Recent Advances in Phenazine Natural Products: Biosynthesis and Metabolic Engineering.

Phenazine natural products are a class of nitrogen-containing heterocyclic compounds produced by microorganisms. The tricyclic ring molecules show various chemical structures and extensive pharmacological activities, such as antimicrobial, anticancer, antiparasitic, anti-inflammatory, and insecticidal activities, with low toxicity to the environment. Since phenazine-1-carboxylic acid has been developed as a registered biopesticide, the application of phenazine natural products will be promising in the field of agriculture pathogenic fungi control based on broad-spectrum antifungal activity, minimal toxicity to the environment, and improvement of crop production. Currently, there are still plenty of intriguing hidden biosynthetic pathways of phenazine natural products to be discovered, and the titer of naturally occurring phenazine natural products is insufficient for agricultural applications. In this review, we spotlight the progress regarding biosynthesis and metabolic engineering research of phenazine natural products in the past decade. The review provides useful insights concerning phenazine natural products production and more clues on new phenazine derivatives biosynthesis.

The burden of cardiovascular disease attributable to high fasting plasma glucose：Findings from the global burden of disease study 2019.

AIM: High fasting plasma glucose (HFPG) is a key risk factor for cardiovascular disease (CVD). Few studies have evaluated the CVD burden attributable to HFPG globally. It is urgent to investigate the current epidemiological pattern and past trends of CVD attributable to HFPG. METHODS: We used the Global Burden of Disease Study (GBD) 2019 to describe the CVD burden attributable to HFPG in 2019 and evaluate temporal trends between 1990 and 2019. RESULTS: Global Disability-Adjusted Life Years (DALYs) cases and death cases of HFPG-related CVD were approximately 72,591,163 and 3,763,298 in 2019, with an increase of 107.4 % and 114.6 % compared with 1990, respectively. Despite the increases, the age-standardized DALYs rate (ASDAR) and age-standardized death rate (ASDR) of HFPG-related CVD contributed to 895.2 per 100,000 people and 48.4 per 100,000 people in 2019, with an estimated annual percentage change (EAPC) of -0.22 and -0.31, respectively, from 1990. The highest ASDAR and ASDR of HFPG-related CVD were in 2019 observed in the low-middle SDI (Socio-demographic Index) and middle-SDI regions. Low SDI and some low-middle SDI regions showed an increase in ASDAR and ASDR of HFPG-related CVD from 1990 to 2019. Males are more affected by HFPG-related CVD than females across all years. The CVD burden attributable to HFPG in the elderly are higher than those in the young in 2019. The main causes of the global CVD burden attributable to HFPG in 2019 were ischemic heart disease, stroke, and peripheral arterial disease. CONCLUSION: The CVD burden attributable to HFPG remains a serious public health challenge threatening human health worldwide. It is necessary to develop more targeted and specific strategies to reduce CVD burden attributable to HFPG, especially in males, elderly, and lower SDI regions.

The burden of cardiovascular disease attributable to high body mass index-an observational study.

AIM: This study aims to provide a timely and comprehensive estimate of the current burden and temporal trend of cardiovascular disease (CVD) attributable to high body mass index (HBMI). METHODS: We systematically assessed the current burden and temporal trend of CVD attributable to HBMI by calendar year, age, sex, region, nation, socioeconomic status, and specific CVD based on the most recent Global Burden of Disease Study (GBD) 2019. RESULTS: Globally, the numbers of CVD-related disability-adjusted life years (DALYs) and deaths attributable to HBMI has more than doubled from 1990 to 2019. Conversely, the age-standardized rates (ASRs) of CVD-related DALYs and deaths attributable to HBMI showed a slight downward trend, with estimated annual percentage change (EAPC) of -0.18 and -0.43, respectively. The ASRs of CVD-related DALYs and deaths attributable to HBMI were lower in low and high Socio-demographic Index (SDI) regions in 2019, but higher in middle and high-middle SDI regions. The ASRs of CVD-related DALYs and deaths attributable to HBMI showed a downward trend in the high SDI regions from 1990 to 2019, but showed an upward trend in the low and low-middle SDI regions. The leading causes of CVD burden attributable to HBMI were ischemic heart disease, stroke, hypertensive heart disease, and atrial fibrillation/flutter in 2019. CONCLUSION: The CVD burden attributable to HBMI remains a challenging global health concern. Policymakers in high and increasing burden regions can learn from some valuable experiences of low and decreasing burden regions and develop more targeted and specific strategies to prevent and reduce CVD burden attributable to HBMI.

