Yunzhi Chen’s research while affiliated with China Academy of Traditional Chinese Medicine and other places

Purpose: Periodontitis and heart failure (HF) impact millions of individuals globally with heavy social and economic burden. Prior research has indicated a connection between them. However, the conclusions have been somewhat inconsistent. Our objective is to confirm, through meta-analysis and Mendelian randomisation studies, whether patients with periodontitis have an increased risk of HF. Therefore, we conducted a comprehensive analysis to explore the causal association between periodontitis and the risk of HF. Materials and methods: In this meta-analysis, we searched online to identify studies involving periodontitis on the risk of HF. The main endpoint assessed in this study was the risk of HF. We used R language to calculate the pooled results and create plots. A random-effects model was employed in the analyses. In the Mendelian randomisation (MR) analyses, we obtained data from public databases. MR analyses were conducted using genome-wide association data for acute and chronic periodontitis. Independent genetic variants associated significantly with each exposure (P 5*10-6) were considered as instruments. The primary analysis employed the inverse variance weighted (IVW) method, which was subsequently supplemented by a series of sensitivity analyses to ensure the robustness and reliability of the findings. Results: Our meta-analysis included three publications, with a total of 21,997 participants. The pooled result demonstrated that periodontitis increased the risk of HF (OR = 1.62, 95% CI 1.29-2.03). Periodontitis increased the risk of heart failure with reduced ejection fraction (HFrEF) with a low level of heterogeneity (OR = 1.99, 95% CI 1.22-3.23) and heart failure with preserved ejection fraction (HFpEF) with little heterogeneity (OR = 1.36, 95% CI 1.00-1.86). In the MR study, acute or chronic periodontitis did not increase the risk of HF. Sensitivity analyses revealed that the causal association estimations were robust. Conclusion: In summary, the meta-analysis results indicate that individuals with periodontitis are at a higher risk of HF. The findings from the MR study fail to establish a causal link between the two variables under investigation. To validate this assertion and elucidate the fundamental mechanism, additional research is imperative. Clinical significance: Based on the current evidence, it cannot be concluded that there is a causal relationship between acute or chronic periodontitis and HF.

Background Asthma seriously affects people’s survival and quality of life, causing a huge economic burden on society. Modern clinical use of Qianjinweijing Decoction (QJWJ) for the treatment of asthma has achieved good results. However, there is still a lack of research on its efficacy and mechanism of action. Therefore, the purpose of this study is to evaluate the efficacy of QJWJ in the treatment of asthma by systematic review and meta-analysis, and to explore its potential mechanism by network pharmacology. Methods The meta-analysis was performed to search for studies published before May 2023 in 7 databases, and Revman 5.4 and R language softwares were used for analysis. Network pharmacology was based on open databases and softwares such as Cytoscape, Perl, Autoduck Vina, and R language. Results A total of 14 studies were included, involving 1200 patients. The results of the meta-analysis showed that QJWJ could significantly improve the clinical efficacy of asthma patients compared with routine pharmacotherapy (risk ratio = 1.22, 95% CI [1.16, 1.28], P < .00001), enhance lung function, such as FEV 1 /FVC (mean difference [MD] = 5.63, 95% CI [1.45, 9.81], P = .008), FEV 1 % (MD = 5.03, 95% CI [4.32, 5.74], P < .00001), PEF (standardized mean difference = 1.37, 95% CI [1.03, 1.71], P < .00001), and increase traditional Chinese medicine syndrome score (MD = −2.50, 95% CI [−4.81, −0.19], P = .03). The results of network pharmacology suggested that the 4 traditional Chinese medicines in QJWJ included 35 active ingredients and 34 potential targets for the treatment of asthma. The core ingredients involved were stigmasterol, β-sitosterol, hederagenin, and gibberellin 7. The core targets were PTGS2, BCL2, and CASP3. The interaction pathway between QJWJ and asthma was mainly enriched in p53, cyclic guanosine monophosphate–protein kinase G, IL-17, and advanced glycation end products-receptor for advanced glycation end products signaling pathways. Molecular docking showed that the core ingredients had good binding activity with the core targets. Conclusion QJWJ is effective in the treatment of asthma, and the therapeutic mechanism may be related to its regulation of inflammation, immunity, and apoptosis.

