Predicting Mutational Effects on Ca2+-Activated Chloride Conduction of TMEM16A Based on a Simulation Study.

The dysfunction and defects of ion channels are associated with many human diseases, especially for loss-of-function mutations in ion channels such as cystic fibrosis transmembrane conductance regulator mutations in cystic fibrosis. Understanding ion channels is of great current importance for both medical and fundamental purposes. Such an understanding should include the ability to predict mutational effects and describe functional and mechanistic effects. In this work, we introduce an approach to predict mutational effects based on kinetic information (including reaction barriers and transition state locations) obtained by studying the working mechanism of target proteins. Specifically, we take the Ca2+-activated chloride channel TMEM16A as an example and utilize the computational biology model to predict the mutational effects of key residues. Encouragingly, we verified our predictions through electrophysiological experiments, demonstrating a 94% prediction accuracy regarding mutational directions. The mutational strength assessed by Pearson's correlation coefficient is -0.80 between our calculations and the experimental results. These findings suggest that the proposed methodology is reliable and can provide valuable guidance for revealing functional mechanisms and identifying key residues of the TMEM16A channel. The proposed approach can be extended to a broad scope of biophysical systems.

Refining risk stratification in paediatric B-acute lymphoblastic leukaemia: Combining IKZF1plus and Day 15 MRD positivity.

This study investigates the potential utility of IKZF1 deletion as an additional high-risk marker for paediatric acute lymphoblastic leukaemia (ALL). The prognostic impact of IKZF1 status, in conjunction with minimal/measurable residual disease (MRD), was evaluated within the MRD-guided TPOG-ALL-2013 protocol using 412 newly diagnosed B-ALL patients aged 1-18. IKZF1 status was determined using multiplex ligation-dependent probe amplification. IKZF1 deletions, when co-occurring with CDKN2A, CDKN2B, PAX5 or PAR1 region deletions in the absence of ERG deletions, were termed IKZF1plus. Both IKZF1 deletion (14.6%) and IKZF1plus (7.8%) independently predicted poorer outcomes in B-ALL. IKZF1plus was observed in 4.1% of Philadelphia-negative ALL, with a significantly lower 5-year event-free survival (53.9%) compared to IKZF1 deletion alone (83.8%) and wild-type IKZF1 (91.3%) (p < 0.0001). Among patients with Day 15 MRD ≥0.01%, provisional high-risk patients with IKZF1plus exhibited the worst outcomes in event-free survival (42.0%), relapse-free survival (48.0%) and overall survival (72.7%) compared to other groups (p < 0.0001). Integration of IKZF1plus and positive Day 15 MRD identified a subgroup of Philadelphia-negative B-ALL with a 50% risk of relapse. This study highlights the importance of assessing IKZF1plus alongside Day 15 MRD positivity to identify patients at increased risk of adverse outcomes, potentially minimizing overtreatment.

Establishment of an in vitro model of monocyte-like THP-1 cells for trained immunity induced by bacillus Calmette-Guérin.

BACKGROUND: Mycobacteria bloodstream infections are common in immunocompromised people and usually have disastrous consequences. As the primary phagocytes in the bloodstream, monocytes and neutrophils play critical roles in the fight against bloodstream mycobacteria infections. In contrast to macrophages, the responses of monocytes infected with the mycobacteria have been less investigated. RESULTS: In this study, we first established a protocol for infection of non-adherent monocyte-like THP-1 cells (i.e. without the differentiation induced by phorbol 12-myristate 13-acetate (PMA) by bacillus Calmette-Guérin (BCG). Via the protocol, we were then capable of exploring the global transcriptomic profiles of non-adherent THP-1 cells infected with BCG, and found that NF-κB, MAPK and PI3K-Akt signaling pathways were enhanced, as well as some inflammatory chemokine/cytokine genes (e.g. CCL4, CXCL10, TNF and IL-1ß) were up-regulated. Surprisingly, the Akt-HIF-mTOR signaling pathway was also activated, which induces trained immunity. In this in vitro infection model, increased cytokine responses to lipopolysaccharides (LPS) restimulation, higher cell viability, and decreased Candida albicans loads were observed. CONCLUSIONS: We have first characterized the transcriptomic profiles of BCG-infected non-adherent THP-1 cells, and first developed a trained immunity in vitro model of the cells.