Novel STAT1 mutation in a paediatric case of chronic mucocutaneous candidiasis complicated by primary hypothyroidism: clinical presentation, genetic analysis and prognostic implications.

This case report presents a young girl in her early childhood diagnosed with chronic mucocutaneous candidiasis (CMC) and primary hypothyroidism. Genetic analysis revealed a novel de novo mutation in the STAT1 gene (exon 11, c.972C>G, p.Cys324Trp), adding to the existing literature on STAT1 mutations, which account for approximately 53% of CMC cases. The identified mutation is predicted to have a more severe pathogenic impact based on PolyPhen-2 scoring. Our findings emphasise the importance of comprehensive genetic testing in CMC diagnosis and suggest that the specific mutation site may correlate with disease prognosis. The case underscores the need for vigilant monitoring and targeted therapeutic interventions, given the potential for poorer outcomes.

Systematic Large Fragment Deletions in the Genome of Synechococcus elongatus and the Consequent Changes in Transcriptomic Profiles.

Genome streamlining, as a natural process in the evolution of microbes, has become a common approach for generating ideal chassis cells for synthetic biology studies and industrial applications. However, systematic genome reduction remains a bottleneck in the generation of such chassis cells with cyanobacteria, due to very time-consuming genetic manipulations. Synechococcus elongatus PCC 7942, a unicellular cyanobacterium, is a candidate for systematic genome reduction, as its essential and nonessential genes have been experimentally identified. Here, we report that at least 20 of the 23 over 10 kb nonessential gene regions could be deleted and that stepwise deletions of these regions could be achieved. A septuple-deletion mutant (genome reduced by 3.8%) was generated, and the effects of genome reduction on the growth and genome-wide transcription were investigated. In the ancestral triple to sextuple mutants (b, c, d, e1), an increasingly large number of genes (up to 998) were upregulated relative to the wild type, while slightly fewer genes (831) were upregulated in the septuple mutant (f). In a different sextuple mutant (e2) derived from the quintuple mutant d, much fewer genes (232) were upregulated. Under the standard conditions in this study, the mutant e2 showed a higher growth rate than the wild type, e1 and f. Our results indicate that it is feasible to extensively reduce the genomes of cyanobacteria for generation of chassis cells and for experimental evolutionary studies.

Global, regional and national burden of alcohol cardiomyopathy from Global Burden of Disease Study 2019.

This study aimed to provide up-to-date and comprehensive estimates on the global alcohol cardiomyopathy (ACM) from 1990 to 2019. Detailed data on the prevalence, disability-adjusted life-years (DALYs), deaths,percentage change in the number of cases and estimated annual percentage change (EAPC) of ACM worldwide from 1990 to 2019 were obtained or calculated from the Global Burden of Disease Study (GBD) 2019. Globally, the estimated prevalent cases of ACM in 2019 were 707,652 [95% uncertainty interval (UI): 545,182-924,392], with a 35.4% (28.2-44.2) increase from 522,616 (95% UI: 394,118-683,206) in 1990, while the age-standardized prevalence rate (ASPR) was slightly decreased with an overall EAPC of - 1.30 (- 1.38 - - 1.22). Similar to ASPR, the global age-standardized DALYs rate and age-standardized death rate (ASDR) also declined, with an EAPC of - 1.12(- 2.09 - - 0.14) and - 1.53(- 2.36 - - 0.70) from 1990 to 2019, respectively. Conversely, the number of ACM-related DALYs cases in 2019 was 2,441,108 (95% UI: 2,046,734-2,782,542), with an increase of 38.8%(2.8-59.9) over the past 30 years, and the number of ACM-related deaths in 2019 was 71,723 (95% UI: 60,167-81,995), with an increase of 33.1% (0.5- 51.9) compared with 1990. A significant variation in the burden of ACM was observed between different regions and countries. Although the ASPR, age-standardized DALYs rate and ASDR slightly decreased from 1990 to 2019, the absolute number of prevalent cases, DALYs cases and deaths significantly increased. This showed that the burden of ACM remains an important global public health concern. Public health policy and decision-makers should develop and implement more effective strategies specific to geographical location to combat and reduce the burden of ACM in the future.

