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.

Mechanism of Yougui Pills in the treatment of knee osteoarthritis based on network pharmacology and molecular docking / 西安交通大学学报(医学版)

【Objective】 To explore the mechanism of Yougui Pills in the treatment of knee osteoarthritis （KOA） based on network pharmacology and molecular docking. 【Methods】 The active components of Yougui Pills were obtained by searching TCMSP database. With the active component targets predicted by TCMSP， SwissTargetPrediction and TargetNet， we searched TCMIP， CTD， DisGeNET and GeneCards databases for KOA related targets. By crossing the two sets of targets， we obtained therapeutic targets of Yougui Pills for KOA. FDA-approved drugs for KOA and their targets were searched in the DrugBank database， and the drug-target network was constructed by using Cytoscape. Then the protein-protein interaction （PPI） network was constructed by using STRING database. After Go and KEGG enrichment analyses， the network of “traditional Chinese Medicine-active components-key targets-significant pathways-biological process” was constructed. 【Results】 A total of 132 active components were obtained from the nine herbal medicines of Yougui Pills， corresponding to 490 targets， of which 76 were potential therapeutic targets. Of them 13 were the same as the targets of 5 Western medicines for KOA. We screened out 18 key targets by the PPI network. Go enrichment analysis revealed 1281 biological processes， 60 molecular functions， and 17 cellular components， which were mainly related to inflammation， infection and oxidative stress. KEGG enrichment analysis showed that 50 pathways were significantly enriched， including IL-17 signaling pathway and TNF signaling pathway， whose functions were mainly involved in immune system， signal transduction， endocrine system， cell growth and death and other biological processes. 【Conclusion】 With multiple compounds acting on multiple molecular targets， Yougui Pills can treat KOA through molecular mechanisms including inhibiting inflammation， reducing oxidative stress， and promoting cartilage cell proliferation.

Cognition and cerebrovascular function in primary hyperparathyroidism before and after parathyroidectomy.

PURPOSE: There are cognitive changes in primary hyperparathyroidism (PHPT) that improve with parathyroidectomy, but the mechanism of cognitive dysfunction has not been delineated. We assessed if cerebrovascular function is impaired in PHPT, improves post-parathyroidectomy and is associated with PTH level and cognitive dysfunction. METHODS: This is an observational study of 43 patients with mild hypercalcemic or normocalcemic PHPT or goiter. At baseline, cerebrovascular function (dynamic cerebral autoregulation and vasomotor reactivity) by transcranial Doppler and neuropsychological function were compared between all three groups. A subset underwent parathyroidectomy or thyroidectomy, and was compared 6 months post-operatively. RESULTS: Mean cerebrovascular and neuropsychological function was normal and no worse in PHPT compared to controls preoperatively. Higher PTH was associated with worse intracerebral autoregulation (r = - 0.43, p = 0.02) and worse cognitive performance on some tests. Post-parathyroidectomy, mood improved significantly, but changes did not differ compared to those having thyroidectomy (p = 0.84). There was no consistent improvement in cognition or change in vascular function in either surgical group. CONCLUSIONS: Although higher PTH was associated with worse intracerebral autoregulation, cerebrovascular function, cognition and mood were normal in mild PHPT. PTX did not improve vascular or cognitive function. The observed improvement in mood cannot be clearly attributed to PTX. Notwithstanding the small sample size, the results do not support changing current criteria for parathyroidectomy to include cognitive complaints. However, the associations between PTH, cognition and cerebral autoregulation merit future studies in those with more severe hyperparathyroidism.

microRNA-564 inhibits the aggressive phenotypes of papillary thyroid cancer by directly targeting astrocyte-elevated gene-1.

