Clinical Characteristics and Treatment Efficacy for Co-Morbid Insomnia and Sleep Apnea (COMISA): Evidence from Qualitative and Quantitative Analysis.

OBJECTIVES: A multitude of physical and mental challenges are being faced in the population with Co-morbid Insomnia and Sleep Apnea (COMISA). Unfortunately, research about clinical characteristics and management of COMISA based on quantitative evidence is lacking. METHOD: Standard procedures for literature retrieval, selection and quality assessment, data extraction, analysis, and interpretation were conducted step by step. For studying the sleep characteristics, common complications and widely recognized treatment options for COMISA, Weighted Mean Difference (WMD) and Odds Ratio (OR) were applied to assess the mean and risk differences between compared groups. Outcomes included sleep health parameters and secondary impairments in physical and mental well-being. RESULTS: COMISA showed worse sleep quality than OSA only by PSQI (WMD = 3.38 point) and heavier sleep fragmentation (WMD = 11.46 min) than insomnia only. Besides, COMISA patients showed a higher risk for depression (OR [95%CI] = 5.03[2.31, 10.93]) and PTSD (OR [95%CI] = 3.96[1.85, 8.46]) in comparison with OSA alone. Compared to insomnia alone, COMISA patients suffered from more than two times higher risk of cardiovascular diseases, hypertension, and diabetes. In treating COMISA patients, combining CBTI with PAP treatment can enhance the improvement of insomnia severity (ISI, WMD [95%CI] =-3.26[-4.51, -2.00] point) and sleep efficiency (WMD [95%CI] = 6.39[1.97, 10.81] %) compared to PAP alone. CONCLUSIONS: Impaired sleep domains in COMISA cover sleep quality and sleep structure. Also, COMISA has a higher risk for cardiometabolic diseases and mental disorders. Combining CBTI with PAP can be a recommended treatment to relieve sleep impairments for COMISA.

Effects of common lifestyle factors on obstructive sleep apnea: precautions in daily life based on causal inferences.

Background: This study aimed to evaluate the causal impact of common modifiable lifestyles on obstructive sleep apnea (OSA), which is beneficial for recommendations to prevent and manage OSA. Method: Published genome-wide association study (GWAS) summary statistics were used to perform two-sample Mendelian randomization (MR). Variants associated with each exposure of smoking, drinking, and leisure sedentary behaviors at the genetic level were used as instrumental variables (IVs). Then, inverse-variance weighting (IVW) was considered the primary result for causality. Moreover, several complimented approaches were also included to verify the observed associations. MR-PRESSO and MR-Egger intercept were applied to test the horizontal pleiotropy. To assess heterogeneity, Cochran's Q test by IVW and MR-Egger were applied. Results: Regular smoking history increased OSA risk in all applied approaches [OR (95% CI)IVW = 1.28 (1.12, 1.45), p = 1.853 × 10-4], while the causality of lifetime smoking index [OR (95% CI)IVW = 1.39 (1.00, 1.91), p = 0.048], alcohol intake frequency [outliers removed OR (95% CI)IVW = 1.26 (1.08, 1.45), p = 0.002], and coffee intake behavior [OR (95% CI)IVW = 1.66 (1.03, 2.68), p = 0.039] on OSA risk were not always consistent in other approaches. In addition, no robust causal associations were observed for the effect of sedentary leisure behaviors on OSA risk. In sensitivity analysis, we observed no sign of horizontal pleiotropy or heterogeneity. Conclusion: Ever regularly smoking has a robust causal role in increasing OSA risk, which should be discouraged as precautions from developing OSA.