Influence Mechanism of Interfacial Oxidation of Li3YCl6 Solid Electrolyte on Reduction Potential.

Halide-based solid electrolytes are promising candidates for all solid-state lithium-ion batteries (ASSLBs) due to their high ionic conductivity, wide electrochemical window, and excellent chemical stability with cathode materials. However, when tested in practice, their intrinsic electrochemical stability windows do not well match the conditions for stable operation of ASSBs. Existing literature reports halide-based ASSBs that still operate well outside the electrochemical stability window, while ASSBs that do not operate within the window are not well studied or the studies are based on the cathode material interface. In this study, we aim to elucidate the mechanism behind all-solid-state battery failure by investigating how the reduction potential of Li3YCl6 solid-state electrolyte itself changes under overcharging conditions. Our findings demonstrate that in Li-In|Li3YCl6|Li3YCl6-C half-cells during the first state of charge, Cl ions participate in charge compensation, resulting in a depletion of ligands. This phenomenon significantly affects the reduction potential of Y3+, causing it to be reduced to Y2Cl3 and ultimately to Y0 at conditions far exceeding its actual reduction potential. Furthermore, we analyze the interfacial impedance induced by this process and propose a novel perspective on battery failure.

N-Alkoxyphthalimides as Nitrogen Electrophiles to Construct C-N Bonds via Reductive Cross-Coupling.

N-Alkoxyphthalimides, one kind of phthalimide derivative, have great importance in synthesis, mainly used as free radical precursors. While the phthalimide unit, for a long time, was treated as part of the waste stream. Construction of C-N bonds has always been a hot spot, especially in reductive cross-coupling. Herein, a nickel-catalyzed reductive cross-coupling reaction of N-methoxyphthalimides with alkyl halides is described, where N-methoxyphthalimides serve as nitrogen electrophiles. This tactic provides a new approach to construct C-N bonds under mild neutral conditions. Alkyl chlorides, bromides, iodides, and sulfonates are all fit to this transformation. Moreover, the reaction could tolerate a broad substrate scope, especially base-sensitive functional groups (boron or silicon groups), as well as competitive nucleophilic groups (phenols and amides), which are incompatible with traditional Gabriel synthesis under basic conditions, demonstrating a complementary role of this work to Gabriel synthesis.

A sensitive monoclonal antibody-based ELISA integrated with immunoaffinity column extraction for the detection of zearalenone in food and feed samples.

Zearalenone (ZEN) is one of the most toxic mycotoxins widely found in agricultural products. In this study, a sensitive enzyme-linked immunosorbent assay (ELISA) integrated with immunoaffinity column extraction for the detection of ZEN in food and feed samples was developed. A ZEN derivative containing a carboxylic group was first synthesized and then linked to bovine serum albumin (BSA). The formed ZEN-BSA conjugate was used as the immunogen for the production of the monoclonal antibody (mAb) against ZEN. The hybridoma clones (1G5) capable of secreting antibodies against ZEN were successfully selected. Based on this mAb, the IC50 and LOD of the ELISA for ZEN were 0.37 ng mL-1 and 0.04 ng mL-1, respectively, which were 1.6-308.1 times lower than those in the published ELISAs, indicating the high sensitivity of our assay. There was no cross-reactivity of the mAb with other four mycotoxins (patulin, AFB1, DON, and OTA). Due to the high similarity in molecular structures among ZEN and its homologs (α-zearalanol, ß-zearalanol, zearalanone, α-zearalenol, ß-zearalenol), the CR values of the mAb with the homologs were within 3.59%-105.71%. Taking advantage of plenty of mAb, the immunoaffinity column was prepared by immobilizing the mAb on Sepharose-4B gel and filling it into an SPE column. ZEN spiked samples (corn, wheat, feed) were extracted using an immunoaffinity column and measured by ELISA and HPLC-FLD simultaneously. The recoveries of the ELISA for ZEN in the spiked samples were 92.46-105.48% with RSDs of 4.87-10.11%. A good correlation between ELISA (x) and HPLC-FLD (y) with the linear regression equation y = 1.0589x + 1.43815 (R2 = 0.998, n = 6) was obtained. To verify the applicability, the proposed ELISA was also applied to some real samples randomly collected from a local market. It was proven that the newly produced mAb-based ELISA was a feasible and sensitive method for the detection of ZEN in food and feed samples.

