Prognosis and personalized treatment prediction in TP53-mutant hepatocellular carcinoma: an in silico strategy towards precision oncology.

TP53 mutation is one of the most common genetic changes in hepatocellular carcinoma (HCC). It is of great clinical significance to tailor specialized prognostication approach and to explore more therapeutic options for TP53-mutant HCCs. In this study, a total of 1135 HCC patients were retrospectively analyzed. We developed a random forest-based prediction model to estimate TP53 mutational status, tackling the problem of limited sample size in TP53-mutant HCCs. A multi-step process was performed to develop robust poor prognosis-associated signature (PPS). Compared with previous established population-based signatures, PPS manifested superior ability to predict survival in TP53-mutant patients. After in silico screening of 2249 drug targets and 1770 compounds, we found that three targets (CANT1, CBFB and PKM) and two agents (irinotecan and YM-155) might have potential therapeutic implications in high-PPS patients. The results of drug targets prediction and compounds prediction complemented each other, presenting a comprehensive view of potential treatment strategy. Overall, our study has not only provided new insights into personalized prognostication approaches, but also thrown light on integrating tailored risk stratification with precision therapy.

The effects and predictive value of calcium and magnesium concentrations on nutritional improvement, inflammatory response and diagnosis in patients with Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a progressive inflammatory disease of the gastrointestinal tract associated with malnutrition, high levels of inflammation and calcium and magnesium deficiencies. However, the relationships between these symptoms are poorly defined. METHOD: Seventy-six adult CD patients who had not yet started treatment and 83 healthy volunteers were recruited. The dietary intakes, serum calcium and magnesium levels, nutritional indicators and biochemical markers of disease activity were measured. RESULTS: Most participants had inadequate magnesium and calcium intake. The serum magnesium and calcium levels, as well as nutritional and inflammatory indicators, differed significantly between CD patients and controls, especially in the active phase. Serum levels of magnesium and calcium correlated with both nutritional status and inflammation. The cut-off values for CD development were 0.835 mmol/L (magnesium) and 2.315 mmol/L (calcium), whereas those for the active phase were 0.785 and 2.28 mmol/L, respectively. CONCLUSION: Adequate intake of magnesium and calcium may both improve the nutritional status of CD patients and reduce inflammation, benefiting disease relief. As both magnesium and calcium reflect CD status, they may be useful markers for CD diagnosis and disease activity.

Risk of skin cancers in thiopurines-treated and thiopurines-untreated patients with inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: The thiopurines are effective in the management of patients with inflammatory bowel disease (IBD), but the association between thiopurines use and the risk of skin cancer (including nonmelanoma skin cancer [NMSC] and melanoma skin cancer) has already been sufficiently reported. However, the results of these studies are inconsistent, and thus, the objective of our analysis was to explore whether thiopurines can lead to an excess risk of skin cancer in IBD patients. METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched to identify relevant studies that evaluated the risk of skin cancer in IBD patients treated with thiopurines. A random effects meta-analysis was conducted to calculate the pooled incidence rate ratios as well as risk ratios (RRs). Subgroup analysis was performed to explore the potential source of heterogeneity. RESULTS: Thirteen studies comprising 149 198 participants were included. The result suggested that thiopurines significantly increased the risk of overall skin cancer in IBD patients (random effects: RR = 1.80, 95% confidence interval [CI] 1.14-2.87, P = 0.013), among which NMSC showed an excess risk associated with thiopurines use (random effects: RR = 1.88, 95% CI 1.48-2.38, P < 0.001) while no increased risk was observed with respect to melanoma skin cancer (random effects: RR = 1.22, 95% CI 0.90-1.65, P = 0.206). Subgroup analysis regarding sample size and geographic distribution in skin cancer and follow-up duration in NMSC reached statistical significance, while other subgroups showed no significance. CONCLUSION: Exposition of thiopurines in patients with IBD is associated with a higher risk of skin cancer. Routine skin screening and daily skin protective practice are recommended for these patients.

Disequilibrium in the CD8+CD28+/CD8+CD28- T Lymphocyte Balance Is Related to Prognosis in Rats with Trinitrobenzenesulfonic Acid-Induced Colitis.

