Effect of long-term intensive cholesterol control on the plaque progression in elderly based on CTA cohort study.

OBJECTIVES: To investigate the long-term effects of intensive LDL cholesterol-lowering treatments on lumen stenosis severity, plaque calcification, spotty calcifications, percent calcified plaque volume (PCPV), and Agatston coronary artery calcium score (CACS) based on coronary computed tomography angiography (CCTA) in elderly patients. METHODS: A total of 240 patients over 60 years old (comprising 754 lesions) who underwent serial CCTA were retrospectively enrolled in this 5-year cohort study. Patients were divided into three groups: an intensive lipid-lowering group, a lipid-lowering group, and a control group. The stenosis severity, plaque volume (PV), plaque composition, PCPV, and high-risk plaque (HRP) presence were quantitatively analyzed. The CACS was calculated at baseline and follow-up. RESULTS: All patients were male with an average age of 66.8 ± 5.8 years old. Over time, increases in the percentages of obstructive coronary lesions (p < 0.001) were observed. Compared with those at baseline, the percentage of obstructive lesions remained unchanged (p = 0.077), and the percentage of spotty calcifications significantly decreased (p < 0.05) at the follow-up CCTA scan in the intensive lipid-lowering group. Patients in the intensive lipid-lowering group demonstrated a higher progression in calcified PV, CACS, and PCPV (all p < 0.05), and a significantly greater attenuation in fibrous-fatty and lipid-rich PV (all p < 0.05) than patients in other groups. CONCLUSIONS: The PV and contents increased gradually with time in all groups. Intensive LDL-C lowering was associated with slower progression of stenosis severity and reduction of high-risk plaque features, with increased plaque calcification and higher progression in PCPV. Comprehensive serial plaque evaluations by CCTAs may contribute to further refinement of risk stratification and reasonable lipid-lowering treatment in elderly patients. KEY POINTS: • Intensive LDL-C lowering increased coronary calcification and percent calcified plaque volume progression. • Comprehensive serial plaque evaluations by serial CCTAs may help to refine risk stratification.

Inactivation and subsequent reactivation of Aspergillus species by the combination of UV and monochloramine: Comparisons with UV/chlorine.

Ultraviolet (UV)/monochloramine (NH2Cl) as an advanced oxidation process was firstly applied for Aspergillus spores inactivation. This study aims to: i) clarify the inactivation and photoreactivation characteristics of UV/NH2Cl process, ii) compared with UV/Cl2 in inactivation efficiency, photoreactivation and energy consumption. The results illustrated that UV/NH2Cl showed better inactivation efficiency than that of UV alone and UV/Cl2, and could effectively control the photoreactivation. For instance, the inactivation rates for Aspergillus flavus, Aspergillus niger and Aspergillus fumigatus in the processes of UV/NH2Cl (2.0 mg/L) was 0.034, 0.030 and 0.061 cm2/mJ, respectively, which were higher than that of UV alone (0.027, 0.026 and 0.024 cm2/mJ) and UV/Cl2 (0.023, 0.026 and 0.031 cm2/mJ). However, there was no synergistic effect for Aspergillus flavus and Aspergillus fumigatus. As for Aspergillus niger, the best synergistic effect can reach 1.86-log10. This may be due to their different resistance to disinfectants, which were related to the size, an outer layer of rodlets (hydrophobins) and pigments. After UV/NH2Cl inactivation, the degree of cell membrane damage and intracellular reactive oxygen species were higher than that of UV alone. UV/NH2Cl had the advantages of high inactivation efficiency and inhibition of photoreactivation, which provides a new entry point for the disinfection of waterborne fungi.

Plasma Homocysteine Is a Predictive Factor for Accelerated Renal Function Decline and Chronic Kidney Disease in a Community-Dwelling Population.

