Genetic correlation between smoking behavior and gastroesophageal reflux disease: insights from integrative multi-omics data.

BACKGROUND: Observational studies have preliminarily revealed an association between smoking and gastroesophageal reflux disease (GERD). However, little is known about the causal relationship and shared genetic architecture between the two. This study aims to explore their common genetic correlations by leveraging genome-wide association studies (GWAS) of smoking behavior-specifically, smoking initiation (SI), never smoking (NS), ever smoking (ES), cigarettes smoked per day (CPD), age of smoking initiation(ASI) and GERD. METHODS: Firstly, we conducted global cross-trait genetic correlation analysis and heritability estimation from summary statistics (HESS) to explore the genetic correlation between smoking behavior and GERD. Then, a joint cross-trait meta-analysis was performed to identify shared "pleiotropic SNPs" between smoking behavior and GERD, followed by co-localization analysis. Additionally, multi-marker analyses using annotation (MAGMA) were employed to explore the degree of enrichment of single nucleotide polymorphism (SNP) heritability in specific tissues, and summary data-based Mendelian randomization (SMR) was further utilized to investigate potential functional genes. Finally, Mendelian randomization (MR) analysis was conducted to explore the causal relationship between the smoking behavior and GERD. RESULTS: Consistent genetic correlations were observed through global and local genetic correlation analyses, wherein SI, ES, and CPD showed significantly positive genetic correlations with GERD, while NS and ASI showed significantly negative correlations. HESS analysis also identified multiple significantly associated loci between them. Furthermore, three novel "pleiotropic SNPs" (rs4382592, rs200968, rs1510719) were identified through cross-trait meta-analysis and co-localization analysis to exist between SI, NS, ES, ASI, and GERD, mapping the genes MED27, HIST1H2BO, MAML3 as new pleiotropic genes between SI, NS, ES, ASI, and GERD. Moreover, both smoking behavior and GERD were found to be co-enriched in multiple brain tissues, with GMPPB, RNF123, and RBM6 identified as potential functional genes co-enriched in Cerebellar Hemisphere, Cerebellum, Cortex/Nucleus accumbens in SI and GERD, and SUOX identified in Caudate nucleus, Cerebellum, Cortex in NS and GERD. Lastly, consistent causal relationships were found through MR analysis, indicating that SI, ES, and CPD increase the risk of GERD, while NS and higher ASI decrease the risk. CONCLUSION: We identified genetic loci associated with smoking behavior and GERD, as well as brain tissue sites of shared enrichment, prioritizing three new pleiotropic genes and four new functional genes. Finally, the causal relationship between smoking behavior and GERD was demonstrated, providing insights for early prevention strategies for GERD.

Heavy metal levels and flavonoid intakes are associated with chronic obstructive pulmonary disease: an NHANES analysis (2007-2010 to 2017-2018).

BACKGROUND: The association between exposure to environmental metals and chronic obstructive pulmonary disease (COPD) is preventing chronic lung diseases. However, little is currently known about the interaction between heavy metals and flavonoids in relation to the risk of COPD. This study aims to bridge this knowledge gap by leveraging The National Health and Nutrition Examination Survey (NHANES) database to evaluate thecorrelation between blood levels of heavy metals (cadmium, lead, mercury) and the intake of various flavonoid compounds (isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, flavonols, total flavonoids). Additionally, appropriate dietary recommendations are provided based on the study findings. MATERIALS AND METHODS: Cross-sectional analysis was conducted using the 2007-2010 and 2017-2018 NHANES data. Specialized weighted complex survey design analysis software was used for data analysis. Multivariate logistic regression models and restricted cubic splines (RCS) were used to evaluate the relationship between blood heavy metal levels, flavonoids intake, and COPD incidence in all participants, and to explore the effect of different levels of flavonoids intake on COPD caused by heavy metal exposure. RESULTS: A total of 7,265 adults aged ≥ 40 years were analyzed. Higher levels of blood cadmium (Cd), blood lead and Anthocyanidin (AC) intake were independently associated with an increased risk of COPD (Cd highest quantile vs. lowest: OR = 1.73, 95% CI, 1.25-2.3; Lead highest quantile vs. lowest quantile: OR = 1.44, 95% CI, 1.11-1.86; AC highest quantile vs. lowest: OR = 0.73, 95% CI, 0.54-0.99). When AC intake exceeded 11.56 mg/d, the effect of Cd exposure on COPD incidence decreased by 27%, and this finding was more significant in smokers. CONCLUSION: Higher levels of Cd (≥ 0.45ug/L) and lead (≥ 0.172 ug/L) were positively correlated with the risk of COPD among participants aged 40 years and above, while AC intake (≥ 11.56 mg/d) could reduce the risk related to blood Cd.

Efficacy and safety of Qing-Feng-Gan-Ke Granules in patients with postinfectious cough: study protocol of a novel-design phase III placebo-controlled, double-blind randomized trial.

