HPV16 E7 oncoprotein test as a triage strategy for HPV16-positive women in cervical cancer screening: long-term follow-up outcome.

Background: Colposcopy is recommended once human papillomavirus (HPV)16/18 infection is detected. However, not all HPV16/18-positive women will necessarily develop cervical lesions. Therefore, this study aimed to investigate the application of quantitative HPV16 E7 oncoprotein detection as a cervical cancer screening method for more efficient screening while minimizing unnecessary colposcopy. Methods: E7 oncoprotein (HPV16) was quantitatively detected in cervical exfoliated cells of HPV16-positive women. The levels of HPV16 E7 oncoprotein in different degrees of cervical lesions were compared, and the optimal cut-off value for identifying HSIL+ was determined by receiver operating characteristic (ROC) curve analysis. With a pathological diagnosis as the gold standard, the sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and Kappa value were calculated to verify the diagnostic value of the method. Women diagnosed with low-grade squamous intraepithelial lesions (LSIL) and normal women were followed up for 5 years to evaluate the predictive value of HPV16 E7 protein for disease progression/persistent infection. Results: The expression level of HPV16 E7 oncoprotein was positively correlated with the degree of the cervical lesion (r = 0.589, P < 0.01). The area under the ROC curve (AUC) was 0.817 (confidence interval: 0.729-0.904). The cut-off value of E7 oncoprotein for identifying HSIL+ was 8.68 ng/ml. The SEN, SPE, PPV, NPV, and Kappa values of HPV16 E7 oncoprotein for the identification of HSIL+ were 87.1%,70.0%, 87.1%, 70.0%, and 0.571, respectively, which were higher than those of ThinPrep cytology test (TCT). The SEN, SPE, PPV, and NPV of HPV16 E7 oncoprotein in predicting disease progression/persistent infection were 93.75%, 91.30%, 88.24%, and 95.45%, respectively. Conclusion: The quantitative detection of HPV 16 E7 oncoprotein can not only accurately screen cervical lesions but also achieve efficient colposcopy referral. Additionally, HPV16 E7 oncoprotein can accurately predict the progression of cervical lesions and persistent HPV infection.

Associations of multiple air pollutants with kidney function in normal-weight and obese adults and effect modification by free fatty acids.

Increasing studies have linked air pollution to kidney dysfunction, however, the associations between the mixture of air pollutants and kidney function and potential effect modifiers remain unclear. We aimed to investigate whether obese adults were more susceptible than normal-weight ones to the joint effects of multiple air pollutants on kidney function and further to explore effect modification by free fatty acids (FFAs). Forty obese and 49 normal-weight adults were recruited from a panel study (252 follow-up visits). Individual exposure levels of air pollutants (PM2.5, PM10, O3, NO2, SO2 and CO) were estimated. Glomerular function (cystatin C (CysC) and estimated glomerular filtration rate (eGFR)) and tubular function (neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1) were evaluated. Plasma levels of FFAs including trans fatty acids (TFAs) and essential fatty acids (EFAs) were quantified using targeted metabolomics. Bayesian kernel machine regression model was applied to estimate the associations between the mixture of air pollutants and kidney function. The results showed significant joint effects of air pollutants on kidney function indicators. In the normal-weight group, the mixture of air pollutants was significantly associated with CysC and eGFRcr-cys when the mixture was at or above its 70 percentile compared with the median, where O3 was identified as the key pollutant. In the obese group, a significantly positive association between the pollutant mixture and NGAL was observed in addition to trends in CysC and eGFRcr-cys, mainly driven by SO2. Interaction analysis suggested that the associations of air pollutants with kidney function were augmented by TFAs in both groups and weakened by EFAs in the normal-weight group. This study highlighted the renal adverse effects of air pollutants and modification of FFAs, which has implications for target prevention for kidney dysfunction associated with air pollution, especially among vulnerable populations.

Uridine Inhibits Hepatocellular Carcinoma Cell Development by Inducing Ferroptosis.