Global burden of atrial fibrillation/atrial flutter and its attributable risk factors from 1990 to 2019.

AIMS: The aim of this study was to estimate the global burden of atrial fibrillation (AF)/atrial flutter (AFL) and its attributable risk factors from 1990 to 2019. METHODS AND RESULTS: The data on AF/AFL were retrieved from the Global Burden of Disease Study (GBD) 2019. Incidence, disability-adjusted life years (DALYs), and deaths were metrics used to measure AF/AFL burden. The population attributable fractions (PAFs) were used to calculate the percentage contributions of major potential risk factors to age-standardized AF/AFL death. The analysis was performed between 1990 and 2019. Globally, in 2019, there were 4.7 million [95% uncertainty interval (UI): 3.6 to 6.0] incident cases, 8.4 million (95% UI: 6.7 to 10.5) DALYs cases, and 0.32 million (95% UI: 0.27 to 0.36) deaths of AF/AFL. The burden of AF/AFL in 2019 and their temporal trends from 1990 to 2019 varied widely due to gender, Socio-Demographic Index (SDI) quintile, and geographical location. Among all potential risk factors, age-standardized AF/AFL death worldwide in 2019 were primarily attributable to high systolic blood pressure [34.0% (95% UI: 27.3 to 41.0)], followed by high body mass index [20.2% (95% UI: 11.2 to 31.2)], alcohol use [7.4% (95% UI: 5.8 to 9.0)], smoking [4.3% (95% UI: 2.9 to 5.9)], diet high in sodium [4.2% (95% UI: 0.8 to 10.5)], and lead exposure [2.3% (95% UI: 1.3 to 3.4)]. CONCLUSION: Our study showed that AF/AFL is still a major public health concern. Despite the advancements in the prevention and treatment of AF/AFL, especially in regions in the relatively SDI quintile, the burden of AF/AFL in regions in lower SDI quintile is increasing. Since AF/AFL is largely preventable and treatable, there is an urgent need to implement more cost-effective strategies and interventions to address modifiable risk factors, especially in regions with high or increased AF/AFL burden.

Salivary metabolomics of burning mouth syndrome: A cross-sectional study.

OBJECTIVE: There is a lack of systematic studies on salivary metabolomic profiles in burning mouth syndrome (BMS); metabolomics could help explore BMS pathogenesis. We aimed to explore the salivary metabolomic profile of patients with BMS using untargeted metabolomics techniques. DESIGN: A cross-sectional study was designed to analyze the characteristics of unstimulated whole salivary metabolomics of patients with BMS (n = 34) and healthy participants (n = 30). Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry, principal component, orthogonal partial least-squares-discriminant, hierarchical clustering, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to identify differentially expressed metabolites and metabolic pathways in which they were enriched. RESULTS: We identified 12,982 metabolite ions. Among them, 394 differentially expressed metabolites were identified with variable importance in projection scores of > 1 (P < 0.05) compared with those in the controls. Based on the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, 30 metabolites were identified, and 16 of them were enriched in 25 metabolic pathways. The levels of caffeine (log2-fold change = -2.91) and its metabolites, paraxanthine (-2.01) and theophylline (-2.03), were low, and the caffeine metabolism pathway was downregulated in the BMS group compared with those in the controls (P < 0.05). CONCLUSIONS: The salivary metabolomic profile of patients with BMS presented characteristics distinct from those of the controls. A low caffeine level may be associated with BMS. This study provides a novel insight for further exploration of the pathogenesis of and potential therapeutic approaches for BMS.

