Gut microbiome-based machine learning for diagnostic prediction of liver fibrosis and cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Invasive detection methods such as liver biopsy are currently the gold standard for diagnosing liver cirrhosis and can be used to determine the degree of liver fibrosis and cirrhosis. In contrast, non-invasive diagnostic methods, such as ultrasonography, elastography, and clinical prediction scores, can prevent patients from invasiveness-related discomfort and risks and are often chosen as alternative or supplementary diagnostic methods for liver fibrosis or cirrhosis. However, these non-invasive methods cannot specify the pathological grading and early diagnosis of the lesions. Recent studies have revealed that gut microbiome-based machine learning can be utilized as a non-invasive diagnostic technique for liver cirrhosis or fibrosis, but there is no evidence-based support. Therefore, this study conducted a systematic review and meta-analysis for the first time to investigate the accuracy of machine learning based on the gut microbiota in the prediction of liver fibrosis and cirrhosis. METHODS: A comprehensive and systematic search of publications published before April 2th, 2023 in PubMed, Cochrane Library, Embase, and Web of Science was conducted for relevant studies on the application of gut microbiome-based metagenomic sequencing modeling technology to the diagnostic prediction of liver cirrhosis or fibrosis. A bivariate mixed-effects model and Stata software 15.0 were adopted for the meta-analysis. RESULTS: Ten studies were included in the present study, involving 11 prediction trials and 838 participants, 403 of whom were fibrotic and cirrhotic patients. Meta-analysis showed the pooled sensitivity (SEN) = 0.81 [0.75, 0.85], specificity (SEP) = 0.85 [0.77, 0.91], positive likelihood ratio (PLR) = 5.5 [3.6, 8.7], negative likelihood ratio (NLR) = 0.23 [0.18, 0.29], diagnostic odds ratio (DOR) = 24 [14, 41], and area under curve (AUC) = 0.86 [0.83-0.89]. The results demonstrated that machine learning methods had excellent potential to analyze gut microbiome data and could effectively predict liver cirrhosis or fibrosis. Machine learning provides a powerful tool for non-invasive prediction and diagnosis of liver cirrhosis or liver fibrosis, with broad clinical application prospects. However, these results need to be interpreted with caution due to limited clinical data. CONCLUSION: Gut microbiome-based machine learning can be utilized as a practical, non-invasive technique for the diagnostic prediction of liver cirrhosis or fibrosis. However, most of the included studies applied the random forest algorithm in modeling, so a diversified prediction system based on microorganisms is needed to improve the non-invasive detection of liver cirrhosis or fibrosis.

Systematic review of Yougui pills combined with levothyroxine sodium in the treatment of hypothyroidism.

BACKGROUND: Yougui pills have long been used to treat hypothyroidism, usually in combination with levothyroxine sodium in clinical treatment, while their clinical efficacy and safety are still controversial when compared to levothyroxine treatment alone. AIM: To explore the clinical efficacy and safety of Yougui pills combined with levothyroxine sodium in the treatment of hypothyroidism. METHODS: This meta-analysis was performed in accordance with the PRISMA guidelines. Randomized controlled trials on Yougui pills in the treatment of hypothyroidism published from 2008 to May 2021 were searched in a total of 8 databases (4 databases in Chinese and 4 databases in English). The quality of the included studies was evaluated according to the Cochrane risk assessment tool. Weighted mean difference (WMD) was used for continuous variables, and relative risk (RR) was used for binary variables. Data were extracted, and the meta-analysis was conducted with the statistical software of Stata15.0 and RevMan5.0. RESULTS: A total of 140 articles were retrieved, and 9 of them were finally included, with a total sample size of 936 cases. The main meta-analysis results are as follows: (1) The group of Yougui pills combined with levothyroxine sodium had a significantly higher overall response rate than the group of levothyroxine sodium (RR = 1.20, 95%CI 1.12, 1.28, P < 0.00001); (2) Yougui pills combined with levothyroxine sodium achieved significantly better efficacy than levothyroxine sodium alone in alleviating adverse symptoms [standard mean difference (SMD) = -1.10, 95%CI: -1.37, -0.84, P < 0.00001]; (3) The level of thyrotropin stimulating hormone in the group of Yougui pills combined with levothyroxine sodium was significantly lower than in the control group of levothyroxine sodium (WMD = -1.38, 95%CI: -2.10, -0.67, P = 0.00001); (4) The level of free triiodothyronine in the group of Yougui pills combined with levothyroxine sodium was higher than that in the control group of levothyroxine sodium (WMD = 0.41, 95%CI: 0.03, 0.79, P = 0.03); (5) The level of free thyroxine in the group of Yougui pills combined with levothyroxine sodium was significantly higher than that in the control group of levothyroxine sodium (SMD = 0.83, 95%CI: 0.44, 1.22, P ≤ 0.0001); and (6) The adverse reactions in the group of Yougui pills combined with levothyroxine sodium were significantly less than those in the control group of levothyroxine sodium (RR = 0.33, 95%CI: 0.20, -0.53, P < 0.00001). CONCLUSION: In the treatment of hypothyroidism, the combination of Yougui pills with levothyroxine sodium may be better than levothyroxine sodium treatment alone.

