Association of Serum Bilirubin With Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Objective: Metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) are the leading chronic diseases worldwide. There are still many controversies about the association between serum bilirubin and MetS or NAFLD. This study aims to evaluate the association of serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL) with MetS and NAFLD. Methods: Multiple databases were searched for relevant studies until November 2021. Randomized controlled trials, cross-sectional and cohort studies evaluating the association between serum bilirubin levels and MetS or NAFLD were included. Results: Twenty-four cross-sectional and cohort studies with 101, 517 participants were finally analyzed. Fifteen studies and 6 studies evaluated the association between bilirubin and MetS or NAFLD in health screening population, respectively, while 3 studies evaluated the association between bilirubin and non-alcoholic steatohepatitis (NASH) in NAFLD patients. Random effect model analysis showed the inverse association between TBIL and MetS in male (95%CI=0.71-0.96) and gender-neutral (95%CI=0.61-0.91) group. However, no significant association was found in females. Notably, the inverse association between DBIL and MetS was noticed in male (95%CI=0.36-0.75), female (95%CI=0.16-0.58) and gender-neutral population (95%CI=0.67-0.92). IBIL level was inversely associated with MetS in females (95%CI=0.52-0.96), whereas no statistical correlation presented in males. TBIL was not statistically correlated with NAFLD in gender-neutral or male subgroup. Similarly, there were no association between DBIL or IBIL and NAFLD in gender-neutral subgroup. However, the negative correlation between DBIL and NAFLD existed in males (95%CI=0.76-0.96). In NAFLD patients, IBIL analysis showed an inverse association with NASH (95%CI=0.01-0.12). Conclusion: Serum TBIL and DBIL levels, especially DBIL levels, assume an inverse correlation with MetS in healthy population. Serum IBIL is inversely associated with the onset and degree of NASH in NAFLD patients. Exogenous bilirubin supplement may be a potential strategy to assist in lowering the risk of developing MetS and NAFLD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021293349.

Serum HBV DNA plus RNA reflecting cccDNA level before and during NAs treatment in HBeAg positive CHB patients.

Background & Aims: Correlations between serum viral markers and intrahepatic cccDNA in patients undergoing long-term nucleos(t)ide analogues (NAs) treatment haven't been fully explored. In this study, we evaluate the correlation between intrahepatic cccDNA and other serum viral markers and intrahepatic HBV DNA in HBeAg positive chronic hepatitis B (CHB) patients during 60-month treatment with NAs. Methods: Fifty-four HBeAg positive CHB patients received long-term NAs treatment were included in this study. Serial serum samples were regularly collected and quantitatively analyzed for HBsAg, HBV DNA, HBV RNA and HBcrAg. Histological samples from liver biopsy at baseline and month 60 were analyzed for intrahepatic HBV DNA and cccDNA. Results: At baseline, serum HBV DNA plus RNA was positively associated with intrahepatic cccDNA in multivariate regression analysis (ß=0.205, P<0.001). In the correlation analysis between cccDNA and serum viral markers, HBV DNA plus RNA had the highest correlation coefficient (r=0.698, P<0.001), followed by serum HBV DNA (r=0.641, P<0.001), HBV RNA (r=0.590, P<0.001), and HBcrAg (r=0.564, P<0.001). At month 60, correlations between these serum viral markers and cccDNA were not observed (P>0.05). Multivariate regression analysis showed that only the decreased HBV DNA plus RNA was positively associated with cccDNA decline (ß=0.172, P =0.006). Changes of HBV DNA plus RNA (r=0.525, P=0.001) was better correlated with cccDNA decline as compared to HBV RNA (r=0.384, P=0.008), HBV DNA (r=0.431, P=0.003), and HBsAg (r=0.342, P=0.029). Conclusions: Serum HBV DNA plus RNA better correlated with intrahepatic cccDNA than other viral makers before and during NAs treatment in HBeAg positive CHB patients.

The Influence of Patient and Hospital Characteristics on Inpatient Satisfaction at Beijing District-Level Hospitals.

