Search

Man Yang,1– 3,* Xiang Xu,4,5,* Xing-an Zhao,1,2 Yun-na Ge,1,2 Juan Qin,1 Xi-ya Wang,1,2 Hua-lei Dai,1 Ji Jia,1 Si-ming Tao1 1Department of Cardiology, The Affiliated Hospital of Yunnan University, Kunming City, Yunnan Province, People’s Republic of China; 2School of Medicine, Dali University, Dali City, Yunnan Province, People’s Republic of China; 3Department of Cardiology, The First People’s Hospital of Dali, Dali City, Yunnan Province, People’s Republic of China; 4School of Medicine, Yunnan University, Kunming City, Yunnan Province, People’s Republic of China; 5Department of Cardiology, The Second Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Si-ming Tao, Department of Cardiology, The Affiliated Hospital of Yunnan University, No. 176, Youth Road, Kunming, Yunnan Province, 650021, People’s Republic of China, Email taosm6450@ynu.edu.cnBackground: Macrophages play a crucial role in the progression of AF, closely linked to atrial inflammation and myocardial fibrosis. However, the functions and molecular mechanisms of different phenotypic macrophages in AF are not well understood. This study aims to analyze the infiltration characteristics of atrial immune cells in AF patients and further explore the role and molecular expression patterns of M2 macrophage-related genes in AF.Methods: This study integrates single-cell and large-scale sequencing data to analyze immune cell infiltration and molecular characterization of the LAA in patients with AF, using SR as a control group. CIBERSORT assesses immune cell types in LAA tissues; WGCNA identifies signature genes; cell clustering analyzes cell types and subpopulations; cell communication explores macrophage interactions; hdWGCNA identifies M2 macrophage gene modules in AF. AF biomarkers are identified using LASSO and Random Forest, validated with ROC curves and RT-qPCR. Potential molecular mechanisms are inferred through TF-miRNA-mRNA networks and single-gene enrichment analyses.Results: Myeloid cell subsets varied considerably between the AF and SR groups, with a significant increase in M2 macrophages in the AF group. Signals of inflammation and matrix remodeling were observed in AF. M2 macrophage-related genes IGF1, PDK4, RAB13, and TMEM176B were identified as AF biomarkers, with RAB13 and TMEM176B being novel markers. A TF-miRNA-mRNA network was constructed using target genes, which are enriched in the PPAR signaling pathway and fatty acid metabolism.Conclusion: Over infiltration of M2 macrophages may be an important factor in the progression of AF. The M2 macrophage-related genes IGF1, RAB13, TMEM176B and PDK4 may regulate the progression of AF through the PPAR signaling pathway and fatty acid metabolism.Keywords: atrial fibrillation, M2 macrophage, cardiac fibrosis, inflammation, single-cell RNA-sequencing, bulk RNA-sequencing

Children make inferences about the social world by observing human actions. However, human actions can be ambiguous: They can be sources of information about personal, idiosyncratic characteristics of individuals or socially shared knowledge. In two cross-cultural studies ( N = 420; M age = 4.05 years, SD = 0.77, 47% female), we ask if U.S. and Chinese children's inferences about whether an action is personal or social vary by domain, statistical evidence, and culture. We did this with a generalization method: Preschoolers learn about one agent's actions and then are asked what they think a new agent will do. Low rates of generalization suggest children inferred something unique to an individual, while high rates suggest that children inferred that the action represented socially shared knowledge. In a mixed between- and within-participant design, children observed agents demonstrate sequences of statistically random (or nonrandom, between participants) actions that were verbally framed as relevant to a particular domain (agent's personal preferences, labels, object functions, or game rules). We found that children's social generalizations about actions were on a continuum: with linguistic conventions (e.g., labels) being the most social, preferences being the most personal, and nonlinguistic conventions (i.e., object functions, game rules) falling somewhere in between. Furthermore, the influence of statistical evidence and cultural variation varied for each domain. These findings highlight how children combine knowledge and evidence to infer social meaning from actions and have implications for rational constructivist accounts of cultural learning. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Postinfarction cardiac remodeling presents a compensatory mechanism aimed at mitigating congestive heart failure. It is distinguished by progressive dilatation and hypertrophy of the ventricular chambers, fibrotic alterations, and prolonged apoptosis of cardiomyocytes. The primary objective of this study was to assess the effects of icariin on myocardial fibrosis and ventricular remodeling in rats subjected to myocardial infarction (MI)., Methods: Male Sprague‒Dawley (SD) rats were subjected to randomization and subsequently divided into distinct groups: the control group, the sham group (undergoing sham operation), the MI group (experiencing ligation of the left anterior descending artery), and the icariin group. Within the icariin group, rats were further categorized into three different dose groups based on the administered icariin dosage: the MI30 group (30 mg/kg/day), the MI60 group (60 mg/kg/day), and the MI120 group (120 mg/kg/day). Cardiac function evaluation was carried out using echocardiography. Histological examinations, including hematoxylin and eosin (HE) staining, Masson staining, and immunohistochemistry studies, were conducted 90 days after the occurrence of MI. Additionally, Western blotting was employed to assess TGF-β1, p-Smad2, and p-Smad3 levels., Results: The administration of icariin revealed a noteworthy enhancement in cardiac function among rats afflicted with left anterior descending coronary artery (LAD) ligation. In comparison to the icariin groups, the MI group exhibited reduced EF and FS, along with elevated LVEDD and LVESD. Furthermore, the cardiac fibrosis levels in the MI group rats exhibited a considerable increase compared to those in the icariin group. Notably, the levels of Collagen I, Collagen III, MMP2, and MMP9 were significantly higher in the MI group than in the icariin group, with evident distinctions. Moreover, the expression levels of TGF-β, IL-13, p-Smad2, and p-Smad3 were notably upregulated in the MI group compared to the icariin group., Conclusions: In an experimental rat model of MI, the administration of icariin resulted in the amelioration of both cardiac function and remodeling processes, operating through the intricate TGF-β1/Smad signaling pathway., (© 2023. The Author(s).)

