Machine learning-based models for advanced fibrosis and cirrhosis diagnosis in chronic hepatitis B patients with hepatic steatosis.

BACKGROUND AND AIMS: The global rise of chronic hepatitis B (CHB) superimposed on hepatic steatosis (HS) warrants non-invasive, precise tools for assessing fibrosis progression. This study leveraged machine learning (ML) to develop diagnostic models for advanced fibrosis and cirrhosis in this patient population. METHODS: Treatment-naive CHB patients with concurrent HS who underwent liver biopsy in ten medical centers were enrolled as a training cohort and an independent external validation cohort (NCT05766449). Six ML models were implemented to predict advanced fibrosis and cirrhosis. The final models, derived from Shapley Additive exPlanations, were compared to Fibrosis-4 Index (FIB-4), Nonalcoholic fatty liver disease Fibrosis Score (NFS), and Aspartate transaminase to platelet ratio index (APRI) using the area under receiver operating characteristic curve (AUROC), and decision curve analysis (DCA). RESULTS: Of 1,198 eligible patients, the random forest (RF) model achieved AUROCs of 0.778 [95% confidence interval (CI) 0.749-0.807] for diagnosing advanced fibrosis (RF-AF model) and 0.777 (95%CI 0.748-0.806) for diagnosing cirrhosis (RF-C model) in the training cohort, and maintained high AUROCs in the validation cohort. In the training cohort, the RF-AF model obtained an AUROC of 0.825 (95% CI 0.787-0.862) in patients with HBV DNA ≥105 IU/ml, and RF-C model had an AUROC of 0.828 (95% CI 0.774-0.883) in female patients. The two models outperformed FIB-4, NFS, and APRI in the training cohort, and also performed well in the validation cohort. CONCLUSION: The RF models provide reliable, non-invasive tools for identifying advanced fibrosis and cirrhosis in CHB patients with concurrent HS, offering a significant advancement in the co-management of the two diseases.

Development of a machine learning-based model to predict hepatic inflammation in chronic hepatitis B patients with concurrent hepatic steatosis: a cohort study.

Background: With increasingly prevalent coexistence of chronic hepatitis B (CHB) and hepatic steatosis (HS), simple, non-invasive diagnostic methods to accurately assess the severity of hepatic inflammation are needed. We aimed to build a machine learning (ML) based model to detect hepatic inflammation in patients with CHB and concurrent HS. Methods: We conducted a multicenter, retrospective cohort study in China. Treatment-naive CHB patients with biopsy-proven HS between April 2004 and September 2022 were included. The optimal features for model development were selected by SHapley Additive explanations, and an ML algorithm with the best accuracy to diagnose moderate to severe hepatic inflammation (Scheuer's system ≥ G3) was determined and assessed by decision curve analysis (DCA) and calibration curve. This study is registered with ClinicalTrials.gov (NCT05766449). Findings: From a pool of 1,787 treatment-naive patients with CHB and HS across eleven hospitals, 689 patients from nine of these hospitals were chosen for the development of the diagnostic model. The remaining two hospitals contributed to two independent external validation cohorts, comprising 509 patients in validation cohort 1 and 589 in validation cohort 2. Eleven features regarding inflammation, hepatic and metabolic functions were identified. The gradient boosting classifier (GBC) model showed the best performance in predicting moderate to severe hepatic inflammation, with an area under the receiver operating characteristic curve (AUROC) of 0.86 (95% CI 0.83-0.88) in the training cohort, and 0.89 (95% CI 0.86-0.92), 0.76 (95% CI 0.73-0.80) in the first and second external validation cohorts, respectively. A publicly accessible web tool was generated for the model. Interpretation: Using simple parameters, the GBC model predicted hepatic inflammation in CHB patients with concurrent HS. It holds promise for guiding clinical management and improving patient outcomes. Funding: This research was supported by the National Natural Science Foundation of China (No. 82170609, 81970545), Natural Science Foundation of Shandong Province (Major Project) (No. ZR2020KH006), Natural Science Foundation of Jiangsu Province (No.BK20231118), Tianjin Key Medical Discipline (Specialty), Construction Project, TJYXZDXK-059B, Tianjin Health Science and Technology Project key discipline special, TJWJ2022XK034, and Research project of Chinese traditional medicine and Chinese traditional medicine combined with Western medicine of Tianjin municipal health and Family Planning Commission (2021022).