PURPOSE: Patient satisfaction is a key indicator of healthcare quality and hospital performance. This study aims to assess inpatient satisfaction at district-level hospitals and explore the determinants of inpatient satisfaction. PATIENTS AND METHODS: A total of 1458 adults from inpatient departments of 47 district-level hospitals in 16 districts across Beijing were recruited with a multi-stage stratified sample at Beijing in 2019. Univariate analysis and multivariate logistic regression were used to identify the influence of patient and institutional characteristics on inpatient satisfaction in four domains - administrative process, hospital environment, medical care, hospitalization expenses, and overall satisfaction. RESULTS: Of the 1458 participants, 577 (39.6%) were men, 581 (39.8%) were over 60 years of age. The average value of satisfaction score measured by a 5-point Likert scale were 4.37, 4.00, 4.44, 3.89, and 4.33 for the four domains and overall satisfaction. Patient and institutional characteristics were strongly associated with inpatient satisfaction. Patients with higher educational level were more satisfied with administrative process (P<0.05). Elder patients and patients with worse self-reported health status were less satisfied with hospital environment (P<0.05). Female, higher monthly family income and Urban Employees Basic Medical Insurance were positively associated with patient satisfaction in hospitalization expenses (P<0.05). And patients receiving care in suburban hospitals were less satisfied with administrative process, hospital environment and overall satisfaction (P<0.05). Patients receiving care in Traditional Chinese Medicine hospitals were more satisfied with medical care and expenses but less satisfied with environment (P<0.05). Chronic disease and hospital grade were not significantly associated with satisfaction in all domains. CONCLUSION: Patient satisfaction was influenced by demographic characteristics and hospital features. These determinants should be considered in hospital evaluation.

Removal of odors and VOCs in municipal solid waste comprehensive treatment plants using a novel three-stage integrated biofilter: Performance and bioaerosol emissions.

A novel three-stage integrated biofilter (TSIBF) composed of acidophilic bacteria reaction segment (ABRS), fungal reaction segment (FRS) and heterotrophic bacteria reaction segment (HBRS) was constructed for the treatment of odors and volatile organic compounds (VOCs)from municipal solid waste (MSW) comprehensive treatment plants. The performance, counts of predominant microorganisms, and bioaerosol emissions of a full-scale TSIBF system were studied. High and stable removal efficiencies of hydrogen sulfide, ammonia and VOCs could be achieved with the TSIBF system, and the emissions of culturable heterotrophic bacteria, fungi and acidophilic sulfur bacteria were relatively low. The removal efficiencies of different odors and VOCs, emissions of culturable microorganisms, and types of predominant microorganisms were different in the ABRS, FRS and HBRS due to the differences in reaction conditions and mass transfer in each segment. The emissions of bioaerosols from the TSIBF depended on the capture of microorganisms and their volatilization from the packing. The rational segmentation, filling of high-density packings and the accumulation of the predominant functional microorganisms in each segment enhanced the capture effect of the bioaerosols, thus reducing the emissions of microorganisms from the bioreactor.

Inhibitory effects of alkaline extract from the pericarp of Citrus reticulata Blanco on collagen behavior in bleomycin-induced pulmonary fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Peel of Citrus reticulata, a Chinese herbal drug with functions of regulating Qi and expelling phlegm, has been used for the treatment of lung related diseases in Chinese medicine for a long time. Its detailed effects on collagen in anti-idiopathic pulmonary fibrosis (IPF) is still unclear. AIM OF THE STUDY: To explore the effects of citrus alkaline extract (CAE) on collagen synthesis, crosslinking and deposition in pulmonary fibrosis and understand the possible signal pathways involved in the activity. MATERIALS AND METHODS: CAE was prepared from C. reticulata. Bleomycin-induced pulmonary fibrosis mouse model was applied. Pulmonary fibrosis of lung was estimated with histopathology analysis, and collagen deposition was evaluated with immunohistochemistry. Collagen crosslinking related biomarkers and enzymes were analyzed with chemical methods, immunohistochemical and western blot analyses. RESULTS: CAE oral administration lowered hydroxyproline content, inhibited the collagen deposition including expressions of collagen I and III, and relieved bleomycin-induced pulmonary fibrosis in mice model. The productions of a collagen crosslink pyridinoline and crosslinking related enzymes including lysyl oxidase (LOX), lysyl oxidase-like protein 1 (LOXL1) in lung were suppressed by CAE treatment. Furthermore, the protein expressions of TGF-ß1 and Smad3 levels in lungs were also downregulated by CAE. CONCLUSIONS: This study demonstrated that CAE inhibited collagen synthesis, crosslinking and deposition, and ameliorated bleomycin-induced pulmonary fibrosis. Preliminary mechanism study revealed that CAE exerted its bioactivity at least via downregulation of TGF-ß1/Smad3 pathway. Our findings provided a great potential in fighting IPF based on CAE.

Delivery luteolin with folacin-modified nanoparticle for glioma therapy.