Background: Accumulating evidence has revealed that an increasing number of microRNAs (miRNAs) are dysregulated in papillary thyroid cancer (PTC) and that their dysregulation plays an important role in PTC onset and progression. Reportedly, miRNA-564 (miR-564) is downregulated in several types of human cancer. However, its expression profile and specific functions in PTC remain unclear to date. Methods: In this study, we used reverse transcription-quantitative polymerase chain reaction to detect miR-564 expression in PTC tissues and cell lines. Further, the regulatory roles of miR-564 in the malignant development of PTC in vitro and in vivo were examined using a series of functional experiments. In addition, the possible underlying mechanisms and signaling pathways involved were investigated. Results: We demonstrated that miR-564 expression markedly decreased in PTC tissues and cell lines, and this decrease correlated with the lymph node metastasis and tumor-node-metastasis stage. miR-564 upregulation significantly inhibited cell proliferation, migration, and invasion and induced cell apoptosis in vitro as well as hindered tumor growth in vivo. Furthermore, astrocyte-elevated gene-1 (AEG-1) was identified as a direct target gene of miR-564 in PTC cells. Its expression was upregulated and inversely correlated with miR-564 expression in clinically PTC tissues. Additionally, the silencing of AEG-1 expression could imitate the action of miR-564 overexpression in PTC cells. Remarkably, the restoration of AEG-1 expression partially abolished the tumor-suppressing effects induced by a miR-564 upregulation in PTC cells. Ectopic miR-564 expression deactivated the PTEN/Akt pathway in PTC cells in vitro and in vivo. Conclusion: Overall, the findings of the current study suggest that miR-564 is a tumor-suppressive miRNA that exerts crucial roles in the development and progression of PTC. Therefore, this miRNA might be a promising candidate target in the anticancer treatment of patients with PTC.

Combination of chemical fingerprinting with bioassay, a preferable approach for quality control of Safflower Injection.

Safflower Injection is one kind of injections derived from traditional Chinese medicine. It is widely applied to treat cerebrovascular diseases such as acute cerebral infarction, stroke, coronary heart disease, and angiitis. However, most adverse reactions of Safflower Injection in clinic are caused by its quality problems. In this study, 10 batches of normal and 42 batches of abnormal Safflower Injections were obtained from the clinical practice. Their quality fluctuations were detected by chemical fingerprinting (CF, ultra-performance liquid chromatography tandem mass spectrometry) and bioassays including cell-based biological profile (CBP) assay and enzymatic assay. CF identified 33 compounds in the Safflower Injections, and scutellarin and kaempferol-3-O-rutinoside were identified to be the possible components responsible for clinical adverse reaction. In addition, 59.5% (25/42), 85.7% (36/42) and 38.1% (16/42) of abnormal samples could be identified by CF, CBP assay and enzymatic assay, respectively. Interestingly, further integration of the three methods could entirely identify all the abnormal samples. It indicated that it is advisable to integrate CF, CBP assay and enzymatic assay for developing quality standard of Safflower Injections.

Molecular mechanism of heat-clearing and detoxifying efficacy of Forsythia suspensa based on network pharmacology / 药学学报

Forsythia suspensa is a herbal medicine that widely used for heat-clearing and detoxification in clinical practice. However, the molecular mechanism of its heat-clearing and detoxifying effect is still unclear. Based on the theory and methods of network pharmacology, the efficacy of the heat-clearing and detoxification of Forsythia suspensa was analyzed in this study. A total of 114 of compounds in Forsythia suspensa were collected, and 15 of effective compounds were obtained by analyzing the bioavailability (OB) and drug-like properties (DL). Then 26 corresponding targets were obtained using reverse pharmacophore-docking method. Using the BioGPS database, the organ location of the target initially was revealed. The compound-targetdisease network model of Forsythia suspensa was constructed by using the Cytoscape, which showed that the material basis of the heat-clearing and detoxification of Forsythia suspensa was to synthesize and synergize the effects by combining various active ingredients of multiple targets, simultaneously. This study explains the scientific mechanism of the heat-clearing and detoxification of Forsythia suspensa, and provides a theoretical foundation for clinical rational usage of Forsythia suspensa.

[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.

Low vitamin D levels have become less common in primary hyperparathyroidism.