PURPOSE: The CD8+CD28+/CD8+CD28- T lymphocyte balance is vital for human ulcerative colitis (UC) but has not been defined in experimental colitis. This investigation will try to identify the changes that occur in the CD8+CD28+/CD8+CD28- T lymphocyte balance during the progression of trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. METHODS: The frequencies of blood CD8+CD28+ and CD8+CD28- T lymphocytes were detected in the rats belonging to the normal, model, and treated groups on five days using flow cytometry. The treated rats were administered with mesalazine and were euthanized after a 14-day treatment, as were the normal and model rats. The sensitivity and specificity of the CD8+CD28+/CD8+CD28- T lymphocyte balance in diagnosing early colitis were analyzed by receiver operating characteristics (ROC) curves. The frequencies of CD8+CD28+ and CD8+CD28- T lymphocytes in the colon tissue were tested via immunofluorescence. ELISA was used to measure the levels of the cytokines. Immunohistochemistry and Western blotting were used to detect the colonic expression of JAK3, STAT6, NFATc2, and GATA3. RESULTS: We found that the ratio of CD8+CD28+/CD8+CD28- T lymphocytes decreased, as did the level of interleukin-7, but not IL-12p40, IL-13, or IL-15, in the blood; however, the ratio increased along with JAK3, STAT6, NFATc2, and GATA3 in the colon of the rats with colitis. The changes were effectively reversed through the administration of mesalazine for 13 days. Surprisingly, the balance in the blood could sensitively distinguish rats with early colitis from normal rats. CONCLUSION: These data show that increase in CD8+CD28+ T cells in blood and decrease in CD8+CD28- T cells in colon are associated with experimental colitis.

Circulating leptin levels in the assessment of Crohn's disease activity and its relation to nutritional status.

Introduction: Objective: to evaluate leptin levels and its relation to nutritional status in Crohn's disease (CD). Methods: the study included 154 CD patients and healthy controls. Leptin level was determined before treatment. Nutrition levels were assessed using the Nutrition Risk Screening 2002 (NRS-2002) and Patient-Generated Subjective Global Assessment (PG-SGA). Indicators included body mass index (BMI), mid-arm circumference, the circumference of the upper-arm muscle, triceps skinfold thickness, and circumference of legs. Results: leptin levels differed between CD patients (1,025 ± 874 ng/ml) and controls (18,481,222 ng/ml). Significant differences were seen in NRS-2002, PG-SGA scores, BMI and other nutritional indicators. Negative correlations were observed between leptin and NRS-2002, PG-SGA scores, while positive correlations were observed with other nutritional indicators. The receiver operating characteristic (ROC) curve showed association between leptin and the diagnosis of CD, suggesting leptin concentration below 803.02 ng/ml as a threshold for CD. Conclusion: dysfunctional leptin regulation may relate to poor nutritional status associated with CD. The leptin level is thus an additional tool for evaluating CD patients, predicting disease activity and clinical response. Leptin may be a potential target for intervention in CD to improve nutritional status.

Introducción: Objetivo: evaluar los niveles de leptina y su relación con el estado nutricional en la enfermedad de Crohn (EC). Métodos: se incluyeron 154 pacientes con EC y controles sanos. El nivel de leptina se determinó antes del tratamiento. La situación nutricional se evaluó mediante el examen de riesgo nutricional 2002 (NRS-2002) y la Valoración Global Subjetiva Generada por el Paciente (VGS-GP). Los indicadores incluyen el índice de masa corporal (IMC), la circunferencia media del brazo, la circunferencia del músculo superior del brazo, el grosor del pliegue cutáneo del tríceps y la circunferencia de las piernas. Resultados: los niveles de leptina difirieron entre los pacientes con EC (1.025 ± 874 ng/ml) y los controles (18.481.222 ng/ml). Se observaron diferencias significativas en NRS-2002, puntajes de VGS-GP, IMC y otros indicadores nutricionales. Se observaron correlaciones negativas entre leptina y NRS-2002, puntuaciones de VGS-GP, mientras que se observaron correlaciones positivas con otros indicadores nutricionales. La curva ROC mostró asociación entre leptina y el diagnóstico de EC, sugiriendo concentraciones de leptina por debajo de 803,02 ng/ml como umbral para EC. Conclusión: puede relacionarse la alteración en la regulación de la leptina con la peor situación nutricional en enfermos con EC.La leptina puede ser un objetivo potencial para la intervención en EC a fin de mejorar el estado nutricional.