BACKGROUND: Whether elevated plasma total homocysteine (tHcy) is a risk factor for the progression of kidney disease in general population has not been well established. The purpose of this study was to investigate the prognostic properties of plasma tHcy for renal function decrement and early chronic kidney disease (CKD) in community-dwelling populations with normal renal function at baseline. METHODS: A total of 1,426 participants were enrolled and followed for a median of 4.8 years (interquartile range, 4.5-5.2), and estimated glomerular filtration rate (eGFR) was evaluated. One main outcome was the rapid eGFR decline defined as a decline in eGFR of >3 mL/min per 1.73 m2 per year; the other was the new incidence of CKD. RESULTS: At the end of follow-up, the incidence of rapid eGFR decline and new-onset CKD was 20.7 and 5.6%, respectively. In multivariate linear regression analysis, age, central pulse pressure, fasting blood glucose, and concentration of tHcy were independent determinants of the change in eGFR. There was a graded association between tHcy quartiles and eGFR decline. Compared with participants with the lowest quartile of tHcy levels, those with the highest quartile had significantly increased risk for rapid eGFR decline (adjusted odds ratio [aOR] = 1.81; 95% confidence interval [CI]: 1.25-2.94) and new onset of CKD (adjusted hazard ratio = 4.29; 95% CI: 1.42-12.99) after adjusting for various confounders. Similarly, significant associations were also found when baseline tHcy was classified as hyperhomocysteinemia (>15 µmol/L) versus normal tHcy level (≤15 µmol/L). However, there was only association between the change in tHcy levels and new occurrence of CKD but not with rapid eGFR decline (aOR = 0.99, p = 0.613). CONCLUSIONS: In this prospective cohort of individuals from community-based population, elevated plasma tHcy emerged as an independent predictor of renal function decline and incident CKD, which might support selection of at-risk individuals.

The formation kinetics and control of biofilms by three dominant fungi species isolated from groundwater.

Filamentous fungi can enter drinking water supply systems in various ways, and exist in suspended or sessile states which threatens the health of individuals by posing a high risk of invasive infections. In this study, the biofilms formation kinetics of the three genera of fungal spores, Aspergillus niger (A. niger), Penicillium polonicum (P. polonicum) and Trichoderma harzianum (T. harzianum) isolated from the groundwater were reported, as well as the effects of water quality parameters were evaluated. In addition, the efficiency of low- concentrations of chlorine-based disinfectants (chlorine, chlorine dioxide and chloramine) on controlling the formation of fungal biofilms was assessed. The results showed that the biofilms formation of the three genera of fungi could be divided into the following four phases: induction, exponential, stationary and sloughing off. The optimum conditions for fungal biofilms formation were found to be neutral or weakly acidic at 28 °C with rich nutrition. In fact, A. niger, P. polonicum, and T. harzianum were not observed to form mature biofilms in actual groundwater within 120 hr. Carbon was found to have the maximum effect on the fungal biofilms formation in actual groundwater, followed by nitrogen and phosphorus. The resistance of fungal species to disinfectants during the formation of biofilms decreased in the order: A. niger > T. harzianum > P. polonicum. Chlorine dioxide was observed to control the biofilms formation with maximum efficiency, followed by chlorine and chloramine. Consequently, the results of this study will provide a beneficial understanding for the formation and control of fungal biofilms.

Enhanced nitrogen removal of aerobic denitrifier using extracellular algal organic matter as carbon source: application to actual reservoir water.

Man-made organic matter acting as carbon source for oligotrophic aerobic denitrification has been studied extensively, while less attention has been paid to the actual organic matter derived from drinking water reservoir. In this study, the effect of extracellular organic matter (EOM) released from Microcystis aeruginosa and Chlorella sp. and organic matter in actual reservoir water on aerobic denitrification performance of Acinetobacter johnsonii strain WGX-9 has been investigated, by measuring nitrogen removal and determining changes in the properties of organic matter. Results indicated that the Acinetobacter johnsonii strain WGX-9 showed effective nitrogen removal efficiency when cultural conditions were low C/N of 5, pH of 5-11, and low temperature of 8 °C. The nitrate removal efficiency with EOM as the sole carbon source was relatively higher than that with intracellular organic matter or natural organic matter as the sole carbon source. This is probably due to that EOM exerts a lower molecular weight and better ability of donating electrons. Besides, the findings can elucidate that nitrate and total organic matter removal efficiency with actual high-density algal water as the carbon source was higher than that with actual low-density algal water as the carbon source. This was attributed to that more EOM was released in high-density algal water, which highlighted the aerobic denitrification performance of Acinetobacter johnsonii strain WGX-9. This study will provide a reference for the application of aerobic denitrifier in drinking water reservoirs.

Quantitative Structure-Activity Relationship Study of Antioxidant Tripeptides Based on Model Population Analysis.