UNLABELLED: We compared temporal trends in serum 25-hydroxyvitamin D and parathyroid hormone (PTH) in two primary hyperparathyroidism (PHPT) cohorts recruited 20 years apart. The prevalence of 25-hydroxyvitamin D levels <20 and <30 ng/mL declined by 30-50 %, respectively, and was accompanied by lower PTH. In the older cohort, higher PTH may be due to lower 25-hydroxyvitamin D. INTRODUCTION: Vitamin D deficiency may exacerbate PHPT. Whether there have been temporal trends in 25-hydroxyvitamin D (25OHD) levels in PHPT is unclear. The prevalence of low vitamin D levels (25OHD <20 and <30 ng/mL) and associated biochemical and bone mineral density (BMD) profiles were assessed in two PHPT cohorts recruited over 20 years apart. METHODS: This is a cross-sectional comparison of serum 25OHD levels, calciotropic hormones, and BMD between two PHPT cohorts recruited at the same hospital: the "old" (N = 103) and "new" (N = 100) cohorts were enrolled between 1984 and 1991 and between 2010 and 2014, respectively. RESULTS: Mean 25OHD levels were 26 % higher in the new cohort (23 ± 10 vs. 29 ± 10 ng/mL, p < 0.0001). Levels of 25OHD <20 and <30 ng/mL declined from 46 and 82 %, respectively, to 19 and 54 % (both p < 0.0001). Supplemental vitamin D use was common in the new (64 %) but not the old cohort (0 %). The new cohort demonstrated 33 % lower serum PTH levels (p < 0.0001). Neither serum nor urine calcium differed. BMD was higher in the new cohort at all skeletal sites (all p < 0.001). CONCLUSION: With the rise in vitamin D supplementation over the last two decades, low 25OHD levels are no longer common in PHPT patients in the New York area. Those with 25OHD <20 and <30 ng/mL have declined by over 50 and 30 %, respectively. The lower mean PTH levels in the new cohort are most likely accounted for by higher vitamin D intake. Whether improved vitamin D status also underlies the relatively higher BMD in the more vitamin D replete cohort of PHPT patients is unknown.

Childhood sexual abuse and the risk for recurrent major depression in Chinese women.

BACKGROUND: Studies in Western countries have repeatedly shown that women with a history of childhood sexual abuse (CSA) are at increased risk for developing major depression (MD). Would this relationship be found in China? METHOD: Three levels of CSA (non-genital, genital, and intercourse) were assessed by self-report in two groups of Han Chinese women: 1970 clinically ascertained with recurrent MD and 2597 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression and regression coefficients by linear or Poisson regression. RESULTS: Any form of CSA was significantly associated with recurrent MD [OR 3.26, 95% confidence interval (CI) 1.95-5.45]. This association strengthened with increasing CSA severity: non-genital (OR 2.47, 95% CI 1.17-5.23), genital (OR 2.77, 95% CI 1.32-5.83) and intercourse (OR 13.35, 95% CI 1.83-97.42). The association between any form of CSA and MD remained significant after accounting for parental history of depression, childhood emotional neglect (CEN), childhood physical abuse (CPA) and parent-child relationship. Among the depressed women, those with CSA had an earlier age of onset, longer depressive episodes and an increased risk for generalized anxiety disorder (GAD; OR 1.92, 95% CI 1.39-2.66) and dysthymia (OR 2.16, 95% CI 1.52-3.09). CONCLUSIONS: In Chinese women CSA is strongly associated with MD and this association increases with greater severity of CSA. Depressed women with CSA have an earlier age of onset, longer depressive episodes and increased co-morbidity with GAD and dysthymia. Although reporting biases cannot be ruled out, our results are consistent with the hypothesis that, as in Western countries, CSA substantially increases the risk for MD in China.

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.

Relationship between Back Pain-Lassitude and Kidney-deficiency Syndrome in Diabetes Patients / 中医杂志

Objective To study the importance of back pain-lassitude as the key symptom in the differentiation of kidney-deficiency syndrome in diabetes patients.Methods Totally 460 diabetics were divided into the pain group(154 cases)and non-pain group(306 cases).The 39 symptoms,signs and behavior were abstracted and each patient was scored according to the details of kidney deficiency scale to analyze the constitution and distribution of kidney-deficiency syndrome.Results There was a significant difference in the total symptom score of the two groups(P