Associations of genetically predicted iron status with 24 gastrointestinal diseases and gut microbiota: a Mendelian randomization study.

Background: Iron status has been implicated in gastrointestinal diseases and gut microbiota, however, confounding factors may influence these associations. Objective: We performed Mendelian randomization (MR) to investigate the associations of iron status, including blood iron content, visceral iron content, and iron deficiency anemia with the incidence of 24 gastrointestinal diseases and alterations in gut microbiota. Methods: Independent genetic instruments linked with iron status were selected using a genome-wide threshold of p = 5 × 10-6 from corresponding genome-wide association studies. Genetic associations related to gastrointestinal diseases and gut microbiota were derived from the UK Biobank, the FinnGen study, and other consortia. Results: Genetically predicted higher levels of iron and ferritin were associated with a higher risk of liver cancer. Higher levels of transferrin saturation were linked to a decreased risk of celiac disease, but a higher risk of non-alcoholic fatty liver disease (NAFLD) and liver cancer. Higher spleen iron content was linked to a lower risk of pancreatic cancer. Additionally, higher levels of liver iron content were linked to a higher risk of NAFLD and liver cancer. However, certain associations lost their statistical significance upon accounting for the genetically predicted usage of cigarettes and alcohol. Then, higher levels of iron and ferritin were associated with 11 gut microbiota abundance, respectively. In a secondary analysis, higher iron levels were associated with lower diverticular disease risk and higher ferritin levels with increased liver cancer risk. Higher levels of transferrin saturation were proven to increase the risk of NAFLD, alcoholic liver disease, and liver cancer, but decrease the risk of esophageal cancer. MR analysis showed no mediating relationship among iron status, gut microbiota, and gastrointestinal diseases. Conclusion: This study provides evidence suggesting potential causal associations of iron status with gastrointestinal diseases and gut microbiota, especially liver disease.

Balance of CD8+ CD28+ / CD8+ CD28- T lymphocytes is vital for patients with ulcerative colitis.

BACKGROUND: Immune balances are important for many diseases including ulcerative colitis (UC). This study aimed to explore the role of the balance between CD8+ CD28+ and CD8+ CD28- T lymphocytes for the immunological pathogenesis of UC. METHODS: Sixteen patients with UC, 16 patients with irritable bowel syndrome (IBS) and 15 healthy volunteers were enrolled. The frequencies of CD8+ CD28+ and CD8+CD28- T lymphocytes in peripheral blood and colon tissue were tested using flow cytometry and immunofluorescent, respectively. The cytokines of the two lymphocytes were detected by protein chips and ELISA. The expression of the signal transducers, the JAK3 and STAT6, as well the transcription factors, the NFATc2 and GATA3, was all detected by both western blot and immunohistochemistry. RESULTS: For UC patients, the frequencies of CD8+ CD28+ T lymphocytes, together with the ratios of CD8+ CD28+ / CD8+ CD28- T lymphocytes in blood and colon tissue, were significantly lower than those in both IBS patients and healthy volunteers. But the frequencies of CD8+ CD28- T lymphocytes in blood and colon tissue of the UC patients were significantly higher than the other two groups. The concentration of IL-7 and -13, and the expression of JAK3 and STAT6 in UC patients, were significantly lower when compared with the other two groups. Conversely, the concentration of IL-12p40 and -15, and the expression of GATA3 and NFATc2 in UC patients, were significantly higher than both IBS and control group. CONCLUSIONS: The balance of CD8+ CD28+ / CD8+ CD28- T lymphocytes plays a vital role in UC, while the balance tilt towards CD8+ CD28+ T lymphocytes is beneficial for patients with UC.

Environmental and Microbial Factors in Inflammatory Bowel Disease Model Establishment: A Review Partly through Mendelian Randomization.