Targeting specific gut microbiota (GM) species to prevent and treat acute upper respiratory tract infection (AURTI) has attracted researchers’ attention, but the relationship between the two is unclear. Based on the summary data from genome-wide association studies (GWAS) on GM and five types of AURTIs (acute nasopharyngitis (common cold), acute pharyngitis, acute sinusitis, acute upper respiratory infections, and acute upper respiratory infections of multiple and unspecified sites), we performed two-sample bidirectional Mendelian randomization (MR) to assess the causal relationship. Through inverse variance weighting (IVW) method, we found that 33 potential microbial taxa can influence the occurrence of AURTI. Sensitivity analysis showed no potential horizontal pleiotropy and heterogeneity bias. We further employed multivariable Mendelian randomization to investigate the impact of potential interference factors on the significant associations previously identified, considering aspects such as comorbidities associated with AURTI, seasonal variations, pathogen specificity, and history of antibiotic allergies. Ultimately, 11 microbial taxa remained significantly associated. This study provides robust evidence for a causal relationship between GM and five types of AURTIs, thereby offering a foundation for the development of microbiota-targeted therapies and related probiotic interventions aimed at AURTI.

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disorder with environmental factors being the primary risk determinants. However, genetic factors also substantially contribute to the susceptibility and progression of COPD. Although genome-wide association studies (GWAS) have identified several loci associated with COPD susceptibility, the specific pathogenic genes underlying these loci, along with their biological functions and roles within regulatory networks, remain unclear. This lack of clarity constrains our ability to achieve a deeper understanding of the genetic basis of COPD. This study leveraged the FinnGen R11 genetic dataset, comprising 21,617 cases and 372,627 controls, along with GTEx V8 eQTLs data to conduct a cross-tissue transcriptome-wide association study (TWAS). Initially, we performed a cross-tissue TWAS analysis using the Unified Test for Molecular Signatures (UTMOST), followed by validation of the UTMOST findings in single tissues using the Functional Summary-based Imputation (FUSION) method and conditional and joint (COJO) analyses of the identified genes. Subsequently, candidate susceptibility genes were screened using Multi-marker Analysis of Genomic Annotation (MAGMA). The causal relationship between these candidate genes and COPD was further evaluated through summary data-based Mendelian randomization (SMR), colocalization analysis, and Mendelian randomization (MR). Additionally, the identified results were validated against the COPD dataset in the GWAS Catalog (GCST90399694). GeneMANIA was employed to further explore the functional significance of these susceptibility genes. In the cross-tissue TWAS analysis (UTMOST), we identified 17 susceptibility genes associated with COPD. Among these, a novel susceptibility gene, G protein-coupled receptor kinase 4 (GRK4), was validated through single-tissue TWAS (FUSION) and MAGMA analyses, with further confirmation via SMR, MR, and colocalization analyses. Moreover, GRK4 was validated in an independent dataset. This study identifies GRK4 as a potential novel susceptibility gene for COPD, which may influence disease risk by exacerbating inflammatory responses. The findings address gaps in previous single-tissue GWAS studies, revealing consistent expression and potential function of GRK4 across different tissues. However, considering the study’s limitations, further investigation and validation of GRK4’s role in COPD are warranted.

Although many genome-wide association studies (GWAS) have confirmed the negative associations between rs401681[T] / rs402710[T] in the Cleft lip and cleft palate transmembrane protein 1 (CLPTM1L) region and lung cancer (LC) susceptibility in Caucasian and Asian populations, some other studies haven’t found these negative associations. The purpose of this study is to clarify the associations between them and LC, as well as the differences in these associations between patients of different ethnicities (Caucasians and Asians), LC subtypes and smoking status. Relevant literatures published before July 7, 2023 in PubMed, EMbase, Web of Science, MEDLINE were searched through the Internet. Statistical analysis of data was performed in Revman 5.3, including drawing forest plots, funnel plots and so on. Sensitivity and publication bias were performed in Stata 14.0. TSA software was performed for the trial sequential analysis (TSA) tests to assess the stability of the results. Registration number: CRD42023407890. A total of 41 literatures (containing 44 studies: 16 studies in Caucasians and 28 studies in Asians) were included in this meta-analysis, including 126476 LC patients and 191648 healthy controls. The results showed that the T allele variants of rs401681 and rs402710 were negatively associated with the risk of LC (rs401681[T]: [OR] = 0.87, 95% CI [0.86, 0.88]; rs402710[T]: [OR] = 0.88, 95% CI [0.86, 0.89]), and the negative associations were stronger in Caucasians than in Asians (Subgroup differences: I² > 50%). In LC subtypes, the rs401681[T] was negatively associated with the risk of Non-small-cell lung carcinoma (NSCLC), Lung adenocarcinoma (LUAD) and Lung squamous cell carcinoma (LUSC) (P < 0.05), and these negative associations were stronger in Caucasians than in Asians (Subgroup differences: I² > 50%). The rs402710[T] was negatively associated with the risk of NSCLC, LUAD and LUSC (P < 0.05), and these negative associations in Caucasians were the same as in Asians (Subgroup differences: I² < 50%). The rs401681[T] was negatively associated with the risk of LC in both smokers and non-smokers (P < 0.05), and the negative association for smokers equals to that of non-smokers (Subgroup differences: P = 0.25, I² = 24.2%). In LC subtypes, the rs401681[T] was negatively associated with the risks of NSCLC and LUAD in both Caucasian smokers and Asian non-smokers (P < 0.05). The rs402710[T] was negatively associated with the risk of LC in both smokers and non-smokers (P < 0.05), and there was no difference in the strength of this negative risk association between them in Caucasians (Subgroup differences: I² = 0%). In Asians, this negative association was found to be predominantly among smokers ([OR] = 0.80, 95%CI [0.65, 0.99]). In LC subtypes, the rs402710[T]was negatively associated with the risk of NSCLC in non-smokers, and this negative association was found to be predominantly among non-smokers in Asians ([OR] = 0.75, 95%CI [0.60, 0.94]). The T allele variants of rs401681 and rs402710 are both negatively associated with the risk of developing LC, NSCLC (LUAD, LUSC) in the Caucasian and Asian populations, and the negative associations with the risk of LC are higher in Caucasians. Smoking is an important risk factor for inducing the rs401681 and rs402710 variants and causes LC development in both populations. Other factors like non-smoking are mainly responsible for inducing the development of NSCLC in Asians, and is concentrated in LUAD among Asian non-smoking women.