Randomized control study of the use of faropenem for treating patients with pulmonary tuberculosis.

OBJECTIVES: Faropenem has antituberculosis activity in vitro but its utility in treating patients with tuberculosis (TB) is unclear. METHODS: We conducted an open-label, randomized trial in China, involving newly diagnosed, drug-susceptible pulmonary TB. The control group was treated with the standard 6-month regimen. The experimental group replaced ethambutol with faropenem for 2 months. The primary outcome was the treatment success rate after 6 months of treatment. Noninferiority was confirmed if the lower limit of a 95% one-sided confidence interval (CI) of the difference was greater than -10%. RESULTS: A total of 227 patients eligible for the study were enrolled in the trial group and the control group in a ratio of 1:1. Baseline characteristics of participants were similar in both groups. In the modified intention-to-treat population, 88.18% of patients in the faropenem group achieved treatment success, and 85.98% of those in the control group were successfully treated, with a difference of 2.2% (95% CI, -6.73-11.13). In the per-protocol population, treatment success was 96.04% in the faropenem group and 95.83% in the control group, with a difference of 2.1% (95% CI, -5.31-5.72). The faropenem group showed noninferiority to the control group in the 6-month treatment success rates. The faropenem group had significantly fewer adverse events (P <0.01). CONCLUSIONS: Our study proved that oral faropenem regimen can be used for the treatment of TB, with fewer adverse events. (Chinese Clinical Trial Registry, ChiCTR1800015959).

A novel non-invasive model for the prediction of advanced liver fibrosis in chronic hepatitis B patients with NAFLD.

There are still lack of non-invasive models to evaluate liver fibrosis in chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD). We aimed to establish a predictive model for advanced fibrosis in these patients. A total of 504 treatment-naive CHB patients with NAFLD who underwent liver biopsy were enrolled and randomly divided into a training set (n = 336) and a validation set (n = 168). Receiver operating characteristic (ROC) curve was used to compare predicting accuracy for the different models. One hundred fifty-six patients (31.0%) had advanced fibrosis. In the training set, platelet, prothrombin time, type 2 diabetes, HBeAg positivity and globulin were significantly associated with advanced fibrosis by multivariable analysis. A predictive model namely PPDHG for advanced fibrosis was developed based on these parameters. The areas under the ROC curve (AUROC) of PPDHG with an optimal cut-off value of -0.980 in predicting advanced fibrosis was 0.817 (95% confidence interval 0.772 to 0.862), with a sensitivity of 81.82% and a specificity of 66.81%. The predicting accuracy of PPDHG for advanced fibrosis was significantly superior to AST to platelet ratio index (APRI), fibrosis-4 score (FIB-4) and NAFLD fibrosis score (NFS). Further analysis revealed that the AUROC of PPDHG remained significantly higher than FIB-4 and NFS indexes, while it was comparable with APRI for predicting advanced fibrosis in the validation set. PPDHG had a better predicting performance than established models for advanced fibrosis in CHB patients with NAFLD. The application of PPDHG can reduce the necessary for liver biopsy in these patients.

IgG response to spike protein of SARS-CoV-2 in healthy individuals and potential of intravenous IgG as treatment for COVID-19.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which is currently a worldwide pandemic. There are limited available treatments for severe COVID-19 patients. However, some evidence suggests that intravenous immunoglobulin (IVIg) provides clinical benefits for these patients. METHODS: We administered IVIg to 23 severe COVID-19 patients, and all of them survived. Four related coronaviruses can cause the common cold. We speculated that cross-reactivity of SARS-CoV-2 and other common coronaviruses might partially explain the clinical efficacy of IVIg therapy. Thus, we performed multiple alignment analysis of the spike (S), membrane (M), and nucleotide (N) proteins from SARS-CoV-2 and the common coronaviruses to identify conserved regions. Next, we synthesized 25 peptides that were conserved regions and tested their IVIg seropositivity. RESULTS: The results indicated four peptides had significant or nearly significant seropositivity, and all of them were associated with the S and M proteins. Examination of the immune responses of healthy volunteers to each synthetic peptide indicated high seropositivity to the two peptides from S protein. Blood samples from healthy individuals may have pre-existing anti-SARS-CoV-2 IgGs, and IVIg is a potentially effective therapy for severe COVID-19. CONCLUSION: In conclusion, blood samples from many healthy individuals have pre-existing anti-SARS-CoV-2 IgGs, and IVIg may be an effective therapy for severe COVID-19.