A meta-analysis on randomized controlled trials of treating eosinophilic esophagitis with budesonide.

OBJECTIVE: Eosinophilic esophagitis (EoE) is a chronic, local immune-mediated inflammatory oesophageal disease. Although Budesonide is recommended as one of the first-line drugs for EoE treatment, its efficacy is still controversial in multiple studies. Due to the continuous emergence of new and reliable research evidence in recent years, we updated the meta-analysis using RCT trial results to evaluate the efficacy and safety of budesonide. MATERIALS AND METHOD: Retrieve the data of the randomised controlled trial literature from 2000 to June 20, 2021, on using Budesonide in the treatment of eosinophilic esophagitis from the three major databases. Based on the results achieved with the Cochrane risk assessment tool, evaluate the quality of the included literature to extract the data, and perform the Meta-analysis with RevMan5.4 and Stata15.0. RESULTS: A total of 958 articles were retrieved, with 10 articles finally included, thus forming a sample size of 712 cases. The main outcome indicators of the meta-analysis are as follows: (1) Histological remission: the Budesonide group performs better than the placebo control group when it comes to histological remission of injuries [RR = 23.82, 95%CI = (13.46, 42.21), p < .001]; (2) Eosinophil count: the Budesonide group is superior to the control group in terms of reduced eosinophil count [SMD = -1.34, 95%CI = (-1.52, -1.15), p < .001]. CONCLUSION: More and more high-quality randomised controlled trials show that oral budesonide in the treatment of eosinophils esophagitis was better than the placebo group. Mounting high-quality RCTs have confirmed the efficacy of oral budesonide in the treatment of eosinophilic esophagitis and that the effects of this drug may not be so dose-dependent. It is safe to take budesonide for a long time, and this drug is a relatively ideal option for drug treatment of eosinophilic esophagitis at present, so it is worthy of clinical application.Key MessagesWe used high-quality randomised controlled trials to meta-update the previous results to further confirm the clinical efficacy and safety of budesonide.Oral budesonide in the treatment of eosinophilic esophagitis is significantly better than the placebo control group. We have confirmed the value of its clinical application and promotion by including more high-quality randomised controlled trials.We also found that the efficacy of budesonide in patients is not dose-dependent, and more research is needed to confirm this.

Virtual Screening and Molecular Docking to Study the Mechanism of Chinese Medicines in the Treatment of Coronavirus Infection.

BACKGROUND Heat-clearing and detoxifying herbs (HDHs) play an important role in the prevention and treatment of coronavirus infection. However, their mechanism of action needs further study. This study aimed to explore the anti-coronavirus basis and mechanism of HDHs. MATERIAL AND METHODS Database mining was performed on 7 HDHs. Core ingredients and targets were screened according to ADME rules combined with Neighborhood, Co-occurrence, Co-expression, and other algorithms. GO enrichment and KEGG pathway analyses were performed using the R language. Finally, high-throughput molecular docking was used for verification. RESULTS HDHs mainly acts on NOS3, EGFR, IL-6, MAPK8, PTGS2, MAPK14, NFKB1, and CASP3 through quercetin, luteolin, wogonin, indirubin alkaloids, ß-sitosterol, and isolariciresinol. These targets are mainly involved in the regulation of biological processes such as inflammation, activation of MAPK activity, and positive regulation of NF-kappaB transcription factor activity. Pathway analysis further revealed that the pathways regulated by these targets mainly include: signaling pathways related to viral and bacterial infections such as tuberculosis, influenza A, Ras signaling pathways; inflammation-related pathways such as the TLR, TNF, MAPK, and HIF-1 signaling pathways; and immune-related pathways such as NOD receptor signaling pathways. These pathways play a synergistic role in inhibiting lung inflammation and regulating immunity and antiviral activity. CONCLUSIONS HDHs play a role in the treatment of coronavirus infection by regulating the body's immunity, fighting inflammation, and antiviral activities, suggesting a molecular basis and new strategies for the treatment of COVID-19 and a foundation for the screening of new antiviral drugs.