Objective: Complementary and alternative treatments (CATs) for ADHD have proliferated over the past decade; however, their safety and efficacy remain uncertain. We completed a systematic review and meta-analyses across CAT domains., Methods: Systematic search and data extraction identified randomized controlled trials for pediatric ADHD (ages 3-19 years) that included probably blind ADHD symptom outcome measures. We evaluated basic (RCT of a CAT compared with sham/placebo, attention/active control, treatment as usual, and waitlist control), complementary (RCTs comparing an evidence-based treatment with a CAT and the same evidence-based treatment), and alternative (evidence-based treatment to CAT) efficacy. Random-effect meta-analyses were conducted when at least 3 blinded studies were identified for a specific CAT domain., Results: Eighty-seven of 2253 nonduplicate screened manuscripts met inclusion criteria. No study reported significantly greater adverse effects for CATs than controls; naturopathy reported fewer adverse effects than evidence-based treatments but did not demonstrate basic efficacy. In the systematic review of basic efficacy, evidence of effectiveness was mixed but replicated previous evidence for the possible efficacy of cognitive training, neurofeedback, and essential fatty acid supplementation for certain patients. With respect to alternative and complementary efficacy, no CAT outperformed or enhanced evidence-based treatments (stimulant medications and behavioral therapy) when replication was required. Individual meta-analyses indicated that cognitive training was the only CAT that demonstrated overall basic efficacy ( SMD = 0.216; p = 0.032)., Conclusion: Clinicians may cautiously recommend (but monitor) cognitive training when evidence-based treatments are not feasible or effective for a patient. Additional studies are needed to further understand the potential of CAT domains., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Few studies have investigated the impacts of metabolic syndrome (MS) on coronavirus disease 2019 (COVID-19). We described the clinical features and prognosis of confirmed COVID-19 patients with MS during hospitalization and after discharge., Methods: Two hundred and thirty-three COVID-19 patients from the hospitals in 8 cities of Jiangsu, China were retrospectively included. Clinical characteristics of COVID-19 patients were described and risk factors of severe illness were analyzed by logistic regression analysis., Results: Forty-five (19.3%) of 233 COVID-19 patients had MS. The median age of COVID-19 patients with MS was significantly higher than non-MS patients (53.0 years vs. 46.0 years, P  = 0.004). There were no significant differences of clinical symptoms, abnormal chest CT images, and treatment drugs between two groups. More patients with MS had severe illness (33.3% vs. 6.4%, P  < 0.001) and critical illness (4.4% vs. 0.5%, P  = 0.037) than non-MS patients. The proportions of respiratory failure and acute respiratory distress syndrome in MS patients were also higher than non-MS patients during hospitalization. Multivariate analysis showed that concurrent MS (odds ratio [OR] 7.668, 95% confidence interval [CI] 3.062-19.201, P  < 0.001) and lymphopenia (OR 3.315, 95% CI 1.306-8.411, P  = 0.012) were independent risk factors of severe illness of COVID-19. At a median follow-up of 28 days after discharge, bilateral pneumonia was found in 95.2% of MS patients, while only 54.7% of non-MS patients presented bilateral pneumonia., Conclusions: 19.3% of COVID-19 patients had MS in our study. COVID-19 patients with MS are more likely to develop severe complications and have worse prognosis. More attention should be paid to COVID-19 patients with MS., (© 2021 Elsevier España, S.L.U. All rights reserved.)

Background and Aims: Chronic hepatitis B virus (HBV) infection is a serious health problem worldwide. Evaluating liver injury in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) with detectable HBV DNA and normal alanine aminotransferase (ALT) is crucial to guide their clinical management. We aimed to investigate the stages of liver inflammation and fibrosis as well as the predictive accuracy of gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in these patients., Methods: A total of 184 treatment-naïve HBeAg-negative CHB patients with detectable HBV DNA and normal ALT were enrolled. The Scheuer scoring system was used to classify liver inflammation and fibrosis., Results: The distribution of patients with different liver inflammation grades were as follows: G0, 0 (0%); G1, 97 (52.7%); G2, 68 (37.0%); G3, 12 (6.5%); and G4, 7 (3.8%). The distribution of patients with different liver fibrosis stages were as follows: S0, 22 (12.0%); S1, 72 (39.1%); S2, 42 (22.8%); S3, 19 (10.3%); and S4, 29 (15.8%). The areas under the receiver operating characteristic (AUROC) curves of GPR in predicting significant inflammation, severe inflammation, and advanced inflammation were 0.723, 0.895, and 0.952, respectively. The accuracy of GPR was significantly superior to that of ALT in predicting liver inflammation. The AUROCs of GPR in predicting significant fibrosis, severe fibrosis, and cirrhosis were 0.691, 0.780, and 0.803, respectively. The predictive accuracy of GPR was significantly higher than that of aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) in identifying advanced fibrosis and cirrhosis, and it was superior to FIB-4 but comparable to APRI in identifying significant fibrosis., Conclusions: Nearly half of the HBeAg-negative CHB patients with detectable HBV DNA and normal ALT levels had significant liver inflammation or fibrosis. GPR can serve as an accurate predictor of liver inflammation and fibrosis in these patients., Competing Interests: The authors have no conflict of interests related to this publication., (© 2022 Authors.)