The benefits of hypoglycemic therapy for patients with obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) is often associated with glycemic abnormalities. This study is conducted to investigate the effects of hypoglycemic therapy on OSA-related indicators. METHOD: We systematically searched Web of Science, PubMed, Embase, and the Cochrane Library for articles on OSA patients receiving any hypoglycemic drugs, published until December 25, 2022. Seven original studies were finally included. The proposal was registered with PROSPERO (CRD42022351206). RESULTS: In summary, in addition to reduced glycosylated hemoglobin A1c (HbA1c), we found that hypoglycemic treatment can lower the apnea-hypopnea index (AHI) by 7.07/h (p = 0.0001). Although long-term treatment (> 12 weeks) achieved a more significant reduction in HbA1c (- 1.57% vs. - 0.30%) compared to short-term treatment (≤ 12 weeks), there was no significant difference between the two in terms of AHI (intergroup p-value = 0.27). We also found that patients using sodium glucose cotransporter 2 inhibitors (SGLT2i) experienced a greater reduction in AHI (- 11.00/h, p < 0.00001). Additionally, hypoglycemic treatment also showed certain improvements in related indicators like Epworth Sleepiness Scale, body mass index, and blood pressure. CONCLUSIONS: Our results affirm the benefits of hypoglycemic treatment for OSA patients and highlight the notable effect of SGLT2i. Further researches are needed to help doctors gain a comprehensive understanding of the interaction between OSA and glycemic abnormalities.

Diagnostic value of microRNAs in active tuberculosis based on quantitative and enrichment analyses.

BACKGROUND: Tuberculosis (TB) infection remains a crucial global health challenge, with active tuberculosis (ATB) representing main infection source. MicroRNA (miRNA) has emerged as a potential diagnostic tool in this context. This study aims to identify candidate miRNAs for ATB diagnosis and explore their possible mechanisms. METHODS: Differentially expressed miRNAs in ATB were summarized in qualitative analysis. The diagnostic values of miRNAs for ATB subtypes were assessed by overall sensitivity, specificity, and area under the curve. Additionally, we conducted enrichment analysis on miRNAs and target genes. RESULTS: Over 100 differentially expressed miRNAs were identified, with miR-29 family being the most extensively studied. The miR-29 family demonstrated sensitivity, specificity, and area under the curve of 80 %, 80 % and 0.86 respectively for active pulmonary TB (PTB). The differentially expressed miR-29-target genes in PTB were enriched in immune-related pathways. CONCLUSIONS: The miR-29 family exhibits good diagnostic value for active PTB and shows association with immune process.

Effect of different anti-cardiovascular disease treatments on the severity of obstructive sleep apnea.

Obstructive sleep apnea (OSA) and cardiovascular co-morbidities have a mutually reinforcing effect, but existing studies have focussed only on the improvement of the associated co-morbidities by treatment for OSA. To provide fresh guidelines for the treatment of OSA from a co-morbidity standpoint, we conducted a systematic search of Web of Science, PubMed, EMBASE, and the Cochrane Library for articles published from inception up to 2 May 2023. Fourteen original studies of patients with OSA with cardiovascular co-morbidities and who received related treatment were included in the analysis. We found that diuretic treatment can reduce the apnea-hypopnea index in patients with OSA and hypertension (-19.41/h, p = 1.0 × 10-5 ), aldosterone-angiotensin inhibitors also have a 9.19/h reduction (p = 0.003), while the effect of renal sympathetic denervation is insignificant (-2.32/h, p = 0.19). The short-term treatment (<4 weeks) did not show an improvement (-2.72/h, p = 0.16), while long-term treatment (>4 weeks) produced surprising outcomes (-12.78/h, p = 0.002). Patients with milder disease (baseline AHI < 35/h) had insignificant improvements (-1.05/h, p = 0.46), whereas those with more severe disease (baseline AHI > 35/h) could achieve satisfactory outcomes (-14.74/h, p < 0.00001). In addition, it also showed some improvement in the oxygen desaturation index and blood oxygen. Our results support the additional benefit of antihypertensive treatment for OSA symptoms, and the efficacy can be affected by different therapy, treatment duration, and severity levels. It could be useful in developing clinical therapy, educating patients, and exploring interaction mechanisms. The proposal was registered with PROSPERO (CRD42022351206).

Unraveling the associations and causalities between glucose metabolism and multiple sleep traits.