Derivation and validation of prognostic models for predicting survival outcomes in Acute-on-chronic liver failure patients.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of chronic liver disease associated with high bacterial infection (BI) and short-term mortality. However, many ACLF prognostic predictive modelsare complicated. The aim of this study is to develop prognostic models for ACLF patients to predict BI and mortality. We retrospective recruited 263 patients with ACLF from Shandong Provincial Hospital and Taizhou Enze Medical Center (Group) Enze Hospital. ACLF was defined according to the Asian Pacific Association for the Study of the Liver (APASL) criteria. Multivariable logistic regression was used to derive prediction models for occurring BI and 28-day mortality in ACLF patients. Ninety seven of 263 patients (37%) occurred BI and 41 of 155 (26%) died within 28 days of admission. C-reactive protein (CRP), glucose, and albumin were the independent predictors for occurring BI during the hospital stay. We also found that hepatic encephalopathy (HE), prothrombin time, activated partial thromboplastin time (APRI), and glucose were the independent predictors of 28-day mortality of ACLF patients. Using logistic regression model, we generated a new modified MELD model (M-MELD) by incorporating HE, APRI, and glucose. AUC of M-MELD model was 0.871, which were significantly higher than MELD score (AUC:0.734), MELD-Na score (AUC:0.742), and integrated MELD score (iMELD) (AUC:0.761). HE, MELD score, APRI, and blood glucose were independent risk factors for 28-day mortality of ACLF patients. The modified MELD model (M-MELD) by incorporating HE, APRI, and glucose has better discriminative performances compared with MELD in predicting 28-day mortality.

Indole-3-carbinol ameliorates necroptosis and inflammation of intestinal epithelial cells in mice with ulcerative colitis by activating aryl hydrocarbon receptor.

Ulcerative colitis (UC) is a disease characterized by inflammation and disruption of the intestinal epithelial barrier. Necroptosis plays a critical role in disease progression. Indole-3-carbinol (I3C), a natural dietary agonist of aryl hydrocarbon receptor (AHR), has shown alleviating effects on UC. However, its mechanisms of action have not been comprehensively elucidated. Therefore, we aimed at investigating the protective role of I3C in DSS-induced colitis mice models. I3C significantly ameliorated body weight loss, colon length shortening and colonic pathological damage in colitis mice, reduced disease activity index (DAI) and histological (HI) scores, as well as alleviated colonic necroptosis and inflammation. In vitro, I3C attenuated necroptosis and inflammation of colonoids and NCM460 cells. AHR, activated by I3C, inhibits activation of receptor-interacting protein kinase 1 (RIPK1) and the subsequent assembly of necrosome in a time-dependent manner, as well as suppressing NF-κB activation and decreasing TNF-α, IL-1ß, IL-6 and IL-8 expression. Silencing of AHR aggravated necroptosis and inflammation of NCM460 cells, and did not be ameliorated by I3C. Furthermore, AHR activation induces the expression of inhibitor of apoptosis proteins (IAPs) and the ubiquitination of RIPK1. In conclusion, I3C exerts a protective effect in DSS-induced colitis mice models by alleviating the necroptosis and inflammation of IECs through activating AHR.

Proteomic and metabolomic investigation of serum lactate dehydrogenase elevation in COVID-19 patients.

