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Numerous metabolomic studies have confirmed the pivotal role of metabolic abnormalities in the development of idiopathic pulmonary fibrosis (IPF). Nevertheless, there is a lack of evidence on the causal relationship between circulating metabolites and the risk of IPF. The potential causality between 486 blood metabolites and IPF was determined through a bidirectional two-sample Mendelian randomization (TSMR) analysis. A genome-wide association study (GWAS) involving 7,824 participants was performed to analyze metabolite data, and a GWAS meta-analysis involving 6,257 IPF cases and 947,616 control European subjects was conducted to analyze IPF data. The TSMR analysis was performed primarily with the inverse variance weighted model, supplemented by weighted mode, MR-Egger regression, and weighted median estimators. A battery of sensitivity analyses was performed, including horizontal pleiotropy assessment, heterogeneity test, Steiger test, and leave-one-out analysis. Furthermore, replication analysis and meta-analysis were conducted with another GWAS dataset of IPF containing 4,125 IPF cases and 20,464 control subjects. Mediation analyses were used to identify the mediating role of confounders in the effect of metabolites on IPF. There were four metabolites associated with the elevated risk of IPF, namely glucose (odds ratio [OR] = 2.49, 95% confidence interval [95%CI] = 1.13-5.49, P = 0.024), urea (OR = 6.24, 95% CI = 1.77-22.02, P = 0.004), guanosine (OR = 1.57, 95%CI = 1.07-2.30, P = 0.021), and ADpSGEGDFXAEGGGVR (OR = 1.70, 95%CI = 1.00-2.88, P = 0.0496). Of note, the effect of guanosine on IPF was found to be mediated by gastroesophageal reflux disease. Reverse Mendelian randomization analysis displayed that IPF might slightly elevate guanosine levels in the blood. Conclusively, hyperglycemia may confer a promoting effect on IPF, highlighting that attention should be paid to the relationship between diabetes and IPF, not solely to the diagnosis of diabetes. Additionally, urea, guanosine, and ADpSGEGDFXAEGGGVR also facilitate the development of IPF. This study may provide a reference for analyzing the potential mechanism of IPF and carry implications for the prevention and treatment of IPF.

Background Xiao-ai-ping injection (XAPI), as patented Chinese medicine, has shown promising outcomes in non-small-cell lung cancer (NSCLC) patients. This meta-analysis investigated the efficacy and safety of XAPI in combination with platinum-based chemotherapy. Methods A comprehensive literature search was conducted to identify relevant studies in Pubmed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure, Wangfang Database, VIP Database, and Chinese Biology Medical Database from the date of their inception to September 2018. The RevMan 5.3 software was applied to calculate the risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI). Results We included and analyzed 24 randomized controlled trials. The meta-analysis showed that XAPI adjunctive to platinum-based chemotherapy had better outcomes in objective tumor response rate (ORR) (RR: 1.27, 95% CI, 1.14–1.40); improved Karnofsky performance scores (KPS) (RR: 1.70, 95% CI, 1.48–1.95); reduction in occurrence of grade 3/4 leukopenia (RR: 0.49, 95% CI, 0.38–0.64), anemia (RR: 0.63, 95% CI, 0.46–0.87) and thrombocytopenia (RR: 0.53, 95% CI, 0.38–0.73), nausea and vomiting (RR: 0.57, 95% CI, 0.36–0.90); and enhanced immune function (CD8 + [MD: 4.96, 95% CI, 1.16–8.76] and CD4 + /CD8 + [MD: 2.58, 95% CI, 1.69–3.47]). However, it did not increase dysregulated liver and kidney function, diarrhea, constipation, and fatigue. Subgroup analysis of ORR and KPS revealed that dosage, treatment duration, and methodological quality did not affect the outcome significantly. Conclusions Our meta-analyses demonstrated that XAPI in combination with platinum-based chemotherapy had a better tumor response, improved the quality of life, attenuated adverse side effects, and enhanced immune function, which suggests that it might be used for advanced NSCLC. Moreover, low dosage (< 60 ml/d) and long-term treatment of XAPI might be a choice for advanced NSCLC patients.