Co/Ce-MOF-Derived Oxygen Electrode Bifunctional Catalyst for Rechargeable Zinc-Air Batteries.

Improving the practicality of rechargeable zinc-air batteries relies heavily on the development of oxygen electrode catalysts that are low-cost, durable, and highly efficient in performing dual functions. In the present study, a catalyst with atomic Ce and Co distribution on a nitrogen-doped carbon substrate was prepared by doping the rare earth elements Ce and Co into a metal-organic framework precursor. Rare earth element Ce, known for its unique structure and excellent oxygen affinity, was utilized to regulate the catalytic activity. The catalyst prepared in this study demonstrated an exceptional electrocatalytic performance. At a current density of 10 mA cm-2, the catalyst exhibited an overpotential of 340 mV for the oxygen evolution reaction (OER), which was lower than that of commercial IrO2 (370 mV), while achieving a half-wave potential of 0.79 V for the process of oxygen reduction reaction (ORR), exhibiting a similar level of effectiveness as commercially accessible Pt/C catalysts (0.8 V). The catalyst's porous structure, interconnected three-dimensional carbon network, and large specific surface area are the factors contributing to the significant improvement in catalytic performance. Furthermore, in comparison to commercial Pt/C+IrO2, the catalyst exhibited good cycling stability and high efficiency in rechargeable zinc-air batteries.

Unraveling the Complexities of Toll-like Receptors: From Molecular Mechanisms to Clinical Applications.

Toll-like receptors (TLRs) are vital components of the innate immune system, serving as the first line of defense against pathogens by recognizing a wide array of molecular patterns. This review summarizes the critical roles of TLRs in immune surveillance and disease pathogenesis, focusing on their structure, signaling pathways, and implications in various disorders. We discuss the molecular intricacies of TLRs, including their ligand specificity, signaling cascades, and the functional consequences of their activation. The involvement of TLRs in infectious diseases, autoimmunity, chronic inflammation, and cancer is explored, highlighting their potential as therapeutic targets. We also examine recent advancements in TLR research, such as the development of specific agonists and antagonists, and their application in immunotherapy and vaccine development. Furthermore, we address the challenges and controversies surrounding TLR research and outline future directions, including the integration of computational modeling and personalized medicine approaches. In conclusion, TLRs represent a promising frontier in medical research, with the potential to significantly impact the development of novel therapeutic strategies for a wide range of diseases.

Biology and Therapeutic Properties of Mesenchymal Stem Cells in Leukemia.

This comprehensive review delves into the multifaceted roles of mesenchymal stem cells (MSCs) in leukemia, focusing on their interactions within the bone marrow microenvironment and their impact on leukemia pathogenesis, progression, and treatment resistance. MSCs, characterized by their ability to differentiate into various cell types and modulate the immune system, are integral to the BM niche, influencing hematopoietic stem cell maintenance and functionality. This review extensively explores the intricate relationship between MSCs and leukemic cells in acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and chronic lymphocytic leukemia. This review also addresses the potential clinical applications of MSCs in leukemia treatment. MSCs' role in hematopoietic stem cell transplantation, their antitumor effects, and strategies to disrupt chemo-resistance are discussed. Despite their therapeutic potential, the dual nature of MSCs in promoting and inhibiting tumor growth poses significant challenges. Further research is needed to understand MSCs' biological mechanisms in hematologic malignancies and develop targeted therapeutic strategies. This in-depth exploration of MSCs in leukemia provides crucial insights for advancing treatment modalities and improving patient outcomes in hematologic malignancies.