Uridine is a key metabolite used as a substrate for the production of DNA, RNA, and glucose, and it is mainly synthesized in the liver. Currently, it is not known whether uridine levels are altered in the tumor microenvironment of patients with hepatocellular carcinoma (HCC) and whether uridine can be a target for tumor therapy. In this study, the detection of genes associated with de novo uridine synthesis, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD) (n = 115), and dihydroorotate dehydrogenase (DHODH) (n = 115) in HCC tissues through tissue microarrays revealed that the expression of CAD and DHODH was higher in tumor compared with paraneoplastic tissues. Next, we collected tumor tissues from surgically resected HCC patients and the corresponding adjacent non-tumor tissues (n = 46) for LC-MS/MS assays. The results showed that the median and interquartile ranges of uridine content in non-tumor and tumor tissues were 640.36 (504.45-807.43) and 484.22 (311.91-626.73) nmol/g, respectively. These results suggest that uridine metabolism is disturbed in HCC patients. To further investigate whether uridine can be used as a tumor-therapeutic target, a series of high concentrations of uridine were incubated with HCC cells in vitro and in vivo. It was observed that uridine dose-dependently inhibited the proliferation, invasion, and migration of HCC cells by activating the ferroptosis pathway. Overall, these results reveal for the first time the range of uridine content in human HCC tissues and suggest that uridine may be a new target for HCC therapy.

Cadmium accumulation in rice grains is mitigated by duckweed-like hydrophyte through adsorption and increased ammonia nitrogen.

Although increasing attention has been paid to agronomic measures for reducing the heavy metal load in rice grain, the effects of duckweed-paddy co-cropping technology on the accumulation of cadmium (Cd) in rice grains remain unclear. To investigate its specific effects on Cd accumulation in paddy fields, three types of duckweed-like hydrophyte (DH), Azolla imbricata, Spirodela polyrrhiza, and Lemna minor were chosen for study. Their use resulted in a reduction of Cd content in rice grains from 0.40 mg/kg to <0.20 mg/kg, with A. imbricata yielding the best results (0.15 mg/kg). The three types of DH reduced the available Cd content in the soil by 10 % to 35 % after the paddy tillering stage. The reduction of available Cd content was attributed to the absorption, high pH, and increase of relative abundance of special bacteria of immobilizing Cd. In addition, DH could regulate soil nitrogen leading to ammonium nitrogen increased from 75 mg/kg to 100 mg/kg, while nitrate nitrogen decreased from 0.55 to 0.1-0.3 mg/kg. The increase of ammonium nitrogen content might induce the low Cd transfer ability in rice plant and then low Cd content in rice grain. This study demonstrated that DH has a good effect on the reduction of the Cd concentration in rice grains. Consequently, duckweed-paddy co-cropping technology offers a potential solution to heavy metal pollution and agricultural non-point source pollution, as it not only reduces Cd levels in rice plants, but also fixes nitrogen, reducing the need for nitrogen application.

Clinical Characteristics and Prognosis of Multiple Myeloma With Myelomatous Pleural Effusion: A Retrospective Single-Center Study.

Objectives: Myelomatous pleural effusion is a rare presentation of extramedullary disease in multiple myeloma, which has been reported with dismal prognosis. We aimed to explore whether it has distinctive clinical characteristics and outcomes compared to other anatomic locations of extramedullary involvements. Methods: Multiple myeloma patients diagnosed at our institution from 2010 to 2020 were retrieved retrospectively. In total, 42 pairs of patients with and without extramedullary disease were enrolled, including 13 with myelomatous pleural effusion. The clinical and laboratory parameters were collected and compared between different groups. Prognostic effect of myelomatous pleural effusion was assessed in cox regression model and Kaplan-Meier curves. Results: Myelomatous pleural effusion patients presented a higher level of ß2-microglobulin (P = .041), greater prevalence of multisites extramedullary lesions (69.2% vs 38.0%, P = .036) and International Staging System stage III (76.9% vs 44.8%, P = .016). Median overall survival was 60.6 months in patients without extramedullary disease versus 35.0 months in patients with extramedullary disease (P = .045). Notably, median overall survival was 13.0 months in myelomatous pleural effusion patients versus 37.0 months in other extramedullary disease patients with a significant difference (P = .029). Furtherly, multivariate analysis recognized myelomatous pleural effusion as an independent prognostic indicator (Hazard ratio: 2.669, 95% CI [1.132-6.293], P = .025). Conclusion: Myelomatous pleural effusion patients presented heavier tumor burden and worse outcomes than other extramedullary diseases.