BACKGROUND: Postinfectious cough (PIC) is a common condition that affects millions of people worldwide every year. There is Western medicine for this condition but the treatment effect is often incomplete. Traditional Chinese medicine (TCM) has been increasingly prescribed for patients with PIC. Preliminary trials on Qing-Feng-Gan-Ke-Granules (QFGKG) conveyed promising results in treating PIC. This protocol describes an ongoing phase III randomized controlled clinical trial, designed according to a novel methodology of "one study, one primary outcome", with the objective of evaluating the efficacy and safety of QFGKG in patients suffering from PIC. METHODS/DESIGN: This is a multicenter, phase III, randomized, double-blind, parallel-group, placebo-controlled clinical trial, comprising two simultaneously conducted study parts, part A and part B, intending to investigate two primary outcomes, i.e. time to cough resolution and cough symptom score, respectively. A total of 480 patients, aged 18 to 65 years, who complain of an ongoing persistent cough that has been lasting ≥ 3 weeks, will be recruited from six participating sites and then randomized to receive QFGKG 12.0 g twice daily or placebo 12.0 g twice daily. Each part will enroll 240 patients, with 180 patients being allocated to the QFGKG group and 60 to the placebo group. DISCUSSION: Although traditional Chinese medicine is a structured intervention that has shown some promise in treating persistent cough, existing unconvincing evidence has noted limitations. This is a rare well-designed and rigorously-controlled, randomized, double-blind trial to evaluate the effects and safety of a Chinese herbal medicine in patients with postinfectious cough, providing tangible benefits for clinical research. Results of this trial are inclined to be conjectured as more truthful by implementing separate study parts that specifically estimate exclusive primary outcome. It will not only provide robust clinical evidence on the efficacy and safety of QFGKG for postinfectious cough, but will also provide a critical piece of information on the availability and superiority of a novel methodology for future clinical trials. The current trial is ongoing with recruitment of the predetermined number of patients being in progress. TRIAL REGISTRATION: The two parts of this trial were separately registered with the Chinese Clinical Trial Registry: ChiCTR-TRC-13003278 (part A); and ChiCTR-TRC-13003337 (part B).

Sex differences in the combined influence of inflammation and nutrition status on depressive symptoms: insights from NHANES.

Background: Both nutrition and inflammation are associated with depression, but previous studies have focused on individual factors. Here, we assessed the association between composite indices of nutrition and inflammation and depression. Methods: Adult participants selected from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 were chosen. The exposure variable was the Advanced Lung Cancer Inflammation Index (ALI) integrating nutrition and inflammation, categorized into low, medium, and high groups. The outcome variable was depression assessed using the Patient Health Questionnaire-9 (PHQ-9). A multivariable logistic regression model was employed to evaluate the relationship between ALI and the risk of depression. Results: After extensive adjustment for covariates, in the overall population, participants with moderate and high levels of ALI had a decreased prevalence of depression compared to those with low ALI levels, with reductions of 17% (OR, 0.83; 95% CI: 0.72-0.97) and 23% (OR, 0.77; 95% CI: 0.66-0.91), respectively. Among females, participants with moderate and high ALI levels had a decreased prevalence of depression by 27% (OR, 0.73; 95% CI: 0.60-0.88) and 21% (OR, 0.79; 95% CI: 0.64-0.98), respectively, compared to those with low ALI levels, whereas no significant association was observed among males. Subgroup analyses based on females and males yielded consistent results. Conclusion: In this study, we observed a negative correlation between moderate to high levels of ALI and the prevalence of depression, along with gender differences. Specifically, in females, greater attention should be given to the nutritional and inflammatory status.

Association between genetically proxied lipid-lowering drug targets, lipid traits, and amyotrophic lateral sclerosis: a mendelian randomization study.

BACKGROUND: The use of circulating lipid traits as biomarkers to predict the risk of amyotrophic lateral sclerosis (ALS) is currently controversial, and the evidence-based medical evidence for the use of lipid-lowering agents, especially statins, on ALS risk remains insufficient. Our aim was to apply a Mendelian randomization (MR) approach to assess the causal impact of lipid-lowering agents and circulating lipid traits on ALS risk. MATERIALS AND METHODS: Our study included primary and secondary analyses, in which the risk associations of lipid-lowering gene inhibitors, lipid traits, and ALS were assessed by the inverse variance weighting method as the primary approach. The robustness of the results was assessed using LDSC assessment, conventional MR sensitivity analysis, and used Mediating MR to explore potential mechanisms of occurrence. In the secondary analysis, the association of lipid-lowering genes with ALS was validated using the Summary data-based Mendelian Randomization (SMR) method. RESULTS: Our results showed strong evidence between genetic proxies for Apolipoprotein B (ApoB) inhibitor (OR = 0.76, 95% CI = 0.68 - 0.86; P = 5.58 × 10-6) and reduced risk of ALS. Additionally, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitor (OR = 1.06, 95% CI = 0. 85-1.33) was not found to increase ALS risk. SMR results suggested that ApoB expression was associated with increased ALS risk, and colocalization analysis did not support a significant common genetic variation between ApoB and ALS. Mediator MR analysis suggested a possible mediating role for interleukin-6 and low-density lipoprotein cholesterol (LDL-C). While elevated LDL-C was significantly associated with increased risk of ALS among lipid traits, total cholesterol (TC) and ApoB were weakly associated with ALS. LDSC results suggested a potential genetic correlation between these lipid traits and ALS. CONCLUSIONS: Using ApoB inhibitor can lower the risk of ALS, statins do not trigger ALS, and LDL-C, TC, and ApoB levels can predict the risk of ALS.