Inflammatory bowel disease (IBD) is a complex condition resulting from environmental, microbial, immunologic, and genetic factors. With the advancement of Mendelian randomization research in IBD, we have gained new insights into the relationship between these factors and IBD. Many animal models of IBD have been developed using different methods, but few studies have attempted to model IBD by combining environmental factors and microbial factors. In this review, we examine how environmental factors and microbial factors affect the development and progression of IBD, and how they interact with each other and with the intestinal microbiota. We also summarize the current methods for creating animal models of IBD and compare their advantages and disadvantages. Based on the latest findings from Mendelian randomization studies on the role of environmental factors in IBD, we discuss which environmental and microbial factors could be used to construct a more realistic and reliable IBD experimental model. We propose that animal models of IBD should consider both environmental and microbial factors to better mimic human IBD pathogenesis and to reveal the underlying mechanisms of IBD at the immune and genetic levels. We highlight the importance of environmental and microbial factors in IBD pathogenesis and offer new perspectives and suggestions for improving experimental animal modeling. Our goal is to create a model that closely resembles the clinical picture of IBD.

Sarcopenia in liver cirrhosis: perspectives from epigenetics and microbiota.

Sarcopenia is characterized by the loss of muscle mass and function. It is well known that sarcopenia is often associated with aging, while in recent years, sarcopenia comorbid with chronic diseases such as cirrhosis has attracted widespread attention, whose underlying molecular mechanisms remain unclear. Since cirrhosis and sarcopenia are assumed to be closely interrelated in terms of pathogenesis, this review innovatively discussed the role of epigenetic modifications and microecological dysregulation in sarcopenia in the context of liver cirrhosis. Here we illustrated the relationship between sarcopenia and cirrhosis in the aspect of epigenetics, dysbiosis, and the crosstalk between gene modifications and intestinal microecology. Furthermore, the alterations in cirrhosis patients with sarcopenia, such as inflammatory response and oxidative stress, are found to present synergistic effects in the pathways of epigenetics and dysbiosis leading to sarcopenia. This review proposes that microbiome-based therapies are promising to break the vicious cycle between epigenetic modification and dysbiosis, providing strong support for the use of intestinal microecological interventions to prevent sarcopenia in cirrhotic patients.

Causal relationship between asthma and ulcerative colitis and the mediating role of interleukin-18: a bidirectional Mendelian study and mediation analysis.

Objective: Numerous observational investigations have documented a correlation between asthma and ulcerative colitis(UC). In this Mendelian Randomization (MR) study, we utilized extensive summary data from Genome-Wide Association Studies (GWAS) to further estimate the association between adult-onset asthma and the risk of UC, and to investigate the role of Interleukin-18 (IL-18) as a potential mediator. Materials and methods: A two-step, two-sample MR study was conducted through mediation analysis. For this study, we employed a two-sample MR analysis using the inverse variance-weighted (IVW), weighted median, weighted mode, and MR-Egger regression techniques. We utilized publicly accessible summary statistics from a GWAS meta-analysis of adult-onset asthma in the UK Biobank (n=327,253; cases=26,582; controls=300,671) as the exposure factor. The outcomes were derived from GWAS data of individuals with European ancestry (n=26,405; cases=6,687; controls=19,718). GWAS data for IL-18 were obtained from individuals of European ancestry (n=9,785,222; cases=3,636; controls=9,781,586). Results: The MR analysis indicates that adult-onset asthma is associated with an increased risk of UC, with an odds ratio (OR) of 1.019 (95% CI 1.001-1.045, P=0.006). However, there is no strong evidence to suggest that UC significantly impacts the risk of adult-onset asthma. IL-18 may act as a potential mediator in the causal relationship between adult-onset asthma and UC, with a mediation proportion of 3.9% (95% CI, 0.6%-6.9%). Conclusion: In summary, our study established a causal relationship between asthma and UC, in which IL-18 contributes to a small extent. However, the primary factors underlying the influence of asthma on UC remain unclear. Future research should focus on identifying other potential mediators. In clinical practice, it is important to pay greater attention to intestinal lesions in patients with asthma.

Joint Detection of Serum Vitamin D, Body Mass Index, and Tumor Necrosis Factor Alpha for the Diagnosis of Crohn's Disease.