Serum lactate dehydrogenase (LDH) has been established as a prognostic indicator given its differential expression in COVID-19 patients. However, the molecular mechanisms underneath remain poorly understood. In this study, 144 COVID-19 patients were enrolled to monitor the clinical and laboratory parameters over 3 weeks. Serum LDH was shown elevated in the COVID-19 patients on admission and declined throughout disease course, and its ability to classify patient severity outperformed other biochemical indicators. A threshold of 247 U/L serum LDH on admission was determined for severity prognosis. Next, we classified a subset of 14 patients into high- and low-risk groups based on serum LDH expression and compared their quantitative serum proteomic and metabolomic differences. The results showed that COVID-19 patients with high serum LDH exhibited differentially expressed blood coagulation and immune responses including acute inflammatory responses, platelet degranulation, complement cascade, as well as multiple different metabolic responses including lipid metabolism, protein ubiquitination and pyruvate fermentation. Specifically, activation of hypoxia responses was highlighted in patients with high LDH expressions. Taken together, our data showed that serum LDH levels are associated with COVID-19 severity, and that elevated serum LDH might be consequences of hypoxia and tissue injuries induced by inflammation.

Mycobacterial identification on homogenised biopsy facilitates the early diagnosis and treatment of laryngeal tuberculosis.

INTRODUCTION: The incidence of laryngeal tuberculosis has increased gradually in recent years. Laryngeal tuberculosis has strong infectivity and atypical clinical manifestations. Hence, establishing the early diagnosis of laryngeal tuberculosis is considered difficult, resulting in the high rate of misdiagnosis of laryngeal tuberculosis and increased rates of tuberculosis infection. OBJECTIVE: This study aimed to describe a case of laryngeal tuberculosis detected using the mycobacteria gene chips technology, facilitating the early diagnosis and the treatment of laryngeal tuberculosis. CASE PRESENTATION: A 27-year-old woman presented with a 7-day history of hoarseness, with a normal routine blood chemistry test and chest computed tomography results. Histological analysis of the vocal cord biopsy showed granulomatous inflammation and the negative acid-fast stain test. The mycobacteria gene chips method was used to directly examine the vocal cord tissue treated with homogenate, and the Mycobacterium tuberculosis was successfully identified. Thus, the early diagnosis of laryngeal tuberculosis and the drug sensitivity of rifampin and isoniazid were confirmed. The patient recovered after undergoing a 1-year standard anti-tuberculosis therapy. CONCLUSIONS: Mycobacterial identification on homogenised biopsy using the mycobacteria gene chips method significantly facilitates the early diagnosis and the treatment of tuberculosis.

Mask wearing in pre-symptomatic patients prevents SARS-CoV-2 transmission: An epidemiological analysis.

OBJECTIVES: Pandemic COVID-19 has become a seriously public health priority worldwide. Comprehensive strategies including travel restrictions and mask-wearing have been implemented to mitigate the virus circulation. However, detail information on community transmission is unavailable yet. METHODS: From January 23 to March 1, 2020, 127 patients (median age: 46 years; range: 11-80) with 71 male and 56 female, were confirmed to be infected with the SARS-CoV-2 in Taizhou, Zhejiang, China. Epidemiological trajectory and clinical features of these COVID-19 cases were retrospectively retrieved from electronic medical records and valid individual questionnaire. RESULTS: The disease onset was between January 9 to February 14, 2020. Among them, 64 patients are local residents, and 63 patients were back home from Wuhan from January 10 to 24, 2020 before travel restriction. 197 local residents had definite close-contact with 41 pre-symptomatic patients back from Wuhan. 123 and 74 of them contact with mask-wearing or with no mask-wearing pre-symptomatic patients back from Wuhan, respectively. Data showed that incidence of COVID-19 was significantly higher for local residents close-contact with no mask-wearing Wuhan returned pre-symptomatic patients (19.0% vs. 8.1%, p < 0.001). Among 57 close-contact individuals, 21 sequential local COVID-19 patients originated from a pre-symptomatic Wuhan returned couple, indicated dense gathering in congested spaces is a high risk for SARS-CoV-2 transmission. CONCLUSIONS: Our findings provided valuable details of pre-symptomatic patient mask-wearing and restriction of mass gathering in congested spaces particularly, are important interventions to mitigate the SARS-CoV-2 transmission.

Proteomic and Metabolomic Characterization of COVID-19 Patient Sera.

Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 COVID-19 patients, leading to 16 correct assignments. We identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation, complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation.

Clinical evaluation of a rapid colloidal gold immunochromatography assay for SARS-Cov-2 IgM/IgG.

BACKGROUND: Since December 2019, there had been an outbreak of COVID-19 in Wuhan, China. At present, diagnosis COVID-19 were based on real-time RT-PCR, which have to be performed in biosafe laboratory and is unsatisfactory for suspect case screening. Therefore, there is an urgent need for rapid diagnostic test for COVID-19. OBJECTIVE: To evaluate the diagnostic performance and clinical utility of the colloidal gold immunochromatography assay for SARS-Cov-2 specific IgM/IgG anti-body detection in suspected COVID-19 cases. METHODS: In the prospective cohort, 150 patients with fever or respiratory symptoms were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang province, China, between January 20 to February 2, 2020. All patients were tested by the colloidal gold immunochromatography assay for COVID-19. At least two samples of each patient were collected for RT-PCR assay analysis, and the PCR results were performed as the reference standard of diagnosis. Meanwhile 26 heathy blood donor were recruited. The sensitivity and specificity of the immunochromatography assay test were evaluated. Subgroup analysis were performed with respect to age, sex, period from symptom onset and clinical severity. RESULTS: The immunochromatography assay test had 69 positive result in the 97 PCR-positive cases, achieving sensitivity 71.1% [95% CI 0.609-0.797], and had 2 positive result in the 53 PCR-negative cases, achieving specificity 96.2% [95% CI 0.859-0.993]. In 26 healthy donor blood samples, the immunochromatography assay had 0 positive result. In subgroup analysis, the sensitivity was significantly higher in patients with symptoms more than 14 days 95.2% [95% CI 0.741-0.998] and patients with severe clinical condition 86.0% [95% CI 0.640-0.970]. CONCLUSIONS: The colloidal gold immunochromatography assay for SARS-Cov-2 specific IgM/IgG anti-body had 71.1% sensitivity and 96.2% specificity in this population, showing the potential for a useful rapid diagnosis test for COVID-19. Further investigations should be done to evaluate this assay in variety of clinical settings and populations.

Clinical characteristics of 60 discharged cases of 2019 novel coronavirus-infected pneumonia in Taizhou, China.

BACKGROUND: The number of patients with pneumonia stemming from the 2019 novel coronavirus (COVID-19) infection has increased rapidly. However, the clinical characteristics of discharged patients remain little known. Here, we attempt to describe the clinical characteristics and treatment experiences of discharged cases from Taizhou, China. METHODS: A total of 60 patients with COVID-19-infected pneumonia who were discharged from Taizhou Enze Medical Center (Group), from January 31, 2020, to February 16, 2020, were included in the analysis. The discharge criteria were based on the New Coronavirus Pneumonia Prevention and Control Program (Fifth Edition, China). RESULTS: Of the 60 patients, the median age was 41 years, and 58.3% were male. Only 13.3% of patients were identified as having severe novel coronavirus pneumonia. All patients received combined antiviral treatment on admission, including ß-interferon, lopinavir/tonavir, Abidol and oseltamivir. All patients with severe conditions received gamma globulin and hormone therapy. No patients had endotracheal intubation or died. The median duration from symptom onset to hospitalization was 3 (range, 0-15) days. The median duration of COVID-19 shedding was 14 (range, 5-26) days, and the median duration of hospital stay was 15 (range, 7-23) days. CONCLUSIONS: Early therapy and comprehensive therapy are key to the outcome for patients with COVID-19-infected pneumonia, especially for those with severe pneumonia. TRIAL REGISTRATION NUMBER: ChiCTR2000029866.

HBV DNA integrates into upregulated ZBTB20 in patients with hepatocellular carcinoma.