Association between high-density lipoprotein cholesterol and type 2 diabetes mellitus: dual evidence from NHANES database and Mendelian randomization analysis.

Background: Low levels of high-density lipoprotein cholesterol (HDL-C) are commonly seen in patients with type 2 diabetes mellitus (T2DM). However, it is unclear whether there is an independent or causal link between HDL-C levels and T2DM. This study aims to address this gap by using the The National Health and Nutrition Examination Survey (NHANES) database and Mendelian randomization (MR) analysis. Materials and methods: Data from the NHANES survey (2007-2018) with 9,420 participants were analyzed using specialized software. Logistic regression models and restricted cubic splines (RCS) were used to assess the relationship between HDL-C and T2DM incidence, while considering covariates. Genetic variants associated with HDL-C and T2DM were obtained from genome-wide association studies (GWAS), and Mendelian randomization (MR) was used to evaluate the causal relationship between HDL-C and T2DM. Various tests were conducted to assess pleiotropy and outliers. Results: In the NHANES study, all groups, except the lowest quartile (Q1: 0.28-1.09 mmol/L], showed a significant association between HDL-C levels and reduced T2DM risk (all P < 0.001). After adjusting for covariates, the Q2 [odds ratio (OR) = 0.67, 95% confidence interval (CI): (0.57, 0.79)], Q3 [OR = 0.51, 95% CI: (0.40, 0.65)], and Q4 [OR = 0.29, 95% CI: (0.23, 0.36)] groups exhibited average reductions in T2DM risk of 23%, 49%, and 71%, respectively. In the sensitivity analysis incorporating other lipid levels, the Q4 group still demonstrates a 57% reduction in the risk of T2DM. The impact of HDL-C levels on T2DM varied with age (P for interaction = 0.006). RCS analysis showed a nonlinear decreasing trend in T2DM risk with increasing HDL-C levels (P = 0.003). In the MR analysis, HDL-C levels were also associated with reduced T2DM risk (OR = 0.69, 95% CI = 0.52-0.82; P = 1.41 × 10-13), and there was no evidence of pleiotropy or outliers. Conclusion: This study provides evidence supporting a causal relationship between higher HDL-C levels and reduced T2DM risk. Further research is needed to explore interventions targeting HDL-C levels for reducing T2DM risk.

The relationship between dietary intake of ω-3 and ω-6 fatty acids and frailty risk in middle-aged and elderly individuals: a cross-sectional study from NHANES.

Background: Frailty is a complex clinical syndrome characterized by a decline in the functioning of multiple body systems and reduced adaptability to external stressors. Dietary ω-3 fatty acids are considered beneficial dietary nutrients for preventing frailty due to their anti-inflammatory and immune-regulating properties. However, previous research has yielded conflicting results, and the association between ω-6 fatty acids, the ω-6: ω-3 ratio, and frailty remains unclear. This study aims to explore the relationship between these factors using the National Health and Nutrition Examination Survey (NHANES) database. Materials and methods: Specialized weighted complex survey design analysis software was employed to analyze data from the 2005-2014 NHANES, which included 12,315 participants. Multivariate logistic regression models and restricted cubic splines (RCS) were utilized to assess the relationship between omega intake and frailty risk in all participants. Additionally, a nomogram model for predicting frailty risk was developed based on risk factors. The reliability of the clinical model was determined by the area under the receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA). Results: In dietary ω-3 intake, compared to the T1 group (≤1.175 g/d), the T3 group's intake level (>2.050 g/d) was associated with approximately 17% reduction in frailty risk in model 3, after rigorous covariate adjustments (odds ratio (OR) = 0.83, 95% confidence interval (CI): (0.70, 0.99)). In dietary ω-6 intake, the T2 group's intake level (>11.423, ≤19.160 g/d) was associated with a 14% reduction in frailty risk compared to the T1 group (≤11.423 g/d) (OR: 0.86, 95% CI: 0.75, 1.00, p = 0.044). RCS results indicated a non-linear association between ω-3 and ω-6 intake and frailty risk. Both ROC and DCA curves demonstrated the stability of the constructed model and the effectiveness of an omega-rich diet in reducing frailty risk. However, we did not find a significant association between the ω-6: ω-3 ratio and frailty. Conclusion: This study provides support for the notion that a high intake of ω-3 and a moderate intake of ω-6 may contribute to reducing frailty risk in middle-aged and elderly individuals.