Association of Hashimoto's thyroiditis and anti-thyroid antibodies with oral lichen planus: A cross-sectional study.

Hashimoto's thyroiditis (HT) and its autoantibodies may be associated with oral lichen planus (OLP). In this cross-sectional study, we aimed to assess the relationship among HT, auto-anti-thyroid antibodies, and OLP in a Chinese population of 247 patients with oral lichen planus. Clinical manifestations of OLP were evaluated using the Thongprasom scoring system and clinical type. The diagnosis of HT was based on thyroid function, anti-thyroid peroxidase antibody (anti-TPOAb) and anti-thyroglobulin antibody (anti-TgAb) detection, and ultrasonography. The prevalence of HT in all patients with OLP was 39.68% (98/247); the prevalence in females with OLP was 46.24% (86/186), which was higher than that in males with OLP 19.67% (12/61) (P < 0.01). The titers of the two HT autoantibodies in females with OLP were higher than those in males (P < 0.01). The clinical manifestations of OLP, regardless of being evaluated using the Thongprasom system or clinical type, were not significantly associated with HT development or TPOAb (P = 0.864) or TgAb titers (P = 0.745). In this population-based southern Chinese cohort, the prevalence of HT in patients with OLP, particularly in female patients with OLP, was significantly higher than that in the general population. Female patients had higher HT autoantibody titers than male patients. However, the clinical manifestations of OLP were not significantly correlated with either HT development or auto-anti-thyroid antibody levels. The findings could help further elucidate the factors involved in the relationship between oral lichen planus and Hashimoto's thyroiditis.

Efficacy of topical administration for oral lichen planus: A network meta-analysis.

OBJECTIVE: To examine the comparative efficacy and safety of topical administration for oral lichen planus. MATERIALS AND METHODS: An electronic database search (1st January 1946 to 1st May 2020) for randomised controlled trials identified 34 studies involving eight interventions (clobetasol, betamethasone, triamcinolone, dexamethasone, fluocinolone, tacrolimus, pimecrolimus, and cyclosporine); these studies were subjected to network meta-analysis using direct and indirect comparisons [efficacy indicators: clinical response rate, symptom-reducing effect (visual analogue scale score), sign-reducing effect (Thongprasom-scale score) and relapse; safety indicator: adverse event occurrence]. RESULTS: Compared with placebo, tacrolimus had the best clinical response rate (odds ratio (OR), 57.78 [95% CI 3.15-1060.52]; P-score, 0.8654) and cyclosporine had the worst (OR, 3.61[95% CI 0.20-66.62]; P-score, 0.2236); tacrolimus had the best symptom-reducing effect (standardised mean difference (SMD), 1.06 [95% CI 0.41-1.71]; P-score, 0.9323) and fluocinolone had the worst (SMD, -0.54 [95% CI -1.44-0.36]; P-score, 0.0157); dexamethasone had the best sign-reducing effect (SMD, 3.60 [95% CI 1.74-5.45]; P-score, 0.8306) and clobetasol had the worst (SMD, 2.63 [95% CI 1.66-3.61]; P-score, 0.2581); and pimecrolimus performed best (OR, 0.04 [95% CI 0.00-0.64]; P-score, 0.9227) and clobetasol performed the worst [OR, 0.60; 95% CI 0.15-2.45; P-score, 0.2545] in reducing relapse. Regarding safety, dexamethasone was the safest compared with placebo [OR, 0.37; 95% CI 0.05-2.57; P-score, 0.9337), whereas fluocinolone ranked low for safety [OR, 9.48; 95% CI 1.50- 60.03; P-score, 0.1189]. CONCLUSIONS: The relative ranking of topical administration varies according to the different indicators. Based on the joint consideration of clinical response rate and adverse event occurrence, dexamethasone, triamcinolone and betamethasone are recommended for better efficacy and safety. The optimal treatment for oral lichen patients varies under different conditions.

