A comprehensive approach to quantify the source identification and human health risk assessment of toxic elements in park dust.

In this research, enrichment factor (EF) and pollution load index were utilized to explore the contamination characteristics of toxic elements (TEs) in park dust. The results exhibited that park dust in the study area was mainly moderately polluted, and the EF values of dust Cd, Zn, Pb, Cu and Sb were all > 1. The concentrations of Cr, Cu, Zn and Pb increased with the decrease of dust particle size. The investigation results of chemical speciation and bioavailability of TEs showed that Zn had the highest bioavailability. Three sources of TEs were determined by positive matrix factorization model, Pearson correlation analysis and geostatistical analysis, comprising factor 1 mixed sources of industrial and transportation activities (46.62%), factor 2 natural source (25.56%) and factor 3 mixed source of agricultural activities and the aging of park infrastructures (27.82%). Potential ecological risk (PER) and human health risk (HHR) models based on source apportionment were exploited to estimate PER and HHR of TEs from different sources. The mean PER value of TEs in the park dust was 114, indicating that ecological risk in the study area was relatively high. Factor 1 contributed the most to PER, and the pollution of Cd was the most serious. There were no significant carcinogenic and non-carcinogenic risks for children and adults in the study area. And factor 3 was the biggest source of non-carcinogenic risk, and As, Cr and Pb were the chief contributor to non-carcinogenic risk. The primary source of carcinogenic risk was factor 2, and Cr was the cardinal cancer risk element.

A comprehensive exploration on the health risk quantification assessment of soil potentially toxic elements from different sources around large-scale smelting area.

Non-ferrous metal smelting activities have always been considered as one of the foremost anthropogenic sources of potentially toxic elements (PTEs). The enrichment factor (EF) and pollution load index (PLI) were used to evaluate the pollution level of soil PTEs; positive matrix factorization (PMF), correlation analysis, and geostatistics were utilized to quantify the sources of soil PTEs; and potential ecological risk (PER) and human health risk (HHR) of different sources from farmland, construction land, and natural land were quantifiably determined via combined PTE sources with PER and HHR assessment models. Taking the smelting area of Daye City as an example, the evaluation results of EF and PLI showed that the soil PTE pollution in the study area was serious, especially Cd and Cu. And four sources were quantitatively allocated as agricultural practices (12.14%), traffic emissions (23.07%), natural sources (33.46%), and industrial activities (31.33%). For PER, industrial activities were the largest contributor to PER, accounting for 55.66%, 56.30%, and 55.36% of farmland, construction land, and natural land, respectively, and Cd was the most dangerous element. In terms of HHR, industrial activities were also the cardinal contributors under the three land use types. Children were exposed to serious non-carcinogenic risks under three land use patterns and slight carcinogenic risk in construction land (1.06E - 04). Significantly, the carcinogenic risk of children in farmland (9.06 × 10-5) was very close to the threshold (1 × 10-4), which requires attention. Both non-carcinogenic and carcinogenic risk for adults were all at acceptable levels. The health risks (carcinogenic and non-carcinogenic risks) of children from four different sources were distinctly higher than those of adults. Consequently, strict management and control of industrial activities should be given priority, and the management of agricultural practices should not be ignored.

Berberine alleviates pulmonary hypertension through Trx1 and ß-catenin signaling pathways in pulmonary artery smooth muscle cells.