The association between systemic immune-inflammation index and chronic obstructive pulmonary disease in adults aged 40 years and above in the United States: a cross-sectional study based on the NHANES 2013-2020.

Background: Inflammation is the core of Chronic obstructive pulmonary disease (COPD) development. The systemic immune-inflammation index (SII) is a new biomarker of inflammation. However, it is currently unclear what impact SII has on COPD. This study aims to explore the relationship between SII and COPD. Methods: This study analyzed patients with COPD aged ≥40 years from the National Health and Nutrition Examination Survey (NHANES) in the United States from 2013 to 2020. Restricted Cubic Spline (RCS) models were employed to investigate the association between Systemic immune-inflammation index (SII) and other inflammatory markers with COPD, including Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR). Additionally, a multivariable weighted logistic regression model was utilized to assess the relationship between SII, NLR and PLR with COPD. To assess the predictive values of SII, NLR, and PLR for COPD prevalence, receiver operating characteristic (ROC) curve analysis was conducted. The area under the ROC curve (AUC) was used to represent their predictive values. Results: A total of 10,364 participants were included in the cross-sectional analysis, of whom 863 were diagnosed with COPD. RCS models observed non-linear relationships between SII, NLR, and PLR levels with COPD risk. As covariates were systematically adjusted, it was found that only SII, whether treated as a continuous variable or a categorical variable, consistently remained positively associated with COPD risk. Additionally, SII (AUC = 0.589) slightly outperformed NLR (AUC = 0.581) and PLR (AUC = 0.539) in predicting COPD prevalence. Subgroup analyses revealed that the association between SII and COPD risk was stable, with no evidence of interaction. Conclusion: SII, as a novel inflammatory biomarker, can be utilized to predict the risk of COPD among adults aged 40 and above in the United States, and it demonstrates superiority compared to NLR and PLR. Furthermore, a non-linear association exists between SII and the increased risk of COPD.

Association between genetically proxied HMGCR inhibition and male reproductive health: A Mendelian randomization study.

BACKGROUND: The causal associations between statin use and male sex hormone levels and related disorders have not been fully understood. In this study, we employed Mendelian randomization for the first time to investigate these associations. METHODS: In two-sample Mendelian randomization framework, genetic proxies for hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibition were identified as variants in the HMGCR gene that were associated with both levels of gene expression and low density lipoprotein cholesterol (LDL-C). We assessed the causal relationship between HMGCR inhibitor and 5 sex hormone levels/2 male-related diseases. Additionally, we investigated the association between 4 circulating lipid traits and outcomes. The "inverse variance weighting" method was used as the primary approach, and we assessed for potential heterogeneity and pleiotropy. In a secondary analysis, we revalidated the impact of HMGCR on 7 major outcomes using the summary-data-based Mendelian randomization method. RESULTS: Our study found a significant causal association between genetic proxies for HMGCR inhibitor and decreased levels of total testosterone (TT) (LDL-C per standard deviation = 38.7mg/dL, effect = -0.20, 95% confidence interval [CI] = -0.25 to -0.15) and bioavailable testosterone (BT) (effect = -0.15, 95% CI = -0.21 to -0.10). Obesity-related factors were found to mediate this association. Furthermore, the inhibitor were found to mediate a reduced risk of prostate cancer (odds ratio = 0.81, 95%CI = 0.7-0.93) by lowering bioavailable testosterone levels, without increasing the risk of erectile dysfunction (P = .17). On the other hand, there was a causal association between increased levels of LDL-C, total cholesterol, triglycerides (TG) and decreased levels of TT, sex hormone-binding globulin, and estradiol. CONCLUSIONS: The use of HMGCR inhibitor will reduce testosterone levels and the risk of prostate cancer without the side effect of erectile dysfunction. LDL-C, total cholesterol, and TG levels were protective factors for TT, sex hormone-binding globulin, and estradiol.

Dietary pyrroloquinoline quinone improvement of the antioxidant capacity of laying hens and eggs are linked to the alteration of Nrf2/HO-1 pathway and gut microbiota.