De Novo Biosynthesis and Whole-Cell Catalytic Production of 2-Acetamidophenol in Escherichia coli.

2-Acetamidophenol (AAP) is an aromatic product with promising activities in agricultural applications and medical research. At present, AAP is synthesized by chemical methods from nonrenewable fossil fuel resources, which cause environmental pollution and the reaction conditions are harsh. In this study, we constructed the artificial biosynthetic pathway of AAP with five different expressed proteins in Escherichia coli for the first time. By introducing the hydrogen peroxide degrading enzyme catalase and improving cell tolerance to toxic intermediates or products, the yield of AAP reached 33.54 mg/L using shaking-flask culture. The best-engineered strain could produce 568.57 mg/L AAP by fed-batch fermentation from glucose and precursor (2-aminophenol, 2-AP) addition. Furthermore, a one-pot whole-cell cascade biocatalytic pathway to AAP and analogues was developed and optimized. This method can efficiently produce 1.8 g/L AAP using the methyl anthranilate hydrolysis product as the substrate. This study provides not only the de novo artificial biosynthetic pathway of AAP in E. coli but also a promising sustainable and efficient strategy to enable the synthesis of AAP on a gram scale.

Homocysteine (HCY) levels in patients with atrial fibrillation (AF): A meta-analysis.

PURPOSE: Atrial fibrillation (AF) is one of the most common persistent arrhythmia, and its complications include cerebral embolism, arterial embolism and heart failure. Some studies have found that elevated Homocysteine (HCY) levels is a new risk factor for AF. Currently, there is no meta-analysis to explore whether the HCY levels is related to AF. Therefore, a meta-analysis was conducted to evaluate the relationship between the HCY levels and AF, in order to draw the attention of clinicians to the HCY levels. METHODS: A meta-analysis was performed in the study to evaluated the association between the HCY levels and AF. In order to identify eligible original articles, The EMBASE, PubMed, and web of science were systematically searched until November 2020. All data were analyzed with Review Manager 5.3. The meta-analysis results were evaluated depending on standardized mean differences (SMD) with 95% confidence intervals (CI). Moreover, the subgroup analysis and sensitivity analysis were also analyzed. RESULTS: The HCY levels was significantly associated with AF (WMD = 0.81, 95% CI: 0.58 to 1.03; P < .00001). In the analysis, there was a medium degree of heterogeneity (I2 = 73%). Subgroup analysis showed that female < 60, BMI≥25, BMI <25, age ≥60 and publication year ≥2010 were identified as possible sources of heterogeneity. Sensitivity analysis showed that the main results remained unchanged after omitting any single study or converting the random effects model (REM) to fixed effects model (FEM). CONCLUSIONS: The meta-analysis showed that there is a significant correlation between the HCY levels and AF, and the role of HCY in AF patients should not be ignored in clinical.

Focal nodular hyperplasia mimicking hepatocellular adenoma and carcinoma in two cases.

Focal nodular hyperplasia (FNH) is a solid benign tumor of the liver, predominantly in young women. A correct diagnosis of FNH is essential for making appropriate clinical decisions and avoiding unnecessary liver resection. Herein, we reported that two male cases with FNH, who initially presented with persistent abdominal discomfort, were misdiagnosed with hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) on contrast-enhanced magnetic resonance imaging and computed tomography scans, respectively. After surgery, a histological diagnosis of FNH was finally established. In this paper, we also reviewed the knowledge regarding diagnosis and differential diagnosis of FNH on imaging examinations, which are helpful for avoiding misdiagnoses and guiding clinical interventions.