Antibody to hepatitis B core antigen (anti-HBc) is one of the most classical serological markers of HBV infection. This study aimed to investigate the association of serum anti-HBc and HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) after antiviral treatment. Two hundred and seventeen HBeAg-positive CHB patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) for 48 weeks were retrospectively enrolled. Serological response (SR) is defined as HBeAg seroconversion at 48 weeks of antiviral treatment. Serum anti-HBc level was measured using the Abbott ARCHITECT assay. After 48 weeks of antiviral treatment, twenty-two (10.1 %) patients achieved SR. Baseline level of serum anti-HBc in the SR patients (11.8 S/CO) was significantly higher than patients with non-SR (9.6 S/CO, P < 0.001). The median anti-HBc level was significantly declined after 48 weeks of antiviral therapy (9.9 vs. 8.9 S/CO, P < 0.001). Multivariate logistic regression analysis showed baseline of serum anti-HBc was an independent predictor of SR (odds ratio [OR]: 1.462, 95 % confidence interval [CI] 1.170-1.825, P = 0.001). The area under receiver operating characteristic curve (AUROC) of baseline anti-HBc level for predicting SR was 0.781 with the cut-off of 11.1 S/CO, with a sensitivity of 77.27 % and a specificity of 72.82 %. Our findings highlighted that baseline serum anti-HBc level is a promising indictor for predicting HBeAg seroconversion in HBeAg-positive CHB patients after antiviral treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: There is still little knowledge about the association of liver fibrosis with the clinical outcomes of COVID-19 patients with non-alcoholic fatty liver disease (NAFLD). The aim of the study was to determine the association of NAFLD fibrosis score (NFS)-determined liver fibrosis with clinical outcomes of COVID-19 patients with NAFLD., Methods: The NAFLD was diagnosed by the Hepatic Steatosis Index (HSI) in the absence of other causes of chronic liver diseases. NFS was used to evaluate the severity of liver fibrosis., Results: A total of 86 COVID-19 patients with NAFLD were included. The median age was 43.5 years, and 58.1% of patients were male. Thirty-eight (44.2%) patients had advanced liver fibrosis according to the NFS. Multivariate analysis indicated that concurrent diabetes (odds ratio [OR] 8.264, 95% confidence interval [CI] 1.202-56.830, p = 0.032) and advanced liver fibrosis (OR 11.057, 95% CI 1.193-102.439, p = 0.034) were independent risk factors of severe illness in COVID-19 patients with NAFLD., Conclusion: NAFLD patients with NFS-determined advanced liver fibrosis are at higher risk of severe COVID-19., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: The clinical and virological course of patients with coronavirus disease 2019 (COVID-19) are lacking. We aimed to describe the clinical and virological characteristics of COVID-19 patients from 10 designated hospitals in 10 cities of Jiangsu province, China. The factors associated with the clearance of SARS-CoV-2 were investigated., Methods: A total of 328 hospitalized patients with COVID-19 were retrospectively recruited. The epidemiological, clinical, laboratory, radiology and treatment data were collected. The associated factors of SARS-CoV-2 clearance were analyzed., Results: The median duration of hospitalization was 16.0 days (interquartile range [IQR] 13.0-21.0 days). On multivariate Cox regression analysis, age > 60 years (hazard ratio [HR] 0.643, 95% confidence interval [CI] 0.454-0.911, P = 0.013) was associated with the delayed SARS-CoV-2 clearance, while the atomized inhalation of interferon α-2b could improve the clearance of SARS-CoV-2 (HR, 1.357, 95% CI 1.050-1.755, P = 0.020). Twenty-six (7.9%) patients developed respiratory failure and 4 (1.2%) patients developed ARDS. Twenty (6.1%) patients were admitted to the ICU, while no patient was deceased., Conclusions: Our study found that age > 60 years was associated with the delayed SARS-CoV-2 clearance, while treated with atomized inhalation of interferon α-2b could promote the clearance of SARS-CoV-2., (© 2021. The Author(s).)

Background: The follow-up data of discharged patients with coronavirus disease 19 (COVID-19) have not yet been fully analyzed and reported. This study aimed to evaluate the clinical features, test results, and outcomes of COVID-19 patients after discharge., Methods: 149 COVID-19 patients with follow-up data after discharge were included. Post-hospitalization data related to clinical features and outcomes were obtained by following the patients up to 6 weeks., Results: The COVID-19 patients were followed for a median of 28.0 days (range of 22 days to 42 days) after discharge from hospital. At the end of follow-up, four patients (2.7%) still had cough. The proportions of leukopenia and lymphopenia were 7.4% and 4.7%, respectively. The proportions of ALT, AST, and Cr abnormalities were 26.2%, 6.0%, and 0%, respectively. Abnormal chest CT was detected in 94 (63.1%) patients, including 14 (9.4%) unilateral pneumonia and 80 (53.7%) bilateral pneumonia. However, the proportion of chest CT abnormality significantly decreased compared to that at the time of admission., Conclusions: One month after discharge, few patients with COVID-19 had clinical symptoms; however, a substantial proportion of COVID-19 patients harbored abnormal laboratory and radiological examinations. Moderately long-term medical follow-up would justifiably benefit COVID-19 patients after discharge.

