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.

Dead-zone-compensated design as general method of flow field optimization for redox flow batteries.

One essential element of redox flow batteries (RFBs) is the flow field. Certain dead zones that cause local overpotentials and side effects are present in all conventional designs. To lessen the detrimental effects, a dead-zone-compensated design of flow field optimization is proposed. The proposed architecture allows for the detection of dead zones and their compensation on existing flow fields. Higher reactant concentrations and uniformity factors can be revealed in the 3D multiphysical simulation. The experiments also demonstrate that at an energy efficiency (EE) of 80%, the maximum current density of the novel flow field is 205 mA cm-2, which is much higher than the values for the previous ones (165 mA cm-2) and typical serpentine flow field (153 mA cm-2). Extensions of the design have successfully increased system EE (2.7 to 4.3%) for a variety of flow patterns. As a result, the proposed design is demonstrated to be a general method to support the functionality and application of RFBs.

Obesity-related cardiometabolic indicators modify the associations of personal noise exposure with heart rate variability: A further investigation on the Study among Obese and Normal-weight Adults (SONA).

Elucidating the associations between environmental noise and heart rate variability (HRV) would be beneficial for the prevention and control of detrimental cardiovascular changes. Obese people have been found to manifest heightened susceptibility to the adverse effects of noise on HRV. However, the underlying mechanisms remain unclear. Based on 53 normal-weight and 44 obese young adults aged 18-26 years in Beijing, China, this study aimed to investigate the role of obesity-related cardiometabolic indicators for associations between short-term environmental noise exposure and HRV in the real-world context. The participants underwent personal noise exposure and ambulatory electrocardiogram monitoring using portable devices at 5-min intervals for 24 continuous hours. Obesity-related blood pressure, glucose and lipid metabolism, and inflammatory indicators were subsequently examined. Generalized mixed-effect models were used to estimate the associations between noise exposure and HRV parameters. The C-peptide, homeostasis model assessment of insulin resistance (HOMA-IR), and leptin levels were higher in obese participants compared to normal-weight participants. We observed amplified associations between short-term noise exposure and decreases in HRV among participants with higher C-peptide, HOMA-IR, and leptin levels. For instance, a 1 dB(A) increment in 3 h-average noise exposure level preceding each measurement was associated with changes of -0.20% (95%CI: -0.45%, 0.04%) and -1.35% (95%CI: -1.85%, -0.86%) in standard deviation of all normal to normal intervals (SDNN) among participants with lower and higher C-peptide levels, respectively (P for interaction <0.05). Meanwhile, co-existing fine particulate matter (PM2.5) could amplify the associations between noise and HRV among obese participants and participants with higher C-peptide, HOMA-IR, and leptin levels. The more apparent associations of short-term exposure to environmental noise with HRV and the effect modification by PM2.5 may be partially explained by the higher C-peptide, HOMA-IR, and leptin levels of obese people.

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.

Joint effect of multiple air pollutants on cardiometabolic health in normal-weight and obese adults: A novel insight into the role of circulating free fatty acids.

The cardiometabolic effects of air pollution in the context of mixtures and the underlying mechanisms remain not fully understood. This study aims to investigate the joint effect of air pollutant mixtures on a broad range of cardiometabolic parameters, examine the susceptibility of obese individuals, and determine the role of circulating fatty acids. In this panel study, metabolically healthy normal-weight (MH-NW, n = 49) and obese (MHO, n = 39) adults completed three longitudinal visits (257 person-visits in total). Personal exposure levels of PM2.5, PM10, O3, NO2, SO2, CO and BC were estimated based on fixed-site monitoring data, time-activity logs and infiltration factor method. Blood pressure, glycemic homeostasis, lipid profiles, systematic inflammation and coagulation biomarkers were measured. Targeted metabolomics was used to quantify twenty-eight plasma free fatty acids (FFAs). Bayesian kernel machine regression models were applied to establish the exposure-response relationships and identify key pollutants. Significant joint effects of measured air pollutants on systematic inflammation and coagulation biomarkers were observed in the MHO group, instead of the MH-NW group. Lipid profiles showed the most significant changes in both groups and O3 contributed the most to the total effect. Specific FFA patterns were identified, and de novo lipogenesis (DNL)-related pattern was most closely related to blood lipid profiles. In particular, interaction analysis suggested that DNL-related FFA pattern augmented the effects of O3 on triglyceride (TG, Pinteraction = 0.040), high-density lipoprotein cholesterol (HDL-C, Pinteraction = 0.106) and TG/HDL-C (Pinteraction = 0.020) in the MHO group but not MH-NW group. This modification was further confirmed by interaction analysis with estimated activity of SCD1, a key enzyme in the DNL pathway. Therefore, despite being metabolically healthy, obese subjects have a higher cardiometabolic susceptibility to air pollution, especially O3, and the DNL pathway may represent an intrinsic driver of lipid susceptibility. This study provides new insights into the cardiometabolic susceptibility of obese individuals to air pollution.

