Xiaozheng Wu’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.

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 Danhong injection, a compound injection of Chinese herbal medicine, has been widely used in idiopathic pulmonary fibrosis (IPF) at present as an adjuvant treatment. However, the clinical efficacy and molecular mechanism of IPF are still unclear. This study will evaluate and explore the clinical efficacy and molecular mechanism of Danhong injection in the treatment of IPF. Methods In meta-analysis, the computer was used to search 8 databases (PubMed, EMbase, CENTRAL, MEDLINE, CBM, CNKI, WanFang, and VIP) to collect the RCTs, and RevMan 5.3 and Stata 14.0 were used for statistical analysis. It has been registered on PROSPERO: CRD42020221096. In network pharmacology, the main chemical components and targets of the chemical components of Danhong injection were obtained in TCMSP and Swiss Target Prediction databases. The main targets of IPF were obtained through Gencards, Disgenet, OMIM, TTD, and DRUGBANK databases. The String platform was used to construct PPI networks. Cytoscape 3.8.2 was used to construct the “Danhong components – IPF targets-pathways” network. The molecular docking verification was conducted by Auto Dock. Results Twelve RCTs were finally included with a total of 896 patients. The meta-analysis showed that Danhong injection could improve the clinical efficiency ([OR] = 0.25, 95% CI [0.15, 0.41]), lung function, arterial blood gas analysis, inflammatory cytokines, and serum cytokines associated with pulmonary fibrosis of IPF patients, respectively ( P < .05). The core active components of Danhong injection on IPF were Luteolin, Quercetin, and Kaempferol, and the core targets were PTGS2, AR, ESR1, PPARG, and RELA. Danhong injection mainly improved IPF through PD-L1 expression and PD-1 checkpoint path in cancer, pathways in cancer, PI3K-Akt signaling pathway, etc. Conclusion These results provided scientific basis for the clinical use of Danhong injection for the treatment of IPF, and provided a new direction to explore the potential mechanism of action of Danhong injection.

Objective Randomized controlled trials(RCTs) of multiple drugs for Idiopathic pulmonary fibrosis(IPF) have been reported and achieved a certain degree of efficacy, however, the difference in safety and efficacy of them for IPF is not yet well understood. The aim of this network meta-analysis is to assess their safety and efficacy in the treatment of IPF and differences in this safety and efficacy comprehensively. Methods The PubMed, EMbase, CENTRAL and MEDLINE were retrieved to find out the RCTs of drugs in the treatment of IPF. The retrieval date is from construction to November 10, 2022. Stata 14.0 and RevMan 5.3 was used for statistical analysis. Registration number: CRD42023385689. Results Twenty-four studies with a total of 6208 patients were finally included, including RCTs of 13 drugs. The results of safety showed that there' s no difference in the incidence of SAEs of 13 drugs treated with IPF compared to placebo (P>0.05), and it’s also found that Warfarin had a higher all-cause mortality for IPF than placebo (OR = 5.63, 95% CI [1.54 to 20.55]). SUCRA' s scatterplot showed that Pirfenidone, Nintedanib, Sildenafil and Imatinib were lower than placebo, and Warfarin, Ambrisentan and N-acetylcysteine were higher than placebo. The results of effectiveness showed that Nintedanib (MD = -0.08, 95% CI [-0.12 to -0.04]) improved FVC (L)absolute change from baseline in patients better than placebo, and Nintedanib (OR=1.81, 95% CI [1.23 to 2.66]), Pirfenidone (OR=1.85, 95%CI [1.26 to 2.71]) and Pamrevlumab (OR=4.11, 95% CI [1.25 to 13.58]) improved the proportion of patients with a decline in FVC ≥10% predicted better than placebo. SUCRA' s scatterplot showed that Pamrevlumab, Pirfenidone and Nintedanib were lower than placebo, and Warfarin and Ambrisentan were higher than placebo. Conclusion Compared with other drugs, Nintedanib and Pirfenidone can significantly slow the decline of lung function in patients with IPF, and the safety is higher. Therefore, they can be further promoted in clinical practice. Warfarin and Ambrisentan shouldn’t be used clinically for IPF as the safety and efficacy of them are poor compared to other drugs and placebo. Pamrevlumab may become important drugs for the treatment of IPF in the future.