Prognostic Factors of AL-PCMM and AL-MM: A Single-Center Retrospective Study.

Background: Patients with amyloid light-chain (AL) amyloidosis with a bone marrow plasma cell ratio > 10% (AL-PCMM) have a poorer prognosis than patients with AL amyloidosis with a bone marrow plasma cell ratio of <10% (AL-only), similar to that of patients with AL amyloidosis and multiple myeloma (AL-MM). However, the prognostic factors for AL-PCMM and AL-MM have not been studied. Methods: A total of 49 patients with AL-PCMM or AL-MM in the Peking University First Hospital registry in 2010-2018 were enrolled. Clinical and follow-up data were collected. The relationship between clinical parameters and survival time was also assessed. Results: Compared with patients with AL-PCMM, patients with AL-MM only had a higher incidence of bone marrow plasma cell ratio ≥ 20%. In AL-PCMM and AL-MM, the survival time was significantly shorter in patients with alkaline phosphatase (ALP) ≥ 187.5 IU/L, γ-glutamyl transpeptidase (GGT) ≥ 85 IU/L, total bilirubin (TBIL) ≥ 20 µmol/L, cardiac troponin I (CTNI) ≥ 0.1 ng/mL, ejection fraction (EF) < 50%, initial therapeutic effect (ITE) < very good partial response (VGPR), and Boston University (BU) staging system stage ≥ III. ALP at diagnosis was correlated with brain natriuretic peptide (BNP) level, CTNI level, and EF rather than TBIL level. Cox regression analyses revealed that BU staging system stage ≥ III (P=0.001, hazard ratio [HR]=5.579), ALP ≥ 187.5 IU/L (P=0.011, HR=3.563), and ITE < VGPR (P=0.002, HR=7.462) were independent significant risk factors for a poor prognosis of AL-PCMM and AL-MM. Conclusion: ALP level, which is related to cardiac amyloidosis rather than liver involvement, can be a prognostic factor for this group of patients. A BU staging system stage ≥ III, ALP ≥ 187.5 IU/L, and ITE < VGPR were independent significant risk factors for a poor prognosis of AL-PCMM and AL-MM.

Comprehensive analysis of DOK family genes expression, immune characteristics, and drug sensitivity in human tumors.

Introduction: DOK is a new type of regulatory protein family that participates in the regulation of tumor cell growth. However, most of the studies are conducted in cell lines, and systematic studies have not been conducted in human tumors. Objectives: We conducted a comprehensive analysis of DOK based on its expression profile and its relationship with patient survival, immune infiltration, tumor microenvironment, and drug sensitivity. Methods: We used the TCGA database to analyze the correlation between DOK family gene expression and prognosis and clinical stage. The protein expression of DOK in tumor tissues was analyzed by immunohistochemistry. Use the cBioPortal database to analyze the alteration frequency in DOK family genes in human tumors. In addition, we used ESTIMATE algorithm and TIMER website to analyze the correlation between DOK family genes and tumor immunity. Finally, we further analyzed the relationship between DOK family genes and tumor stemness and the sensitivity of cancer cells to chemotherapy. Results: We conducted a comprehensive analysis of DOK family genes based on its expression profile and its relationship with patient survival. We also confirmed this conclusion by immunohistochemistry. The expression of DOK family genes is related to OS, clinical stage, tumor mutation, methylation, CNV, and SNV. DOK family genes are significantly associated with poor prognosis of UVM. DOK1-DOK3 has obvious correlation with tumor immunity. DOK2 can increase the sensitivity of chemotherapy drugs, while DOK4 reduces the sensitivity of multiple chemotherapy drugs. In addition, the expression level of DOK family genes is significantly correlated with the activity of cancer marker-related pathways. Conclusions: DOK plays a role of tumor suppressor gene or tumor-promoting gene in different tumors. However, DOK family genes play a role in promoting cancer in UVM. DOK family genes are significantly associated with drug sensitivity.

STK25 enhances hepatocellular carcinoma progression through the STRN/AMPK/ACC1 pathway.