The combination of Aidi injection (ADI) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in treating non-small cell lung cancer (NSCLC) has been reported, but the effects of this therapy have not been systematically assessed. Randomized controlled trials (RCTs) published before June 2020 were searched from 6 databases. Two reviewers independently assessed the methodological quality of 8 RCTs involving 667 patients diagnosed with stage III-IV NSCLC. We found that ADI combined with EGFR-TKI increased the objective response rate (ORR) significantly (relative risk [RR]: 1.60; 95% confidence interval [CI]: 1.28-1.99, P < 0.0001). There was also improvement in the disease control rate (DCR) (RR: 1.25; 95% CI: 1.11-1.40, P = 0.0002) as compared with EGFR-TKI alone. This therapy also increased the percentage of CD3+ cells (weighted mean difference [WMD]: 9.86; 95% CI: 4.62-15.10), CD4+ cells (WMD: 6.10; 95% CI: 1.67-10.53), and the CD4+/CD8+ (WMD: 0.35; 95% CI: 0.28-0.43). With regard to drug toxicity, the occurrence of rash was significantly reduced by ADI combined with EGFR-TKI (RR: 0.78, 95% CI: 0.63-0.97, P = 0.03); however, we did not find a significant reduction in the occurrence of dry skin, nausea and vomiting, as well as diarrhea between the 2 therapies. ADI combined with first-generation EGFR-TKIs may be more effective in improving tumor response, reducing the occurrence of rash, and enhancing immune function in NSCLC than EGFR-TKI alone.

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal lung disease with poor prognosis and limited treatment options. N-acetylcysteine (NAC), an anti-oxidant drug, has promising potential in the treatment of IPF. In the present systematic review and meta-analysis, the efficacy and safety of NAC for IPF were investigated. The following databases were comprehensively searched for relevant studies published until August 2018: Pubmed, Embase, Cochrane library, Chinese National Knowledge Infrastructure, Wangfang Database, VIP and the Chinese Biology Medical Database. A total of 21 controlled trials assessing the efficacy and safety of NAC therapy for IPF were identified and primary outcomes [forced vital capacity (FVC), adverse side effects] and secondary outcomes [diffusing capacity for carbon monoxide (DLCO) and its percentage predicted value (DLCO%), vital capacity (VC), partial arterial oxygen pressure (PaO2), 6-min walking distance test and mortality] were extracted for the meta-analysis. The risk ratio and mean difference or standardized mean difference with 95% confidence interval were calculated using RevMan 5.3 software. Analysis of the pooled data revealed that, compared with control treatments (routine treatment or drugs other than anti-oxidants), NAC therapy reduced the decline in lung function, as indicated by the FVC and DLCO, and slowed the progression of the disease, as indicated by the PaO2, while complications and mortality were similar. These results suggest good efficacy, tolerability and safety of the treatment. Furthermore, subgroup analysis revealed that combined therapy including NAC for IPF might be more effective than NAC monotherapy, while oral administration of NAC was safer than inhalation. In conclusion, the results of the present review and meta-analysis provide important information that may serve as a guide regarding NAC therapy for IPF in clinical practice.

Idiopathic pulmonary fibrosis (IPF) is a worsening fibrotic condition characterized by a short survival rate and limited treatment options. This study evaluates the potential anti-fibrotic properties of Schisandrin B (Sch B) through network pharmacology and experimental validation. A mouse model of bleomycin-induced pulmonary fibrosis was established, and the modeled mice were treated with Sch B at three doses (20 mg/kg/day, 40 mg/kg/day, and 80 mg/kg/day). A fibrotic model was developed in NIH/3T3 cells by treating them with TGF-β (10 ng/mL) and administering Sch B at various concentrations (10, 20, and 40 µM). The results revealed that Sch B treatment delayed the development of bleomycin-induced pulmonary fibrosis and substantially decreased the transcription levels of collagen I and α-SMA in TGF-β-induced fibroblasts. Core targets were screened with protein-protein interaction network analysis, molecular complex detection (MCODE), and CytoHubba plugin. The application of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and molecular docking highlighted the significance of the HIF-1α signaling pathway in the potential mechanism of Sch B in IPF therapy. Western blot, PCR, and immunofluorescence were performed to validate the effects of Sch B on HIF-1α. In vivo and in vitro , Sch B administration reduced HIF-1α expression. These outcomes provide valuable insights into the potential mechanism by which Sch B delays IPF development, with HIF-1α potentially serving as a key target. However, further investigation is warranted to assess the safety and efficacy of Sch B in clinical settings.