OBJECTIVE: Vitamin D (VD) deficiency was reported to contribute to the progression of Crohn's disease (CD) and affect the prognosis of CD patients. This study investigated the role of serum VD, body mass index (BMI), and tumor necrosis factor alpha (TNF-α) in the diagnosis of Crohn's disease. METHODS: CD patients (n=76) and healthy subjects (n=76) were enrolled between May 2019 and December 2020. The serum 25-hydroxyvitamin D [25(OH)D] levels, BMI, and TNF-α levels, together with other biochemical parameters, were assessed before treatment. The diagnostic efficacy of the single and joint detection of serum 25(OH)D, BMI, and TNF-α was determined using receiver operating characteristic (ROC) curves. RESULTS: The levels of 25(OH) D, BMI, and nutritional indicators, including hemoglobin, total protein, albumin, and high-density lipoprotein cholesterol, were much lower, and the TNF-α levels were much higher in the CD patients than in the healthy subjects (P<0.05 for all). The areas under the ROC curve for the single detection of 25(OH)D, BMI, and TNF-α were 0.887, 0.896, and 0.838, respectively, with the optimal cutoff values being 20.64 ng/mL, 19.77 kg/m2, and 6.85 fmol/mL, respectively. The diagnostic efficacy of the joint detection of 25(OH)D, BMI, and TNF-α was the highest, with an area under the ROC curve of 0.988 (95%CI: 0.968-1.000). CONCLUSION: The joint detection of 25(OH)D, TNF-α, and BMI showed high sensitivity, specificity, and accuracy in CD diagnosis; thus, it would be effective for the diagnosis of CD in clinical practice.

Baicalin down-regulates the expression of macrophage migration inhibitory factor (MIF) effectively for rats with ulcerative colitis.

The purpose of this study was to investigate whether baicalin, a Chinese herbal extract, down-regulates the expression of macrophage migration inhibitory factor (MIF), an inflammatory factor that regulates the function of macrophages (MΦ), in rats with trinitrobenzene sulphonic acid (TNBS)-induced ulcerative colitis (UC). The results showed that baicalin simultaneously down-regulated the expression of MIF, the quantity of MΦs and the amount of MΦ-related cytokines, including macrophage chemotactic factor-1 (MCP-1, CCL2) and macrophage inflammatory protein-3α (MIP-3α, CCL20), in rats with UC. There was no statistical difference between baicailin and mesalazine in down-regulating the expression of MIF. Our study demonstrated that baicalin, an inexpensive but effective monomer, could be a new and alternative pharmaceutical for UC.

Corrigendum: New Insights and Advances in Pathogenesis and Treatment of Very Early Onset Inflammatory Bowel Disease.

[This corrects the article DOI: 10.3389/fped.2022.714054.].

New Insights and Advances in Pathogenesis and Treatment of Very Early Onset Inflammatory Bowel Disease.

Very early onset inflammatory bowel disease (VEO-IBD) is characterized by multifactorial chronic recurrent intestinal inflammation. Compared with elderly patients, those with VEO-IBD have a more serious condition, not responsive to conventional treatments, with a poor prognosis. Recent studies found that genetic and immunologic abnormalities are closely related to VEO-IBD. Intestinal immune homeostasis monogenic defects (IIHMDs) are changed through various mechanisms. Recent studies have also revealed that abnormalities in genes and immune molecular mechanisms are closely related to VEO-IBD. IIHMDs change through various mechanisms. Epigenetic factors can mediate the interaction between the environment and genome, and genetic factors and immune molecules may be involved in the pathogenesis of the environment and gut microbiota. These discoveries will provide new directions and ideas for the treatment of VEO-IBD.

Comparison and recommendation of dietary patterns based on nutrients for Eastern and Western patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD), a non-specific chronic idiopathic inflammatory condition of the digestive system, requires lifelong treatment in which drugs are the mainstay, along with surgery when necessary. In adjuvant therapies, the diet is considered to be an essential, controllable, and economical component. However, the majority of recent nutrition research has focused on the general effects of nutrients on IBD, with little attention given to the advantages and negative aspects of individual foods and dietary combinations. To cover these shortcomings, we surveyed the benefits and drawbacks of typical foods and their chemical compositions on intestinal pathophysiology by comparing nutrients existing in the foods in Eastern and Western countries. Moreover, for Eastern and Western patients with IBD, we innovatively propose a 3-step dietary recommendation based on modified customary eating habits, including lowering the triggering foods, modifying dietary advice to control disease progression, and improving surgery prognosis.