BACKGROUND: Serine/threonine protein kinase 25 (STK25) plays an important role in regulating glucose and insulin homeostasis and in ectopic lipid accumulation. It directly affects the progression and prognosis of nonalcoholic fatty liver disease (NAFLD). However, the effects of STK25 on lipid metabolism in hepatocellular carcinoma (HCC) remain unexplored. The aim of this study was to investigate the role of STK25 in HCC and to elucidate the underlying mechanisms. METHODS: Immunohistochemistry was used to measure the expression of STK25 in hepatic tissues of HCC patients, and public datasets were used as supplementary material for predicting the expression of STK25 and the prognosis of patients with HCC. The interaction between STK25 and striatin (STRN) was determined by the STRING database, immunohistochemistry and western blot analyses. The involved signaling pathway was detected by the KEGG database and western blot. Moreover, the biological behaviors of the HCC cells were detected by wound healing assays, Transwell invasion assays and oil red O staining. Finally, it was verified again by xenograft model. RESULTS: STK25 is highly expressed in HCC patients and is associated with poor prognosis. STK25 knockdown inhibited the HCC cell invasion and proliferation, promotes apoptosis. Consistently, STK25 knockdown inhibited tumor growth in xenograft mouse model. Besides, STK25 deficiency decreased lipid synthesis, energy reserve, epithelial-mesenchymal transition (EMT) by down-regulating lipid metabolism signaling pathway. STRN could reverse the change of lipid metabolism. CONCLUSIONS: Our results demonstrated that STK25 interacted with STRN to regulates the energy reserve and EMT via lipid metabolism reprogramming. Accordingly, high expression of STK25 may be associated with HCC patients and poor prognosis, which implicates STK25 could be a potential target for lipid metabolism in cancer therapy.

Potential Role of Pleural Fluid Cytokine Profile in Myelomatous Pleural Effusions.

BACKGROUND: Myelomatous pleural effusion (MPE), as a presentation of extramedullary infiltration of multiple myeloma (MM), is rare and currently associated with poor outcomes without effective therapy. The potential value of cytokine detection in pleural effusion to MPE has not been reported to date. CASE PRESENTATION: We herein report a case of refractory and relapsed multiple myeloma that developed bilateral MPE due to disease progression caused by intolerance to various chemotherapy regimens. Cytomorphology and flow cytometry were adopted for diagnosis confirmation. Chemotherapy containing immunomodulators combined with thoracic catheterization drainage was applied to the patient, showing a certain therapeutic effect. During the course of disease, the change of cytokine profile in pleural effusion was monitored by cytometric bead array (CBA) technology, revealing that cytokines related to tumor load such as interleukin 6 (IL-6) and interleukin 10 (IL-10) in pleural effusion decreased with the improvement of disease, while other cytokines such as interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 17A (IL-17A), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), granzyme A, granzyme B, perforin and granulysin increased with the improvement of disease. CONCLUSION: There is a prospect that cytokine level in pleural effusion may indicate treatment response of MPE, and in light of this case, immunomodulators may be utilized in treating patients suffering MPE. Due to limitations of our single case, we urge more groups to evaluate the potential role of cytokine profile in MPE.

Effects of Amyloid Light-Chain Amyloidosis on Clinical Characteristics and Prognosis in Multiple Myeloma: A Single-Center Retrospective Study.

BACKGROUND: Amyloid light-chain amyloidosis (AL amyloidosis) is commonly associated with multiple myeloma. However, the clinical characteristics and prognosis of symptomatic and smoldering multiple myeloma with AL amyloidosis are not particularly clear. METHODS: Patients with symptomatic and smoldering multiple myeloma in the Peking University First Hospital registry from 2010 to 2018 were studied. The clinical and laboratory information was collected from first presentation to death or until the last available clinical follow-up. The patients' survival and outcomes were analyzed, and the relationship between the clinical parameters and survival was also assessed. RESULTS: Compared with symptomatic multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/mL (P<0.001), ALP>187.5IU/L (P=0.032) and ALB<25g/L (P<0.001). Similarly, compared with smoldering multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/mL (P=0.030) and Alb<25g/L (P=0.024). The existence of AL amyloidosis, especially those with the heart involvement, was related to shorter long-term survival of symptomatic and smoldering multiple myeloma according to univariate analyses. Renal involvement and gastrointestinal tract involvement had an impact on the prognosis of smoldering multiple myeloma but not on the symptomatic multiple myeloma. Cox regression model for overall survival detected BNP≧700pg/mL in symptomatic multiple myeloma having independent poorer prognostic significance (HR=2.455, P=0.004). Interestingly, BNP at diagnosis was significantly correlated with cardiac amyloidosis (r=0.496, P<0.001). Cox regression model for overall survival detected the presence of AL amyloidosis in smoldering multiple myeloma having independent poorer prognostic significance (HR=8.741, P=0.002). CONCLUSION: AL amyloidosis is an independent poor prognostic factor for not only symptomatic multiple myeloma but also smoldering multiple myeloma. It is mainly because of involvement of important organs, especially the heart. AL amyloidosis probably has a greater impact on the prognosis of smoldering multiple myeloma than on the symptomatic multiple myeloma.