Pulmonary arterial hypertension (PAH) is closely associated with profound vascular remodeling, especially pulmonary arterial medial hypertrophy and muscularization, due to aberrant proliferation of pulmonary artery smooth muscle cells (PASMCs). Berberine, a drug commonly used to treat inflammation, may be a novel therapeutic option for PAH by improving pulmonary artery remodeling. The present study investigated whether berberine affected Trx1/ß-catenin expression and/or activity and whether it could reduce the development of pulmonary hypertension in an experimental rat model and proliferation in human PASMCs (HPASMCs). The results showed that increased proliferation in hypoxia-induced healthy PASMCs or PAH PASMCs was associated with a significant increase in Trx1 and ß-catenin expression. Treatment with the Trx1-specific inhibitor PX-12 significantly reduced pulmonary arterial pressure and vascular remodeling, as well as improved in vivo cardiac function and right ventricular hypertrophy, in Su/Hox-induced PAH rats. Berberine reversed right ventricular systolic pressure and right ventricular hypertrophy and decreased pulmonary vascular remodeling in the rats. Furthermore, berberine had an antiproliferative effect on hypoxia-induced HPASMC proliferation in a manner likely mediated by inhibiting Trx1 and its target gene ß-catenin expression. Our work will help elucidate novel strategies for PAH treatment involving the traditional Chinese medicine berberine, and Trx1/ß-catenin may be a promising therapeutic target.

Protective Effect of CXCR3⁺CD4⁺CD25⁺Foxp3⁺ Regulatory T Cells in Renal Ischemia-Reperfusion Injury.

Regulatory T cells (Tregs) suppress excessive immune responses and are potential therapeutic targets in autoimmune disease and organ transplantation rejection. However, their role in renal ischemia-reperfusion injury (IRI) is unclear. Levels of Tregs and expression of CXCR3 in Tregs were analyzed to investigate their function in the early phase of renal IRI. Mice were randomly divided into Sham, IRI, and anti-CD25 (PC61) + IRI groups. The PC61 + IRI group was established by i.p. injection of PC61 monoclonal antibody (mAb) to deplete Tregs before renal ischemia. CD4(+)CD25(+)Foxp3(+) Tregs and CXCR3 on Tregs were analyzed by flow cytometry. Blood urea nitrogen (BUN), serum creatinine (Scr) levels, and tubular necrosis scores, all measures of kidney injury, were greater in the IRI group than in the Sham group. Numbers of Tregs were increased at 72 h after reperfusion in kidney. PC61 mAb preconditioning decreased the numbers of Tregs and aggravated kidney injury. There was no expression of CXCR3 on Tregs in normal kidney, while it expanded at 72 h after reperfusion and inversely correlated with BUN, Scr, and kidney histology score. This indicated that recruitment of Tregs into the kidney was related to the recovery of renal function after IRI and CXCR3 might be involved in the migration of Tregs.

Protective effect of CD4(+)CD25(high)CD127(low) regulatory T cells in renal ischemia-reperfusion injury.

Ischemia reperfusion injury (IRI) is critical in the pathogenesis of acute renal failure and graft rejection. Regulatory T cells (Tregs) suppress excessive immune responses in IRI. We investigated the role of CD4(+)CD25(high)CD127(low) Tregs in the early phase of renal IRI pathogenesis in a mouse model. CD4(+)CD25(high)CD127(low) Tregs in the kidney, tubular necrosis scores, and renal function were measured 24 or 72 h after reperfusion. PC61, an anti-CD25 monoclonal antibody, was used to deplete Tregs before renal ischemia to confirm the effect of these Tregs. CD4(+)CD25(high)CD127(low) Tregs were expanded 24 and 72 h after reperfusion. Depletion of CD4(+)CD25(high)CD127(low) Tregs was associated with worsening of renal function and histology, particularly at 72 h after reperfusion. These results indicated that expansion of CD4(+)CD25(high)CD127(low) Tregs in the early phase of renal IRI may participate in tissue repair. These data reveal new insights into the pathogenesis of ischemic acute renal failure and a novel therapeutic approach.

TACE Plus Lenvatinib Versus TACE Plus Sorafenib for Unresectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Prospective Cohort Study.

