. The maximum concentration of benzene in air samples is 4.98 µg·m-3. Benzene, at 5.9% of the site, shows a low flux with negative values, while other components at various locations all exhibit a trend of transport from the soil phase to the atmospheric phase. Benzene is the pollutant that contributes the most to the transport flux from soil to air within the site. The coking area and sewage treatment area are key areas within the steel mill where BTEX accumulate easily in the soil. The non-carcinogenic risk values of the individual components of BTEX in the soil are below the acceptable risk level. However, the carcinogenic risk value of benzene in the children's exposure scenario exceeds the carcinogenic risk level of 10-6. The carcinogenic risk range of various components of BTEX in the air is 2.63 × 10-6~3.88 × 10-5, with 28.6% of the locations exceeding the threshold of 10-6. The range of the total HI (hazard index) is 2.08 × 10-4~1.81 × 10-1, all of which is below the safety threshold of 1. The results of this study will provide scientific support for the fine pollution control and environmental management of industrial contaminated sites with BTEX as their typical pollutants.

Asbestos-Environment Pollution Characteristics and Health-Risk Assessment in Typical Asbestos-Mining Area.

Asbestos has been confirmed as a major pollutant in asbestos-mining areas that are located in western China. In general, asbestos-fibre dust will is released into the environment due to the effect of intensive industrial activities and improper environmental management, such that the health of residents in and around mining areas is jeopardised. A typical asbestos mining area served as an example in this study to analyse the content and fibre morphology of asbestos in soil and air samples in the mining area. The effects of asbestos pollution in and around the mining areas on human health were also assessed based on the U.S. Superfund Risk Assessment Framework in this study. As indicated by the results, different degrees of asbestos pollutions were present in the soil and air, and they were mainly concentrated in the mining area, the ore-dressing area, and the waste pile. The concentration of asbestos in the soil ranged from 0.3% to 91.92%, and the concentration of asbestos fibres in the air reached 0.008-0.145 f·cc-1. The results of the scanning-electron microscope (SEM) energy suggested that the asbestos was primarily strip-shaped, short columnar, and granular, and the asbestos morphology of the soils with higher degrees of pollution exhibited irregular strip-shaped fibre agglomeration. The excess lifetime cancer risk (ELCR) associated with the asbestos fibres in the air of the mining area was at an acceptable level (10-4-10-6), and 40.6% of the monitoring sites were subjected to unacceptable non-carcinogenic risks (HQ > 1). Moreover, the waste pile was the area with the highest non-carcinogenic risk, followed by the ore dressing area, a residential area, and a bare-land area in descending order. In the three scenarios of adult offices or residences in the mining area, adults' outdoor activities in the peripheral residence areas, and children's outdoor activities, the carcinogenic-and non-carcinogenic-risk-control values in the air reached 0.1438, 0.2225 and 0.1540 f·cc-1, and 0.0084, 0.0090 and 0.0090 f·cc-1, respectively. The results of this study will lay a scientific basis for the environmental management and governance of asbestos polluted sites in China.

Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: The CAPTURE study.

CAPTURE (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable neutralizing antibody titers (NAbT) against SARS-CoV-2 variants of concern (VOCs) vs wildtype (WT). Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT vs solid cancers against both WT and VOCs. In comparison with individuals without cancer, patients with haematological, but not solid, malignancies had reduced NAb responses. Seroconversion showed poor concordance with NAbT against VOCs. Prior SARS-CoV-2 infection boosted NAb response including against VOCs, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T-cell responses were detected in 80% of patients, and were comparable between vaccines or cancer types. Our results have implications for the management of cancer patients during the ongoing COVID-19 pandemic.

Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study.

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer.

Cytokine release syndrome in a patient with colorectal cancer after vaccination with BNT162b2.

Patients with cancer are currently prioritized in coronavirus disease 2019 (COVID-19) vaccination programs globally, which includes administration of mRNA vaccines. Cytokine release syndrome (CRS) has not been reported with mRNA vaccines and is an extremely rare immune-related adverse event of immune checkpoint inhibitors. We present a case of CRS that occurred 5 d after vaccination with BTN162b2 (tozinameran)-the Pfizer-BioNTech mRNA COVID-19 vaccine-in a patient with colorectal cancer on long-standing anti-PD-1 monotherapy. The CRS was evidenced by raised inflammatory markers, thrombocytopenia, elevated cytokine levels (IFN-γ/IL-2R/IL-18/IL-16/IL-10) and steroid responsiveness. The close temporal association of vaccination and diagnosis of CRS in this case suggests that CRS was a vaccine-related adverse event; with anti-PD1 blockade as a potential contributor. Overall, further prospective pharmacovigillence data are needed in patients with cancer, but the benefit-risk profile remains strongly in favor of COVID-19 vaccination in this population.

Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study.

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer.

Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study.

Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) ( NCT03226886 ) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic.

Pre-surgery beliefs about pain and surgery as predictors of acute and chronic post-surgical pain: A prospective cohort study.