Exploration of the Two-Way Adjustment Mechanism of Rhei Radix et Rhizoma for Cardiovascular Diseases.

AIM AND OBJECTIVE: Myocardial infarction, cerebral infarction, and other diseases caused by vascular obstruction have always jeopardized human life and health. Several reports indicate that Rhei Radix et Rhizoma has a good clinical effect in the prevention and treatment of cardiovascular diseases. Owing to the complexity of herbal medicine, the pharmacodynamic mechanism of Rhei Radix et Rhizoma is still unclear. The objectives of this study were to explore the two-way adjustment mechanism of Rhei Radix et Rhizoma and provide a new solution for the prevention and treatment of cardiovascular disease. MATERIALS AND METHODS: This study used data mining, reverse pharmacophore matching, network construction, GO and KEGG Analysis, and molecular docking to investigate the two-way adjustment mechanism of Rhei Radix et Rhizoma. The methods used were based on systems pharmacology and big data analysis technology. RESULTS: The results suggest that Rhei Radix et Rhizoma uses a two-way adjustment of activating blood circulation, as well as blood coagulation in the prevention and treatment of cardiovascular diseases. The components involved in activating blood circulation are mainly anthraquinone components. The corresponding targets are NOS2, NOS3, CALM1, and the corresponding pathways are calcium signaling pathway, VEGF signaling pathway, platelet activation, and the PI3K-Akt signaling pathway. For blood coagulation, the components are mainly tannin components; the corresponding targets are F2, F10, ELANE, and the corresponding pathways are the neuroactive ligand-receptor interaction, complement and coagulation cascades. CONCLUSION: This study indicated that Rhei Radix et Rhizoma exerts the two-way adjustment of activating blood circulation and blood coagulation in the prevention and treatment of cardiovascular diseases. It can make up for the side effects of the existing blood circulation drugs for cardiovascular disease, only activating blood circulation, and the uncontrollable large-area bleeding due to the long-term use of the drugs. This study provides a material basis for the development of new blood-activating drugs based on natural medicine.

Virtual Screening of the Multi-pathway and Multi-gene Regulatory Molecular Mechanism of Dachengqi Decoction in the Treatment of Stroke Based on Network Pharmacology.

BACKGROUND: Stroke is ranked second among diseases that cause mortality worldwide. Owing to its complicated pathogenesis, no satisfactory treatment strategies for stroke are available. Dachengqi decoction (DCQD), a traditional Chinese herbal medicine, has been widely used in China for a long time, as it has a good effect on stroke. However, the molecular mechanism underlying this effect of DCQD is unclear. OBJECTIVE: In the present study, we aimed to reveal and explore the multi-pathway and multi-gene regulatory molecular mechanism of Dachengqi decoction in the treatment of stroke. METHODS: In this study, a network pharmacology method, in combination with oral bioavailability prediction and drug-likeness evaluation, was employed to predict the active ingredients of DCQD. The target genes of the active components and the traced pathways related to these target genes were predicted. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using clusterProfiler software package on the R platform and ClueGo+CluePedia plug-ins. Finally, the key DCQD targets were verified using the Gene Expression Omnibus (GEO) dataset. RESULTS AND DISCUSSION: According to the ADME model, 52 active components were screened from 296 active components of DCQD. After prediction and screening, 215 stroke-related targets were obtained and analyzed via GO and KEGG analyses. GO analysis showed that DCQD targets were mainly involved in the regulation of oxidative stress, lipid metabolism, inflammation, and other biological processes. KEGG pathway analysis further revealed pathways involved in stroke, such as arachidonic acid metabolic, HIF-1 signaling pathway, estrogen signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, platelet activation pathway, VEGF signaling pathway, and cAMP signaling pathway. Network analysis revealed that DCQD might be involved in the regulation of lipid metabolism, blood pressure, inflammation, angiogenesis, neuroprotection, platelet aggregation, apoptosis, and oxidation in stroke treatment. GEO dataset analysis showed that DCQD's therapeutic effects might be exerted via the bidirectional regulation principle. CONCLUSION: Based on the methods of network pharmacology and GEO analysis, it was found that, during stroke treatment, DCQD regulates and controls multiple genes and multiple pathways in a synergistic manner, providing a new strategy for stroke treatment.