Advancements in Allergen Immunotherapy for the Treatment of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects individuals of all age groups, manifesting as a spectrum of symptoms varying from mild to severe. Allergen immunotherapy (AIT) involves the administration of allergen extracts and has emerged as a potential treatment strategy for modifying immune responses. Its pathogenesis involves epidermal barrier dysfunction, microbiome imbalance, immune dysregulation, and environmental factors. Existing treatment strategies encompass topical steroids to systemic agents, while AIT is under investigation as a potential immune-modifying alternative. Several studies have shown reductions in the severity scoring of atopic dermatitis (SCORAD) scores, daily rescue medication use, and visual analog scale (VAS) scores following AIT. Biomarker changes include increased IgG4 levels and decreased eosinophil counts. This review provides valuable insights for future research and clinical practice, exploring AIT as a viable option for the management of AD.

A Highly Sensitive and Group-Specific Enzyme-Linked Immunosorbent Assay (ELISA) for the Detection of AFB1 in Agriculture and Aquiculture Products.

Aflatoxins (AFs) including AFB1, AFB2, AFG1 and AFG2 are widely found in agriculture products, and AFB1 is considered one of the most toxic and harmful mycotoxins. Herein, a highly sensitive (at the pg mL-1 level) and group-specific enzyme-linked immunosorbent assay (ELISA) for the detection of AFB1 in agricultural and aquiculture products was developed. The AFB1 derivative containing a carboxylic group was synthesized and covalently linked to bovine serum albumin (BSA). The AFB1-BSA conjugate was used as an immunogen to immunize mice. A high-quality monoclonal antibody (mAb) against AFB1 was produced by hybridoma technology, and the mAb-based ELISA for AFB1 was established. IC50 and limit of detection (LOD) of the ELISA for AFB1 were 90 pg mL-1 and 18 pg mL-1, respectively. The cross-reactivities (CRs) of the assay with AFB2, AFG1, and AFG2 were 23.6%, 42.5%, and 1.9%, respectively, revealing some degree of group specificity. Corn flour, wheat flour, and crab roe samples spiked with different contents of AFB1 were subjected to ELISA procedures. The recoveries and relative standard deviation (RSD) of the ELISA for AFB1 in spiked samples were 78.3-116.6% and 1.49-13.21% (n = 3), respectively. Wheat flour samples spiked with the mixed AF (AFB1, AFB2, AFG1, AFG2) standard solution were measured by ELISA and LC-MS/MS simultaneously. It was demonstrated that the proposed ELISA can be used as a screening method for evaluation of AFs (AFB1, AFB2, AFG1, AFG2) in wheat flour samples.

Clinical impact of minimal residual disease and genetic subtypes on the prognosis of childhood acute lymphoblastic leukemia.

BACKGROUND: This study analyzed data from two consecutive protocols for children newly diagnosed with acute lymphoblastic leukemia (ALL) to determine the clinical impact of minimal/measurable residual disease (MRD) and recently identified tumor genetic subtypes. METHODS: Genetic subtypes were determined by sequential approaches including DNA indexing, reverse transcriptase-polymerase chain reaction, multiplex ligation-dependent probe amplification, and RNA-sequencing. MRD was assessed by flow cytometry. The Taiwan Pediatric Oncology Group TPOG-ALL-2013 study enrolled patients who received MRD-directed therapy. RESULTS: The 5-year event-free survival (EFS) and overall survival rates in the 2013 cohort were 77.8% and 86.9% compared to those of the 2002 cohort, which were 62.4% and 76.5%. Among patients treated with MRD-guided therapy, those with ETV6-RUNX1 fusion and high hyperdiploidy had the highest 5-year EFS (91.4% and 89.6%, respectively). The addition of dasatinib improved outcomes in patients with BCR-ABL1 ALL. Recently identified subtypes like DUX4-rearranged, ZNF384-rearranged, MEF2D-rearranged, and PAX5alt subtypes were frequently positive for MRD after remission induction, and these patients consequently received intensified chemotherapy. Treatment intensification according to the MRD improved the outcomes of patients presenting DUX4 rearrangements. In high-risk or very-high-risk subtypes, the TPOG-ALL-2013 regimen did not confer significant improvements compared to TPOG-ALL-2002, and the outcomes of BCR-ABL1-like, MEF2D-rearranged, and KMT2A-rearranged ALL subtypes (in addition to those of T-cell ALL) were not sufficiently good. Novel agents or approaches are needed to improve the outcomes for these patients. CONCLUSIONS: The TPOG-ALL-2013 study yielded outcomes superior to those of patients treated in the preceding TPOG-ALL-2002 study. This study provides important data to inform the design of future clinical trials in Taiwan. PLAIN LANGUAGE SUMMARY: MRD-directed therapy improved the outcomes for pediatric ALL, especially standard-risk patients. Genomic analyses and MRD might be used together for risk-directed therapy of childhood ALL. Our work provides important data to inform the design of future clinical trials in Taiwan.