Background Although the G allele variant of TERT-CLPTM1L rs4975616 has been confirmed to be negatively associated to the risk of lung cancer (LC), some other studies haven’t found this negative association. The purpose of this study is to clarify the association of the rs4975616 with the risk of developing LC and the differences of this association among patients with different ethnicities (Caucasians and Asians), different subtypes of LC, and different smoking status. Methods Relevant literatures published before July 20, 2023 in PubMed, EMbase, Web of Science, MEDLINE databases were searched through the Internet. Statistical analysis of data was performed in Revman5.3, including drawing forest plots, funnel plots and so on. Sensitivity and publication bias were performed in Stata 14.0. The stability of the results was assessed using Test Sequence Analysis (TSA) software. Registration number: CRD42024568348. Results The G allele variant of rs4975616 was negatively associated with the risk of LC ([OR] = 0.86, 95%CI [0.84, 0.88]), and that this negative association was present in both Caucasians ([OR] = 0.85, 95%CI [0.83, 0.87]) and Asians ([OR] = 0.91, 95%CI [0.86, 0.95]), and the strength of the negative association was higher in Caucasians than in Asians (subgroup differences: P = 0.02, I² = 80.3%). Across LC subtypes, rs4975616[G] was negatively associated with the risk of NSCLC (LUAD, LUSC) in both Caucasians and Asians (P<0.05) and the strength of the association with NSCLC (LUAD) was higher in Caucasians than in Asians (Subgroup differences: I²>50%). In Caucasians, rs4975616[G] was negatively associated with the risk of LC in both smokers and non-smokers (P<0.05), and the strength of the association did not differ between smokers and non-smokers (Subgroup differences: P = 0.18, I² = 45.0%). In Asians, rs4975616[G] was mainly negatively associated with the risk of LC in smokers (P<0.05) but not in non-smokers ([OR] = 0.97, 95%CI [0.78, 1.20]). Comparisons between the two populations showed that the strength of this negative association was higher in Caucasian non-smokers than in Asian non-smokers (Subgroup differences: P = 0.04, I² = 75.3%), whereas the strength of this negative association was the same for Caucasian smokers as for Asian smokers (Subgroup differences: P = 0.42, I² = 0%). Among the different LC subtypes, rs4975616[G] was negatively associated with the risk of NSCLC (LUAD) incidence in both Asian smokers and Caucasian non-smokers (P<0.05), whereas it was not associated with the risk of NSCLC development in Asian non-smokers (P>0.05). Comparisons between the two populations showed that the strength of the association was higher in Caucasian non-smokers than in Asian non-smokers (Subgroup differences: I²>50%). Conclusion The G allele variant of rs4975616 is negatively associated with the risk of LC and NSCLC (LUAD, LUSC). Compared with Asians, Caucasians are more likely to have a higher risk of LC and NSCLC (LUAD) due to the rs4975616 variant. In Caucasians, smoking and other factors like non-smoking contribute to rs4975616 variations leading to LC, and other factors like non-smoking also induce rs4975616 variations leading to NSCLC (LUAD). In Asians, smoking is the major risk factor for the induction of rs4975616 variations leading to LC and NSCLC(LUAD).