Pyrroloquinoline quinone disodium (PQQ·Na2) has been considered a human food supplement for human health promotion with its antioxidant properties. To determine whether PQQ·Na2 had similar functions to improve the antioxidant ability of layers and eggs, 180 laying hens were fed with 0 or 0.4 mg/kg PQQ·Na2 diets. Supplementation with PQQ·Na2 increased the albumen height, Haugh unit of the eggs. PQQ·Na2 also led to a higher glutathione peroxidase (GSH-Px) concentration in plasma and a lower malondialdehyde (MDA) content in the liver and egg yolk. Similarly, liver gene and protein expression of nuclear factor erythroid 2-related 2 (Nrf2) and heme oxygenase 1 (HO-1) were up-regulated by PQQ·Na2. Moreover, PQQ·Na2 increased the abundance of Firmicutes, Microbacterium, Erysipelatoclostridium, Mailhella, Lachnospiraceae_UCG-010, and Herbaspirillum in gut. Overall, these results suggested PQQ·Na2 increased the antioxidant ability of layers and eggs which might be in connection with the activation of the Nrf2/HO-1 pathway and optimized gut microflora.

Increased fruit intake is associated with reduced risk of depression: evidence from cross-sectional and Mendelian randomization analyses.

Background: The association between dietary patterns and depression has gained significant attention, but the relationship between fruit intake and depression remains unclear. This study aimed to investigate the role of fruit intake in the risk of depression using data from the National Health and Nutrition Examination Survey (NHANES) and Mendelian randomization (MR) analysis, and further explore the causal relationship between them. Materials and methods: Cross-sectional analysis was conducted using the 2005-2018 NHANES data. Specialized weighted complex survey design analysis software was used for multivariate logistic analysis. Additionally, genetic variants for fruit intake and depression, as well as its related neuroticism traits, from the GWAS were used as instrumental variables in MR analysis. The inverse variance weighted (IVW) method was employed as the primary analysis method to evaluate the causal relationship between them. MR-Egger regression, MR-PRESSO test, and leave-one-out analysis were conducted to assess heterogeneity and pleiotropy. Results: In NHANES, compared to the lowest quartile (Q1, <0.12 cup], the highest quartile (Q4, >1.49 cups) of fruit intake showed a significant reduction in the risk of depression after adjusting for relevant covariates. Model 3, after rigorous adjustment for multiple covariates, demonstrated improved predictive performance in both Receiver operating characteristic (ROC) curve and Decision curve analysis (DCA). In Model 3, the proportion of reduced depression risk associated with fruit intake reached 31% (OR = 0.69, 95% CI: 0.50-0.95). This association remained significant in the MR analysis (OR = 0.92, 95% CI = 0.87-0.96; p = 5.09E-04). Fruit intake was also associated with a decreased risk of neuroticism traits related to depression, including feeling lonely (OR = 0.82, 95% CI = 0.74-0.90; p = 2.91E-05), feeling miserable (OR = 0.79, 95% CI = 0.72-0.87; p = 2.35E-06), feeling fed-up (OR = 0.75, 95% CI = 0.68-0.83; p = 2.78E-08), irritable mood (OR = 0.89, 95% CI = 0.79-0.99; p = 0.03), and neuroticism (OR = 0.85, 95% CI = 0.76-0.96; p = 9.94E-03). The causal relationship between feeling lonely and fruit intake was bidirectional. Conclusion: Increased fruit intake has a causal effect in reducing the risk of depression and is beneficial for related psychological well-being.

Multiform-based Baduanjin exercise prevention and treatment for idiopathic pulmonary fibrosis: study protocol for a randomized controlled trial.

INTRODUCTION: In this study, we will combine the traditional Baduanjin with Yijin Jing and Wuqinxi to create an optimized Baduanjin exercise program with three different forms (vertical, sitting, and horizontal) to adapt to idiopathic pulmonary fibrosis (IPF) patients in vairous stages of the disease. The purpose of this study is to explore and compare the therapeutic effects of this multi-form Baduanjin, traditional Baduanjin, and resistance training on lung function and limb motor function in IPF patients. The goal of this study is to prove a novel optimal exercise prescription strategy of Baduanjin exercise for improving and protecting lung function in IPF patients. METHODS/DESIGN: A single-blind and randomized controlled trial is used to conduct this study, while the randomization list will be generated using a computerized random number generator and opaque sealed envelopes with group allocation will be prepared. It will be strictly followed to blind the outcome assessors. and until the experiment's conclusion, participants won't know which group they are enrolled in. Patients between the ages of 35 and 80 who have stable diseases and have not regularly practiced Baduanjin exercise in the past will be included. They are divvied up into the following five groups at random: (1) The conventional care group (control group, CG), (2) The traditional Baduanjin exercise group (TG), (3) The modified Baduanjin exercise group (IG), (4) The resistance exercise group (RG) (5) The modified Baduanjin exercise combined with resistance exercise group (IRG). Those CG participants only received the usual treatment, while TC, IG, and RG participants exercised 1 h twice a day for 3 months. MRG participants will have a 3-month intervention with 1 h of Modified Baduanjin Exercise and 1 H of Resistance Training for each day. Every week, all groups underwent will supervis one-day training, with the exception of the control group. The Pulmonary Function Testing (PFT), HRCT, and 6MWT are the main outcome variables. The St. George Respiratory Questionnaire and mMRC are used as secondary outcome measures. DISCUSSION: This study may produce a new Baduanjin exercise prescription that is user-friendly, simple to execute, more targeted, and adaptable. Because it consists of three forms, including vertical, sitting, and horizontal, it is more adaptable to the various disease stages and actual situations of IPF patients and may compensate for the shortcomings of conventional pulmonary rehabilitation and traditional Baduanjin. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200055559 . Registered on 12 January 2022.