Dysbiosis of intestinal microbiota in critically ill patients and risk of in-hospital mortality.

BACKGROUND: Despite the essential functions of the intestinal microbiota in human physiology, little research was reported on gut microbiota alterations in intensive care patients. This investigation examined the dysbacteriosis of intestinal flora in critically ill patients and evaluated the prognostic performance of this dysbiosis to predict in-hospital mortality. METHODS: A prospective cohort of patients were consecutively recruited in the Intensive Care Units (ICUs) in Guangdong Provincial People's Hospital from March 2017 through October 2017. Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score were assessed, and fecal samples were taken for examination within 24 hours of ICU admission. The taxonomic composition of the intestinal microbiome was determined using 16S rDNA gene sequencing. Patients were divided into survival and death groups based on hospital outcomes. The two groups were statistically compared using the Wilcoxon test and Metastats analysis. The genera of bacteria showing significantly different abundance between groups were assessed as predictors of in-hospital death. The prognostic value of bacterial abundance alone and in combination with APACHE II or SOFA score was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS: Among the 61 patients examined, 12 patients (19.7%) died during their hospital stay. Bifidobacterium abundance was higher in the survival group than the death group (P = 0.031). The AUROC of Bifidobacterium abundance in identifying in-hospital death at a cut-off probability of 0.0041 was 0.718 (95% confidence interval [CI], 0.588-0.826). The panel of Bifidobacterium abundance plus SOFA (AUROC, 0.882; 95% CI, 0.774-0.950) outperformed SOFA (AUROC, 0.649; 95% CI, 0.516-0.767; P = 0.012) and Bifidobacterium abundance alone (P = 0.007). The panel of Bifidobacterium abundance plus APACHE II (AUROC, 0.876; 95% CI, 0.766-0.946) outperformed APACHE II (AUROC, 0.724; 95% CI, 0.595-0.831; P = 0.035) and Bifidobacterium abundance alone (P = 0.012). CONCLUSIONS: Dysbiosis of intestinal microbiota with variable degrees of reduction in Bifidobacterium abundance exhibited promising performance in the predicting of in-hospital mortality and provides incremental prognostic value to existing scoring systems in the adult intensive care unit (ICU) setting.

Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence.

The novel coronavirus infection that initially found at the end of 2019 has attracted great attention. So far, the number of infectious cases has increased globally to more than 100 thousand and the outbreak has been defined as a pandemic situation, but there are still no "specific drug" available. Relevant reports have pointed out the novel coronavirus has 80% homology with SARS. In the difficulty where new synthesized drug cannot be applied immediately to patients, "conventional drug in new use" becomes a feasible solution. The first medication experience of the recovered patients in the US has led remdesivir to be the "specific drug". China has also taken immediate action to put remdesivir into clinical trials with the purpose of applying it into clinical therapeutics for Corona Virus Disease 2019 (COVID-19). We started from the structure, immunogenicity, and pathogenesis of coronavirus infections of the novel coronavirus. Further, we analyzed the pharmacological actions and previous trials of remdesivir to identify the feasibility of conducting experiments on COVID-19.

Application of Herbaceous Medications for Inflammatory Bowel Disease as a Complementary and Alternative Therapy.

BACKGROUND: Conventional medicine for the treatment of IBD is prevailingly composed of sulfadiazine, 5-aminosalicylic acid, glucocorticoid, and immunosuppressants, which have the merits of alleviating intestine inflammation, but long-term use of these drugs may cause toxic side effects; additionally, these drugs may be expensive. In the pursuit of novel and more economic therapies, patients may increasingly look at complementary and alternative medicine (CAM). Recently, CAM is increasingly favored by the general public on account of its safety, low toxicity, and effectiveness. As a branch of CAM, herbal plants and their extracts have a significant effect on the treatment of IBD. Treatment of IBD with herbaceous plants has been reported, but specific mechanisms and effects have not yet been elaborated. METHODS: English abstracts were identified in PubMed and Science Direct by multiple search terms, such as "herbal," "CAM," "IBD," "ulcerative colitis," "abdominal pain," and so on. Full-length articles were selected for review. RESULTS: Herbaceous plants and their extracts have been shown to be effective against IBD in many studies, and herbaceous plants may be effective in treating symptoms such as abdominal pain, diarrhea, mucus, and bloody stools. CONCLUSIONS: Herbal medications could be used as a complementary and alternative treatment for IBD, but they require more rigorous scientific testing.