BACKGROUND AND OBJECTIVES: This study aimed to compare the efficacy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S) to TACE plus lenvatinib (TACE-L) for the treatment of HCC with portal vein tumor thrombus (PVTT). METHODS: This cohort study recruited patients from September 2017 to September 2020. A total of 59 and 57 consecutive patients were treated with TACE-L and TACE-S, respectively. RESULTS: Before propensity score matching (PSM), comparing TACE-L to TACE-S, the median overall survival (OS) time was 16.4 months and 12.7 months, respectively [hazard ratio (HR) 1.34; 95% confidence interval (CI): 0.81-2.20; p = 0.25]. The median progression-free survival (PFS) time was 8.4 months and 7.43 months, respectively (HR 1.54; 95% CI: 0.98-2.41; p = 0.081). After PSM, the median OS time was 18.97 months and 10.77 months, respectively (HR 2.21; 95% CI: 1.12-4.38; p = 0.022); the median PFS time was 10.6 months (95% CI: 6.6-18.0 months) and 5.4 months (95% CI: 4.2-8.1 months), respectively (HR 2.62; 95% CI: 1.43-4.80; p = 0.002). After PSM, the overall response rate (ORR) was 66.8% vs. 33.3% [odds ratio (OR) 0.85; 1.05-6.90; p = 0.037]. CONCLUSION: Both TACE-L and TACE-S are safe, well-tolerated treatments for HCC with PVTT. In HCC with PVTT, TACE-L was significantly superior to TACE-S with respect to OS, PFS, and ORR. A larger-scale randomized clinical trial is needed.

CpG island methylator phenotype of multigene in serum of sporadic breast carcinoma.

CpG island methylator phenotype (CIMP) involves methylation targeted toward the promoters of multiple genes. We determined a methylation profile of tumor-related genes in serum of sporadic breast cancer (SBC). The multigene methylation was examined by methylation-specific polymerase chain reaction assay in serum of 50 SBCs and 50 paired nontumors, and CIMP+ was defined as having three genes that are concordantly methylated. The methylation frequency of ten genes in serum of 50 SBCs varied from 10% in FHIT to 74% in RASSF1A. The methylation status of RASSF1A, BRCA1, p16, CDH1, ER, RARbeta2, APC, and DAPK was significantly correlated with SBC and nontumor serum (P < 0.05). Methylation of at least one gene was found in 92% SBC; CIMP was more frequent in SBC than nontumor serum (P < 0.001). There was a significant association between CIMP and methylation of RASSF1A, BRCA1, p16, CDH1, ER, RARbeta2, APC, and DAPK (P < 0.05); the methylation link profile of CDH1, RASSF1A, BRCA1, and RARbeta2 as breast cancer marker may contribute high sensitivity (90%) and specificity (88%). ER and RARbeta2 methylation was associated with elevated serum CA153 levels in 39 SBC samples with CIMP+ (P < 0.05). Multivariate analysis showed that living area of patients was found to provide independent prognostic information associated with a relative risk of tumor recurrence of 5.3. Multigene-specific methylation profile in serum was association with the recurrence risk of rural SBC, and positive correlation of CIMP can serve as a promising molecular marker of SBC.

Progress in the functional modification of graphene/graphene oxide: a review.

Graphene and graphene oxide have attracted tremendous interest over the past decade due to their unique and excellent electronic, optical, mechanical, and chemical properties. This review focuses on the functional modification of graphene and graphene oxide. First, the basic structure, preparation methods and properties of graphene and graphene oxide are briefly described. Subsequently, the methods for the reduction of graphene oxide are introduced. Next, the functionalization of graphene and graphene oxide is mainly divided into covalent binding modification, non-covalent binding modification and elemental doping. Then, the properties and application prospects of the modified products are summarized. Finally, the current challenges and future research directions are presented in terms of surface functional modification for graphene and graphene oxide.

miR-30 inhibits proliferation of trophoblasts in preeclampsia rats partially related to MAPK/ERK pathway.