Identification of 8-Azaguanine Biosynthesis-Related Genes Provides Insight Into the Enzymatic and Non-enzymatic Biosynthetic Pathway for 1,2,3-Triazole.

8-Azaguanine (1) is a special 1,2,3-triazole containing natural product that possesses potent antibacterial and antitumor activities. In the present study, the entire 8-azaguanine biosynthetic gene cluster was located from Streptomyces CGMCC4.1633. Targeted gene disruption, heterologous expression analysis, and feeding experiments identified crucial genes for 8-azaguanine production. Moreover, we characterized the structure of two novel metabolites, analyzed NO (or reactive nitrogen species) related genes 8-azgA/B and radical SAM enzyme homologous 8-AzgG, and verified the non-enzymatic ring formation reaction of 8-azaguanine 1,2,3-triazole. All of the data and presumptions provide insight into the timing and mechanism of the enzymatic and non-enzymatic pathway that produce 8-azaguanine-type 1,2,3-triazole.

Recent advances of metabolic engineering strategies in natural isoprenoid production using cell factories.

Covering: up to 2019As abundant natural products, isoprenoids have many useful industrial applications in the manufacturing of drugs, fragrances, food additives, colorants, rubber and advanced biofuels. The microbial production of isoprenoids has received much attention in recent years. Metabolic engineering approaches and synthetic biology have been utilized to reconstruct and optimize the metabolic pathways for isoprenoid production in cell factories. In this review, the recent advances in isoprenoid production using microbes are summarized, with a focus on MEP and MVA pathway engineering, downstream isoprenoid pathway engineering and microbial host engineering, which mainly includes central carbon pathway engineering. Finally, future perspectives for the improvement of isoprenoid production are discussed.

Whole-exome sequencing identification of a novel splicing mutation of RUNX2 in a Chinese family with cleidocranial dysplasia.

OBJECTIVES: Cleidocranial dysplasia (CCD) is a congenital autosomal dominant skeletal disease characterized by multiple craniofacial and dental anomalies. Here, we investigated mutation of the runt-related transcription factor 2 (RUNX2) gene, which is considered responsible for most instances of CCD in patients, in a Chinese family with CCD. METHODS: Genomic DNA was extracted from the peripheral blood lymphocytes of all participants, and mutation analysis was performed using whole-exome and Sanger sequencing. Biophysical predictions of the altered protein were analyzed using various bioinformatics tools, and direct sequencing via reverse transcription polymerase chain reaction (PCR) was performed for functional analysis of the mutation. To determine the function of the mutated protein, expression of RUNX2 and integrin-binding sialoprotein (IBSP) was investigated via quantitative PCR. RESULTS: We identified a novel splicing mutation (c.581-9 T > G) in all affected members, with this RUNX2 mutation incorporating in a new splice site to replace the canonical splice site, thereby resulting in insertion of an 8-bp fragment within the terminal exon 5 splice-acceptor site and premature translation termination. qPCR results confirmed attenuated RUNX2 expression and IBSP overexpression in the peripheral blood lymphocytes of patients. CONCLUSIONS: These results suggested that the newly identified splice-site mutation (c.581-9 T > G) in RUNX2 was responsible for CCD in this family through its alteration of RUNX2 activity and upregulated IBSP levels. These findings extend the mutational spectrum of the RUNX2 gene and might contribute to genetic diagnosis and counseling of families with CCD.

A novel PAX9 mutation found in a Chinese patient with hypodontia via whole exome sequencing.