Influence of Severe Gastrointestinal Complications in Primary Gastrointestinal Diffuse Large B-Cell Lymphoma.

BACKGROUND: This study assessed the clinical characteristics of gastrointestinal bleeding (GIB), obstruction (GIO), and perforation (GIP) in patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) and the influence on long-term survival. METHODS: A retrospective analysis was performed of 148 patients with PGI-DLBCL admitted to Peking University First Hospital from August 1994 to May 2018. The clinical characteristics of GIB, GIO, and GIP before and after chemotherapy were recorded. The associated overall survival and progression-free survival were analyzed. RESULTS: Among 148 patients, 56.8% had gastrointestinal complications (GICs), including GIB, GIO, GIP, and multiple complications, and 22.6% of them occurred after chemotherapy, mostly during the first 4 cycles. The most common clinical manifestations of patients with GICs were abdominal pain or discomfort (79.8%), hematemesis or melena (22.6%), and abnormal bowel habits (17.9%). Patients with Eastern Cooperative Oncology Group (ECOG) score ≥2, tumor mass ≥10 cm, or intestinal involvement had significantly higher risk of severe GICs as initial manifestations. Among 130 patients who received chemotherapy, B symptoms, tumor mass ≥10 cm, and Lugano stage (IIE, IV) strongly correlated with GICs after chemotherapy (P < 0.05). Rituximab did not increase the risk of GICs. GICs which occurred before or after chemotherapy reduced the objective response rate at the end of chemotherapy. The prognosis of patients was significantly worsened by GIP, GIB, or multiple complications after chemotherapy (P < 0.05). GIB at presentation or GIO before or after chemotherapy had no prognostic value (both P > 0.05). CONCLUSION: GICs adversely affect the quality of life, prolong the length of hospitalization, and shorten the long-term survival of patients with PGI-DLBCL.

C3 glomerulonephritis along with light chain proximal tubulopathy without crystal deposits in multiple myeloma: a case report.

BACKGROUND: Multiple myeloma causes different types of renal injury. C3 glomerulonephritis (C3GN) is characterised by an abnormal deposition of complement C3 in the glomeruli due to abnormal activation of the alternative pathway of the complement system. While the association between C3GN and multiple myeloma has been well established, mild renal injury by C3GN in multiple myeloma patients with high levels of light chain has not been reported. CASE PRESENTATION: A 55-year-old Chinese man presented with proteinuria. Combined with immunofixation electrophoresis, bone marrow biopsy, and renal biopsy, he was diagnosed with IgA-type multiple myeloma accompanied by C3GN and light chain proximal tubulopathy without crystal deposits. Although he had a higher level of lambda serum-free light chain, the renal injury in this patient was mild. After treatment with four courses of BD, one course of PAD, and autologous stem cell transplantation, he achieved a very good partial hematologic response with stable renal function. CONCLUSIONS: In multiple myeloma, the light chain reaches a certain level and persists, resulting in C3GN renal impairment. Early diagnosis and early intensive treatment are critical for the prognosis of such patients.

Prognostic and Clinicopathological Role of PD-L1 in Endometrial Cancer: A Meta-Analysis.