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.

Associations between personal noise exposure and heart rate variability were modified by obesity and PM2.5: The study among obese and normal-weight adults (SONA).

Noise pollution has been documented to increase the risks of cardiovascular disorders, which can be predicted by heart rate variability (HRV), nevertheless, there has been limited evidence on the modifiers of noise pollution. Environmental fine particulate matter (PM2.5) and obesity status are both growing major concerns of cardiovascular disease burden. Our study aims to investigate whether these two factors may modify the associations between noise exposure and HRV indices. An investigation was performed on 97 (53 normal-weight and 44 obese) participants aged 18-26 years, with continuous 5-min personal exposure assessment and ambulatory electrocardiogram monitoring for 24 h. This study found that personal exposure to noise was associated with decreased HRV level and imbalanced cardiac autonomic function, as indicated by decreases in standard deviation of normal-to-normal intervals (SDNN), square root of the mean squared differences of successive intervals (rMSSD), the percentage of R-R intervals that differ from each other by more than 50 ms (pNN50), low-frequency (LF) power, high-frequency (HF) power, and increases in LF-HF-Ratio. Stronger associations between personal noise exposure and HRV indices were observed among obese participants and participants with higher PM2.5 exposure levels compared to their counterparts. For SDNN, a 1 dB(A) increment in personal noise exposure at 3h-average was associated with a 1.25% (95%CI: -1.64%, -0.86%) decrease among obese participants, and a 0.11% (95%CI: -0.38%, 0.16%) decrease among normal-weight participants (P for subgroup difference<0.001); and a 0.87% (95%CI: -1.20%, -0.54%) decrease among participants with higher PM2.5 exposure levels, and a 0.22% (95%CI: -0.58%, 0.14%) decrease among participants with lower PM2.5 exposure levels (P for subgroup difference = 0.008). Obesity and PM2.5 may aggravate the adverse effects of noise on HRV, which has implications for targeted prevention of cardiovascular disease burden associated with noise pollution.

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.

Joint effect of multiple air pollutants on lipid profiles in obese and normal-weight young adults: The key role of ozone.

Dyslipidemia may be a potential mechanism linking air pollution to adverse cardiovascular outcomes and this may differ among obese and normal-weight populations. However, the joint effect of multiple air pollutants on lipid profiles and the role of each pollutant are still unclear. This panel study aims to investigate and compare the overall associations of major air pollutants with lipid parameters in obese and normal-weight adults, and assess the relative importance of each pollutant for lipid parameters. Forty-four obese and 53 normal-weight young adults were recruited from December 2017 to June 2018 in Beijing, China. Their fasting blood was collected and serum lipid levels were measured in three visits. Six major air pollutants were included in this study, which were PM2.5, PM10, NO2, SO2, O3 and CO. Bayesian kernel machine regression (BKMR) was implemented to estimate the joint effect of the six air pollutants on various lipid parameters. We found that decreased high-density lipoprotein cholesterol (HDL-C) in the obese group and increased low-density lipoprotein cholesterol (LDL-C) and non-HDL-C in the normal-weight group were associated with the exposure to the mixture of six air pollutants above. Significant increases in total cholesterol (TC)/HDL-C and non-HDL-C/HDL-C were observed in both groups, and the effect was stronger in obese group. Of the six air pollutants above, O3 had the largest posterior inclusion probability in above lipid indices, ranging from 0.75 to 1.00. In the obese group, approximately linear exposure-response relationships were observed over the whole range of logarithmic O3-8 h max concentration, while in the normal-weight group, these relationships existed when the logarithmic concentration exceeded about 2.8. Therefore, lipid profiles of obese adults may be more sensitive to air pollution and this study highlights the importance of strengthening emissions control efforts for O3 in the future.

Short-term ozone exposure and metabolic status in metabolically healthy obese and normal-weight young adults: A viewpoint of inflammatory pathways.

Unhealthy metabolic status increases risks of cardiovascular and other diseases. This study aims to explore whether there is a link between O3 and metabolic health indicators through a viewpoint of inflammatory pathways. 49 metabolically healthy normal-weight (MH-NW) and 39 metabolically healthy obese (MHO) young adults aged 18-26 years were recruited from a panel study with three visits. O3 exposure were estimated based on fixed-site environmental monitoring data and time-activity diary for each participant. Compared to MH-NW people, MHO people were more susceptible to the adverse effects on metabolic status, including blood pressure, glucose, and lipid indicators when exposed to O3. For instance, O3 exposure was associated with significant decreases in high-density lipoprotein cholesterol (HDL-C), and increases in C-peptide and low-density lipoprotein cholesterol (LDL-C) among MHO people, while only weaker changes in HDL-C and LDL-C among MH-NW people. Mediation analyses indicated that leptin mediated the metabolic health effects in both groups, while eosinophils and MCP-1 were also important mediating factors for the MHO people. Although both with a metabolically healthy status, compared to normal-weight people, obese people might be more susceptible to the negative effects of O3 on metabolic status, possibly through inflammatory indicators such as leptin, eosinophils, and MCP-1.