We aimed to describe liver injury and identify the risk factors of liver injury in coronavirus disease (COVID-19) patients without chronic liver diseases (CLD). The clinical data of 228 confirmed COVID-19 patients without CLD were retrospectively collected from ten hospitals in Jiangsu, China. Sixty-seven (29.4%) of 228 patients without CLD showed abnormal liver function on admission, including increased alanine aminotransferase (ALT) (25 [11.0%]) U/L, aspartate aminotransferase (AST) 30 [13.2%]) U/L, gamma-glutamyl transferase (GGT) 28 [12.4%]) U/L, total bilirubin (Tbil) 16 [7.0%] μmol/L, and alkaline phosphatase (ALP) 10 [4.5%]) U/L. During hospitalization, 129 (56.3%) of 228 patients showed abnormal liver function, including elevated ALT (84 [36.8%]), AST (58 [25.4%]), GGT (67 [29.5%]), and Tbil (59 [25.9%]). Age over 50 years (odds ratio [OR], 2.086; 95% confidence interval [CI], 1.030-4.225; p = .041), male sex (OR, 2.737; 95% CI, 1.418-5.284; p = .003), and lopinavir-ritonavir (OR, 2.504; 95% CI, 1.187-5.283; p = .016) were associated with higher risk of liver function abnormality, while the atomized inhalation of interferon α-2b (OR, 0.256; 95% CI 0.126-0.520; p < .001) was associated with reduced risk of liver function abnormality during hospitalization. Mild to moderate liver injury was common in COVID-19 patients in Jiangsu, China. Age over 50 years, male sex, and lopinavir-ritonavir were the independent risk factors of liver impairment in COVID-19 patients during hospitalization., (© 2020 Wiley Periodicals LLC.)

Background: C-C motif ligand 5 (CCL5) is reported to play a key role in acute and chronic liver diseases. However, the association between CCL5 and chronic hepatitis B (CHB) remains to be explored. We aimed to investigate the CCL5 expression in the liver tissues of CHB patients and compared the CCL5 expression among CHB patients with different stages of liver inflammation and fibrosis., Methods: Liver tissue specimens from 51 CHB patients who underwent liver biopsy and twelve healthy liver donors were included in the present study. CCL5 expression in the liver tissues was analyzed using immunohistochemistry. The hepatic inflammation grades and fibrotic stages of CHB patients were assessed by the Scheuer classification system., Results: Livers of CHB patients exhibited significantly accumulated CCL5+ cells when compared to those of healthy controls (42.80 ± 4.37 vs. 7.25 ± 0.99/HPF, P < .001). CHB patients with higher hepatic inflammation grades had more CCL5+ cells in their livers than those with lower grades (P < .05). However, the numbers of CCL5+ cells were not correlated with the fibrotic stages in CHB patients (r = .073, P = .61). The number of CCL5+ cells in the liver tissues of CHB patients was positively correlated with alanine transaminase levels (r = .278, P = .041) and aspartate aminotransferase levels (r = .328, P = .009)., Conclusions: CHB patients have a significant accumulation of CCL5+ cells in the liver, and CCL5 may play a pathological role in hepatic inflammation of CHB.

The impact of corticosteroid treatment on virological course of coronavirus disease 2019 (COVID-19) patients remains unclear. This study aimed to explore the association between corticosteroid and viral clearance in COVID-19. The clinical data of COVID-19 patients from 10 hospitals of Jiangsu, China, were retrospectively collected. Cox regression and Kaplan-Meier analysis were used to analyze the adverse factors of virus clearance. Of the 309 COVID-19 patients, eighty-nine (28.8%) patients received corticosteroid treatment during hospitalization. Corticosteroid group showed higher C-reactive protein (median 11.1 vs. 7.0 mg/l, P = 0.018) and lower lymphocytes (median 0.9 vs. 1.4 × 10 9 /l, P < 0.001) on admission. Fever (93.3% vs. 65.0%, P < 0.001) and cough (69.7% vs. 57.3%, P = 0.043) were more common in corticosteroid group. The proportions of patients with severe illness (34.8% vs. 1.8%, P < 0.001), respiratory failure (25.8% vs. 1.4%, P < 0.001), acute respiratory distress syndrome (4.5% vs. 0%, P = 0.002), and admission to ICU (20.2% vs. 0.9%, P < 0.001) were significantly higher in corticosteroid group than non-corticosteroid group. The duration of virus clearance (median 18.0 vs. 16.0 days, P < 0.001) and hospitalization (median 17.0 vs. 15.0 days, P < 0.001) were also significantly longer in corticosteroid group than non-corticosteroid group. Treated with corticosteroid (Hazard ratio [HR], 0.698; 95% confidence interval [CI], 0.512 to 0.951; P = 0.023) was an adverse factor of the clearance of SARS-CoV-2, especially for male patients (HR, 0.620; 95% CI, 0.408 to 0.942; P = 0.025). The cumulative probability of SARS-CoV-2 clearance was lower in corticosteroid group (P < 0.001). Corticosteroid treatment may delay the SARS-CoV-2 clearance of COVID-19 patients and should be used with cautions., (Copyright © 2020. Published by Elsevier B.V.)