Background: A series of studies have explored the prognostic value of programmed death-ligand 1 (PD-L1) in patients with endometrial cancer (EC); however, the results are controversial. Therefore, this meta-analysis was performed to estimate the associations between PD-L1 expression and the prognosis and clinicopathological features of EC. Methods: A comprehensive literature search of PubMed, Web of Science, and Embase was conducted up until September 06, 2019. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) were computed using the random-effects model (REM) or fixed-effects model (FEM). Odds ratios (ORs) and 95% CIs were calculated to evaluate the relationship between PD-L1 and clinicopathological factors. Results: A total of 9 studies with 1,615 patients were included in the meta-analysis. The combined data showed that high expression of PD-L1 was not significantly correlated with OS (HR = 1.20, 95% CI = 0.41-3.52, p = 0.737) or PFS (HR = 1.12, 95% CI = 0.50-2.54, p = 0.778) in EC. In addition, PD-L1 expression was significantly associated with poor differentiation (OR = 2.82, 95% CI = 1.96-4.06, P < 0.001) and advanced stage (OR = 1.71, 95% CI = 1.12-2.60, p = 0.013). Conclusion: This meta-analysis suggests that PD-L1 expression is not associated with poor prognosis in patients with EC. However, PD-L1 expression is positively correlated with poor differentiation and advanced tumor stage in EC.

Expression of human Krüppel-like factor 3 in peripheral blood as a promising biomarker for acute leukemia.

BACKGROUND: Universal gene targets are in persistent demand by real-time quantitative polymerase chain reaction (RT-qPCR)-based methods in acute leukemia (AL) diagnosis and monitoring. Human Krüppel-like factor 3 (hKLF3), a newly cloned human transcription factor, has proved to be a regulator of hematopoiesis. METHODS: Sanger sequencing was performed in bone marrow (BM) samples from 17 AL patients for mutations in hKLF3 coding exons. hKLF3 expression in peripheral blood (PB) and BM samples from 45 AL patients was dynamically detected by RT-qPCR. PB samples from 31 healthy donors were tested as normal controls. RESULTS: No mutation was sequenced in hKLF3 coding exons. hKLF3 expression in PB of AL was significantly lower than that in healthy donors [0.30 (0.02-1.07) vs 1.18 (0.62-3.37), P < .0001]. Primary acute myeloid leukemia (AML) exhibited the least expression values compared with secondary AML and acute lymphoblastic leukemia. Receiver operating characteristic (ROC) analyses suggested that hKLF3 expression in PB was a good marker for AML diagnosis with an AUC of 0.99 (95% CI 0.98-1.00) and an optimum cutoff value of 0.67 (sensitivity 93.94% and specificity 93.55%). hKLF3 expression was upregulated significantly when AML patients acquired morphological complete remission (CR), and the level of hKLF3 seemed to be higher in patients with deeper CR than in patients with minimal residual disease (MRD). Paired PB and BM samples showed highly consistent alteration in hKLF3 expression (r = .6533, P = .001). Besides, a significantly converse correlation between decreased hKLF3 expression in PB and markers for leukemic load was observed. CONCLUSIONS: hKLF3 expression in PB may act as a potential marker for AL diagnosis and monitoring.

Different cardiorespiratory effects of indoor air pollution intervention with ionization air purifier: Findings from a randomized, double-blind crossover study among school children in Beijing.

Indoor air pollution is associated with numerous adverse health outcomes. Air purifiers are widely used to reduce indoor air pollutants. Ionization air purifiers are becoming increasingly popular for their low power consumption and noise, yet its health effects remain unclear. This randomized, double-blind crossover study is conducted to explore the cardiorespiratory effects of ionization air purification among 44 children in Beijing. Real or sham purification was performed in classrooms for 5 weekdays. Size-fractionated particulate matter (PM), black carbon (BC), ozone (O3), and negative air ions (NAI) were monitored, and cardiorespiratory functions were measured. Mixed-effect models were used to establish associations between exposures and health parameters. Real purification significantly decreased PM and BC, e.g. PM0.5, PM2.5, PM10 and BC were decreased by 48%, 44%, 34% and 50%, respectively. O3 levels were unchanged, while NAI was increased from 12 cm-3 to 12,997 cm-3. Real purification was associated with a 4.4% increase in forced exhaled volume in 1 s (FEV1) and a 14.7% decrease in fractional exhaled nitrogen oxide (FeNO). However, heart rate variability (HRV) was altered negatively. Interaction effects of NAI and PM were observed only on HRV, and alterations in HRV were greater with high NAI. Ionization air purifier could bring substantial respiratory benefits, however, the potential negative effects on HRV need further investigation.