Purpose: The aim of our study is to estimate the associations and causalities of glucose metabolism traits of fasting blood glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), and 2-h glucose post-challenge (2hGlu) with sleep traits consisting of excessive daytime sleepiness (EDS), insomnia, and sleep duration. Methods: We employed standard quantitative analysis procedures to assess the associations between sleep traits and glucose metabolism. Moreover, we acquired published genome-wide association studies (GWAS) summary statistics for these traits and conducted Mendelian randomization (MR) analyses to estimate their causal directions and effects. Inverse variance weighting (IVW) was employed as the primary approach, followed by sensitivity analyses. Results: A total of 116 studies with over 840,000 participants were included in the quantitative analysis. Our results revealed that participants with abnormal glucose metabolism had higher risks for EDS (OR [95% CI] = 1.37 [1.10,1.69]), insomnia (OR [95% CI] = 1.65 [1.24,2.20]), and both short and long sleep duration (OR [95% CI] = 1.35 [1.12,1.63]; OR [95% CI] = 1.38 [1.13,1.67] respectively). In addition, individuals with these sleep traits exhibited alterations in several glycemic traits compared with non-affected controls. In MR analysis, the primary analysis demonstrated causal effects of 2hGlu on risks of EDS (OR [95% CI] = 1.022 [1.002,1.042]) and insomnia (OR [95% CI] = 1.020[1.001,1.039]). Furthermore, FINS was associated with short sleep duration (OR [95% CI] = 1.043 [1.018,1.068]), which reversely presented a causal influence on HbA1c (ß [95% CI] = 0.131 [0.022,0.239]). These results were confirmed by sensitivity analysis. Conclusion: Our results suggested mutual risk and causal associations between the sleep traits and glycemic traits, shedding new light on clinical strategies for preventing sleep disorders and regulating glucose metabolism. Future studies targeting these associations may hold a promising prospect for public health.

The causal associations of altered inflammatory proteins with sleep duration, insomnia and daytime sleepiness.

STUDY OBJECTIVES: Growing evidence linked inflammation with sleep. This study aimed to evaluate the associations and causal effects of sleep traits including insomnia, excessive daytime sleepiness (EDS), and sleep duration (short: <7 h; normal: 7-9 h; long: ≥9 h), with levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukins. METHODS: Standard procedures of quantitative analysis were applied to estimate the expression differences for each protein in compared groups. Then, a two-sample Mendelian randomization (MR) analysis was performed to explore their causal relationships with published genome-wide association study summary statistics. The inverse-variance weighted was used as the primary method, followed by several complementary approaches as sensitivity analyses. RESULTS: A total of 44 publications with 51 879 participants were included in the quantitative analysis. Our results showed that the levels of CRP, interleukin-1ß (IL-1ß), IL-6, and TNF-α were higher from 0.36 to 0.58 (after standardization) in insomnia compared with controls, while there was no significant difference between participants with EDS and controls. Besides, there was a U/J-shaped expression of CRP and IL-6 with sleep durations. In MR analysis, the primary results demonstrated the causal effects of CRP on sleep duration (estimate: 0.017; 95% confidence intervals [CI], [0.003, 0.031]) and short sleep duration (estimate: -0.006; 95% CI, [-0.011, -0.001]). Also, IL-6 was found to be associated with long sleep duration (estimate: 0.006; 95% CI, [0.000, 0.013]). These results were consistent in sensitivity analyses. CONCLUSIONS: There are high inflammatory profiles in insomnia and extremes of sleep duration. Meanwhile, elevated CRP and IL-6 have causal effects on longer sleep duration. Further studies can focus on related upstream and downstream mechanisms.

How information processing and risk/benefit perception affect COVID-19 vaccination intention of users in online health communities.

Objective: To investigate the relationship among information processing, risk/benefit perception and the COVID-19 vaccination intention of OHCs users with the heuristic-systematic model (HSM). Methods: This study conducted a cross-sectional questionnaire via an online survey among Chinese adults. A structural equation model (SEM) was used to examine the research hypotheses. Results: Systematic information processing positively influenced benefit perception, and heuristic information processing positively influenced risk perception. Benefit perception had a significant positive effect on users' vaccination intention. Risk perception had a negative impact on vaccination intention. Findings revealed that differences in information processing methods affect users' perceptions of risk and benefit, which decide their vaccination intention. Conclusion: Online health communities can provide more systematic cues and users should process information systematically to increase their perceived benefits, consequently increase their willingness to receive COVID-19 vaccine.

Quantitative and causal analysis for inflammatory genes and the risk of Parkinson's disease.