BACKGROUND: Chronic pain post-surgical pain (CPSP) is common and has far-reaching negative consequences for patients, yet relatively few studies have evaluated the impact of both deficit- and resource-based beliefs about pain and surgery on subjective intensities of acute and chronic post-surgical pain. To address this issue a prospective cohort study was performed. METHOD: 259 consecutive surgery patients from general surgery, gynecology, and thoracic departments completed a self-report battery of demographics, pain experiences, and psychological factors 24 h before surgery (T1) and provided follow-up pain intensity ratings 48 h-72 h after surgery (T2), and at a 4-month follow-up (T3). RESULTS: In the hierarchical regression model for acute post-operative pain intensity, pre-surgery pain self-efficacy beliefs made a significant unique contribution independent of all other pre-surgery and surgery-related factors (i.e., age, presence of pre-surgical pain, type of anesthesia, surgery duration). In the prediction model for intensity of chronic post-surgical pain, beliefs about long-term effects of surgery had a unique impact after controlling other significant pre-surgery and surgery influences (gender, education, surgery time). CONCLUSION: Results underscored the potential utility of considering specific pre-surgery pain- and surgery-related beliefs as factors that predict patient experiences of acute and chronic post-operative pain.

Identifying At-Risk Subgroups for Acute Postsurgical Pain: A Classification Tree Analysis.

Objective: Acute postsurgical pain is common and has potentially negative long-term consequences for patients. In this study, we evaluated effects of presurgery sociodemographics, pain experiences, psychological influences, and surgery-related variables on acute postsurgical pain using logistic regression vs classification tree analysis (CTA). Design: The study design was prospective. Setting: This study was carried out at Chongqing No. 9 hospital, Chongqing, China. Subjects: Patients (175 women, 84 men) completed a self-report battery 24 hours before surgery (T1) and pain intensity ratings 48-72 hours after surgery (T2). Results: An initial logistic regression analysis identified pain self-efficacy as the only presurgery predictor of postoperative pain intensity. Subsequently, a classification tree analysis (CTA) indicated that lower vs higher acute postoperative pain intensity levels were predicted not only by pain self-efficacy but also by its interaction with disease onset, pain catastrophizing, and body mass index. CTA results were replicated within a revised logistic regression model. Conclusions: Together, these findings underscored the potential utility of CTA as a means of identifying patient subgroups with higher and lower risk for severe acute postoperative pain based on interacting characteristics.

Toward Identifying Moderators of Associations Between Presurgery Emotional Distress and Postoperative Pain Outcomes: A Meta-Analysis of Longitudinal Studies.

UNLABELLED: Presurgery emotional distress has had variable associations with outcomes of surgery in past narrative reviews. This meta-analysis was designed to evaluate the overall strengths of relations between presurgical emotional distress and key postsurgical pain outcomes (ie, pain intensity, analgesic use, functional impairment) and to identify moderators that might explain effect size heterogeneity between studies. PubMed, Web of Science, PsychINFO, Google Scholar, and Science Direct databases were searched to identify studies subjected to meta-analysis. Forty-seven studies of 6,207 patients met all 10 inclusion criteria. High presurgery emotional distress levels were associated with significantly more postsurgical pain, analgesic use, and impairment after surgery, with small to medium average effect sizes. Moderator analyses for relations between distress and pain intensity indicated effect sizes were larger in studies that assessed catastrophizing, anxiety, and/or depression than other types of emotional distress as well as those with lower rather than higher quality scores. Associations between presurgery distress and postoperative impairment were moderated by type of surgery. Heterogeneity in these relations was reduced or no longer significant after statistically controlling for moderators. Moderator analyses also supported the role of presurgery emotional distress as a risk factor for, rather than simply a correlate of, elevations in postoperative pain and disability. PERSPECTIVE: This meta-analysis indicates presurgery emotional distress has significant associations with postoperative outcomes but specific methodological factors and sample characteristics contribute to effect size variability in the literature. Considering emotional distress within presurgical assessment protocols may aid in identifying vulnerable patients who can benefit from interventions targeting distress reductions.

MicroRNA-203 down-regulation is associated with unfavorable prognosis in human glioma.

BACKGROUND AND OBJECTIVES: MicroRNA-203 (miR-203) serves as a tumor suppressor or a tumor promoter in different human malignancies. However, its involvement in human gliomas is still unclear. The aim of this study was to investigate the clinical significance of miR-203 expression in gliomas. METHODS: Real-time quantitative PCR was employed to measure the expression level of miR-203 in clinical glioma tissues. RESULTS: The expression of miR-203 was reduced in high WHO grade glioma tissues compared with that in low WHO grade and normal brain tissues, and decreased with ascending tumor WHO grades (P < 0.001). The reduced miR-203 expression in gliomas was significantly associated with higher WHO grade (P < 0.001), lower KPS score (P = 0.008) and poorer disease-specific survival of patients (P = 0.001). More importantly, subgroup analyses according to tumor WHO grade revealed that the disease-specific survival of patients with low miR-203 expression in high WHO grades (III-IV) subgroup was significantly shorter than those with high miR-203 expression (P < 0.001), but no significant difference was found for patients in WHO grades I-II subgroup (P = 0.08). CONCLUSION: Our data validate an important clinical significance of miR-203 in gliomas, and reveal that it might be an intrinsic regulator of tumor progression and a potential prognostic factor for this dismal disease.