Effect of micro ribonucleic acid (miR)-30 on the proliferation of trophoblasts in preeclampsia (PE) rats through the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway was studied. The miR-30 mimic was transfected into the trophoblast HTR8/SVNEO cell lines. The effects of expression level of miR-30 on the proliferation and hypoxia-induced apoptosis of HTR8/SVNEO cells were detected via methyl thiazolyl tetrazolium (MTT) assay and Annexin V/propidium iodide staining, respectively, using the flow cytometer. A total of 30 pregnant Sprague-Dawley rats were randomly divided into control group (CTL group, n=10), PE rat group (PE group, n=10) and PE + miR-30 Mimic group (PE+agomiR-30 group, n=10) using a random number table. The protein expression levels of phosphorylated ERK (p-ERK)1/2, ERK1/2, proliferating cell nuclear antigen (PCNA) and tubulin were determined using western blot analysis, and the mRNA expression level of ERK1/2 was detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression level of PCNA in tissues was detected via immunohistochemistry. The results of MTT assay showed that the proliferation of HTR8/SVNEO cells significantly declined in hypoxic environment, while miR-30 promoted the proliferation of HTR8/SVNEO cells and alleviated the hypoxia-induced inhibition on cell proliferation. It was found that the trophoblast apoptosis rate was increased in hypoxia group compared with that in CTL group, while it was significantly decreased in miR-30 Mimic group compared with that in hypoxia group. PE group had obviously decreased p-ERK and PCNA expression levels as well as p-ERK/ERK ratio in placental tissues compared with CTL group, while PE+agomiR-30 group had an obviously increased expression level of PCNA as well as p-ERK/ERK ratio in placental tissues compared with PE group. MiR-30 activates the MAPK/ERK signaling pathway and increases the expression level of PCNA through raising the p-ERK level and p-ERK/ERK ratio, thereby inhibiting cell apoptosis and promoting cell proliferation.

The development and psychometric evaluation of the Chinese Big Five Personality Inventory-15.

The Chinese Big Five Personality Inventory (CBF-PI), a 134-item self-report scale, and its 40-item brief version (CBF-PI-B) are sound psychometric instruments used to measure the Big Five personality domains in the Chinese population. However, their applicability is limited by their length, as well as restricted by assessment conditions. In this study, we developed and validated a new shortened version with 15 items (CBF-PI-15) through exploratory factor analysis and confirmatory factor analysis in a large sample (Sample 1) of 10,738 Chinese adults (mean = 33.90 years, SD = 9.39 years, range 17-57 years). Measurement invariance results suggested the CBF-PI-15 were invariant across gender and age groups. Convergent, discriminant and criterion validities were tested in Sample 2 (N = 256, mean = 21.62 years, SD = 3.06 years, range 18-35 years) and findings showed an expected correlational pattern with external variables. Results revealed positive correlations of Neuroticism with the Barratt Impulsiveness Scale Brief Version (BIS-Brief), the Patient Health Questionnaire, and the Generalized Anxiety Disorder Screener, as well as a strongly negative correlation between Conscientiousness and BIS-Brief. Additionally, Conscientiousness positively correlated with academic performance as expected. In conclusion, the CBF-PI-15 holds promise as an informative alternative for the original CBF-PI-B when administration time or conditions are limited, and our findings provide preliminary support for the utility of the CBF-PI-15.

Gene Mutation in Neonatal Jaundice - Mutations in UGT1A1 and OATP2 Genes.

This study evaluated the correlation of UGT1A1, OATP2 gene mutations and hyperbilirubinemia in newborns in Northern China. Gene mutations were analyzed at the 211 locus of UGT1A1 (Gly71Arg) and 388 locus of OATP2 (Asn130Asp). The 226 enrolled infants were divided into high, moderate, and low risk subgroups according to American Academy of Pediatrics guideline. Blood samples of the enrolled infants were collected for the analysis of the PCR-restriction fragment length polymorphism. The genotypes and allele frequencies of the polymorphisms were compared in each group. Both UGT1A1 and OATP2 gene mutations occur more often in high risk group and moderate risk group than in low risk group. The results suggested that Gly71Arg and Asn130Asp mutations in UGT1A1 and OATP2 genes might be involved in the development of hyperbilirubinemia in neonates.