Background: The dysfunction of immune system and inflammation contribute to the Parkinson's disease (PD) pathogenesis. Cytokines, oxidative stress, neurotoxin and metabolism associated enzymes participate in neuroinflammation in PD and the genes involved in them have been reported to be associated with the risk of PD. In our study, we performed a quantitative and causal analysis of the relationship between inflammatory genes and PD risk. Methods: Standard process was performed for quantitative analysis. Allele model (AM) was used as primary outcome analysis and dominant model (DM) and recessive model (RM) were applied to do the secondary analysis. Then, for those genes significantly associated with the risk of PD, we used the published GWAS summary statistics for Mendelian Randomization (MR) to test the causal analysis between them. Results: We included 36 variants in 18 genes for final pooled analysis. As a result, IL-6 rs1800795, TNF-α rs1799964, PON1 rs854560, CYP2D6 rs3892097, HLA-DRB rs660895, BST1 rs11931532, CCDC62 rs12817488 polymorphisms were associated with the risk of PD statistically with the ORs ranged from 0.66 to 3.19 while variants in IL-1α, IL-1ß, IL-10, MnSOD, NFE2L2, CYP2E1, NOS1, NAT2, ABCB1, HFE and MTHFR were not related to the risk of PD. Besides, we observed that increasing ADP-ribosyl cyclase (coded by BST1) had causal effect on higher PD risk (OR[95%CI] =1.16[1.10-1.22]) while PON1(coded by PON1) shown probably protective effect on PD risk (OR[95%CI] =0.81[0.66-0.99]). Conclusion: Several polymorphisms from inflammatory genes of IL-6, TNF-α, PON1, CYP2D6, HLA-DRB, BST1, CCDC62 were statistically associated with the susceptibility of PD, and with evidence of causal relationships for ADP-ribosyl cyclase and PON1 on PD risk, which may help understand the mechanisms and pathways underlying PD pathogenesis.

Efficacy of CPAP duration and adherence for cognitive improvement in patients with obstructive sleep apnea: a meta-analysis of randomized controlled trials.

PURPOSE: Obstructive sleep apnea (OSA) can impair cognition. Continuous positive airway pressure (CPAP) is a recommended treatment for OSA but its effectiveness on cognitive improvement is uncertain, a finding which may be biased by various durations and adherence to treatment with CPAP. In a meta-analysis assessing high-quality randomized controlled trials (RCTs), we estimated whether or not CPAP benefits cognition in patients with OSA. METHODS: PRISMA criteria were followed in the performance of this meta-analysis. The weighted mean difference (WMD) and 95% confidence interval (CI) of six neuropsychological scores covering eight cognitive domains were used to evaluate the benefit between CPAP and non-CPAP interventions. Subgroups of different therapeutic durations and adherence, which were divided into short-term (< 8 weeks) and long-term (≥ 12 weeks) durations, and poor (nighttime < 4 h/night) and good (nighttime ≥ 4 h/night) adherence were also analyzed. RESULTS: Among 16 RCTs, 1529 participants with OSA were included. Comparing the CPAP group and the control group for all treatment durations and adherence, a mild improvement for digit span forward which reflected short-term memory was observed (WMD[95%CI] = 0.67[0.03,1.31], p = 0.04). Trail making test-part B, which reflected executive function was improved for participants with OSA who had good adherence to CPAP (WMD[95%CI] = - 6.24[- 12.60,0.12], p = 0.05). Patients with OSA who received short-term CPAP treatment (WMD[95%CI] = - 7.20[- 12.57, - 1.82], p = 0.009) had a significant improvement in executive function when compared with controls. There was no statistical difference for all scales between long-term (≥ 12 weeks) CPAP treatment group and control group. CONCLUSION: The effectiveness of CPAP on cognitive improvement in patients with OSA is limited, although good adherence to CPAP can mildly benefit executive function with short-term effectiveness.