The rs2736100 (A > C) polymorphism of the second intron of Telomerase reverse transcriptase (TERT) has been confirmed to be closely associated with the risk of Lung cancer (LC), but there is still no unified conclusion on the results of its association with LC. This study included Genome-wide association studies (GWAS) and case–control studies reported so far on this association between TERT rs2736100 polymorphism and LC to clarify such a correlation with LC and the differences in it between different ethnicities and different types of LC. Relevant literatures published before May 7, 2022 on ‘TERT rs2736100 polymorphism and LC susceptibility’ in PubMed, EMbase, CENTRAL, MEDLINE databases were searched through the Internet, and data were extracted. Statistical analysis of data was performed in Revman5.3 software, including drawing forest diagrams, drawing funnel diagrams and so on. Sensitivity and publication bias analysis were performed in Stata 12.0 software. The C allele of TERT rs2736100 was associated with the risk of LC (Overall population: [OR] = 1.21, 95%CI [1.17, 1.25]; Caucasians: [OR] = 1.11, 95%CI [1.06, 1.17]; Asians: [OR] = 1.26, 95%CI [1.21, 1.30]), and Asians had a higher risk of LC than Caucasians (C vs. A: Caucasians: [OR] = 1.11 /Asians: [OR]) = 1.26). The other gene models also showed similar results. The results of stratified analysis of LC patients showed that the C allele was associated with the risk of Non-small-cell lung carcinoma (NSCLC) and Lung adenocarcinoma (LUAD), and the risk of NSCLC and LUAD in Asians was higher than that in Caucasians. The C allele was associated with the risk of Lung squamous cell carcinoma (LUSC) and Small cell lung carcinoma(SCLC) in Asians but not in Caucasians. NSCLC patients ([OR] = 1.27) had a stronger correlation than SCLC patients ([OR] = 1.03), and LUAD patients ([OR] = 1.32) had a stronger correlation than LUSC patients ([OR] = 1.09).In addition, the C allele of TERT rs2736100 was associated with the risk of LC, NSCLC and LUAD in both smoking groups and non-smoking groups, and the risk of LC in non-smokers of different ethnic groups was higher than that in smokers. In the Asians, non-smoking women were more at risk of developing LUAD. The C allele of TERT rs2736100 is a risk factor for LC, NSCLC, and LUAD in different ethnic groups, and the Asian population is at a more common risk. The C allele is a risk factor for LUSC and SCLC in Asians but not in Caucasians. And smoking is not the most critical factor that causes variation in TERT rs2736100 to increase the risk of most LC (NSCLC, LUAD). Therefore, LC is a multi-etiological disease caused by a combination of genetic, environmental and lifestyle factors.

Background: Although many genome-wide association studies(GWAS) have confirmed the associations between multiple sites in the TERT-CLPTM1L region and lung cancer(LC) susceptibility in different populations, some of them haven’t found the associations between these sites and LC. The purpose of this study is to clarify the associations between TERT-CLPTM1L polymorphism and LC, as well as the differences in these associations between patients of different ethnicities and different LC subtypes. Methods: Relevant literatures published before May 7, 2022 on ‘TERT-CLPTM1L polymorphisms and LC susceptibility’ in PubMed, EMbase,Web of Science, MEDLINE databases were searched through the Internet. Statistical analysis of data was performed in Revman5.3 software, including drawing forest plots, funnel plots and so on. Sensitivity and publication bias analysis were performed in Stata 14.0 software. TSA 0.9.5.10 software was performed for the Trial sequential analysis(TSA) tests to evaluate the stability of the results. Registration number: CRD42023407890. Results: A total of 51 literatures were included in this meta-analysis, including 6 TERT-CLPTM1L polymorphisms and a total of 54 studies (12 GWAS and 42 case-control studies), including 11 studies in Caucasians and 43 studies in Asians. The results showed that the minor allele variants of the 6 polymorphisms were positively or negatively associated with the risk of LC (rs2736098[T]: [OR]=1.24, 95% CI [1.18, 1.31]; rs2736100[C]: [OR]=1.25, 95% CI [1.20, 1.30]; rs31489[A]: [OR]=0.87, 95% CI [0.82, 0.92]; rs401681[T]: [OR]=0.87, 95% CI [0.84, 0.90]; rs402710[T]: [OR]=0.86, 95% CI [0.83, 0.88]; rs4975616[G]: [OR]=0.86, 95% CI [0.82, 0.91]). However, there were clear differences in these associations in LC with different pathological subtypes in Caucasian and Asian populations (Subgroup differences: I²≥50%). Conclusions: Our results confirmed the clear associations between 6 TERT-CLPTM1L polymorphisms and the risk of LC, and there were significant differences in these associations among different ethnicities/pathological subtypes of LC.