Several studies have suggested the potential value of Houttuynia cordata as a therapeutic agent in lung cancer, but direct evidence is still lacking. The study aimed to determine the regulatory impact of a major H. cordata constituent derivative (sodium new houttuyfonate [SNH]) on lncRNA networks in non‐small cell lung cancer (NSCLC) to identify new potential therapeutic targets. After exposing NSCLC cells to SNH, we analysed the following: cell death (via flow cytometry, TUNEL and ASC speck formation assays), immune factors (via ELISA), gene transcription (via RT‐qPCR), subcellular localisation (via FISH), gene–gene and gene‐protein interactions (via dual‐luciferase reporter and RNA immunoprecipitation assays, respectively) and protein expression and distribution (via western blotting and immunocytochemistry or immunohistochemistry). In addition, statistical analysis (via one‐way ANOVA or unpaired t‐tests) was performed. Exposure to SNH promoted NSCLC cell pyroptosis, concomitant with significant up‐regulation of TCONS‐14036, a novel lncRNA. Mechanistic research demonstrated that TCONS‐14036 functions as a competing endogenous (ce)RNA by sequestering microRNA (miR)‐1228‐5p, thereby up‐regulating PRKCDBP‐encoding transcript levels. Indeed, PRKCDBP promoted pyroptosis by activating the NLRP3 inflammasome, resulting in CASP1, IL‐1β and GSDMD cleavage. Our findings elucidate the potential molecular mechanisms underlying the ability of SNH to suppress NSCLC growth through activation of pyroptosis via the TCONS‐14036/miR‐1228‐5p/PRKCDBP pathway. Thus, we identify a new potential therapeutic targets for NSCLC. SNH to suppress NSCLC via activating pyroptosis through TCONS‐14036/miR‐1228‐5p/PRKCDBP pathway, which result in CASP1, IL‐1β and GSDMD cleavage.

Background.The efficacy and safety of combined treatment of non-small-cell lung cancer (NSCLC) using Shenyi capsules and platinum-based chemotherapy were comprehensively evaluated. Methods. A computer-based search was used to identify reports on clinical randomized controlled trials (RCTs) on this combined treatment for NSCLC from the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, China Biomedical (CBM), and Wanfang Data electronic databases. The databases were searched from their start to February 2020. The quality of the included studies was evaluated and then crosschecked by two independent evaluators. A meta-analysis was conducted using RevMan5.3. Results. A total of 27 RCTs involving 2,663 patients were included in the meta-analysis, including 1,380 and 1,283 patients in the treatment and control groups, respectively. The results of the meta-analysis showed that, compared to platinum-based chemotherapy alone, the 1-year survival rate (relative risk (RR) = 1.27, 95% confidence interval (CI) [1.10, 1.47], P<0.01), 2-year survival rate (RR = 1.35, 95% CI [1.10, 1.65], P<0.01), objective tumour remission rate (RR = 1.52, 95% CI [1.35, 1.71], P<0.01), and body CD4+/CD8+ ratio (standardized mean difference (SMD) = 0.12, 95% CI [0.07, 0.17], P<0.01) were increased for the combined treatment of NSCLC using Shenyi capsules and platinum-based chemotherapy; moreover, quality of life was also improved (RR = 2.09, 95%CI [1.75, 2.50], P<0.01) and it reduced leukocyte toxicity (RR = 0.49, 95%CI [0.39, 0.63], P<0.01), haemoglobin toxicity (RR = 0.48, 95% CI [0.28, 0.81], P<0.01), platelet toxicity (RR = 0.44, 95% CI [0.28, 0.70], P<0.01), vomiting reaction (RR = 0.60, 95% CI [0.45, 0.78], P<0.01), and serum vascular endothelial growth factor level (SMD = −63.67, 95% CI [−67.59, −59.75], P<0.01). Conclusions. The treatment of NSCLC using Shenyi capsules together with routine platinum-based chemotherapy could enhance short- and long-term efficacy, improve patient quality of life, alleviate toxicity and side-effects of platinum-based chemotherapeutic drugs, boost body immune function, and inhibit tumour neovascularisation. These findings require further validation in large-sample, high-quality RCTs.