Associations between cardiometabolic phenotypes and levels of TNF-α, CRP, and interleukins in obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) shows a chronic inflammatory state which is often accompanied by cardiometabolic phenotypes. The aim of this study was to investigate whether or not there were differences of inflammatory proteins levels in patients with OSA with and without a certain phenotype so as to explore the associations between inflammation and additional OSA phenotypes. METHODS: The literature was systematically screened and available data were collected on levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and several interleukins (ILs) in patients with OSA with and without a certain phenotype. Overall effect size of standard mean difference (SMD) was used to compare the expression of differences between the two groups. Data analysis was conducted by Review Manager 5.3, and the threshold of p value was set as < 0.05. RESULTS: A total of 31 articles were included, covering five traits of obesity, hypertension (HBP), metabolic syndrome (MS), heart disease, and sex. There were elevated levels of TNF-α (SMD = 0.63, p = 0.03), CRP (SMD = 0.64, p = 0.0001), and IL-6 (SMD = 0.83, p = 0.008) levels in OSA with obesity. Also, OSA with HBP showed significant increases of TNF-α (SMD = 0.36, p = 0.02), CRP (SMD = 0.98, p = 0.01), and IL-6 (SMD = 0.76, p < 0.0001) levels. A higher CRP level was also observed in OSA with MS (SMD = 0.31, p = 0.004) and female sex (SMD = 0.21, p = 0.002). There were no statistical differences for IL-1ß (p = 0.22) and CRP (p = 0.14) levels of OSA with obesity and heart disease respectively compared with OSA without corresponding phenotype. TNF-α (p = 0.66) and IL-6 (p = 0.49) levels also lacked statistically significant differences between female and male patients with OSA. CONCLUSIONS: Our results revealed that inflammatory proteins TNF-α, CRP, and IL-6 levels were higher in obese and hypertensive patients with OSA and CRP levels were higher in OSA with metabolic syndrome, highlighting a link between inflammation and cardiometabolic complications in patients with OSA.

Causal analysis between altered levels of interleukins and obstructive sleep apnea.

Background: Inflammation proteins including interleukins (ILs) have been reported to be related to obstructive sleep apnea (OSA). The aims of this study were to estimate the levels for several key interleukins in OSA and the causal effects between them. Method: Weighted mean difference (WMD) was used to compare the expression differences of interleukins between OSA and control, and the changed levels during OSA treatments in the meta-analysis section. A two-sample Mendelian randomization (MR) was used to estimate the causal directions and effect sizes between OSA risks and interleukins. The inverse-variance weighting (IVW) was used as the primary method followed by several other MR methods including MR Egger, Weighted median, and MR-Robust Adjusted Profile Score as sensitivity analysis. Results: Nine different interleukins-IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-12, IL-17, IL-18, and IL-23-were elevated in OSA compared with control to varying degrees, ranging from 0.82 to 100.14 pg/ml, and one interleukin, IL-10, was decreased by 0.77 pg/ml. Increased IL-1ß, IL-6, and IL-8 rather than IL-10 can be reduced in OSA by effective treatments. Further, the MR analysis of the IVW method showed that there was no significant evidence to support the causal relationships between OSA and the nine interleukins-IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, and IL-18. Among them, the causal effect of OSA on IL-5 was almost significant [estimate: 0.267 (-0.030, 0.564), p = 0.078]. These results were consistent in the sensitivity analysis. Conclusions: Although IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-12, IL-17, IL-18, and IL-23 were increasing and IL-10 was reducing in OSA, no significant causal relationships were observed between them by MR analysis. Further research is needed to test the causality of OSA risk on elevated IL-5 level.

DNA repair in lung cancer: a large-scale quantitative analysis for polymorphisms in DNA repairing pathway genes and lung cancer susceptibility.

BACKGROUND: The results of associations between single nucleotide polymorphisms (SNPs) of genes in DNA repairing pathway and lung cancer (LC) risk are inconsistent. METHODS: We applied allele, dominant and recessive models to explore the risk of researched variants to LC in total LC and subgroups by ethnicity or LC subtypes with a cutoff point of p < 0.05. RESULTS: A total of 76,935 cases and 88,649 controls from 192 articles were included. Among the analyzed 40 variants from 20 genes, we found 9 statistically significant variants in overall populations by allele model, including five SNPs (rs1760944, rs9344, rs13181, rs1001581, and rs915927) increasing LC risk (odd ratios [ORs] = 1.10-1.71) and four SNPs (rs1042522, rs3213245, rs11615, and rs238406) decreasing the risk (ORs = 0.75-0.94). We identified rs1042522 and rs13181 as significant variants for LC in three models. Additionally, we identified differential significant SNPs in ethnic and subtype's analysis with comparison to total population. CONCLUSIONS: There are five SNPs in DNA repairing pathway associated with increased LC risk and four others decreased LC risk. Besides, the risky SNPs in different ethnicities and various LC subtypes were partly different, and the contribution of different genotypes to risk alleles were various as well.