Children with chronic myeloid leukaemia treated with front-line imatinib have a slower molecular response and comparable survival compared with adults: a multicenter experience in Taiwan.

BACKGROUND: The direct comparison of molecular responses of front-line imatinib (IM) monitored at the same laboratory between children and adults with chronic phase (CP) of chronic myeloid leukaemia (CML) had not been reported. In this multicenter study, we compared the landmark molecular responses and outcomes of paediatric and adult CML-CP cohorts treated with front-line IM in whom the BCR::ABL1 transcript levels were monitored at the same accredited laboratory in Taiwan. METHODS: Between June 2004 and July 2020, 55 newly diagnosed paediatric and 782 adult CML-CP patients, with molecular diagnosis and monitoring at the same reference laboratory in Taiwan, were enrolled. The criteria of 2020 European LeukemiaNet were applied to evaluate the molecular responses. RESULTS: By year 5, the cumulative incidences of IS <1%, MMR, MR4.0 and MR4.5 of paediatric patients were all significantly lower than those of adult patients (58 vs 75%, 48 vs 66%, 25 vs 44%, 16 vs 34%, respectively). The 10-year progression-free survival (PFS) (90%) and overall survival (OS) (94%) of paediatric patients did not differ from those (92%) of adult patients. CONCLUSIONS: We demonstrated the paediatric cohort had slower molecular responses to front-line IM and similar outcomes in 10-year PFS and OS in real-world practice.

Potential-Resolved Electrochemiluminescence Multiplex Immunoassay for Florfenicol and Chloramphenicol in a Single Sample.

The simultaneous detection of multiple antibiotic residues in food is of great significance for food safety. In this work, a novel dual-potential electrochemiluminescence (ECL) immunoassay was designed for the simultaneous detection of chloramphenicol and fluorfenicol residues in food. Ru@MOF was used as an anodic probe, and SnS2 QDs-PEI-Au-MoS2 was used as a cathodic probe. Notably, the coreactant for both luminophores was K2S2O8, avoiding interactions caused by different kinds of coreactants. Au nanoparticles functionalized with a nitrogen- and sulfur-doped graphene oxide-modified glassy carbon electrode to improve the electron transfer efficiency and provide a larger surface area for immobilization of antigen. The linear range for the detection of florfenicol was determined to be 0.1-1000 ng mL-1 with a detection limit of 0.03 ng mL-1, and the linear range for the detection of chloramphenicol was 0.01-1000 ng mL-1 with a detection limit of 3.2 pg mL-1 by recording the ECL responses at two different excitation potentials. The proposed immunoassay achieved a more stable recovery in the detection of actual samples and provided a new analytical method for the simultaneous detection of florfenicol and chloramphenicol residues with high sensitivity and specificity.

Localizing Oxygen Lattice Evolutions Eliminates Oxygen Release and Voltage Decay in All-Mn-Based Li-Rich Cathodes.

All-Mn-based Li-rich cathodes Li2 MnO3 have attracted extensive attention because of their cost advantage and ultrahigh theoretical capacity. However, the unstable anionic redox reaction (ARR), which involves irreversible oxygen releases, causes declines in cycling capacity and intercalation potential, thus hindering their practical applications. Here, it is proposed that introducing stacking-fault defects into the Li2 MnO3 can localize oxygen lattice evolutions and stabilize the ARR, eliminating oxygen releases. The thus-made cathode has a highly reversible capacity (320 mA h g-1 ) and achieves excellent cycling stability. After 100 cycles, the capacity retention rate is 86% and the voltage decay is practically eliminated at 0.19 mV per cycle. Attributing to the stable ARR, samples show reduced stress-strain and phase transitions. Neutron pair distribution function (nPDF) measurements indicate that there is a structure response of localized oxygen lattice distortion to the ARR and the average oxygen lattice framework is well-preserved which is a prerequisite for the high cycle reversibility.