Hepatitis B virus (HBV) affects the malignant phenotype of hepatocellular carcinoma (HCC). The aim of the present study was to investigate the integration sites of HBV DNA and the expression of the zinc finger protein, zinc finger and BTB domain containing 20 (ZBTB20) in patients with hepatocellular carcinoma. Integration of the HBV gene was detected using a high­throughput sequencing technique based on the HBV­Alu­PCR method. The expression of ZBTB20 was detected by western blotting. HBVX integration sites were detected in ~70% of the HCC tissue samples. HBV­integrated subgene X detection suggested that 67% of the integrated specimens were inserted into the host X gene in a forward direction, 57% in a reverse direction, 24% in both forward and reverse directions, and 38% had two HBV integration sites. A total of 3,320 HBV integration sites were identified, including 1,397 in HCC tissues, 1,205 in paracancerous tissues and 718 in normal liver tissues. HBV integration fragments displayed enrichment in the 200­800 bp region. Additionally, the results suggested that HBV was highly integrated into transmembrane phosphatase with tensin homology, long intergenic non­protein coding RNA (LINC)00618, LOC101929241, ACTR3 pseudogene 5, LINC00999, LOC101928775, deleted in oesophageal cancer 1, LINC00824, EBF transcription factor 2 and ZBTB20 in tumour tissues. Furthermore, the expression of ZBTB20 was upregulated in HCC tissues compared with normal control liver tissues, and was associated with HBV integration frequency. The present study suggested that HBV DNA integrated into upregulated ZBTB20 in patients with hepatocellular carcinoma, which might promote the occurrence and development of HCC. Furthermore, the results of the present study may provide a theoretical basis for the diagnosis and treatment of HCC.

Early Risk Factors for the Duration of Severe Acute Respiratory Syndrome Coronavirus 2 Viral Positivity in Patients With Coronavirus Disease 2019.

BACKGROUND: Pneumonia coronavirus disease 2019 (COVID-19) has became a pandemic. However, information on early risk factors for the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral positivity is not yet available. METHODS: In this prospective study, a cohort of 137 patients with confirmed SARS-CoV-2 were enrolled. Clinical information and laboratory data were retrieved from electronic medical records. Viral positivity duration was calculated by the interval from the day of confirmed SARS-CoV-2 positive results to the day SARS-CoV-2 testing showed negative results in these 137 patients with COVID-19. Early risk factors for the duration of SARS-CoV-2 viral positivity were evaluated. RESULTS: The median SARS-CoV-2 viral positivity duration is 12 days (range, 4 to ~45) for this cohort. Cox regression results showed a significantly shorter viral positivity duration was related to younger age (hazard ratio [HR], .658; P = .017); disease not being severe (HR, .653; P = .076); higher lymphocyte (HR, 1.464; P = .033), eosinophil (HR, 1.514; P = .020), and CD8+ T-cell (HR, 1.745; P = .033) counts; and lower IL-6 (HR, .664; P = .036) and IL-10 (HR, .631; P = .021). Multivariate analysis with covariable-adjusted results showed that the CD8+ T-cell count (HR, 2.376; P= .114) was a predominant risk factor for the duration of SARS-CoV-2 viral positivity. CONCLUSIONS: Our findings show early laboratory parameters such as CD8+ T-cell count to be risk factors for the duration of SARS-CoV-2 viral positivity, which has significance in the control and prevention of the disease.

Both gut microbiota and cytokines act to atherosclerosis in ApoE-/- mice.

BACKGROUND: Several studies have suggested a role for the gut microbiome and cytokines in atherosclerosis development, but combined analyses of the changes of the gut microbiota and cytokines have not been explored previously. METHODS: We treated ApoE-/- and wild-type mice with a high-fat diet for 12 weeks. The gut microbiome and cytokine composition were analyzed using 16S ribosomal DNA sequencing and RayBio Quantibody Arrays, respectively. GO and KEGG analysis were performed to rationalize the potential mechanisms involved in the process of atherosclerosis. RESULTS: Gut bacterial characteristics in ApoE-/- mice were clearly separated and 21 gut bacterial clades were detected by the LEfSe analysis showing significant differences during the development of atherosclerosis. The relative abundance of Verrucomicrobia, Bacteroidaceae, Bacteroides, and Akkermansia showed significant positive correlations with serum total cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Additionally, the relative abundance of Ruminococcaceae was positive with the level of HDL and the abundance of Rikenellaceae showed a negative relationship with the level of TG and LDL. Thirteen differentially expressed proteins were identified with P-value < 0.05. CXCL5, FGF2, and E-Selectin were significantly negatively associated with Akkermansia and Verrucomicrobia. Additionally, CXCL5 was significantly negatively correlated with Bacteroides and Bacteroidaceae. Three "cellular component" subcategories, 24 ″molecular function" subcategories, 752 ″biological process" subcategories and 29 statistically remarkable KEGG pathway categories were identified. CONCLUSIONS: Gut microbiota changes of the mice having atherosclerosis and their relationship with the inflammatory status could be one of the major etiological mechanisms underlying atherosclerosis.