Elevated fasting insulin results in snoring: A view emerged from causal evaluation of glycemic traits and snoring.

BACKGROUND: Snoring and impaired glucose metabolism are common clinical manifestations and associated. The purpose of our study is to estimate the causal associations between snoring and glycemic traits. METHODS: We compared the weighted mean differences (WMD) for fasting insulin (FINS), glycosylated haemoglobin (HbA1c), fasting blood glucose (FBG) and 2 h-glucose post-challenge (2hGlu) levels between snorers and non-snorers by meta-analysis. Then, we obtained summary statistics from published GWAS of snoring and glycemic traits to perform bidirectional two-sample MR. Inverse variance weighting (IVW) method was applied as major estimate while MR Egger, Weighted median and MR-Robust Adjusted Profile Score (RAPS) played a subsidiary role. RESULTS: Snoring participants had higher FBG (WMD = 0.14 mmol/L, 95%CI = [0.10,0.19]), HbA1c (WMD = 0.10%, 95%CI = [0.07,0.13]), FINS (WMD = 0.92µIU/mL, 95%CI = [0.59,1.26]) and 2hGlu (WMD = 0.30 mmol/L, 95%CI = [0.06,0.55]) levels than non-snorers. Further, elevated FINS levels shown robust causal effect on snoring (IVW: OR = 1.07, 95%CI = [1.02,1.12], p = 2.2 × 10-3 ), which was consistent by complementary methods of MR Egger (OR = 1.14, 95%CI = [1.01-1.30], p = 4.72 × 10-2 ), Weighted median (OR = 1.11, 95%CI = [1.07,1.15], p = 1.53 × 10-7 ) and MR RAPS (OR = 1.07, 95% CI = [1.05,1.10], p = 2.81 × 10-9 ). Such causal situation was stable after identifying and removing the outliers in sensitivity analysis. However, there was no causality of snoring on increasing FINS levels. Additionally, there were no causal associations between snoring and other three traits of FBG, HbA1c and 2hGlu levels from either direction. CONCLUSIONS: Snorers are subjected to higher FBG, HbA1c, FINS and 2hGlu levels, and elevated FINS levels further provides robust causality on snoring, suggesting that behind common snoring may lie hyperinsulinemia or insulin resistance.

Efficacy comparison of immune treating strategies for NSCLC patients with negative PD-L1 expression.

BACKGROUND: We intended to compare and grade the proposed immune treating strategies for non-small cell lung cancer (NSCLC) with negative Programmed Cell Death Ligand 1(PD-L1). METHODS: We compared the efficacy of single immune checkpoint inhibitor (ICI), single ICI plus chemotherapy, and doublet ICIs with chemotherapy alone, as well as single ICI plus radiotherapy with single ICI for negative PD-L1 (<1%) NSCLC patients. Hazard Ratio (HR) and 95% confidence interval (CI) of progression-free survival (PFS) and overall survival (OS) were used as outcomes. RESULTS: We included 23 randomized control trials with 4665 patients. Compared with chemotherapy alone, single ICI, single ICI plus chemotherapy and doublet ICIs all showed a better OS (0.84 [0.71, 0.99] ; 0.77 [0.69, 0.85] ; 0.64 [0.53, 0.77])), while single ICI plus chemotherapy and doublet ICIs showed a better PFS (0.68 [0.61, 0.75] ; 0.69 [0.56, 0.85]). Additionally, single ICI plus radiotherapy obtained a greater pooled PFS (0.49 [0.28-0.87]) than single ICI. CONCLUSIONS: Both single ICI plus chemotherapy and doublet ICIs were probably better treatment decisions than chemotherapy alone for negative PD-L1 NSCLC patients. Also, single ICI plus radiotherapy carved out a new strategy.

The causal relationships between obstructive sleep apnea and elevated CRP and TNF-α protein levels.