Objective: This study aimed to observe the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with overweight and obesity., Methods: Consecutive patients with COVID-19 from 10 hospitals of Jiangsu province, China, were enrolled., Results: A total of 297 patients with COVID-19 were included, and 39.39% and 13.47% of patients had overweight and obesity, respectively. The proportions of bilateral pneumonia (92.50% vs. 73.57%, P = 0.033) and type 2 diabetes (17.50% vs. 3.57%, P = 0.006) were higher in patients with obesity than lean patients. The proportions of severe illness in patients with overweight (12.82% vs. 2.86%, P = 0.006) and obesity (25.00% vs. 2.86%, P < 0.001) were significantly higher than lean patients. More patients with obesity developed respiratory failure (20.00% vs. 2.86%, P < 0.001) and acute respiratory distress syndrome (5.00% vs. 0%, P = 0.024) than lean patients. The median days of hospitalization were longer in patients with obesity than lean patients (17.00 days vs. 14.00 days, P = 0.029). Overweight (OR, 4.222; 95% CI: 1.322-13.476; P = 0.015) and obesity (OR, 9.216; 95% CI: 2.581-32.903; P = 0.001) were independent risk factors of severe illness. Obesity (HR, 6.607; 95% CI: 1.955-22.329; P = 0.002) was an independent risk factor of respiratory failure., Conclusions: Overweight and obesity were independent risk factors of severe illness in COVID-19 patients. More attention should be paid to these patients., (© 2020 The Obesity Society.)

Previous studies reported that coronavirus disease 2019 (COVID-19) was likely to result in liver injury. However, few studies investigated liver injury in patients with COVID-19 with chronic liver diseases. We described the clinical features in patients with COVID-19 with nonalcoholic fatty liver disease (NAFLD). Confirmed patients with COVID-19 from hospitals in 10 cities of Jiangsu Province, China, were retrospectively included between January 18, 2020, and February 26, 2020. The hepatic steatosis index (HSI) was used to defined NAFLD. A total of 280 patients with COVID-19 were enrolled. Eighty-six (30.7%) of 280 patients with COVID-19 were diagnosed as NAFLD by HSI. One hundred (35.7%) patients presented abnormal liver function on admission. The median alanine aminotransferase (ALT) levels (34.5 U/L vs. 23.0 U/L; P  < 0.001) and the proportion of elevated ALT (>40 U/L) (40.7% vs. 10.8%; P  < 0.001) were significantly higher in patients with NAFLD than in patients without NAFLD on admission. The proportion of elevated ALT in patients with NAFLD was also significantly higher than patients without NAFLD (65.1% vs. 38.7%; P  < 0.001) during hospitalization. Multivariate analysis showed that age over 50 years (odds ratio [OR], 2.077; 95% confidence interval [CI], 1.183, 3.648; P  = 0.011) and concurrent NAFLD (OR, 2.956; 95% CI, 1.526, 5.726; P  = 0.001) were independent risk factors of ALT elevation in patients with COVID-19, while the atomized inhalation of interferon α-2b (OR, 0.402; 95% CI, 0.236, 0.683; P  = 0.001) was associated with a reduced risk of ALT elevation during hospitalization. No patient developed liver failure or death during hospitalization. The complications and clinical outcomes were comparable between patients with COVID-19 with and without NAFLD. Conclusion: Patients with NAFLD are more likely to develop liver injury when infected by COVID-19. However, no patient developed severe liver-related complications during hospitalization., (© 2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Limited data are available for clinical characteristics of patients with coronavirus disease 2019 (COVID-19) outside Wuhan. This study aimed to describe the clinical characteristics of COVID-19 and identify the risk factors for severe illness of COVID-19 in Jiangsu province, China. Clinical data of hospitalized COVID-19 patients were retrospectively collected in 8 hospitals from 8 cities of Jiangsu province, China. Clinical findings of COVID-19 patients were described and risk factors for severe illness of COVID-19 were analyzed. By Feb 10, 2020, 202 hospitalized patients with COVID-19 were enrolled. The median age of patients was 44.0 years (interquartile range, 33.0-54.0). 55 (27.2%) patients had comorbidities. At the onset of illness, the common symptoms were fever (156 [77.2%]) and cough (120 [59.4%]). 66 (32.7%) patients had lymphopenia. 193 (95.5%) patients had abnormal radiological findings. 11 (5.4%) patients were admitted to the intensive care unit and none of the patients died. 23 (11.4%) patients had severe illness. Severe illness of COVID-19 was independently associated with body mass index (BMI) ≥ 28 kg/m2 (odds ratio [OR], 9.219; 95% confidence interval [CI], 2.731 to 31.126; P<0.001) and a known history of type 2 diabetes (OR, 4.326; 95% CI, 1.059 to 17.668; P = 0.041). In this case series in Jiangsu Province, COVID-19 patients had less severe symptoms and had better outcomes than the initial COVID-19 patients in Wuhan. The BMI ≥ 28 kg/m2 and a known history of type 2 diabetes were independent risk factors of severe illness in patients with COVID-19., Competing Interests: The authors have declared that no competing interests exist.