Due to their beneficial effects on human health, antioxidant peptides have attracted much attention from researchers. However, the structure-activity relationships of antioxidant peptides have not been fully understood. In this paper, quantitative structure-activity relationships (QSAR) models were built on two datasets, i.e., the ferric thiocyanate (FTC) dataset and ferric-reducing antioxidant power (FRAP) dataset, containing 214 and 172 unique antioxidant tripeptides, respectively. Sixteen amino acid descriptors were used and model population analysis (MPA) was then applied to improve the QSAR models for better prediction performance. The results showed that, by applying MPA, the cross-validated coefficient of determination (Q²) was increased from 0.6170 to 0.7471 for the FTC dataset and from 0.4878 to 0.6088 for the FRAP dataset, respectively. These findings indicate that the integration of different amino acid descriptors provide additional information for model building and MPA can efficiently extract the information for better prediction performance.

Body mass index is an independent predictive factor for kidney function evaluated by glomerular filtration rate in a community-dwelling population.

BACKGROUND: The effects of overweight and obesity on kidney function have since been identified and become a subject of increased study and concern. But the association between body mass index (BMI) and estimated glomerular filtration rate (eGFR) is not well characterized. The aim of this study was to determine the relationship between BMI and eGFR. METHODS: To better understand the relationship between BMI and kidney function, we investigated the association between BMI and eGFR using both the baseline BMI level and the follow-up eGFR level and investigated the relationship between the change in BMI and the change in eGFR in 1447 patients from a 4.8-year prospective study in Beijing, People's Republic of China. RESULTS: In multiple linear regression analysis, age, antihypertensive treatment, and BMI were negatively associated with the follow-up eGFR levels in all participants (R = -0.622, -0.926, and -0.266, respectively; P < 0.05), or in the elderly (R = -0.883, -1.035, and -0.630, respectively; P < 0.05); sex was found to be associated with the follow-up eGFR levels independently not only in all participants (R = 6.783; P < 0.001), but also in the elderly (R = 3.518; P < 0.05). In addition, the change in eGFR levels was positively related to age, the change in LDL-C, the change in TC, and the change in SBP, but negatively related to the change in BMI and the change in HDL-C (all P < 0.05). CONCLUSIONS: The present study clearly indicated that BMI is an independent predictive factor for kidney function evaluated by the eGFR level during a median 4.8 years of follow-up in Chinese population. LEVEL OF EVIDENCE: Level III, prospective cohort study.

High-density lipoprotein 3 cholesterol is a predictive factor for arterial stiffness: a community-based 4.8-year prospective study.

BACKGROUND: Although drug trials with niacin and cholesteryl ester transfer protein inhibitors that substantially increase high-density lipoprotein-cholesterol (HDL-C) failed to reduce the risk of coronary heart disease, HDL protection of the cardiovascular system cannot be easily denied. Hence, it may be HDL subfractions that are responsible for the long-held and consistent cardioprotective association of HDL. Arterial stiffness has been increasingly recognized as a strong predictor of subclinical vascular disease, atherosclerotic disease, and cardiovascular mortality. As the association of HDL subfractions and arterial stiffness is not well characterized, we aimed to determine the relations between these two entities in a community-based longitudinal Chinese population sample. METHODS: We evaluated the associations of plasma HDL2-C and HDL3-C subfractions with arterial stiffness measured using carotid-femoral pulse wave velocity (cf-PWV) and then multivariate logistic regression in 1447 subjects (mean age 61.3 years) from a community-based population in Beijing, China. RESULTS: After a median follow-up of 4.8 years, Pearson's correlation analysis revealed that HDL3-C was negatively associated with follow-up cf-PWV (r = -0.114; P = 0.001), and there was no correlation between HDL2-C and follow-up cf-PWV (r = -0.045; P = 0.181). In the multivariate logistic regression analysis, each standard deviation (SD) increase in HDL3-C was associated with a 1.490-increased likelihood of the presence of follow-up cf-PWV [odds ratio (per SD increase in HDL3-C) 1.490; 95% confidence interval 1.021-1.470; P = 0.039), whereas there was no relation between HDL2-C and follow-up cf-PWV. CONCLUSIONS: HDL3-C subfractions were significantly and inversely associated with arterial stiffness, suggesting that HDL subfractions are likely more important than HDL-C in preventing cardiovascular disease.

