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BACKGROUND: Previous studies have reported associations between obstructive sleep apnea (OSA) and several mental disorders. However, further research is required to determine whether these associations are causal. Therefore, we evaluated the bidirectional causality between the genetic liability for OSA and nine mental disorders by using Mendelian randomization (MR). METHOD: We performed two-sample bidirectional MR of genetic variants for OSA and nine mental disorders. Summary statistics on OSA and the nine mental disorders were extracted from the FinnGen study and the Psychiatric Genomics Consortium. The primary analytical approach for estimating causal effects was the inverse-variance weighted (IVW), with the weighted median and MR Egger as complementary methods. The MR Egger intercept test, Cochran's Q test, Rucker's Q test, and the MR pleiotropy residual sum and outlier (MR-PRESSO) test were used for sensitivity analyses. RESULT: MR analyses showed that genetic liability for major depressive disorder (MDD) was associated with an increased risk of OSA (odds ratio [OR] per unit increase in the risk of MDD, 1.29; 95% CI, 1.11-1.49; P < 0.001). In addition, genetic liability for OSA may be associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) (OR = 1.26; 95% CI, 1.02-1.56; p = 0.032). There was no evidence that OSA is associated with other mental disorders. CONCLUSION: Our study indicated that genetic liability for MDD is associated with an increased risk of OSA without a bidirectional relationship. Additionally, there was suggestive evidence that genetic liability for OSA may have a causal effect on ADHD. These findings have implications for prevention and intervention strategies targeting OSA and ADHD. Further research is needed to investigate the biological mechanisms underlying our findings and the relationship between OSA and other mental disorders.
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Transtorno Depressivo Maior , Análise da Randomização Mendeliana , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/genética , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtornos Mentais/genética , Transtornos Mentais/epidemiologia , Predisposição Genética para Doença/genéticaRESUMO
BACKGROUND: Since the twenty-first century, the prevalence of diabetes has risen globally year by year. In Gansu Province, an economically underdeveloped province in northwest China, the cost of drugs for diabetes patients accounted for one-third of their total drug costs. To fundamentally reduce national drug expenditures and the burden of medication on the population, the relevant departments of government have continued to reform and improve drug policies. This study aimed to analyse long-term trends in antidiabetic drug use and expenditure in Gansu Province from 2012 to 2021 and to explore the role of pharmaceutical policy. METHODS: Data were obtained from the provincial centralised bidding and purchasing (CBP) platform. Drug use was quantified using the anatomical therapeutic chemistry/defined daily dose (ATC/DDD) method and standardised by DDD per 1000 inhabitants per day (DID), and drug expenditure was expressed in terms of the total amount and defined daily cost (DDC). Linear regression was used to analyse the trends and magnitude of drug use and expenditure. RESULTS: The overall trend in the use and expenditure of antidiabetic drugs was on the rise, with the use increasing from 1.04 in 2012 to 16.02 DID in 2021 and the expenditure increasing from 48.36 in 2012 to 496.42 million yuan in 2021 (from 7.66 to 76.95 million USD). Some new and expensive drugs changed in the use pattern, and their use and expenditure shares (as the percentage of all antidiabetic drugs) increased from 0 to 11.17% and 11.37%, but insulins and analogues and biguanides remained the most used drug class. The DDC of oral drugs all showed a decreasing trend, but essential medicines (EMs) and medical insurance drugs DDC gradually decreased with increasing use. The price reduction of the bid-winning drugs was over 40%, and the top three drugs were glimepiride 2mg/30, acarbose 50mg/30 and acarbose 100mg/30. CONCLUSIONS: The implementation of pharmaceutical policies has significantly increased drug use and expenditure while reducing drug prices, and the introduction of novel drugs and updated treatment guidelines has led to changes in use patterns.
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Diabetes Mellitus , Transtornos Relacionados ao Uso de Substâncias , Humanos , Hipoglicemiantes/uso terapêutico , Gastos em Saúde , Acarbose , Hospitais Públicos , Custos de Medicamentos , China/epidemiologiaRESUMO
Non-radical activation of persulfate (PS) by photocatalysts is an effective approach for removing organic pollutants from aqueous environments. In this study, a novel Bi2O3/BiO1.3I0.4 heterojunction was synthesized using a facile solvothermal approach and used for the first time for non-radical activation of PS to degrade propranolol (PRO) in the presence of visible light. The findings found that the degradation rate of PRO in the Bi2O3/BiO1.3I0.4/PS system was significantly increased from 19% to more than 90% within 90 min compared to the Bi2O3/BiO1.3I0.4 system. This indicated that the composite system exerted an excellent synergistic effect between the photocatalyst and the persulfate-based oxygenation. Quenching tests and electron paramagnetic resonance demonstrated that the non-radical pathway with singlet oxygen as the active species played a major role in the photocatalytic process. The existence of photo-generated holes during the reaction could also be directly involved in the oxidation of pollutants. Meanwhile, a possible PRO degradation pathway was also proposed. Furthermore, the impacts of pH, humic acid and common anions on the PRO degradation by the Bi2O3/BiO1.3I0.4/PS were explored, and the system's stability and reusability were also studied. This study exhibits a highly productive catalyst for PS activation via a non-radical pathway and provides a new idea for the degradation of PRO.