IgG4-related spinal pachymeningitis.

The aim of this study is to study the clinical, laboratory, imaging pathology, and prognosis features of IgG4-related spinal pachymeningitis. We worked with a 55-year-old man suffering from IgG4-related spinal pachymeningitis who had the most widespread lesion in his dura mater. We also review previous related studies and discuss the clinical characteristics of this rare disease. In total, eight IgG4-related spinal pachymeningitis patients have been reported in the literature since 2009. They were mostly male patients, 51.7 ± 11.9 years old on average. Cervical and thoracic vertebrae were the most common sites for lesions. The most prominent symptom was varying numbness and weakness of the limbs and/or body associated with spinal cord compression. There was one patient (1/5) with elevated serum IgG4 levels and three patients (3/3) with increased cerebrospinal fluid (CSF) IgG4 index. Positive histopathologic findings are the strongest basis for a diagnosis. All the patients with IgG4-related spinal pachymeningitis responded well to glucocorticoid therapy. IgG4-related spinal pachymeningitis is an orphan disease that mainly occurs in cervical and thoracic vertebrae. Older males are the most susceptible group. Serum IgG4 levels were consistently normal in these cases, so analysis of CSF for IgG4 production (IgG4 index) could become a useful tool. Pathological findings remain the gold standard for diagnosis. Most patients responded favorably to glucocorticoid treatment.

Can routine oral care with antiseptics prevent ventilator-associated pneumonia in patients receiving mechanical ventilation? An update meta-analysis from 17 randomized controlled trials.

BACKGROUND: Whether oral antiseptics could reduce the risk of ventilator associated pneumonia (VAP) in patients receiving mechanical ventilation remains controversial. We performed a meta-analysis to assess the effect of oral care with antiseptics on the prevalence of ventilator associated pneumonia in adult critically ill patients. METHODS: A comprehensive search of PubMed, Embase and Web of Science were performed to identity relevant studies. Eligible studies were randomized controlled trials of mechanically ventilated adult patients receiving oral care with antiseptics. The quality of included studies was assessed by the Jadad score. Relative risks (RRs), weighted mean differences (WMDs), and 95% confidence intervals (CIs) were calculated and pooled using a fixed-effects model or random-effects model. Heterogeneity among the studies was assessed with I (2) test. RESULTS: 17 studies with a total number of 4249 met the inclusion criteria. Of the 17 studies, 14 assessed the effect of chlorhexidine, and 3 investigated the effect of povidone-iodine. Overall, oral care with antiseptics significantly reduced the prevalence of VAP (RR=0.72, 95% CI: 0.57, 0.92; P=0.008). The use of chlorhexidine was shown to be effective (RR=0.73, 95% CI: 0.57, 0.93; P=0.012), whereas this effect was not observed in povidone-iodine (RR=0.51, 95% CI: 0.09, 2.82; P=0.438). Subgroup analyses showed that oral antiseptics were most marked in cardiac surgery patients (RR=0.54, 95% CI: 0.39, 0.74; P=0.00). Patients with oral antiseptics did not have a reduction in intensive care unit (ICU) mortality (RR=1.11, 95% CI: 0.95, 1.29; P=0.201), length of ICU stay (WMD=-0.10 days, 95% CI: -0.25, 0.05; P=0.188), or duration of mechanical ventilation (WMD=-0.05 days, 95% CI: -0.14, 0.04; P=0.260). CONCLUSION: Oral care with antiseptics significantly reduced the prevalence of VAP. Chlorhexidine application prevented the occurrence of VAP in mechanically ventilated patients but povidone-iodine did not. Further large-scale, well-designed randomized controlled trials are needed to identify the findings and determine the effect of povidone-iodine application.