The association between Hepcidin and arterial stiffness in a community-dwelling population.

BACKGROUND: An association of hepcidin with cardiovascular (CV) disease and atherosclerosis has been reported in different patient groups. However, it has not been well described clinically the association between hepcidin and arterial stiffness. In this study,We analysed the possible mechanism of Hepcidin and arterial stiffness. METHODS: This article related measurements of plasma hepcidin and arterial stiffness (carotid-femoral pulse wave velocity [PWV]) in a community-based sample. RESULTS: After a median follow-up interval of 4.8 years, multiple linear regression analysis revealed that hepcidin was independently associated with carotid-femoral PWV (ß = 1.498, P < 0.001). In a multivariable linear regression analysis, HDL3-C levels were negatively and independently associated with hepcidin at baseline (ß = - 0.857, P = 0.024). HDL2-C was not associated with hepcidin at baseline (ß = - 1.121, P = 0.133). CONCLUSIONS: We found an association between baseline hepcidin and follow-up arterial stiffness that was independent of age, gender and other vascular risk factors. We also identified an association between hepcidin and HDL3-C at baseline, which indicates that the HDL3-C level may reflect the change in cholesterol efflux from peripheral arteries and partly explain the relationship between hepcidin and the change of arterial stiffness.

Oncological miR-182-3p, a Novel Smooth Muscle Cell Phenotype Modulator, Evidences From Model Rats and Patients.

OBJECTIVE: Vascular smooth muscle cell (VSMC) phenotype change is a hallmark of vascular remodeling, which contributes to atherosclerotic diseases and can be regulated via microRNA-dependent mechanisms. We recently identified that asymmetrical dimethylarginine positively correlates to vascular remodeling-based diseases. We hypothesized that asymmetrical dimethylarginine induces smooth muscle cell (SMC) phenotypic change via a microRNA-dependent mechanism. APPROACH AND RESULTS: Microarray analysis enabled the identification of downregulation of miR-182-3p in asymmetrical dimethylarginine-treated human aortic artery SMCs. The myeloid-associated differentiation marker (MYADM) was identified as the downstream target of miR-182-3p and implicated to contribute to miR-182-3p knockdown-mediated SMC phenotype change, which was evidenced by the increased proliferation and migration and reduced expression levels of phenotype-related genes in human aortic artery SMCs through the ERK/MAP (extracellular signal-regulated kinase/mitogen-activated protein) kinase-dependent mechanism. When inhibiting MYADM in the presence of miR-182-3p inhibitor or overexpressing MYADM in the presence of pre-miR-182-3p, human aortic artery SMCs were reversed to the differentiation phenotype. In vivo, adeno-miR-182-3p markedly suppressed carotid neointimal formation by using balloon-injured rat carotid artery model, specifically via decreased MYADM expression, whereas adeno-miR-182-3p inhibitor significantly promoted neointimal formation. Atherosclerotic lesions from patients with high asymmetrical dimethylarginine plasma levels exhibited decreased miR-182-3p expression levels and elevated MYADM expression levels. CONCLUSIONS: miR-182-3p is a novel SMC phenotypic modulator by targeting MYADM.

Triglycerides are a predictive factor for arterial stiffness: a community-based 4.8-year prospective study.