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Poluentes Ambientais , Propranolol , Oxigênio Singlete , Oxirredução , LuzRESUMO
The severe shuttle effect and the depletion of active sulfur result in performance deterioration, presenting two formidable issues that must be overcome to achieve high-mass-loading lithium-sulfur batteries. Herein, we reported a composite separator by introducing carbon photonic crystals with a hierarchically ordered porous structure on a commercial separator. The ordered structure and interconnected hierarchical macro-meso-micropore network of the composite separator facilitate efficient trapping of polysulfides and rapid transport of lithium ions. The high ion diffusivity promotes the conversion of polysulfides enhancing sulfur utilization and mitigating the occurrence of "dead sulfur" on the surface of the separator. Impressively, under a high sulfur loading of 3 mg cm-2, the lithium-sulfur battery with the composite separator displayed a high reversible capacity of 1582 mA h g-1 at 0.1 C and an excellent long-term cycling performance with a decay rate of as low as 0.033% per cycle over 1500 cycles at 1 C. Surprisingly, the battery represented a high reversible capacity of 935 mA h g-1 at 0.2 C even at a sulfur loading of 6.71 mg cm-2. The design of the composite separator underscores the pivotal role of carbon architecture in improving battery performance and brings a bright prospect to enable the commercialization of high-mass-loading lithium-sulfur batteries.
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Background: Economic data on congenital heart disease are scarce in economically underdeveloped areas of China. Therefore, this study aimed to shed light on the level and changing trend of congenital heart disease inpatients' economic burden in underdeveloped areas. Method: This study used a multi-stage stratified cluster sampling method to select 11,055 inpatients with congenital heart disease from 197 medical and health institutions in Gansu Province. Their medical records and expenses were obtained from the Hospital Information System. Univariate analysis was conducted using the rank sum test and Spearman rank correlation. Quantile regression and random forest were used to analyze the influencing factors. Results: From 2015 to 2020, the average length of stay for congenital heart disease patients in Gansu Province was 10.09 days, with an average inpatient cost of USD 3,274.57. During this period, the average inpatient costs per time increased from USD 3,214.85 to USD 3,403.41, while the average daily inpatient costs increased from USD 330.05 to USD 376.56. The average out-of-pocket costs per time decreased from USD 2,305.96 to USD 754.77. The main factors that affected the inpatient costs included length of stay, cardiac procedure, proportion of medications, age, and hospital level. Conclusion: Congenital heart disease causes a significant economic burden on both families and society. Therefore, to further reduce the patient's financial burden, the length of stay should be reasonably reduced, and the rational distribution of medical resources should be continuously promoted to ensure equitable access to healthcare services.
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Cardiopatias Congênitas , Hospitalização , Humanos , Pacientes Internados , Gastos em Saúde , China/epidemiologia , Cardiopatias Congênitas/epidemiologiaRESUMO
Metals have been proved to be one of risk factors for chronic kidney disease (CKD) and diabetes, but the effect of mixed metal co-exposure and potential interaction between metals are still unclear. We assessed the urine and whole blood levels of cadmium (Cd), manganese (Mn), lead (Pb), mercury (Hg), and renal function in 3080 adults from National Health and Nutrition Survey (NHANES) (2011-2018) to explore the effect of mixed metal exposure on CKD especially in people with type 2 diabetes mellitus (T2DM). Weighted quantile sum regression model and Bayesian Kernel Machine Regression model were used to evaluate the overall exposure impact of metal mixture and potential interaction between metals. The results showed that the exposure to mixed metals was significantly associated with an increased risk of CKD in blood glucose stratification, with the risk of CKD being 1.58 (1.26,1.99) times in urine and 1.67 (1.19,2.34) times in whole blood higher in individuals exposed to high concentrations of the metal mixture compared to those exposed to low concentrations. The effect of urine metal mixture was elevated magnitude in stratified analysis. There were interactions between urine Pb and Cd, Pb and Mn, Pb and Hg, Cd and Mn, Cd and Hg, and blood Pb and Hg, Mn and Cd, Mn and Pb, Mn and Hg on the risk of CKD in patients with T2DM and no significant interaction between metals was observed in non-diabetics. In summary, mixed metal exposure increased the risk of CKD in patients with T2DM, and there were complex interactions between metals. More in-depth studies are needed to explore the mechanism and demonstrate the causal relationship.