BACKGROUND: Glioblastoma mutliforme is the most common and has the poorest prognosis of any malignant tumor of the central nervous system. Luteolin, the most abundant xanthone extracted from vegetables and medicinal plants, has been shown to have treatment effects in various cancer cell types. Luteolin is however, hydrophobic and has poor biocompatibility, which leads to low bioavailability. PATIENTS AND METHODS: In this study, folic acid modifiedpoly(ethylene glycol)-poly(e-caprolactone) (Fa-PEG-PCL) nano-micelles was used to encapsulate the luteolin, creating luteolin loaded PEG-PCL (Lut/Fa-PEG-PCL) micelles to treat glioma both in vitro and in vivo. RESULTS: When compared with the free luteolin and Lut/MPEG-PCL, Lut/Fa-PEG-PCL induced a significant cell growth inhibition and more apoptosis of GL261 cells both in vitro and in vivo. The safety assessment also showed no obvious side effects were observed in mice which were administrated with free luteolin or Lut/MPEG-PCL and Lut/Fa-PEG-PCL. CONCLUSION: These results suggested Lut/Fa-PEG-PCL may be used as an excellent intravenously injectable formulation for the treatment and chemoprevention.

Spectrum-effect relationship between HPLC fingerprints and bioactive components of Radix Hedysari on increasing the peak bone mass of rat.

The traditional Chinese medicine of Radix Hedysari plays an important role in invigorating gas for ascending, benefiting blood for promoting production of fluid, and promoting circulation for removing obstruction in collaterals, which is consistent with the principle of treatment for osteoporosis. This study is designed to investigate the bioactive components on increasing peak bone mass (PBM) by exploring the spectrum-effect relationship between chromatography fingerprints and effect. Multiple indicators are selected to evaluate the pharmacological activity. In fingerprints, 21 common peaks are obtained, five of which are identified. Furthermore, gray relational analysis (GRA) is a quantitative method of gray system theory and is used to describe the correlation degree of common peaks and pharmacological activities with relational value. 21 components are then divided into three different regions, of which ononin and calycosin play an extremely significant role in increasing PBM. In addition, factor analysis and hierarchical cluster analysis (HCA) are used to screen the optimal producing area for Radix Hedysari. This provides a comprehensive and efficient method to improve the quality evaluation of Radix Hedysari, confirming the bioactive components for PBM-enhancement and further develop its medicinal value.

Lipid-lowering, hepatoprotective, and atheroprotective effects of the mixture Hong-Qu and gypenosides in hyperlipidemia with NAFLD rats.

BACKGROUND: Hyperlipidemia and its complications are among the most harmful of diseases with a worldwide impact, which creates an urgent imperative to find safe and effective drugs for treatment. HG is mainly composed of two kinds of traditional Chinese medicines (TCM), Hong-Qu and gypenosides. Previously, the ingredients of the mixture mainly composed by Hong-Qu and gypenosides (HG) were widely used for purposes of lipid-lowering, antiatherosclerosis effects, and maintaining cardiovascular health in China. The purpose of this study was to determine whether HG provides any benefit to patients with hyperlipidemia. METHODS: Forty-eight adult male Sprague-Dawley rats with fatty liver disease were randomly divided into six groups: normal, model, two positive controls, and two doses of HG-treated groups. The normal rats were fed a basal diet, and the other rats were fed a high-fat diet. Thereafter, the serum lipid profiles, hepatic steatosis, cytokines, enzymes, and relevant mRNA of rats were analyzed in serum, aorta tissue or hepatic tissues, respectively. RESULTS: After 65 days of feeding the high-fat diet to rats, there were significantly disordered serum lipid profiles, elevated oxidative stress biomarkers, and decreased antiinflammatory cytokines in the serum levels. Additionally, aortic foam cell formation was increased. The gene expression levels including hydroxymethylglutaryl-CoA reductase (HMGR), peroxisome proliferator-activated receptor alpha (PPAR-α), sterol response element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA carboxylase-1 (ACC-1) and carnitine palmitoyl transferase-1(CPT-1) in hepatic tissue were also altered by a high-fat diet fed to Sprague-Dawley rats, and HG treatment significantly resolved and normalized these alterations. Moreover, HG not only caused a significant decrease in the lipid drops on the hepatic tissues, but also restored the antioxidant components. CONCLUSION: HG is beneficial for regulating the stability of blood lipids, has atheroprotective characteristics and may prevent nonalcoholic fatty liver disease (NAFLD), providing more than just a theoretical basis for drug research of cardiovascular disease (CVD) treatment.

[Determination of eight active components in Radix Hedysari by HPLC and its cluster analysis].