[Serum Proteomic Analysis and Construction of Protein-protein Interaction Networks about Ejaculation Praecox with Shen-yang Deficiency].

Objective To identify serum proteome of ejaculation praecox(EP) with Shen-yang de- ficiency, and to explore its pathogenesis of EP in the protein-protein interaction ( PPI) network. Methods The serum samples were respectively collected from 4 EP with Shen-yang deficiency patients and 4 healthy controls. After the serum proteome of EP with Shen-yang deficiency was obtained, the technology of isobaric tags for relative and absolute quantitation (iTRAQ) was adopted for identification. The STRING data- base was applied to construct the PPI network whose function was analyzed through bioinformatics meth- ods. Results A group of 238 serum proteins were identified in total, of which, 162 proteins reached the strict quantitative standard. Nine proteins were differently expressed, including 1 up-regulated and 8 down-regulated. The constructed PPI network was constituted by 72 protein nodes and 283 protein couples, and could be clustered to 16 clusters, in which 10 clusters were composed of 3 or more proteins. Each cluster could be found with a core protein correspondingly. The core protein of C3,C5,C1S and MASP2 were all main constituents of complement system, whose function involves in biological process of complement ac- tivation. Conclusions The protein models in PPI network of differently expressed serum proteome about EP with Shen-yang deficiency were functional enriched in the biological process of complement activa-, tion; which indicate that a immune dysfuction dominated by abnormal process of complent activation may' be one of the main mechanisms of EP with Shen-yang deficiency.

Preliminary correlation between warm needling treatment for knee osteoarthritis of deficiency-cold syndrome and metabolic functional genes and pathways.

The warm needling technique used in traditional Chinese medicine has been shown to be effective in the treatment and prevention of knee osteoarthritis (OA), but the biological mechanisms behind this action have not been well explored. This study investigated the molecular mechanisms behind warm needling using cDNA microarray technology, thus providing further scientific evidence for its efficacy. Ten patients with knee OA of deficiency-cold syndrome were selected for 2 weeks of warm needling treatment. This treatment involved stimulating the selected acupoints using needles with a burning moxa stick on their handle for 40 minutes per session. Pain intensity and accumulated clinical scores of deficiency-cold syndrome were assessed pretreatment and posttreatment using a 40-factor questionnaire of OA with deficiency-cold syndrome. Four patients with the best therapeutic efficacy were selected for cDNA microarray testing. Among the four patients, 41, 246, 57 and 70 differentially expressed genes were obtained, with more than 50% of these differentially expressed genes functionally linked to primary, cellular and energy metabolism pathways. This work demonstrates that the molecular mechanism behind warm needling treatment may be associated with the regulation of metabolism-related genes and pathways.

Bridging the gap between traditional Chinese medicine and systems biology: the connection of Cold Syndrome and NEI network.

Systems biology is a general trend of contemporary scientific development. When coupling the classical traditional Chinese medicine (TCM) Cold Syndrome and methodology of systems biology, we conformed to the genome, transcriptome, proteome, and metabolome that are supposed to run through the overall macro behavior, and explored the macro and micro framework of systems biology of TCM Syndrome. We introduced a new way to probe into the implicit stratification of Cold Syndrome, after surveying 4575 cases of Cold Syndrome patients and examining gene expression information of a typical Cold Syndrome pedigree by microarray. We underlined the genetic background of the Cold Syndrome family based on the molecular foundation to understand Syndrome, one of our earlier discoveries in which genes and chemical compounds in neuro-endocrine-immune (NEI) system are scored as Cold or Hot (or both) property. Results indicate that Cold Syndrome related genes play an essential role in energy metabolism, which are tightly correlated with the genes of neurotransmitters, hormones and cytokines in the NEI interaction network. Therefore, NEI interaction not only opens out mechanism of classical TCM theory on Syndrome but also enriches current research on complex diseases as well as systems biology.