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Exposição Ambiental , Inquéritos Nutricionais , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/urina , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Exposição Ambiental/efeitos adversos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Cádmio/sangue , Cádmio/urina , Cádmio/efeitos adversos , Cádmio/toxicidade , Fatores de Risco , Chumbo/sangue , Chumbo/urina , Chumbo/toxicidade , Metais Pesados/sangue , Metais Pesados/urina , Metais Pesados/efeitos adversos , Metais Pesados/toxicidade , Idoso , Metais/urina , Metais/sangue , Metais/efeitos adversos , Manganês/urina , Manganês/sangue , Manganês/efeitos adversos , Teorema de BayesRESUMO
The multi-domain protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) recruits DNMT1 for DNA methylation maintenance during DNA replication. Here, we show that MOF (males absent on the first) acetylates UHRF1 at K670 in the pre-RING linker region, whereas HDAC1 deacetylates UHRF1 at the same site. We also identify that K667 and K668 can also be acetylated by MOF when K670 is mutated. The MOF/HDAC1-mediated acetylation in UHRF1 is cell-cycle regulated and peaks at G1/S phase, in line with the function of UHRF1 in recruiting DNMT1 to maintain DNA methylation. In addition, UHRF1 acetylation significantly enhances its E3 ligase activity. Abolishing UHRF1 acetylation at these sites attenuates UHRF1-mediated H3 ubiquitination, which in turn impairs DNMT1 recruitment and DNA methylation. Taken together, these findings identify MOF as an acetyltransferase for UHRF1 and define a mechanism underlying the regulation of DNA methylation maintenance through MOF-mediated UHRF1 acetylation.
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Metilação de DNA , Histonas , Masculino , Humanos , Metilação de DNA/genética , Histonas/metabolismo , Acetilação , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Ubiquitinação , DNA (Citosina-5-)-Metiltransferase 1/metabolismoRESUMO
There is evidence to support the links between lead and cadmium exposure with hypertension and also with leukocyte telomere length (LTL). The objective of this study is to investigate the role that LTL may play in the relationship between lead and cadmium exposure and hypertension. This study consisted of 3718 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Logistic regression was used to analyze the relationship between blood metals with hypertension, and the mediating model was used to evaluate the mediating effect of LTL. In the fully adjusted model, both blood lead and cadmium ln-transformed concentrations were significantly positively associated with hypertension risk, as were all quartiles of blood lead. Additionally, we observed positive linear dose-response relationships with hypertension by restricted cubic spline analysis (both p overall < 0.001, p non-linear = 0.3008 for lead and p non-linear = 0.7611 for cadmium). The ln-transformed blood lead and cadmium concentrations were associated with shorter LTL. LTL was inversely related to hypertension and the OR was 0.65 (95% CI: 0.47 to 0.89). Furthermore, LTL had mediating effects on the associations of blood lead and cadmium with hypertension risk, and the mediation proportions were 2.25% and 4.20%, respectively. Our findings suggested that exposure to lead and cadmium raised the risk of hypertension, while LTL played as a mediating factor.
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Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are associated with adverse health effects. This study examined the trend of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) levels in individuals with and without pre-existing comorbidities. We analyzed the characteristics of 13,887 participants across nine U.S. NHANES cycles (1999-2000 to 2017-2018) and calculated the geometric mean (GM) of PFOA and PFOS levels, standardized by sex and age. A joinpoint regression model was used to analyze the temporal trends of serum PFOA and PFOS levels. We observed declining PFOA and PFOS serum levels among adults in NHANES from 1999-2000 to 2017-2018. Serum PFOA and PFOS concentrations were higher in men, smokers, and individuals with pre-existing CKD, hyperlipidemia, CVD, and cancer. We observed faster decline rates in PFOA levels among individuals with diabetes and CKD and faster decline rates in PFOS levels among individuals with diabetes and those without CKD. This study provided evidence of varying levels and changing trends of PFOA and PFOS between groups with and without established chronic disease, highlighting the role of environmental chemicals in the onset and development of chronic diseases.