At present, the angiotensin‐converting enzyme (ACE) I/D polymorphism was considered to be associated to the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the association between it and the risk of COPD in different ethnic groups is still unclear. The purpose of this study is to conduct an updated meta‐analysis of the association between them; collect literatures published before 10 February 2023 by searching PubMed, Embase, MEDLINE, CBM, CNKI, Wanfang, and VIP Chinese scientific databases; and display the analysis results by drawing forest plots. At the same time, publication bias, sensitivity analysis, and trial sequential analysis (TSA) were performed to evaluate the stability and reliability of the results. In the overall population, the result of the DD versus II model showed the association with the risk of COPD ([OR] = 1.30, 95% CI [1.08, 1.56]), and there were no associations in other genetic models (p > 0.05). In Caucasians, the results of all genetic models showed no associations (p > 0.05). In Asians, the results of D versus I, DD versus II, and DD versus II + ID models showed the associations with the risk of COPD (D vs. I: [OR] = 1.48, 95% CI [1.14, 1.93]; DD vs. II: [OR] = 2.04, 95% CI [1.53, 2.72]; DD vs. II + ID: [OR] = 2.19, 95% CI [1.45, 3.29]), while the results of ID versus II and DD + ID versus II models showed no associations (p > 0.05). Therefore, the D allele and “DD” genotype variation of the ACE I/D gene polymorphism are associated with susceptibility to COPD in Asians but not in Caucasians.

Background Observational studies have suggested an association between gut microbiota and Alzheimer’s disease (AD); however, the causal relationship remains unclear, and the role of blood metabolites in this association remains elusive. Purpose To elucidate the causal relationship between gut microbiota and AD and to investigate whether blood metabolites serve as potential mediators. Materials and methods Univariable Mendelian randomization (UVMR) analysis was employed to assess the causal relationship between gut microbiota and AD, while multivariable MR (MVMR) was utilized to mitigate confounding factors. Subsequently, a two-step mediation MR approach was employed to explore the role of blood metabolites as potential mediators. We primarily utilized the inverse variance-weighted method to evaluate the causal relationship between exposure and outcome, and sensitivity analyses including Contamination mixture, Maximum-likelihood, Debiased inverse-variance weighted, MR-Egger, Bayesian Weighted Mendelian randomization, and MR pleiotropy residual sum and outlier were conducted to address pleiotropy. Results After adjustment for reverse causality and MVMR correction, class Actinobacteria (OR: 1.03, 95% CI: 1.01–1.06, p = 0.006), family Lactobacillaceae (OR: 1.03, 95% CI: 1.00–1.05, p = 0.017), genus Lachnoclostridium (OR: 1.03, 95% CI: 1.00–1.06, p = 0.019), genus Ruminiclostridium9 (OR: 0.97, 95% CI: 0.94–1.00, p = 0.027) and genus Ruminiclostridium6 (OR: 1.03, 95% CI: 1.01–1.05, p = 0.009) exhibited causal effects on AD. Moreover, 1-ribosyl-imidazoleacetate levels (−6.62%), Metabolonic lactone sulfate levels (2.90%), and Nonadecanoate (19:0) levels (−12.17%) mediated the total genetic predictive effects of class Actinobacteria on AD risk. Similarly, 2-stearoyl-GPE (18:0) levels (−9.87%), Octadecanedioylcarnitine (C18-DC) levels (4.44%), 1-(1-enyl-stearoyl)-2-oleoyl-GPE (p-18:0/18:1) levels (38.66%), and X-23639 levels (13.28%) respectively mediated the total genetic predictive effects of family Lactobacillaceae on AD risk. Furthermore, Hexadecanedioate (C16-DC) levels (5.45%) mediated the total genetic predictive effects of genus Ruminiclostridium 6 on AD risk; Indole-3-carboxylate levels (13.91%), X-13431 levels (7.08%), Alpha-ketoglutarate to succinate ratio (−13.91%), 3-phosphoglycerate to glycerate ratio (15.27%), and Succinate to proline ratio (−14.64%) respectively mediated the total genetic predictive effects of genus Ruminiclostridium 9 on AD risk. Conclusion Our mediation MR analysis provides genetic evidence suggesting the potential mediating role of blood metabolites in the causal relationship between gut microbiota and AD. Further large-scale randomized controlled trials are warranted to validate the role of blood metabolites in the specific mechanisms by which gut microbiota influence AD.