BACKGROUND: Obstructive sleep apnea (OSA) and inflammation are closely related. This study aimed to evaluate the associations and causal effect between C-reactive protein (CRP) and tumour necrosis factor-alpha (TNF-α) levels andOSA. METHODS: Pooled analysis was conducted to compare the expression differences of CRP and TNF-α between OSA patients with different severity and controls, and between continuous positive airway pressure (CPAP) and non-CPAP interventions for OSA patients. Using published GWAS summary statistics, we conducted a bidirectional two-sample Mendelian Randomization (MR) to estimate the causal relationships between CRP and TNF-α levels and OSA risk. Effect estimates were evaluated using inverse-variance weighted (IVW) as primary method, and several other MR methods as sensitivity analysis. RESULTS: Both TNF-α (WMD [95%CI] = 5.86 [4.80-6.93] pg/ml, p < .00001) and CRP (WMD [95%CI] = 2.66 [2.15-3.17] mg/L, p < .00001), showed a significant increase in OSA patients compared with controls and this increasing trend was associated with OSA severity. Besides, compared to blank control (non-CPAP), CPAP treatment can reduce high TNF-α (WMD [95%CI]= -4.44 [-4.81, -4.07]pg/ml, p < .00001) and CRP (WMD [95%CI]= -0.91 [-1.65, -0.17] mg/l, p = .02) in OSA. Moreover, the primary MR analysis by IVW showed that OSA was the genetically predicted cause of elevated CRP (estimate: 0.095; 95% CI, [0.010-0.179]; p = .029) using six SNPs as the instrument variable, which were repeated by weighted median (estimate: 0.053; 95% CI, [0.007, 0.100]; p =.024) and MR RAPS (estimate: 0.109; 95% CI, [0.079, 0.140]; p = 1.98x10-12). Besides, the causal effect from elevated CRP on increased OSA risk was almost significant by IVW (OR:1.053; 95% CI, [1.000, 1.111]; p = .053). However, there were no causal associations between TNF-α and OSA from both directions. CONCLUSIONS: Increased CRP and TNF-α were associated with OSA severity and sensible to CPAP treatment. Also, OSA had a suggestive causal effect on elevated CRP.

Polymorphism of neurodegeneration-related genes associated with Parkinson's disease risk.

BACKGROUND: Neurodegenerative genes are critical in neuronal loss in Parkinson's disease (PD). We performed a systematic meta-analysis including all the studies published on PD risk related to genes encoding enzymes vital for dopamine metabolism and neuron survival. METHODS: We included neurodegeneration-related genes which were divided into four groups according to their functions: main enzymes in dopamine metabolism, receptors and transporters for dopamine or other metabolites, neuroprotective factors for dopaminergic neurons, and genes associated with dopaminergic neurons survival reported in other neurological diseases. We collected original articles from PubMed, Embase, and Web of Science databases. Revman 5.3 software was used to analyze data. The allele model (AM) was used to test the effect size of the effect allele between the case group and the control group and secondary analysis using the dominant model (DM) and recessive model (RM) to analyze the contributions from heterozygote and homozygote to the allele risk. Odds ratio (OR) and 95% confidence interval (CI) were used to present the pooled results. RESULTS: We included 31 variants in 20 genes for the final pooled analysis. Consequently, SLC6A4/5-HTT HTTLPR, BDNF rs56164415, FGF20 rs1721100, PARK16 rs823128, rs823156, rs947211, APOE e2, A2M rs669, RIT2 rs12456492, MAPT intron 9 H1H2, and STH rs62063857 variants were statistically associated with PD risk while researched variants in COMT, DBH, MAO, DAT/SLC6A3, DRD2, GRIN2B, GSK3ß, ATP13A2, LINGO1, PICALM, and GRN were not related to PD risk. CONCLUSION: Several variants from neurodegeneration-related genes are associated with PD risk, which may help deepen the understanding of PD pathogenesis and improve clinical treatment strategies.

Positive airway pressure therapy in heart failure patients comorbid with obstructive sleep apnea: Cardiovascular outcomes and nighttime-duration effect.