Identifying potential biomarkers of idiopathic pulmonary fibrosis through machine learning analysis.

Idiopathic pulmonary fibrosis (IPF) is the most common and serious type of idiopathic interstitial pneumonia, characterized by chronic, progressive, and low survival rates, while unknown disease etiology. Until recently, patients with idiopathic pulmonary fibrosis have a poor prognosis, high mortality, and limited treatment options, due to the lack of effective early diagnostic and prognostic tools. Therefore, we aimed to identify biomarkers for idiopathic pulmonary fibrosis based on multiple machine-learning approaches and to evaluate the role of immune infiltration in the disease. The gene expression profile and its corresponding clinical data of idiopathic pulmonary fibrosis patients were downloaded from Gene Expression Omnibus (GEO) database. Next, the differentially expressed genes (DEGs) with the threshold of FDR < 0.05 and |log2 foldchange (FC)| > 0.585 were analyzed via R package "DESeq2" and GO enrichment and KEGG pathways were run in R software. Then, least absolute shrinkage and selection operator (LASSO) logistic regression, support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF) algorithms were combined to screen the key potential biomarkers of idiopathic pulmonary fibrosis. The diagnostic performance of these biomarkers was evaluated through receiver operating characteristic (ROC) curves. Moreover, the CIBERSORT algorithm was employed to assess the infiltration of immune cells and the relationship between the infiltrating immune cells and the biomarkers. Finally, we sought to understand the potential pathogenic role of the biomarker (SLAIN1) in idiopathic pulmonary fibrosis using a mouse model and cellular model. A total of 3658 differentially expressed genes of idiopathic pulmonary fibrosis were identified, including 2359 upregulated genes and 1299 downregulated genes. FHL2, HPCAL1, RNF182, and SLAIN1 were identified as biomarkers of idiopathic pulmonary fibrosis using LASSO logistic regression, RF, and SVM-RFE algorithms. The ROC curves confirmed the predictive accuracy of these biomarkers both in the training set and test set. Immune cell infiltration analysis suggested that patients with idiopathic pulmonary fibrosis had a higher level of B cells memory, Plasma cells, T cells CD8, T cells follicular helper, T cells regulatory (Tregs), Macrophages M0, and Mast cells resting compared with the control group. Correlation analysis demonstrated that FHL2 was significantly associated with the infiltrating immune cells. qPCR and western blotting analysis suggested that SLAIN1 might be a signature for the diagnosis of idiopathic pulmonary fibrosis. In this study, we identified four potential biomarkers (FHL2, HPCAL1, RNF182, and SLAIN1) and evaluated the potential pathogenic role of SLAIN1 in idiopathic pulmonary fibrosis. These findings may have great significance in guiding the understanding of disease mechanisms and potential therapeutic targets in idiopathic pulmonary fibrosis.

Renal Protective Mechanisms of Shenyuan Particle in Db/Db Mice: A Study Based on Network Pharmacology.

Aim: The renal protective mechanisms of Shenyuan particle (SYP) in the treatment of diabetic kidney disease (DKD) were investigated, focusing on the main targets and pathways. Materials and Methods: In this study, the potential targets of compounds identified in SYP were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and a "herb-compound-target" network was constructed via Cytoscape. Next, the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were dissected using R language. A protein-protein interaction network was fabricated using STRING to obtain the main target information. In addition, db/db mice were used as the DKD models to explore the renal protective effects of SYP. Transmission electron microscopy, western blot, pathological staining, TUNEL staining, and biochemical methods were used to identify the apoptotic pathways and establish the primary mechanism of SYP. Results: Network pharmacology analysis revealed 67 potential targets based on the analysis of different databases. The targets of SYP were primarily associated with apoptosis. The network hub genes included caspase 3, caspase 7, caspase 8, caspase 9, Bax, and Bcl-2. In vivo, SYP materially improved renal function and inhibited apoptosis in the db/db mouse kidneys by improving the mitochondrial health. In addition, our results showed that SYP significantly decreased the expression of Bax, caspase 3, and Cyto-c and increased the expression of Bcl-2. Conclusions: Network pharmacology analysis and experimental results suggest that SYP ameliorates DKD mediated via multiple components, targets, and pathways. Our study further demonstrates that SYP inhibits apoptosis in the kidneys of db/db mice by improving the mitochondrial health and thereby alleviating renal damage.

