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.

[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.

The impact of the Wenchuan earthquake on birth outcomes.

BACKGROUND: Earthquakes and other catastrophic events frequently occurring worldwide can be considered as outliers and cause a growing and urgent need to improve our understanding of the negative effects imposed by such disasters. Earthquakes can intensively impact the birth outcomes upon psychological and morphological development of the unborn children, albeit detailed characteristics remain obscure. METHODS AND FINDINGS: We utilized the birth records at Du Jiang Yan and Peng Zhou counties to investigate the birth outcomes as a consequence of a major earthquake occurred in Wenchuan, China on May 12, 2008. Totally 13,003 of neonates were recorded, with 6638 and 6365 for pre- and post- earthquake, respectively. Significant low birthweight, high ratio of low birthweight, and low Apgar scores of post-earthquake group were observed. In contrast, the sex ratio at birth, birth length and length of gestation did not show statistical differences. The overall ratio of birth-defect in the post-earthquake (1.18%) is statistically high than that of pre-earthquake (0.99%), especially for those in the first trimester on earthquake day (1.47%). The birth-defect spectrum was dramatically altered after earthquake, with the markedly increased occurrences of ear malformations. The ratio of preterm birth post-earthquake (7.41%) is significant increased than that of pre-earthquake (5.63%). For the birth outcomes of twins, significant differences of the ratio of twins, birth weight, ratio of low birthweight and birth-defect rate were observed after earthquake. CONCLUSION: A hospital-based study of birth outcomes impacted by the Wenchuan earthquake shows that the earthquake was associated with significant effects on birth outcomes, indicating it is a major monitor for long-term pregnant outcomes.

Insufficient activity of MAPK pathway is a key monitor of Kidney-Yang Deficiency Syndrome.

OBJECTIVE: To explore the genetic characteristics and molecular regulator of Kidney-Yang Deficiency Syndrome (KDS). DESIGN: A typical KDS family was collected using a questionnaire of cold feeling and a 40-item scoring table of KDS based on Traditional Chinese Medicine (TCM), by single-blind method repeated annually over three years. Their transcriptomes were assayed by microarray and validated by RT-PCR and ELISA. Simultaneously, 10 healthy volunteers were recruited as controls and the same protocols were performed. RESULTS: This typical KDS family has 35 members, of whom 11 were evaluated as having severe KDS and 6 as having common KDS. Results of the cDNA microarray revealed that there were 420 genes/expressed sequence tags differentially expressed in KDS transcriptomes, indicating a global functional impairment in the mass-energy-information carrying network of KDS patients, involving energy metabolism, signal transduction, development, cell cycle, and immunity. Pathway analysis by gene set enrichment assay (GSEA) and other tools demonstrated that mitogenic activated protein kinase (MAPK) is among the most insufficiently activated pathways, while the oxidative phosphorylation and glycolysis/gluconeogenesis pathways, the two main pathways relevant to ATP synthesis, were among the most excessively activated pathways in KDS patients. Results of RT-PCR and ELISA confirmed the status of insufficient activity of the MAPK pathway. CONCLUSION: KDS patients undergo overall attenuated functions in the mass-energy-information carrying network. The marked low level of energy output in KDS may be primarily attributed to the insufficient activity of the MAPK pathway, which may be a key monitor for the abnormal energy metabolism and other impaired activities in KDS.