Cardiorespiratory responses to low-level ozone exposure: The inDoor Ozone Study in childrEn (DOSE).

BACKGROUND: Indoor air pollution has emerged as a significant environmental and public health concern in recent years. However, evidence regarding the cardiorespiratory effects of indoor ozone is limited, and the underlying biological mechanisms are unclear, especially in children. Our study aimed to assess the cardiorespiratory responses to indoor ozone exposure in children. METHODS: A repeated-measure study was conducted in 46 middle-school children in Beijing, China. Real-time concentrations of ozone, along with co-pollutants including particulate matter (PM) and black carbon (BC), were monitored in classrooms from Monday to Friday. Three repeated health measurements of cardiorespiratory functions, including ambulatory electrocardiogram (ECG), blood pressure, fractional exhaled nitric oxide (FeNO) and lung function, were performed on each participant. Mixed-effect models were used to evaluate the effects of indoor ozone exposure. RESULTS: The mean (SD) indoor ozone concentration was 8.7 (6.6) ppb during the study period, which was largely below the current guideline and standards. However, even this low-level ozone exposure was associated with reduced cardiac autonomic function and increased heart rate (HR) in children. For instance, per interquartile range (IQR) increase in ozone at 2-hour moving average was associated with -7.8% (95% CI: -9.9%, -5.6%) reduction in standard deviation of all normal-to-normal intervals (SDNN), and 2.6% (95% CI: 1.6%, 3.6%) increment in HR. In addition, the associations were stronger at high BC levels (BC ≥ 3.7 µg/m3). No significant associations were found for airway inflammation and pulmonary function. CONCLUSIONS: Exposure to low-level indoor ozone that is not associated with respiratory effects was significantly related to disturbed cardiac autonomic function and increased HR in children, which suggested a possible mechanism through which ozone may affect cardiovascular health in children, and indicated more protective measures should be taken to alleviate the acute adverse effects of indoor ozone in this susceptible population.

An efficient method to simultaneously analyze multi-class organic pollutants in human serum.

The degree of population exposure to various organic pollutants (OPs), including polycyclic aromatic hydrocarbons, organochlorinated pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers, can be determined by measuring their concentrations in human serum. However, performing large-scale measurements with such a variety of compounds in serum is challenging in terms of efficiency and cost. We describe herein the development of a high-efficiency extraction and sample cleanup protocol for simultaneous and quantitative analyses of OPs using gas chromatography-mass spectrometry. OPs, together with crude lipid impurities, were extracted from human serum with a mixture of n-hexane and methyl tert-butyl ether. A disperse sorbent composed of primary secondary amine and C18 (PSA/C18) was used to roughly remove co-extracted impurities. A combined column of neutral silica gel and neutral alumina oxide (AlO/SiG) was then used for deep cleanup. For the removal of impurities, the overall performance of our protocol for the analysis of OPs in serum was comparable to that of traditional gel permeation chromatography (GPC) and dramatically better than that of PSA/C18, which is a frequently used QuEChERS (quick, easy, cheap, effective, rugged, safe) based method. While both the proposed protocol and GPC yielded recoveries of 80%-110% for four classes of OPs, our protocol consumed about 10 times less solvent, resulting in lower experimental expenses and a lower risk of contamination from residual OPs in the solvent and other supplies. In contrast to GPC, our protocol also permits efficient batch processing of serum samples, allowing for large sample sizes such as those encountered in epidemiological studies.

miR­144­3p regulates the resistance of lung cancer to cisplatin by targeting Nrf2.

Chemotherapeutic drug resistance is correlated with treatment failure and poor prognosis among lung cancer patients. Numerous studies indicate the relevance of miRNAs in inducing certain drug resistance. In the course of the study, we unexpectedly found that miR­144­3p could regulate the cisplatin resistance of lung cancer cells via Nrf2. However, Nrf2 also could reverse activate the expression of miR­144­3p by binding to the ARE box in the miR­144­3p promoter. This may be a self­protection mechanism of the body. In addition, we also found that in other cancer cell lines, such as HepG2, miR­144­3p also had the function of regulating cisplatin resistance. These findings may provide some theoretical reference for the clinical inhibition of cisplatin resistance.