BACKGROUND: Epidemiological studies have disclosed an independent effect of triglycerides on coronary heart disease despite achievement of low-density lipoprotein cholesterol goals with statin therapy. Arterial stiffness has been increasingly recognized as a strong predictor of cardiovascular disease and atherosclerotic disease. The association between triglycerides and arterial stiffness is not well characterized. We aimed to determine the relationship between triglycerides and arterial stiffness in a community-based longitudinal sample from Beijing, China. METHODS: We related levels of plasma TGs to measures of arterial stiffness (carotid-femoral pulse wave velocity [PWV] and carotid-radial PWV) in 1447 subjects (mean age, 61.3 years) from a community-based population in Beijing, China. RESULTS: After a median follow-up interval of 4.8 years, multiple linear regression analysis revealed that TGs were independently associated with carotid-femoral PWV (ß = 0.747, P < 0.001) and carotid-radial PWV (ß = 0.367, P = 0.001). In the group older than 65 years, the association between baseline TG levels and follow-up carotid-femoral PWV (ß = 1.094, P = 0.001) and carotid-radial PWV (ß = 0.524, P = 0.002) were strengthened. In forward stepwise multivariate logistic regression analysis, every SD increase in TGδ was associated with a 1.296-increased likelihood of the presence of carotid-femoral PWVδII (OR [per SD increase in TGδ]: 1.296; 95% CI: 1.064 ~ 1.580; P = 0.010) in Model 2, whereas the relationship between TGδ and carotid-radial PWVδII disappeared. In addition, the relationship was strengthened between TGδ and the presence of carotid-femoral PWVδII (OR 1.526, 95% CI: 1.088-2.141, P = 0.014) in the group older than 65 years but not carotid-radial PWVδII. No association was noted in subjects younger than 65 years. CONCLUSIONS: Lower triglyceride levels were significantly associated with decreases in carotid-femoral PWV, indicating that achieving low TG levels may be an additional therapeutic consideration in subjects with atherosclerotic disease.

The improved resistance of germinated spores to ultraviolet irradiation: Comparison with chlorine.

Fungi outbreaks in water will include a series of processes, including spore aggregation, germination, biofilm, and finally present in a mixed state in the aquatic environment. More attention is paid to the control of dispersed fungal spores, however, there was little knowledge of the control of germinated spores. This study investigated the inactivation kinetics and mechanism of ultraviolet (UV) treatment for fungal spores with different germination percentages compared with dormant spores. The results indicated that the inactivation rate constants (k) of spores with 5%-45% germination were 0.0278-0.0299 cm2/mJ for Aspergillus niger and 0.0588-0.0647 cm2/mJ for Penicillium polonicum, which were lower than those of dormant spores. It suggested that germinated spores were more tolerant to UV irradiation than dormant spores, and it may be due to the defensive barrier (upregulated pigments) and some reductive substance (upregulated enoyl reductase) by absorbing UV or reacting with reactive oxygen species according to transcriptome analysis. Compared to dormant spores, the k-UV of germinated spores decreased by 18.17%-26.56% for Aspergillus niger, which was less than k-chlorine (62.33%-69.74%). A slighter decrease in k-UV showed UV irradiation can efficiently control fungi contamination, especially when dormant spores and germinated spores coexisted in actual water systems. This study indicates that more attention should be paid to germinated spores.

Changes of characteristics and disinfection by-products formation potential of intracellular organic matter with different molecular weight in metalimnetic oxygen minimum.

Metalimnetic oxygen minimum (MOM) occurs in reservoirs or lakes due to stratification and algal blooms, which has low dissolved oxygen (DO) levels and leads to the deterioration of water quality. The transformation mechanism and the impact on the water quality of intracellular organic matter (IOM) derived from algae are poorly understood under MOM conditions. In this study, IOM extracted by Microcystis aeruginosa was divided into five components according to molecular weight (MW), and the changes of characteristics and correlated disinfection by-products formation potential (DBPFP) were analyzed and compared under MOM conditions. The removal efficiency of dissolved organic carbon (DOC) in the <5 kDa fraction (66.6%) was higher than that in the >100 kDa fraction (41.8%) after a 14-day incubation under MOM conditions. The same tendency also occurred in Fmax and DBPFP. The decrease in Fmax was mainly due to the decline in tryptophan-like and tyrosine-like for all IOM fractions. The diversity of microorganisms degrading the MW > 100 kDa fraction was lower than others. Besides low MW fractions, these findings indicated that more attention should be paid to high MW fractions which were resistant to biodegradation under MOM conditions during water treatment.

The aggregation characteristics of Aspergillus spores under various conditions and the impact on LPUV inactivation: Comparisons with chlorine-based disinfection.