Progressive supranuclear palsy (PSP) is characterized by a rapid and progressive clinical course. A timely and objective image-based evaluation of disease severity before standard clinical assessments might increase the diagnostic confidence of the neurologist. We sought to investigate whether features from diffusion tensor imaging of the entire brain with a machine learning algorithm, rather than a few pathogenically involved regions, may predict the clinical severity of PSP. Fifty-three patients who met the diagnostic criteria for probable PSP were subjected to diffusion tensor imaging. Of them, 15 underwent follow-up imaging. Clinical severity was assessed by the neurological examinations. Mean diffusivity and fractional anisotropy maps were spatially co-registered, normalized, and parcellated into 246 brain regions from the human Brainnetome atlas. The predictors of clinical severity from a stepwise linear regression model were determined after feature reduction by the least absolute shrinkage and selection operator. Performance estimates were obtained using bootstrapping, cross-validation, and through application of the model in the patients who underwent repeated imaging. The algorithm confidently predicts the clinical severity of PSP at the individual level (adjusted R 2 : 0.739 and 0.892, p < 0.001). The machine learning algorithm for selection of diffusion tensor imaging-based features is accurate in predicting motor subscale of unified Parkinson's disease rating scale and postural instability and gait disturbance of PSP.

During the natural history of chronic hepatitis B infection (CHB), the function of B cells is still obscure. Several limited studies have suggested that B cells are highly active in patients with CHB. In the present study, we reported that the 4-1BB ligand (4-1BBL) expression on B cells was significantly higher in patients with CHB than that in healthy subjects, meanwhile, the patients with CHB had higher serological IgG levels. Further, after being stimulated with sCD40L or hepatitis B core antigen (HBcAg), B cells had higher levels of 4-1BBL. After being cocultured with 4-1BBL+ B cells, the expressions of CD69 and 4-1BB on CD4+ T cells were significantly higher than that cocultured with 4-1BB- B cells. Cytokines including interleukin (IL)-2, IL-4, and IL-6 were significantly higher in the supernatant from 4-1BBL+ B cells coculture group than those from coculture group of 4-1BBL- B cell group, respectively; while IFN-γ and TNF-α in cocultured supernatant of 4-1BBL+ B cell group were significantly lower. Consistently, the total IgG levels in culture supernatant were significantly higher in 4-1BBL+ B cell group. Thus, hyperactive status of B cells in patients with CHB could be partially derived from the higher 4-1BBL expression on B cells triggered by HBcAg. 4-1BBL signaling pathway is involved in B cells activation, and further regulates B cell-T cell interaction by modulating the cytokines secretion, which might be critical in B cells dysfunction during CHB infection., (© 2018 Wiley Periodicals, Inc.)

Curcumin has been reported to have anti-fibrotic effect. However, the anti-fibrotic mechanism of curcumin for liver fibrosis remains obscure. In the presenting study, we aimed to investigate whether curcumin reduce chemokines secretion by inhibiting kupffer cells (KCs) activation to decrease Ly6C hi monocyte infiltration in the treatment of liver fibrosis. Liver fibrosis was induced by intraperitoneal carbon tetrachloride (CCl 4 )-injection in mice. Mice in curcumin group received curcumin treatment by gavage. Pretreatment with curcumin significantly protected mice from liver inflammation and fibrosis. Compared to CCl 4 group, mice in the curcumin group showed significantly less intrahepatic infiltration of Ly6C hi monocytes, but no difference of other leucocyte subtypes. Moreover, curcumin significantly reduced Ly6C hi monocytes associated pro-inflammatory and pro-fibrogenic cytokines, which was in line with the decreased numbers of intrahepatic Ly6C hi monocytes. Further study found that curcumin is able to decrease KCs activation and monocyte chemokines, which explains why curcumin can reduce Ly6C hi monocytes infiltration during liver fibrosis. In vitro, we discovered that curcumin prevents the polarization of macrophages toward M1 and reduces monocyte chemokines secretion, which is involved with ERK1/2 and p38 pathways. Taken together, for the first time, we verified that curcumin can reduce chemokines secretion by inhibiting KCs activation to decrease Ly6C hi monocyte infiltration in the treatment of liver fibrosis. These results suggested that curcumin may be considered a promising candidate in the prevention and treatment of liver fibrosis., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Emodin, as a major active component of Rheum palmatum L. and Polygonum cuspidatum , has been reported to have antifibrotic effect. However, the mechanism of emodin on antifibrotic effect for liver fibrosis was still obscure. In the present study, we aimed to investigate whether emodin can alleviate carbon tetrachloride- (CCl 4 -) induced liver fibrosis through reducing infiltration of Gr1 hi monocytes. Liver fibrosis was induced by intraperitoneal CCl 4 injection in mice. Mice in the emodin group received emodin treatment by gavage. Pretreatment with emodin significantly protected mice from liver inflammation and fibrosis revealed by the decreased elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as reduced hepatic necrosis and fibrosis by analysis of hematoxylin-eosin (HE) staining, Masson staining, α -smooth muscle actin ( α -SMA), and collagen-I immunohistochemistry staining. Further, compared to CCl 4 group, mice in the emodin group showed significantly less intrahepatic infiltration of Gr1 hi monocytes. Moreover, emodin significantly inhibited hepatic expression of interleukin-1 β (IL-1 β ), tumor necrosis factor- α (TNF- α ), transforming growth factor- β 1 (TGF- β 1), granulin (GRN), monocyte chemoattractant protein 1 (MCP-1), and chemokine ligand 7 (CCL7), which was in line with the decreased numbers of intrahepatic Gr1 hi monocytes. In conclusion, emodin can alleviate the degree of liver fibrosis by reducing infiltration of Gr1 hi monocytes. These results suggest that emodin is a promising candidate to prevent and treat liver fibrosis.