Cinnamaldehyde regulates mitochondrial quality against hydrogen peroxide induced apoptosis in mouse lung mesenchymal stem cells via the PINK1/Parkin signaling pathway.

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease without effective treatments. Mitochondrial dysfunction weakens the ability of mesenchymal stem cells (MSCs) to repair the distal lung epithelium, which is a probable pathogenesis of IPF. In previous research, we found that cinnamaldehyde (CA) can maintain the mitochondrial morphology of MSCs. Methods: This present study evaluated the effect and mechanism of CA on murine lung MSCs using the hydrogen peroxide model. Antioxidant effects and mitochondrial function were determined using flow cytometry. The mRNA levels of mitochondrial dynamics and the expressions of autophagy-related proteins were also detected. Results: CA can increase the levels of SOD, MMP and ATP, decrease the rate of ROS and apoptosis, and restore the mitochondrial structure. CA can also improve the mRNA expression of MFN1, MFN2, FIS1, DRP1, OPA1, and PGC-1α, increase the expression of LC3 II and p62 and promote the PINK1/Parkin signaling pathway. Our results demonstrated that CA can control mitochondrial quality and avoid apoptosis, which may be associated with the regulation of the PINK1/Parkin signaling pathway.

Treatment with JianPiYiFei II granules for patients with moderate to very severe chronic obstructive pulmonary disease: A 52-week randomised, double-blinded, placebo-controlled, multicentre trial.

BACKGROUND: Complementary and alternative therapy is widely used to treat chronic obstructive pulmonary disease (COPD). A Chinese herbal medicine, JianPiYiFei (JPYF) II granules, have been shown to improve COPD patients' quality of life, however long-term effectiveness has not been examined. PURPOSE: To investigate whether long-term treatment with JPYF II granules is effective and safe for patients with stable, moderate to very severe COPD. STUDY DESIGN AND METHODS: A multicentre, randomised, double-blinded, placebo-controlled trial was conducted. Eligible participants from six hospitals were randomly assigned 1:1 to receive either JPYF II granules or placebo for 52 weeks. The primary outcome was the change in St. George's Respiratory Questionnaire (SGRQ) score during treatment. Secondary outcomes included the frequency of acute exacerbations during treatment, COPD Assessment Test (CAT), 6-minute walking test (6MWT), lung function, body mass index, airflow obstruction, dyspnoea, exercise capacity (BODE) index, and peripheral capillary oxygen saturation (SpO2) at the end of treatment. RESULTS: A total of 276 patients (138 in each group) were included in the analysis. JPYF II granules led to a significantly greater reduction in SGRQ score (-7.33 points, 95% CI -10.59 to -4.07; p < 0.0001) which reflects improved quality of life. JPYF II granules improved CAT (-3.49 points, 95% CI -5.12 to -1.86; p < 0.0001) and 6MWT (45.61 metres, 95% CI 20.26 to 70.95; p = 0.0005), compared with placebo. Acute exacerbations were less frequent with JPYF II granules than with placebo (0.87 vs. 1.34 events per patient; p = 0.0043). There were no significant differences between the groups in lung function, BODE index and SpO2. JPYF II granules were well tolerated and no significant adverse effects were noted. CONCLUSIONS: Long-term treatment with JPYF II granules is effective in moderate to very severe COPD, improving quality of life and exercise capacity, decreasing the risk of acute exacerbation, and relieving symptoms.

Efficacy and safety of Guizhi-Shaoyao-Zhimu decoction in the treatment of rheumatoid arthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Rheumatoid arthritis (RA) is a significant public health problem associated with a substantial burden of functional disability. The Guizhi-Shaoyao-Zhimu decoction (GSZD), a traditional medicine, has been used in China for a long time to treat RA. This study aimed to systematically investigate the efficacy and safety of GSZD in the treatment of RA. METHODS: We will search the electronic databases of PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, Wanfang Database, and China Biomedical Literature Database, and also manually search the Chinese Clinical Trial Register and unpublished studies or references, with the establishment up to February 2021. According to the inclusion and exclusion criteria, we will screen the literature, and the data are extracted independently by the 2 researchers. We will collect RCTs of GSZD in the treatment of RA. RevMan5.3 will be used for statistical analysis. According to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE), we will appraise each outcome quality evidence. RESULTS: We will publish the results in a peer-reviewed journal. CONCLUSION: We will evaluate the efficacy and safety of GSZD in treating RA. UNIQUE INPLASY NUMBER: INPLASY2020120147.

Efficacy of Xiang-Sha-Liu-Jun-Zi on chemotherapy-induced nausea and vomiting: A protocol for systematic review and meta-analysis.