Aggregation is the primary step prior to fungal biofilm development. Understanding the attributes of aggregation is of great significance to better control the emergence of waterborne fungi. In this study, the aggregation of Aspergills spores (A. flavus and A. fumigatus) under various salt, culture medium, and humic acid (HA) conditions was investigated for the first time, and the inactivation via low-pressure ultraviolet (LPUV) upon aggregated Aspergillus spores was also presented. The aggregation efficiency and size of aggregates increased over time and at low salt (NaCl and CaCl2) concentration (10 mM) while decreasing with the continuous increase of salt concentration (100 and 200 mM). Increasing the concentration of culture medium and HA promoted the aggregation of fungal spores. Spores became hydrated, swelled, and secreted more viscous substances during the growth period, which accelerated the aggregation process. Results also suggested that fungal spores aggregated more easily in actual water, posing a high risk of biohazard in real-life scenarios. Inactivation efficiency by LPUV decreased with higher aggregation degrees due to the protection from the damaged spores on the outer layer and the shielding of pigments in the cell wall. Compared to chlorine-based disinfection, the aggregation resulted in the extension of shoulder length yet neglectable change of inactivation rate constant under LPUV treatment. Further investigation of cell membrane integrity and intracellular reactive oxygen species was conducted to elucidate the difference in mechanisms between various techniques. This study provides insight into the understanding and controlling of the aggregation of fungal spores.

Investigation on epitaxial lateral overgrowth of InGaN/GaN multi-quantum-well nanowires.

To achieve semipolar InGaN/GaN multi-quantum-well (MQW) structure, we fabricate InGaN/GaN MQW nanowires by using a combination of selectively epitaxial lateral overgrowth and patterned GaN/sapphire substrate techniques. Basing on the SEM observations, the nanowires along different crystal orientation of GaN substrate have various surface morphologies. Furthermore, cathodoluminescence measurements exhibit the dependence of the emission peaks of InGaN quantum wells on the axial direction of nanowires, being mainly attributed to the change of the morphology situation of the side facet. The shift of the peaks is larger than 30 nm as the axial direction of a nanowire varies between [1120] and [1100].

Occurrence and control of fungi in water: New challenges in biological risk and safety assurance.

Recently, the contamination of fungi in water has aroused widespread concern, which will pose a threat to water quality and safety, and raise diseases risk in the immunocompromised individuals. In this review, the characteristics and different physiological state of fungi in water are summarized. A comprehensive evaluation of the control efficiency and mechanism of waterborne fungi by the commonly used disinfection methods is provided as well. During the disinfection processes of chlorine, chlorine dioxide, chloramine and advanced disinfection processes (ADPs) such as O3-based ADPs and UV-based ADPs, the fungal spores firstly lost their culturability, followed by membrane integrity, and the intracellular reactive oxygen species level increased at the same time, eventually the fungal spores were completely inactivated. The security strategies of drinking water against the contamination of fungi are also discussed in terms of water sources, water treatment plants and pipe network. Finally, future researches need to be explored are proposed: the rapid detection methods, the production laws and control of mycotoxin, and the outbreak conditions of fungi in water. Specifically, exploring efficient, safe and economical technologies, especially ADPs, is still the main direction in the disinfection of fungi in future studies. This review can offer a comprehensive understanding on the occurrence and control of fungi in water to fill the knowledge gap and provide guidance for the future research.

The change of amino acids samples under metalimnetic oxygen minimum condition: Characterization and mechanism.

The metalimnetic oxygen minimum (MOM) is a common anaerobic phenomenon that occur between 5.00 and 40.00 m of reservoirs. Amino acids (AAs) are widely found in water, but their change in MOM remain unclear. In this study, four AAs with different side chain groups were selected to explore the change of their samples and related disinfection by-products formation potential (DBPFPs) under MOM condition. The results showed that the final degradation rate of dissolved organic carbon and dissolved organic nitrogen of four AAs samples were 11.71%-59.87% and 26.50%-100.00% under MOM condition. Aspartic acid samples were the easiest to be degraded, whereas glycine samples were the opposite. While the total fluorescence intensity increased by 6.30%-113.40% for the appearance of tryptophan-like substance. The total DBPFPs of glutamic acid, arginine and aspartic acid samples were finally decreased by 4.73%, 8.00% and 98.88% (glycine sample increased by 2.30 times). Compared with the surface condition, the degradation of AAs samples and the change of DBPFPs were significantly inhibited under MOM condition. In addition, the diversities of bacterial communities were significantly reduced under MOM condition, which was very unfavorable to the degradation of AAs samples, and in turn affected the control of DBPs and deteriorated the water quality.

The formation of double metalimnetic oxygen minima in a drinking water reservoir and its influence on bacterial community.