Background. Aidi injection (ADI) is a compound preparation injection of Chinese herbs used to treat patients of nonsmall cell lung cancer (NSCLC) in China. This study aimed to reveal the mechanism of ADI in the treatment of NSCLC by using network pharmacology and molecular docking. Methods. The related targets of ADI and NSCLC were obtained from multiple databases. The network diagram of disease-drug-components-targets (DDCT) and protein-protein interaction (PPI) was constructed to screen key targets. Then, the key targets and main signaling pathways were screened by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Next, in order to validate the results of network pharmacology, expression analysis and survival analysis of key genes were performed. Finally, we carried out the technology of molecular docking to further validate the accuracy of the above results. Results. A total of 207 targets of ADI and 5282 targets of NSCLC were obtained finally. Through the construction of DDCT and PPI network diagrams, 28 key targets were finally obtained. The results of the KEGG enrichment analysis indicated that multiple signaling pathways were associated with NSCLC, which included the MAPK signaling pathway, the IL-17 signaling pathway, and the PI3K/AKT signaling pathway. The key genes in the signaling pathway mainly include TP53, CASP3, MMP9, AKT1, PTGS2, and MAPK1. The results of differently expressed analysis of key genes showed that TP53, CASP3, MMP9, AKT1, PTGS2, and MAPK1 had statistical differences in lung squamous cell carcinoma (LUSC) compared with normal tissue p<0.001. In lung adenocarcinoma (LUAD), the expression of TP53, CASP3, MMP9, AKT1, and PTGS2 had statistical differences compared with normal tissue p<0.001, while the expression of MAPK1 had no statistical difference p>0.05. The results of survival analysis of key genes showed that AKT1, MAPK1, CASP3, MMP9, TP53, and PTGS2 had statistical differences in the OS or RFS of NSCLC patients p<0.05. In addition, the results of molecular docking indicated that the key genes and the main components have good docking activity. Conclusions. This study revealed the potential mechanism of ADI in the treatment of NSCLC with multipathways and multitargets and provided a scientific basis for the in-depth study of ADI in the treatment of NSCLC.

Maiwei Yangfei (MWYF) is a compound Chinese herb that is safe and effective in the clinical setting in patients with pulmonary fibrosis (PF). The aim of the present study was to assess the role of a (MWYF) decoction in a bleomycin (BLM)-induced PF mouse model and to investigate the underlying functional mechanism. Chemical components within the MWYF decoction were analysed using liquid chromatography-mass spectrometry. A total of 50 C57BL/6 mice were randomly assigned to one of the following five groups with 10 mice per group: Control, model, low dose MWYF (20 g/kg), medium dose MWYF (40 g/kg) and high dose MWYF (60 g/kg). A mouse PF model was established by the tracheal instillation of BLM (5 mg/kg) prior to MWYF treatment, except for mice in the control group. After 21 days of treatment with MWYF, the mice were sacrificed and the body weights were recorded. In addition, pulmonary tissues and bronchial alveolar lavage fluid were collected. TNF-α, IL-6, IL-17, hydroxyproline, pyridinoline and collagen I levels were determined using ELISA. Vimentin, α-smooth muscle actin (α-SMA), fibronectin, TGF-β1, Smad3, TNF-α, IL-6, IL-17, collagen I and collagen III were determined using western blotting. Vimentin and α-SMA levels were also determined using immunofluorescence analysis. Collagens I and III were detected using immunohistochemical analysis and TGF-β1 and Smad3 levels were determined using reverse transcription-quantitative PCR. Following treatment with MWYF decoction, the body weight of the mice in the PF group increased, the degree of pulmonary alveolitis and PF was reduced, collagen levels were reduced and the expression levels of α-SMA, vimentin and fibronectin were decreased. Although both protein and mRNA expression levels of TGF-β1 and Smad3 were reduced, they remained higher than those observed in the control group. To conclude, MWYF decoction delayed the development of BLM-induced PF in mice, where the functional mechanism was likely associated with the TGF-β1/Smad3 signalling pathway.

Purpose. The clinical efficacy of Chansu injection for COVID-19 treatment has been confirmed. Its mechanism of action remains unclear. We used network pharmacology and molecular docking technology to explore the potential material basis and mechanism of action of Chansu injection for COVID-19. Methods. The main components of Chansu injection were determined using HPLC. The PharmMapper, SwissTargetPrediction, SEA, and TCMID databases were used to screen for the active ingredients and therapeutic targets of Chansu injection, while the OMIM and GeneCards Suite databases were used to search for COVID-19-related targets. The STRING database was used for protein-protein interaction (PPI) network construction and topological analysis, while DAVID was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the core targets. The main active compounds of Chansu injection were docked with 3CL protease, ACE2, RdRp, and spike protein. Results. The three Chansu injection compounds were identified using HPLC. A total of 236 drug-related targets and 16,611 disease-related targets were identified, and 77 common targets were determined through mapping. The PPI mapping results revealed that 16 core targets were obtained through topological analysis and screening. Furthermore, GO and KEGG pathway enrichment analyses revealed that the PI3K and JAK-STAT signaling pathways are the major pathways. The molecular docking results suggest that the three Chansu injection components have high binding energies to the S protein. Conclusions. The potential mechanism of Chansu injection for COVID-19 involves multiple targets and pathways, thereby providing a scientific basis for its clinical application and further research.