Electrochemiluminescence immunoassay strategies based on a hexagonal Ru-MOF and MoS2@GO nanosheets: detection of 5-fluorouracil in serum samples.

Herein, a competitive-type electrochemiluminescence immunosensor for ultrasensitive detection of 5-fluorouracil (5-FU) was fabricated. Ruthenium(II)-metal-organic framework (Ru-MOF) nanosheets were selected to act a promising ECL luminophore using tris(4,4'-dicarboxylic acid-2,2'-bipyridyl) ruthenium(II) dichloride (Ru(dcbpy)32+) as the organic ligand. The two-dimensional (2D) Ru-MOF nanosheets achieved an increased loading of Ru(dcbpy)32+ and effectively prevented leakage of the ECL emitter during application, which exhibited satisfactory ECL performance. Thin two-dimensional MoS2@GO was used to modify the electrode as the sensing platform for improving the electron transfer rate and loading more 5-FU coating antigens due to its large specific surface area and piezoelectric catalytic efficiency. Under the optimized conditions, the proposed immunosensor presented high sensitivity, a wide detection range (0.0001 ng-100 ng mL-1), a low limit of detection (0.031 pg mL-1, S/N = 3), good specificity and stability. Furthermore, the immunosensor was successfully applied for the detection of 5-FU in human serum samples with satisfactory results, proving this strategy has potential applications in bioanalysis and clinical diagnosis.

Electrochemiluminescence resonance energy transfer immunoassay based on a porphyrin metal-organic framework and AuNPs/NSG for the sensitive detection of zearalenone.

In this study, a novel electrochemiluminescence resonance energy transfer (ECL-RET) immunoassay was developed for the first time for the detection of zearalenone (ZEN). A porphyrin metal-organic framework (PCN-222), an emerging porphyrin-based ECL luminophore, was prepared by a simple hydrothermal method using tetrakis(4-carboxyphenyl) porphyrin, which has excellent ECL emission as well as good ECL efficiency. Because the ECL emission spectrum of PCN-222 is highly matched to the absorption spectrum of gold nanoparticle-modified graphene oxide (AuNPs/NSG) nanocomposites, they were used as donor-acceptor counterparts in this work for the ECL-RET strategy. Under optimal conditions, the ECL immunosensor showed a sensitive response to ZEN in a wide detection range, with a linearity of 0.0005-1000 ng mL-1 and a detection limit of 0.15 pg mL-1. In addition, the sensor showed good potential for application in the detection of wheat and corn samples, providing a new approach for the detection of mycotoxin-like contaminants such as ZEN in food grains.

Evaluating the Oxygen Electrode Reactions of La Single-Atom Catalysts with the N/C Coordination Effect.

There is a growing demand for bifunctional electrocatalysts for oxygen electrodes in rechargeable metal-air batteries. This article investigates the bifunctional activity of La single-atom catalysts with N/C coordination (LaNxC6-x@Gra) using density functional theory (DFT). The augmentation of N coordination will result in enhanced synthetic stability. The coordination between nitrogen and carbon (N/C) has a significant influence on the working stability of the system under consideration. In the context of active atoms, the coordination between nitrogen and carbon (N/C coordination) has a significant impact on the electronic structure. This, in turn, influences the adsorption performance and catalytic activity of the catalysts. In the case of stable coordination environments, a correlation exists between the f-orbital center (εf) and the overpotential (η) via the adsorption free energy of intermediates (ΔG*ads). This correlation serves as a useful tool for predicting catalytic performance. The LaNxC6-x@Gra exhibits remarkable bifunctional activity due to its complementary performance, with an overpotential for the oxygen reduction reaction (ηORR) of 0.66 V and an overpotential for the oxygen evolution reaction (ηOER) of 0.43 V. This makes it a promising candidate for use as a bifunctional electrocatalyst in oxygen electrodes.

Association Between Smoking Behavior and Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.