Metalimnetic oxygen minima has been reported in many lakes and reservoirs, but the double metalimnetic oxygen minima (DMOM) is so far poorly understood. In this work, we first reported DMOM in the Sanhekou Reservoir, and investigated its formation reason and influence on the bacterial community composition (BCC). The results showed that the two anaerobic layers were formed in DMOM, located at 10 m and 45 m approximately. The rapid water storage process and thermal stratification resulted in the double metalimnions. Algal accumulation, decomposition and oxygen consumption in these regions during the sedimentation process eventually leaded to the formation of DMOM. Water temperature and DO gradients made outstanding contributions to the spatiotemporal environmental heterogeneity and significantly affected the BCC. Depending on the distribution of dissolved oxygen (DO), the storage process could be divided into three periods: DMOM, single MOM period and mixed period. Exiguobacterium and Ralstonia were dominated in DMOM due to the soil discharge and plant decomposition. Besides, BCC presented the largest vertical difference in DMOM and existed the interlayer-similar phenomenon (BCC in the two anaerobic layers were more similar). This study explained the formation of DMOM and its influence on BCC, which was helpful to understand the response of BCC to the storage process and unique DO structure in a moderate eutrophication reservoir.

Combination therapy improves exercise capacity and reduces risk of clinical worsening in patients with pulmonary arterial hypertension: a meta-analysis.

BACKGROUND: Clinical studies on combination therapy in patients with pulmonary arterial hypertension (PAH) revealed mixed results. AIMS: The aim of the present meta-analysis was to evaluate the effect of combination therapy on exercise capacity [measured with 6-minute walk distance (6MWD)] and clinical worsening in PAH patients. METHODS: We identified trials of importance from the Cochrane Library, EMBASE, and PUBMED databases, reviews, and reference lists of relevant articles. We calculated risk ratios for dichotomous data and weighted mean differences, with 95% confidence intervals (CIs), for net changes in 6MWD. RESULTS: Seven trials with a total of 768 patients (386 patients in the combination treatment group and 382 patients in the monotherapy group) were included in the meta-analysis. Compared with the monotherapy group, combination therapy increased 6MWD by 21.59 meters (weighted mean difference 21.59 m, 95% CI of 13.25-29.93; P < 0.001) and reduced the risk of clinical worsening (risk ratio: 0.43, 95% CI: 0.26-0.72, P = 0.001). For both outcomes, no significant heterogeneity and publication bias were found. CONCLUSION: Compared with monotherapy, combination therapy improves exercise capacity and reduces the risk of clinical worsening in PAH patients. In future studies, more large randomized controlled trials should be designed to adequately assess the efficacy and safety of combination therapy.

Association Between Dopaminergic Medications and the Evolution of REM Sleep Behavior Disorder in Parkinson's Disease.

REM sleep behavior disorder (RBD) is closely associated with Parkinson's disease (PD), however, the influence of dopaminergic replacement therapy (DRT) on the clinical course of RBD in PD remains less understood. The objective of our study is to investigate how DRTs modify the evolution of RBD in a longitudinal cohort study of initially de novo PD patients. Four hundred and five drug-naive patients with early-stage PD were included. RBD symptoms were assessed using the 10-item RBD Screening Questionnaire (RBDSQ) at baseline and during the 5-year follow-up. A generalized estimating equation was used to examine predictors of the evolution of RBD symptoms. For patients without baseline pRBD, patients on levodopa treatment showed a greater increase in RBDSQ scores than those not on levodopa treatment, and the increase in RBDSQ scores was significantly correlated with the levodopa-LEDD. Moreover, the changes in RBDSQ scores at a given post-baseline visit were significantly associated with the use of levodopa (OR = 1.875, p = 0.008) and the combined use of levodopa and DA (OR = 2.188, p = 0.012), as well as the levodopa-LEDD (OR = 1.001, p = 0.005) at that visit. The use of DA alone or the DA-LEDD was not a significant predictor of changes in RBDSQ scores. Similarly, a conversion from pRBD negative to pRBD positive was significantly associated with levodopa-LEDD (OR = 1.001, p = 0.014) but not DA-LEDD. Together, these finding implicated that the use of levodopa may act as a contributing factor to the increasing prevalence of RBD after the onset of PD, suggesting different mechanisms underlying prodromal RBD and late-onset RBD.