Comparison of mycophenolate mofetil with standard treatment for autoimmune hepatitis: a meta-analysis.

OBJECTIVE: To systematically evaluate the efficacy of mycophenolate mofetil (MMF) compared with the standard treatment for autoimmune hepatitis. METHODS: Medline (PubMed), Embase, and Cochrane Library databases were searched between 1966 and June 2018 for studies on prednisone and/or azathioprine/mycophenolate mofetil in autoimmune hepatitis. The keywords and descriptor terms used were 'hepatitis', 'autoimmunity', 'prednisone', 'prednisolone', 'azathioprine', and 'mycophenolate mofetil'. The Z test and Cochrane Q test were used in the statistical analysis. RESULTS: Seven hundred and eighty-eight related articles were found; 779 studies were excluded after further review. Ultimately, seven studies (583 participants) were included. The remission rate of aminotransferase and immunoglobulin (Ig)-G levels with standard treatment was 33.33-86.67%, and the nonresponse rate was 15.15-66.67%. Although the remission rate of the aminotransferase level with prednisone and MMF was 55.17-88.89% and that of the IgG level was 61.16-88.89%, the nonresponse rate was 6.42-33.33%. Remission rates of the aminotransferase level (P<0.05, I=49%) and IgG level (P<0.01, I=0) with MMF were superior to those of standard treatment, and the nonresponse rate was lower (P<0.01, I=0). For those with no response to the standard treatment who were switched to MMF, the remission rates were 0, 13.33, 22.22, 25, and 34.04%. Sequential treatment with MMF was effective (P<0.01, I=90%). CONCLUSION: Compared with the standard treatment, the combination of prednisone and MMF as a first-line treatment enables patients with autoimmune hepatitis to obtain higher remission rates of aminotransferase and IgG levels and a lower nonresponse rate. The validity and safety of long-term MMF use needs investigated further.

[Effect of intermittent high glucose on oxygen-glucose deprivation/refurnish neuronal survival].