The short-term effects of indoor size-fractioned particulate matter and black carbon on cardiac autonomic function in COPD patients.

BACKGROUND: Previous studies have reported adverse health effects of indoor air pollutants especially particulate matter (PM) and black carbon (BC). Patients with chronic obstructive pulmonary disease (COPD) have been shown to be more likely with cardiovascular comorbidities in which cardiac autonomic dysfunction plays an important role. However, there is little evidence for the effect of indoor PM and BC exposures on cardiac autonomic function in COPD patients. OBJECTIVES: To evaluate the association between exposure to indoor size-fractioned PM and BC and changes in HRV and HR in COPD patients. METHODS: Forty-three doctor diagnosed, stable COPD patients were recruited and measured for 24-h HRV and HR. Real-time indoor size-fractioned PM and BC were monitored on the day before and the day of performing health measurements. Mixed-effects models were used to estimate the associations between indoor PM and BC and HRV indices and HR after controlling for potential confounders. RESULTS: Increasing levels of size-fractioned PM and BC were associated with decreased HRV indices and increased HR. An IQR (3.14µg/m3) increase in 8-h BC moving average and an IQR (20.72µg/m3) increase in 5-min PM0.5 moving average concentrations were associated with declines of 7.45% (95% CI: -10.89%, -3.88%) and 16.40% (95% CI: -21.06%, -11.41%) in LF, respectively. The smaller the particles size, the greater effects on HRV indices and HR. Patients' BMI modified the associations between size-fractioned PM and BC and their HRV and HR. For an IQR increase in PM0.5, there was decline in HF of 34.85% (95% CI: -39.08%, -30.33%) in overweight patients, compared to a 2.01% (95% CI: -6.44%, 11.19%) increase in normal-weight patients. CONCLUSIONS: Exposures to indoor PM and BC were associated with altered cardiac autonomic function in COPD patients, and the associations for HRV measures of parasympathetic activity (e.g., HF) were more apparent in overweight patients.

Depuration of Cadmium from Blue Mussel (Mytilus edulis) by Protein Hydrolysate-Fe2+ Complex: The Role of Metallothionein.

Metallothionein (MT) plays a major role in the detoxification of toxic metal ions in mussel. This study served to investigate the effects of prepared protein hydrolysate-Fe2+ (PH-Fe2+ ) on depuration of cadmium salt (Cd2+ ) from blue mussel (Mytilus edulis). The results indicated that Cd2+ concentrations in control ranged from 46.1 to 47.1 µg/g during 15 d of depuration. While, 40 mg/L PH-Fe2+ feed mussels exhibited obvious changes in Cd2+ concentration variables, which decreased by 22.8 µg/g after 15 d of depuration, making them significantly lower than the values of the control. Our assumption was that Cd2+ could be dissociated effectively from the complex of MT-Cd2+ in mussels affected by the incorporation of PH-Fe2+ during the feeding period. Further results of homology modeling and molecular dynamics (MD) confirmed that the combined power between MT and Cd2+ weakened significantly by PH-Fe2+ . This condition affected the charge density and/or the loop flexibility of MT and decreased the interaction energy within MT-Cd2+ complex and resulted in the release of Cd2+ from the complex, thereby exhibiting excretion detoxification. Finally, by comparing the experimental results to MD results, significant positive correlations were observed between PH-Fe2+ and the depuration of Cd2+ from MT-Cd2+ complex. Overall, the findings of this study may help better understand the depuration mechanisms of Cd2+ combined with MT, and the PH-Fe2+ can be recommended as a depuration agent to decrease Cd2+ concentrations in mussels. PRACTICAL APPLICATION: Metallothionein (MT) is a low-molecular-weight protein with high metal-ion affinity. If the intracellular concentrations of metals are too high or if toxic metals are present within the cell, then the synthesis of MTs is induced and generated. In our previous work, it was found that the prepared hydrolysate-metal element complex showed obvious depuration activity of heavy metals (Cd2+ ) from blue mussel (Mytilus edulis). This study provided further the depuration mechanisms of Cd2+ from mussel (M. edulis), in particular to the role of MT and its chelate during the depuration process.