Hepatitis B surface antibody (HBsAb) plays a critical role in protecting against infection of hepatitis B virus (HBV) and were extensively studied in literature. At the same time, the status of hepatitis B surface antigen (HBs)-specific B cells in both vaccinated and HBV infected people received limited attention. In the current study, we adopted a highly specific B-cell Enzyme Linked ImmunoSpot (ELISpot) assay to analyze HBs-specific B cells in various clinical settings: healthy individuals with the history of HBV vaccination before and after receiving an extra HBV vaccine boost, people chronically infected with HBV (CHB) in various clinical stages, with or without a particular type anti-viral treatment, or whether receiving a dose of HBV vaccine. In all of these cases, B-cell ELISpot assay was used effectively in enumerating the frequency of HBs-specific B cells. While the focus of the current report was to establish the utility of this assay for HBV research, a number of interesting observations were made in this pilot study based on the profiles and dynamics of HBs-specific B cells in various conditions. Such information is useful to guide the future work in designing novel therapeutic strategies against CHB.

It has been well established that silymarin has hepatoprotective and anti-fibrotic effects. But the mechanisms are poorly understood. In recent years, the role of Ly6C hi monocytes in liver fibrosis has been well demonstrated. Thus, in present study we aimed to investigate whether silymarin can relieve liver fibrosis by reducing Ly6C hi monocytes infiltration. The mouse model of liver fibrosis was established by injected with carbon tetrachloride (CCl 4 ) via intraperitoneal repeatedly. Mice in silymarin group received silymarin treatment by gavage. Silymarin significantly reduced liver inflammation and fibrosis of the mice induced by CCl 4 injection, as revealed by liver histological and pathological analysis. Mice administrated by silymarin exhibited less infiltration of Ly6C hi monocytes. But there was no difference on other tested leukocyte subsets between CCl 4 group and silymarin group. Meanwhile, further study found that silymarin significantly reduced CCl 4 -induced increased expression of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1 and monocyte chemoattractant protein 1 (MCP-1), which was in line with the decreased numbers of intrahepatic Ly6C hi monocytes. In conclusion, our study showed that the anti-inflammatory and anti-fibrotic effects of silymarin could be contributed to the prevention of Ly6C hi monocytes infiltration into the injured livers, which will give us a better understanding on the cellular mechanism of hepatoprotective and anti-fibrotic effect for silymarin., Competing Interests: None., (IJCEP Copyright © 2017.)

Objectives: Noninvasive models have been established for the assessment of liver fibrosis in patients with chronic hepatitis B(CHB). However, the predictive performance of these established models remains inconclusive. We aimed to develop a novel predictive model for liver fibrosis in CHB based on routinely clinical parameters., Results: Platelets(PLT), the standard deviation of red blood cell distribution width(RDW-SD), alkaline phosphatase(ALP) and globulin were independent predictors of significant fibrosis by multivariable analysis. Based on these parameters, a new predictive model namely APRG(ALP/PLT/RDW-SD/globulin) was proposed. The areas under the receiver-operating characteristic curves(AUROCs) of APRG index in predicting significant fibrosis(≥F2), advanced fibrosis(≥F3) and liver cirrhosis(≥F4) were 0.757(95%CI 0.699 to 0.816), 0.763(95%CI 0.711 to 0.816) and 0.781(95%CI 0.728 to 0.835), respectively. The AUROCs of the APRG were significantly higher than that of aspartate transaminase(AST) to PLT ratio index(APRI), RDW to PLT ratio(RPR) and AST to alanine aminotransferase ratio(AAR) to predict significant fibrosis, advanced fibrosis and cirrhosis. The AUROCs of the APRG were also significantly higher than fibrosis-4 score (FIB-4) (0.723, 95%CI 0.663 to 0.783) for cirrhosis(P=0.034) and better than gamma-glutamyl transpeptidase(GGT) to PLT ratio(GPR) (0.657, 95%CI 0.590 to 0.724) for significant fibrosis(P=0.001)., Materials and Methods: 308 CHB patients who underwent liver biopsy were enrolled. The diagnostic values of the APRG for liver fibrosis with other noninvasive models were compared., Conclusions: The APRG has a better diagnostic value than conventionally predictive models to assess liver fibrosis in CHB patients. The application of APRG may reduce the need for liver biopsy in CHB patients in clinical practice., Competing Interests: CONFLICTS OF INTEREST The authors have declared that no conflicts of interest exist.

To better understand the influence of carbonization of the Ti interlayer on diamond nucleation and growth, a series of Ti/diamond composite films were deposited on cemented carbide (WC:Co) substrates using a two-step deposition technique. The microstructural properties of the composite films were then characterized by scanning electron microscopy, X-ray diffractometry, and Raman spectroscopy, and their tribological properties were evaluated using a ball-on-disc tester and a metalloscope. The results showed that differences in carbonization for five Ti interlayers of different thicknesses led to variations in the preferred orientations of the TiC layers and in the subsequent nucleation and oriented growth of diamond. This suggests that Ti carbonization significantly influences the nucleation and growth of diamond and subsequently causes variations in the tribological properties of the produced diamond films.