OBJECTIVE: To investigate the effect of intermittent high glucose on oxygen-glucose deprivation/refurnish (OGD/R) neuronal survival. METHODS: The primary cultured hippocampal neurons of mice were sub-cultured when the cell fusion reached about 80%. Cells in logarithmic growth phase were placed in a hypoxic incubator (37 centigrade, 5% CO2, 95% N2) to simulate cell hypoxia. The culture medium was replaced by glucose-free Hank equilibrium salt solution (HBSS) to simulate cell hypoglycemia. The normal glucose and oxygen control group was set up. Cell morphology was observed under inverted phase contrast microscope after 6 hours of hypoxia and hypoglycemia treatment, and cell viability was detected by CCK-8 cell proliferation assay kit, and then grouping experiment was carried out. The cells were randomly divided into four groups. The cells were cultured in different concentration glucose medium under normal oxygen, 5% CO2 and 37 centigrade for 72 hours to prepare OGD/R model of cell ischemia/reperfusion. The low-glucose control group was cultured in medium containing 5.5 mmol/L glucose. The constant high-glucose group was cultured in medium containing 33.0 mmol/L glucose. The intermittent high-glucose group was cultured in medium containing 33.0 mmol/L glucose for 3 hours then in medium containing 5.5 mmol/L glucose for 2 hours alternately for 3 times during the day, and overnight in medium containing 33.0 mmol/L glucose at night. The hyperosmotic control group was made up of 5.5 mmol/L glucose medium and mannitol. The osmotic pressure was the same as that of the constant high-glucose group, and the effective glucose concentration was the same as that of the normal glucose and oxygen group, so as to eliminate the effect of osmotic pressure changes caused by the high-glucose medium on the results. Cell morphology was observed under inverted phase contrast microscope after 72 hours of cell culture in each group. Cell viability was measured by CCK-8 kit, and apoptotic rate was measured by flow cytometry. RESULTS: The inverted phase contrast microscope showed that the cells in the normal glucose and oxygen control group were plump and refractive, and had obvious nucleus, clear processes and high cell activity. After 6 hours of hypoxia and hypoglycemia treatment, the cells were shrunk, refractive index was poor, the nucleus was unclear, the processes were not clear, and the cell activity was significantly lower than that of normal glucose and oxygen control group (A value: 0.34±0.06 vs. 1.09±0.06, P < 0.01), which indicated that the model of oxygen-glucose deprivation (OGD) was successfully prepared. After 72 hours of culture with different concentrations of glucose, the cells in the low-glucose control group were shrunk, the cell membrane was incomplete, the nucleus was unclear, and number of necrotic cells were more. In the constant high-glucose group, the refractive index of cells was poor, a large number of cells floated, and the nucleus was not obvious. In the intermittent high-glucose group, the cell morphology was normal, the refractive rate of cells was decreased slightly, and the necrotic cells were less. In the hypertonic control group, the cell status was close to that in the constant high-glucose group. Compared with the low-glucose control group or constant high-glucose group,the cell viability in the intermittent high-glucose group was significantly increased (A value: 2.04±0.15 vs. 0.64±0.18, 1.16±0.16, both P < 0.01), the apoptotic rate was significantly decreased [(59.60±2.55)% vs. (78.15±15.77)%, (95.60±0.14)%, both P < 0.05]. There was no significant difference in cell activity or apoptotic rate between the hypertonic control group and the constant high-glucose group [cell activity (A value): 1.07±0.07 vs. 1.16±0.16, apoptotic rate: (87.80±4.53)% vs. (95.60±0.14)%, both P > 0.05]. CONCLUSIONS: Intermittent high glucose within a certain range had protective effect on OGD/R neuronal survival.

Performance assessment of the SAPS II and SOFA scoring systems in Hanta virus Hemorrhagic Fever with Renal Syndrome.

BACKGROUND: Hemorrhagic Fever with Renal Syndrome (HFRS), caused by the hantavirus, is a natural infectious disease characterized by fever, hemorrhage and renal damage. China is the most severely endemic area for HFRS in the world. In recent years, critical scoring systems based on quantitative classification have become an important clinical tool for predicting and evaluating the prognosis of critical illness, and provide guidelines for clinical practice. METHODS: The sample comprised 384 patients with HFRS treated in the Taizhou Hospital from January 2006 to February 2017. The patients were divided into the severe group and the mild group according to their clinical characteristics. By comparing the differences in clinical symptoms, signs and laboratory data between the two groups, the clinically relevant indicators of severe HFRS were explored. According to the previous studies, we incorporated the positive fecal occult blood test (FOBT) into the sepsis-related organ failure assessment (SOFA) tool and formulated a new scoring system specifically for HFRS, named H-SOFA. By comparing the simplified acute physiology score II (SAPS II), SOFA and H-SOFA scores of the two groups, their predictive values for the progression of HFRS were assessed. RESULTS: Compared to the mild group, patients in the severe group had longer hospital stays; higher frequencies of nausea, vomiting, abdomen pain, signs of congestion and hemorrhage; and more pronounced impairment of liver and renal function. The levels of PLT, PCT, TB, and FOBT were positively correlated with the progression of HFRS (P<0.001). Patients with HFRS in the severe group got significantly higher scores on the SAPS II, SOFA, and H-SOFA scoring systems (P<0.001). The values of SAPS II, SOFA and H-SOFA, were significantly correlated with the severity of HFRS, and the AUC values were 0.90, 0.96, and 0.98, respectively. CONCLUSION: PLT, PCT, TB, and FOBT were independent predictors of severe HFRS; SAPS II, SOFA, and H-SOFA had high predictive value for the progression of severe HFRS, with H-SOFA being the highest.