OBJECTIVE: To investigate a novel gene mutation in a Chinese patient with non-syndromic hypodontia. SUBJECTS AND METHODS: Mutation analysis was carried out by whole exome sequencing. Bioinformatics tools were used for the biophysical predictions of the mutative protein. Luciferase reporter assay was performed to analyse the effects of mutation on protein function. PAX9 and BMP4 gene expression from mutant cells was detected by qRT-PCR. RESULTS: A novel heterozygous mutation (c.G1057A) was detected in the patient but was not found in the controls. The novel missense mutation led to a Val111Met substitution in the paired box domain which was completely conserved evolutionarily, as analysed by dbNSFP. The mutation was predicted to be disease-causing and harmful using MutationTaster and CADD, respectively. Protean of Lasergene showed that this mutation may lead to ß-region shortening in the mutant protein compared to the wild type. Luciferase reporter assay indicated that the mutated protein reduced the transactivation activity of PAX9. This mutation led to increased levels of PAX9 transcript and reduced levels of BMP4 transcript, likely due to compensatory activation and lower transactivation activity of mutant PAX9. CONCLUSION: This novel mutation (c.G1057A) in PAX9 caused hypodontia by altering PAX9 gene function and downregulating BMP4 gene expression.

Clinical characteristics and outcomes of traditional Chinese medicine-induced liver injury: a systematic review.

BACKGROUNDS: Traditional Chinese medicine (TCM) is becoming increasingly popular and related adverse events are often ignored or underestimated. AIMS: This systematic review aimed to evaluate the clinical characteristics and outcomes of TCM-induced liver injury (TCM-ILI) and to estimate the proportion of TCM-ILI in all drug-induced liver injuries (DILI). METHODS: China National Knowledge Infrastructure, Wanfang, VIP, PubMed, and Embase databases were searched. Demographic, clinical, and survival data were extracted and pooled. Factors associated with worse outcomes were calculated. For the proportion meta-analyses, the data were pooled by using a random-effects model. RESULTS: Overall, 21,027 articles were retrieved, of which 625 were finally included. There was a predominance of female and older patients. The proportion of liver transplantation was 2.18% (7/321). The mortality was 4.67% (15/321). Male, higher aspartate aminotransferase and direct bilirubin, and lower albumin were significantly associated with an increased risk of death/liver transplantation in TCM-ILI patients. The proportion of TCM-ILI in all DILI was 25.71%. The proportion was gradually increased with year. CONCLUSIONS: Our work summarises current knowledge regarding clinical presentation, disease course, and prognosis of TCM-ILI. TCM can result in hepatotoxicity, even death or necessitate life-saving liver transplantation. Governmental regulation of TCM products should be strictly established.

Ischemic stroke in liver cirrhosis: epidemiology, risk factors, and in-hospital outcomes.

BACKGROUND AND AIMS: Patients with cirrhosis are reportedly more prone to develop hemorrhagic stroke, thereby increasing the risk of death. However, the effect of ischemic stroke on liver diseases remains unclear. In addition, few studies have explored the risk factors for ischemic stroke in patients with liver cirrhosis. Our study aimed to explore the epidemiology, risk factors, and in-hospital outcomes of ischemic stroke in a large cohort of hospitalized patients with cirrhosis. PATIENTS AND METHODS: In this single-center observational study, we retrospectively reviewed the medical records of patients with liver cirrhosis admitted to our hospital from January 2011 to June 2014. A diagnosis of ischemic stroke was further identified. RESULTS: Of the 2444 patients with liver cirrhosis, 160 had ischemic stroke, including 128 patients with previous ischemic stroke and 32 patients with new-onset ischemic stroke during their hospitalizations. Compared with patients with cirrhosis without ischemic stroke, those with ischemic stroke were significantly older; had a significantly higher proportion of arterial hypertension and a significantly lower proportion of hepatitis B virus infection; had significantly higher white blood cell, platelet, blood urea nitrogen, and triglyceride levels; and had significantly lower alanine aminotransferase and aspartate aminotransferase levels and prothrombin time. The in-hospital mortality was significantly higher in patients with ischemic stroke than in those without [8.80% (14/160) vs. 3.2% (72/2284), P=0.001]. CONCLUSION: Ischemic stroke was often observed in patients with cirrhosis, and it significantly increased the in-hospital mortality. The association of inflammation, coagulation disorders, and viral hepatitis with development of ischemic stroke in liver cirrhosis should be further evaluated in prospective cohort studies.