This study was purposed to investigate the diagnosis, typing and influencing factors of the antibody (inhibitor) to coagulation factors in hemophilia. 500 hemophilia patients were enrolled in this study. The activities of coagulation factor FVIII and FIX were tested by one stage assay. The antibodies of FVIII and FIX were detected by Bethesda assay. All data were analyzed by statistical soft SPSS 10.0. The results indicated that there were 411 cases of hemophilia A, out of which 151 cases (30.2%) showed FVIII antibody positive, the titer was 3.50 ± 2.84 Bu/ml; there were 79 cases of hemophilia B, out of which 18 cases (3.6%) showed FIX antibody positive, the titer was 2.92 ± 2.19 Bu/ml. The other 10 cases were acquired autogeneic hemophilia (2.0%). The antibody was divided into three types: high-response (3 cases), intermediate-response (47 cases), and low-response (119 cases). Among the 169 cases with antibody positive, 157 cases (92.9%) were younger than 30 years old; among 151 (89.35%) cases of hemophilia A; 138 cases (81.66%) were moderate or severe hemophilia; 166 case (98.22%) showed intermediate or low-response antibody. There were 158 cases with allogeneic antibody positive, all of which received blood transfusion. It is concluded that the moderate and low responsive antibodies are the dominant in hemophilia patients, the age of patients and transfusion frequency of blood preparation are the influencing factors. The results of this study provide the basis for the hemophilia diagnosis, antibody typing and evaluation of factors influencing hemophilia, and also suggest that the repeated transfusion of blood preparation may influence the production of antibodies.

Two new benzo[j]fluoranthene-based secondary metabolites named daldinone C (1) and daldinone D (2), along with two known metabolites, altechromone A and (4S)-5,8-dihydroxy-4-methoxy-alpha-tetralone, were isolated from the CHCl3/MeOH (1:1) extract of a solid culture of the endophyte Hypoxylon truncatum IFB-18 harbored inside the symptomless stem tissue of Artemisia annua. The structures of the new compounds were elucidated by MS and 1D and 2D NMR spectra and by X-ray diffraction analysis. Their absolute configurations were determined unambiguously by a combination of their CD data and the established exciton chirality rule. Compounds 1 and 2 were substantially cytotoxic against SW1116 cells, with IC50 values of 49.5 and 41.0 microM, respectively, comparable to that (37.0 microM) of 5-fluorouracil. The biosynthetic pathway for 1 and 2 was postulated with the natural occurrence of benzo[j]fluoranthene analogues discussed in brief.

From 1998 to 2001, a sample of 2760 Mongol and Han individuals was investigated in 3 areas (Eerduosi city, Xilinguole and Bayannaoer leagues) from Inner Mongolia. Each individual was studied on 4 genetic characters (thumb type, palmar digital formular, fingernail type and plantar digital formular). The result is as follows: (1) The frequencies of the straight thumb were over 60%, and there were no significant sexual differences in all of 6 groups. (2) The frequencies of the ring-finger-longer were much higher in 6 groups, and there were significant sexual differences in 4 groups. (3) The frequencies of the long-shaped fingernail were the highest in all groups, the squat-shaped were the lowest. (4) The big toes were longer than the second toes in most people of 6 groups,but without significant sexual differences in each groups. (5) There were no significant correlations between 4 characters.

Objective: To investigate the effects of Realgar on procoagulant activity (PCA), tissue factor expression and tissue factor mRNA transcription in acute promyelocytic leukemia (APL) cell lines NB4 and MR2 cells., Method: NB4 and MR2 cells were treated with 300 micrograms.L-1 Realgar PCA of the treated cells was detected using one-stage clotting assay. TF antigen was detected by ELISA and TFmRNA by semi-quantitive RT-PCR., Result: The PCA and TF antigen level in NB4 and MR2 cells were significantly higher than that in HL-60 and K562 cells. Realgar could down-regulate the membrane PCA, TF antigen and TF mRNA transcription of NB4 and MR2 cells in a time-dependent manner., Conclusion: Down-regulating TF expression and PCA of NB4 and MR2 cells by Realgar may be one of the mechanism of its improvement effect on DIC-related hemorrhage of APL patients.

Estimation of the optimal concentrations of residual sugar in medium for a fed-batch culture of Baker's yeast has been studied and practiced. The concentrations, however, depended on different species and targets of the biomass, which was expected to be made. Kinetic changes of the residual phosphate salt in the medium conformed to a logarithmic process until the fourth hour during an 11-h culture. The parabolic method (see ref. 9 later in article) might be qualified to maintain the concentrations of residual sugar around 0.15 g/L. It was demonstrated that cell growth followed a sigmoid process during a fed-batch culture, because the cells consumed the nutrient with two metabolic pathways, one was for cell conversion and another was for non-cell conversion. With the parabolic method, we can estimate kinetics of cell growth and cell growth rate during the culture.

A parabolic nutrient supplementation has been derived by the specific growth rate, sugar conversion rate, and Pasteur effect, followed by high qualitative and quantitative biomass production with the lowest sugar consumption. The method produced about 95% cells in the G1 phase that were more resistant to drying and aging. These features are particularly important in the process of making dry yeast. It appears that the parabolic feed method may be used to species culture that show the Pasteur effect or produce byproducts from sugar. This may be because the supplementation is in conformity with reproducible kinetic growth during the fed-batch culture.