BACKGROUND: Comorbidity of obstructive sleep apnea (OSA) and heart failure (HF) is becoming increasingly common. This is a global analysis of positive airway pressure (PAP) efficacy for the cardiovascular outcomes in those HF Patients with comorbid OSA. METHODS: Related randomized controlled trials were included. Analysed indicators covered primary outcomes (cardiac function, motor ability and life quality) and secondary outcomes (blood pressure and OSA-accompanying symptoms). Weighted mean difference was used to analyse the PAP-control difference in different experimental phases and the baseline-post difference in different groups. RESULTS: Compared with control group, PAP was associated with a 3.48% increase in left ventricle ejection fraction (LVEF) (p < .00001) and little decrease in heart rate (HR) (p = .67). Over 6 h of mean nighttime use was associated with a greater increase in LVEF of 5.21% (p = .0002) and a significant reduction in HR of 3.81 bpm (p = .03). There was no significant difference between PAP and control group in their association with change in motor ability and life quality. Besides, PAP was associated with a 13.08 mm Hg decrease in systolic blood pressure and great improvements in OSA-accompanying symptoms: Apnea-Hypopnea Index, -23.73 e/h; mean oxygen saturation, 1.86%; minimum oxygen saturation, 8.78%; Epworth Sleepiness Scale, -1.39 point; arousal index, -16.41 e/h. There was also no significant difference in diastolic blood pressure. CONCLUSIONS: Positive airway pressure treatment improves cardiac function in HF patients with comorbid OSA, but the improved magnitude is associated with the duration of nighttime use rather than the duration of treatment.

Variants of candidate genes associated with the risk of obstructive sleep apnea.

BACKGROUND: The researches on the associations between different candidate genes and obstructive sleep apnea (OSA) are inconsistent. Here, we performed a comprehensive qualitative and quantitative analysis to estimate the contribution of variants from candidate genes to the risk of OSA. METHODS: Qualitative analysis was conducted to find the relationships for all included genes. Then, quantitative analysis of both allele models and genotype models was applied to evaluate the risk variants for OSA. Furthermore, a similar analysis was performed in different ethnic groups. RESULTS: We included 152 publications containing 75 genes for qualitative analysis. Among them, we included 93 articles containing 28 variants from 16 genes for quantitative analysis. Through allele models, we found 10 risk variants for OSA (rs1801133 of MTHFR, ɛ4 of ApoE, -1438G/A of 5-HT2A, -308G/A of TNF-α, Pro1019Pro of LEPR, rs1130864 and rs2794521 of CRP, D/I of ACE, LPR and VNTR of 5-HTT) with the ORs of 1.21-2.07 in global population. We found that the variant of ɛ2 of ApoE could uniquely decrease the risk of OSA in the East Asian subgroup, while the other 6 variants, including ɛ4 in ApoE, -308G/A in TNF-α, Pro1019Pro in LEPR, D/I in ACE, LPR and VNTR in 5-HTT, could increase the risk of OSA. As for the European subpopulation, we only found that -308G/A in TNF-α could increase the risk for OSA. CONCLUSIONS: Eleven variants from the candidate genes are associated with the risk of OSA, which also show ethnicity differences in East Asian and European subgroups.

High diagnostic value of miRNAs for NSCLC: quantitative analysis for both single and combined miRNAs in lung cancer.

BACKGROUND: MicroRNAs (miRNAs) are good candidates as biomarkers for Lung cancer (LC). The aim of this article is to figure out the diagnostic value of both single and combined miRNAs in LC. METHODS: Normative meta-analysis was conducted based on PRISMA. We assessed the diagnostic value by calculating the combined sensitivity (Sen), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) and the area under the curve (AUC) of single and combined miRNAs for LC and specific subgroups. RESULTS: A total of 80 qualified studies with a total of 8971 patients and 10758 controls were included. In non-small cell lung carcinoma (NSCLC), we involved 20 single-miRNAs and found their Sen, Spe and AUC ranged from 0.52-0.81, 0.66-0.88, and 0.68-0.90, respectively, specially, miR-19 with the maximum Sen, miR-20 and miR-10 with the highest Spe as well as miR-17 with the maximum AUC. Additionally, we detected miR-21 with the maximum Sen of 0.74 [95%CI: 0.62-0.83], miR-146 with the maximum Spe and AUC of 0.93 [95%CI: 0.79-0.98] and 0.89 [95%CI: 0.86-0.92] for early-stage NSCLC. We also identified the diagnostic power of available panel (miR-210, miR-31 and miR-21) for NSCLC with satisfying Sen, Spe and AUC of 0.82 [95%CI: 0.78-0.84], 0.87 [95%CI: 0.84-0.89] and 0.91 [95%CI: 0.88-0.93], and furtherly constructed 2 models for better diagnosis. CONCLUSIONS: We identified several single miRNAs and combined groups with high diagnostic power for NSCLC through pooled quantitative analysis, which shows that specific miRNAs are good biomarker candidates for NSCLC and further researches needed.