Artificial liver research output and citations from 2004 to 2017: a bibliometric analysis.

BACKGROUND: Researches on artificial livers greatly contribute to the clinical treatments for liver failure. This study aimed to evaluate the research output of artificial livers and citations from 2004 to 2017 through a bibliometric analysis. METHODS: A list of included articles on artificial livers were generated after a comprehensive search of the Web of Science Core Collection (from 2004 to 2017) with the following basic information: number of publications, citations, publication year, country of origin, authors and authorship, funding source, journals, institutions, keywords, and research area. RESULTS: A total of 968 included articles ranged from 47 citations to 394 citations with a fluctuation. The publications were distributed in 12 countries, led by China (n = 212) and the US (n = 207). There were strong correlations of the number of citations with authors (r 2 = 0.133, p < 0.001), and countries (r 2 = 0.275, p < 0.001), while no correlations of the number of citations with the years since publication (r 2 = 0.016, p = 0.216), and funding (r 2 < 0.001, p = 0.770) were identified. Keyword analysis demonstrated that with the specific change of "acute liver failure," decrease in "bioartificial livers" and "hepatocyte," and increase in "tissue engineering" were identified. The top 53 cited keyword and keyword plus (including some duplicates counts) were identified, led by bioartificial liver (405 citations) and hepatocyte (248 citations). The top 50 cited keywords bursts were mainly "Blood" (2004-2008), "hepatocyte like cell" (2008-2015), and "tissue engineering" (2014-2017). All keywords could be classified into four categories: bioartificial livers (57.40%), blood purification (25.00%), clinical (14.81%), and other artificial organs (2.78%). DISCUSSION: This study shows the process and tendency of artificial liver research with a comprehensive analysis on artificial livers. However, although it seems that the future of artificial livers seems brighter for hepatocyte transplantation, the systems of artificial livers now are inclined on focusing on blood purification, plasma exchange, etc.

Is a low FODMAP diet beneficial for patients with inflammatory bowel disease? A meta-analysis and systematic review.

BACKGROUND & AIMS: To assess the current evidence regarding the benefit of a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol (FODMAP) diet in the treatment of patients with inflammatory bowel disease (IBD). METHODS: Databases such as PubMed, Web of Science, Medline were comprehensively searched for relevant studies through January 2017. The pooled odds ratio (OR) and weighted mean difference (WMD) with 95% confidence intervals (CIs) were used to analyze the dichotomous variables (diarrhea response, abdominal pain and bloating, etc.) and the continuous variables. Random- and fixed-effects models were chosen according to heterogeneity. RESULTS: Two RCTs and four before-after studies with a total of 319 patients (96% in remission) were identified. Except for the constipation response, there was a significant improvement in other symptoms: diarrhea response (OR: 0.24, 95% CI: 0.11-0.52, p = 0.0003), satisfaction with gut symptoms (OR: 26.84, 95% CI: 4.6-156.54, p < 0.00001), abdominal bloating (OR: 0.10, 95% CI: 0.06-0.16, p < 0.00001), abdominal pain (OR: 0.24, 95% CI: 0.16-0.35, p < 0.00001), fatigue (OR: 0.40, 95% CI: 0.24-0.66, p = 0.0003) and nausea (OR: 0.51, 95% CI: 0.31-0.85, p = 0.009). CONCLUSIONS: The present meta-analysis offers proof to support that a low FODMAP diet is beneficial for reducing gastrointestinal symptoms in patients with quiescent IBD. With the inherent limitations, the findings of this analysis remain to be confirmed and updated by further high-volume, well-designed and long-term follow-up studies.