An HPLC method was established for the determination of adenosine, γ-aminobutyric acid (GABA) and six flavonoids (calycosin-7-glucoside, ononin, calycosin, isoliquiritigenin, formononetin and medicarpin） in Radix Hedysari. The samples were extracted with methanol by refluxing for 4 h. The HPLC-DAD was performed on a Diamonsil C(18) column (250 mm × 4.6 mm, 5 µm) with acetonitrile-water as the mobile phase. The column temperature was at 40 ℃ and the flow rate was 1.0 m L·min(-1), while the temperature of drift tube was 110.5 ℃ and the nebulizing gas flow was 3.1 L·min-1 for the ELSD system. The results showed all the eight components had good linear relationships (r(2) =0.992 8-1.000 0) in the range of the test concentration. The RSD of precision, stability and repeatability were less than 2%.The average recovery rates were 96.78%-103.45%, and RSD were 0.29%-1.61%.The index component contents of Radix Hedysari form 24 different origins were determined and used as variable factors in clustering analysis. The results were classified into 2 groups basically in accordance with the regional cluster. And the consequence was in consistent with the results of principal component analysis. This HPLC method is simple, shows good sensitive and accurate, and provides the experimental basis for multi-index control of Radix Hedysari. Clustering analysis for Radix Hedysari quality control has a certain reliability and objectivity.

[Spectrum-effect relationship on anti-hepatic fibrosis effect of Radix Hedysari].

The spectrum-effect relationship on anti-hepatic fibrosis effect of Radix Hedysari was explored based on high performance liquid chromatographic technique. Hepatic fibrosis was induced in mice by administering a subcutaneous injection of carbon tetrachloride-peanut oil (4:6, v/v) continuously for 35 d at a interval of 5 d (0.1 mL/10 g). And at the same time of modeling, the different extracts of Radix Hedysari were administered orally once daily at a dose of 10 g/kg. The ethanol extract of Radix Hedysari was specified to be most effective on anti-hepatic fibrosis by determining the levels of alanine aminotransferase, aspartate transami- nase, total-protein, albumin, albumin/globulin (ALT, AST, TP, ALB, and A/G) in serum and relative liver weight. Subsequently, the grey relational degree analysis and partial least squares analysis were employed to reveal the correlation between chromatographic fingerprint of ethanol extract of Radix Hedysari from 10 different geographical origins and its anti-hepatic fibrosis efficacy. The results suggest that most chemical constituents of Radix Hedysari have a high correlation with the effect of anti-hepatic fibrosis (> 0.8), which indicates that the effect is related to the various components in Radix Hedysari. Adenosine, calycosin and ononin in ethanol extract of Radix Hedysari have been identified separately among which adenosine and calycosin made the great contribution to the anti-hepatic fibrosis effect.

Screening for oesophageal cancer.

BACKGROUND: Oesophageal cancer is a global heath problem. The prognosis for advanced oesophageal cancer is generally unfavourable, but early-stage asymptomatic oesophageal cancer is basically curable and could achieve better survival rates. The two most commonly used tests are cytologic examination and endoscopy with mucosal iodine staining. The efficacy of the screening tests is controversial, and the true benefit and efficacy of screening remains uncertain because of the potential lead-time and length-time biases. This review was conducted to examine the evidence for the efficacy of screening for oesophageal cancer (squamous cell carcinoma and adenocarcinoma). OBJECTIVES: To determine the efficacy of early screening, using endoscopy with iodine staining or cytologic examination, in reducing mortality from oesophageal cancer in asymptomatic individuals from high-risk and general populations. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 8), The Cochrane Library (2012, Issue 8), MEDLINE (1950 to August 2012), EMBASE (1980 to August 2012), Allied and Complementary Medicine (AMED) (1985 to August 2012), Chinese Biomedical Database (CBM) (January 1975 to August 2012), VIP Database (January 1989 to August 2012), China National Knowledge Infrastructure (CNKI) (January 1979 to August 2012), and the Internet. We also searched reference lists, conference proceedings, and databases of ongoing trials. There was no restriction on language or publication status in the search for trials. SELECTION CRITERIA: We included only randomised controlled trials (RCT) of screening versus no screening for oesophageal cancer. Randomisation of groups or clusters of individuals was acceptable. DATA COLLECTION AND ANALYSIS: Two review authors independently scanned the titles and abstracts from the initial search for potential trials for inclusion. We did not find any trials that met the inclusion criteria. MAIN RESULTS: The electronic search identified 3482 studies. Two authors independently reviewed the references. The reports of 18 studies were retrieved for further investigation. None met the eligibility criteria for a RCT investigation of the effects of screening versus no screening for oesophageal cancer. AUTHORS' CONCLUSIONS: There were no RCTs that determined the efficacy of screening for oesophageal cancer. Non-RCTs showed a high incidence and the reported better survival after screening could be caused by selection bias, lead-time and length-time biases. RCTs are needed to determine the efficacy of screening for oesophageal cancer.