INTRODUCTION: To systematically review the association between smoking behavior and obstructive sleep apnea (OSA). AIMS AND METHODS: PubMed, Medline, the Cochrane Library, EMBASE, and Scopus databases were used to conduct this review. The two researchers independently screened the literatures, conducted the quality assessment, and data extraction according to the inclusion and exclusion criteria. The RevMan 5.3 was used to analysis the apnea hypopnea index (AHI) index, min saturation of oxyhemoglobin (SaO2), Epworth Sleepiness Scale (ESS) score, and oxygen desaturation index (DOI) and publication bias analysis to assess the effect of smoking on OSA patients. Furthermore, we performed subgroup of the severity of OSA, different countries of sample origin (western countries or eastern countries), and pack-years (PYs < 10 or PYs ≥ 20) to analyze the heterogeneity. RESULTS: Thirteen studies were included in this analysis that conformed to inclusion criteria and exclusion criteria. Totally 3654 smokers and 9796 non-smokers have participated. The meta-analysis of 13 studies demonstrated that AHI levels were significantly higher in smoker group compared with non-smoker, ESS scores were also significantly higher in smoker group compared with non-smoker, min SaO2 levels were obviously lower in smoker group compared with non-smoker, however, DOI levels hadn't significantly different between two groups. The subgroup analysis showed that there was an association between severe OSA, eastern countries, pack-years, and smoking. CONCLUSIONS: Smoking behavior is a significant association with OSA. Heavy smokers with histories of more than 20 PYs were at a higher risk of OSA. Moreover, patient with severe OSA exhibited a significantly association with smoking compared with patients with mild or moderate OSA. IMPLICATIONS: The relationship between smoking and OSA was controversial, especially, whether smoking increase or aggravate the risk of OSA. In our review and meta-analysis, we demonstrated that smoking behavior is a significant association with OSA. Heavy smokers with histories of more than 20 PYs were at a higher risk of OSA. Moreover, patient with severe OSA exhibited a significant association with smoking compared with patients with mild or moderate OSA. More prospective long-term follow-up studies about effect of quit smoking on OSA are recommended to establish the further relationship.

Short sleep duration associated with the incidence of cardio-cerebral vascular disease: a prospective cohort study in Shanghai, China.

IMPORTANCE: Sleep duration plays an important role in predicting CCVD incidence, and have implications for reducing the burden of CCVD. However, the association between sleep duration and predicted cardio-cerebral vascular diseases (CCVD) risk remains to be fully understood. OBJECTIVE: To investigate the effects of sleep duration on the development of CCVD among Chinese community residents. DESIGN: A prospective cohort study. The baseline survey was conducted from January 2013 to July 2013. The cohort has been followed until December 31, 2016 using a combination of in-person interviews and record linkages with the vital registry of Pudong New Area, Shanghai, China. SUBJECTS: A total of 8245 Chinese community residents were initially enrolled in the cohort. Of those, 6298 underwent the follow-up examination. EXPOSURE: Self-reported sleep duration and sleep quality were obtained via the questionnaire. Sleep duration was divided into five categories: ≤5, 6, 7, 8, or ≥ 9 h per day. MAIN OUTCOME(S) AND MEASURE(S): CCVD, Coronary heart disease (CHD) and Stroke occurrence, Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using Fine-Gray proportional subdistribution hazards models. RESULTS: During a median follow-up of 3.00 years (IQR 2.92-3.08), we observed 370 participants have had incident CCVD events, of whom 230 had CHDs, 169 had strokes, and 29 had both. After adjustment for relevant confounders, short sleepers (≤ 5 h) had 83% higher risk of total CCVD incidence (HR: 1.83; 95% CI: 1.32-2.54), 82% higher risk of CHD incidence (HR: 1.82; 95% CI: 1.21-2.75), and 82% higher risk of stroke incidence (HR: 1.82; 95% CI: 1.12-2.98) in contrast to the reference group (7 h). Some of these U-shaped relationships varied by age, and were more pronounced in individuals aged < 65 years. Individuals who slept ≤ 5 h per day with baseline hypertension had the highest risk of CCVD incidence (HR: 3.38, 95% CI 2.08-5.48), CHD incidence (HR: 3.11, 95% CI 1.75-5.53), and stroke incidence (HR: 4.33, 95% CI 1.90-9.86), compared with those sleep 7 h and without baseline hypertension. CONCLUSIONS: Short sleep duration is independently associated with greater incidence of CCVD, CHD and stroke.