BACKGROUND: Cancer is the main cause of death worldwide, and chemotherapy is the basic method of treating cancer. However, chemotherapy-induced nausea and vomiting (CINV) is the most common side effect of chemotherapy, and conventional antiemetics for the treatment of CINV also have side effects. At present, a large number of randomized controlled trials have shown that Xiang-Sha-Liu-Jun-Zi (XSLJZ) can effectively treat CINV, but there is no systematic review. Therefore, this systematic review aims to discuss the effectiveness of XSLJZ in the treatment of CINV. METHODS: Search for relevant documents in the Chinese and English databases, and the search time is limited to March 2021. Databases include Embase, Cochrane Library, Web of Science, PubMed, China National Knowledge Infrastructure, Chongqing VIP Information Resource Integration Service Platform, Wanfang Data, Chinese Biomedical Literature, etc. We will search the international clinical trial registration platform and the Chinese clinical trial registration platform to find ongoing and unpublished clinical trials. Randomized controlled trial of the efficacy of XSLJZ in the treatment of CINV were collected. After screening the literature according to the inclusion and exclusion criteria, two researchers independently extracted the data. The effective rate of treatment is the main outcome indicator of this study. The secondary indicators of this study include the incidence of adverse reactions and the improvement rate of quality of life. RevMan 5.3.5 software was used for statistical analysis. Grades of Recommendation, Assessment, Development, and Evaluation system will be used to evaluate the quality evidence for each outcome. RESULTS: This study will provide the latest evidence for the treatment of CINV by XSLJZ. CONCLUSION: : To evaluate the efficacy of XSLJZ in the treatment of CINV. UNIQUE INPLASY NUMBER: INPLASY202140079.

Fabrication of claviform fluorescent polymeric nanomaterials containing disulfide bond through an efficient and facile four-component Ugi reaction.

Multicomponent reactions (MCRs) have attracted broad interest for preparation of functional nanomaterials especially for the synthesis of functional polymers. Herein, we utilized an "old" MCR, the four-component Ugi reaction, to synthesize disulfide bond containing poly(PEG-TPE-DTDPA) amphiphilic copolymers with aggregation-induced emission (AIE) feature. This four-component Ugi reaction was carried out under rather mild reaction conditions, such as room temperature, no gas protection and absent of catalysts. The amphiphilic poly(PEG-TPE-DTDPA) copolymers with high number-average molecular weight (up to 86,440 Da) can self-assemble into claviform fluorescent polymeric nanoparticles (FPNs) in aqueous solution, and these water-dispersed nanoparticles exhibited strong emission, large Stokes shift (142 nm), low toxicity and remarkable ability in cellular imaging. Moreover, owing to the introduction of 3,3'-dithiodipropionic acid with disulfide bond, the resultant AIE-active poly(PEG-TPE-DTDPA) could display reduction-responsiveness and be utilized for synthesis of photothermal agents in-situ. Therefore, the AIE-active poly(PEG-TPE-DTDPA) could be promising for controlled intracellular delivery of biological activity molecules and fabrication of multifunctional AIE-active materials. Therefore, these novel AIE-active polymeric nanoparticles could be of great potential for various biomedical applications, such as biological imaging, stimuli-responsive drug delivery and theranostic applications.

Tracheal intubation of a difficult airway using Airway Scope, Airtraq, and Macintosh laryngoscope: a comparative manikin study of inexperienced personnel.

BACKGROUND: The Airway Scope (AWS) (Pentax-AWS, Hoya Corp., Tokyo, Japan) and the Airtraq (ATQ) (Prodol, Vizcaya, Spain) have similarities in the novel structures of their blades. In this study, we evaluated the ease of use of the AWS and ATQ compared with the Macintosh laryngoscope (ML) by inexperienced personnel in a simulated manikin difficult airway. METHODS: Twenty-four fifth-year medical students with no previous experience in tracheal intubation participated in this study. We used an advanced patient simulator (SimMan(R), Laerdal Medical, Stavanger, Norway) to simulate difficult airway scenarios including cervical spine rigidity, limited mouth opening, and pharyngeal obstruction. The sequences in selecting devices and scenarios were randomized. Success rates for tracheal intubation, and the time required for visualization of the glottis, tracheal intubation, and inflation of the lungs, and the number of optimization maneuvers and dental click sounds were analyzed. The 3 different intubation devices were tested in 4 different scenarios by 24 students. RESULTS: Both the AWS and ATQ had very high success rates of tracheal intubation compared with the ML (AWS 100%*; ATQ 98%*; and ML 89%; *P < 0.05 AWS, ATQ versus ML). The time to intubation with the AWS was significantly shorter than with the ATQ and ML (AWS 11 +/- 6 seconds; ATQ 16 +/- 12 seconds; and ML 16 +/- 11 seconds; *P < 0.05 AWS versus ATQ, ML). The number of optimization maneuvers with the AWS was significantly lower than with the ATQ and ML. There were significantly more audible dental click sounds with the ML than with the AWS and ATQ. CONCLUSION: Both the AWS and ATQ may be suitable devices for difficult intubation by inexperienced personnel in this manikin simulated scenario. Further studies in a clinical setting are necessary to confirm these findings.