Loan default prediction of Chinese P2P market: a machine learning methodology.

Repayment failures of borrowers have greatly affected the sustainable development of the peer-to-peer (P2P) lending industry. The latest literature reveals that existing risk evaluation systems may ignore important signals and risk factors affecting P2P repayment. In our study, we applied four machine learning methods (random forest (RF), extreme gradient boosting tree (XGBT), gradient boosting model (GBM), and neural network (NN)) to predict important factors affecting repayment by utilizing data from Renrendai.com in China from Thursday, January 1, 2015, to Tuesday, June 30, 2015. The results showed that borrowers who have passed video, mobile phone, job, residence or education level verification are more likely to default on loan repayment, whereas those who have passed identity and asset certification are less likely to default on loans. The accuracy and kappa value of the four methods all exceed 90%, and RF is superior to the other classification models. Our findings demonstrate important techniques for borrower screening by P2P companies and risk regulation by regulatory agencies. Our methodology and findings will help regulators, banks and creditors combat current financial disasters caused by the coronavirus disease 2019 (COVID-19) pandemic by addressing various financial risks and translating credit scoring improvements.

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.

Chemical constituents and sources of indoor PM2.5 and cardiopulmonary function in patients with chronic obstructive pulmonary disease: Estimation of individual and joint effects.

BACKGROUND: The cardiopulmonary effects of chemical constituents and sources of indoor fine particulate matter (PM2.5) remain unclear. OBJECTIVES: To examine the individual and joint effects of constituents of indoor PM2.5 on cardiopulmonary function of patients with chronic obstructive pulmonary disease (COPD) and the role of identified sources. METHODS: This panel study recruited 43 stable COPD patients from November 2015 to May 2016 in Beijing, China. Daily indoor and outdoor PM2.5 were collected for five consecutive days simultaneously. Twenty-four elements were measured and principal component analysis was used for source appointment. Pulmonary function and blood pressure (BP) were also measured at daily visit. The linear mixed-effect models were used to estimate the effect of each constituent and source. Bayesian kernel machine regression (BKMR) models were used to estimate the overall effect of all measured constituents. RESULTS: The combustion, indoor soil/dust and road dust sources were identified as the main sources of indoor PM2.5 and combustion sources contributed over 40% during the heating season. Most constituents were significantly associated with elevated BP of COPD patients and the joint effects of mixed exposures were also significant especially during the heating season. Most associations of chemical constituents with pulmonary function were negative but not statistically significant during the heating season, as was the joint effect. Few associations were observed during the non-heating season. Further, we observed combustion sources throughout the study period and road dust sources during the heating season were significantly associated with increased BP but not decreased pulmonary function. CONCLUSION: The combustion and road dust sources and their related constituents of indoor PM2.5 could cause adverse effects on cardiovascular function of COPD patients especially during the heating season, but the effect on pulmonary function still needs to be further studied.

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.

Exposure to fine particulate matter promotes platelet activation and thrombosis via obesity-related inflammation.

Short-term exposure to fine particulate matter (PM2.5) increases thrombotic risk particularly in obese individuals, but the underlying mechanisms remain unclear. This study aims to compare the effects of PM2.5 on inflammation and platelet activation in obese versus normal-weight adults, and investigate potential causal pathways. We conducted a panel study measuring blood markers in 44 obese and 53 normal-weight adults on 3 separate occasions in 2017-2018. Associations between PM2.5/black carbon (BC) and biomarkers were estimated using mixed-effect models. An interaction analysis compared PM2.5/BC-related effects between subgroups. Biomarker combinations and mediation analysis were performed to elucidate the biological pathways. There was a significant "low-high-low" trend of PM2.5 levels across the 3 study periods. Increases in pro-inflammatory cytokines and changes of platelet activation and aggregation markers were associated with PM2.5/BC in obese subgroup only. Among obese subjects, the combination of pro-inflammatory cytokines and that of platelet markers increased 26.8% (95% CI: 16.0%, 37.9%) and 14.7% (95% CI: 1.9%, 27.0%) per IQR increase in PM2.5 over 5-day and 7-day averages. Inflammation mediated 24.5% of the pathways through which PM2.5 promoted platelet activation. This study suggested obese people are susceptible to pro-thrombotic impacts of PM2.5 exposures. PM2.5 may aggravate thrombosis through obesity-related inflammation.