Exosomes from hepatitis B virus-infected hepatocytes activate hepatic stellate cells and aggravate liver fibrosis through the miR-506-3p/Nur77 pathway.

Cumulative evidence indicates the important role of Nur77 in organ fibrogenesis. However, the role of Nur77 in hepatitis B virus (HBV)-related liver fibrosis (LF) remains unclear. Cells were transfected with the microRNA mimic miRNA-506-3p or inhibitor, and pcDNA3.1-Nur77 or Nur77 guide RNA. Exosomes were isolated from HBV-infected HepG2-sodium taurocholate cotransporting polypeptide cells. The levels of miR-506-3p, Nur77, and LF-related genes and proteins were detected by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. The pathology of the liver from HBV-infected patients was examined using hematoxylin-eosin and Masson's staining. The expression of Nur77 in liver tissue was determined by immunohistochemistry, and the LF score was assessed using the METAVIR system. The relationship between miR-506-3p/Nur77 and LF score was analyzed by correlation analysis. HBV infection downregulated miR-506-3p expression and upregulated Nur77 levels in hepatocytes. Exosomes from HBV-infected hepatocytes also displayed decreased gene expression of miR-506-3p and increased expressions of Nur77- and LF-related genes in stellate cells compared with exosomes from hepatocytes with mock infection. These changes were reversed by Nur77 guide RNA. Nur77 expression in liver tissue was strongly correlated with LF, whereas serum miR-506-3p was strongly negatively correlated with LF. Exosomes from HBV-infected hepatocytes activate stellate cells and aggravate LF through the miR-506-3p/Nur77 pathway. These exosomes may be the basis of a promising therapeutic strategy.

Dynamic profile and clinical implications of hematological parameters in hospitalized patients with coronavirus disease 2019.

Objectives As people across the world suffer from coronavirus disease 2019 (COVID-19), further studies are needed to facilitate evaluating the severity and prognosis of COVID-19 patients. In the study, we aimed to dissect the dynamic profile and clinical implications of hematological findings in hospitalized patients with COVID-19. Methods We retrospectively analyzed the hematological findings of 72 patients with COVID-19 admitted from January 21 to February 17, 2020. The final date of follow-up was March 20, 2020. Dynamic profile of vital hematological parameters in severe and non-severe patients was presented at different time points (day 1, 5, 7, 9, 11, 13, 15 after admission), and the correlation of hematological parameters with hospitalization time was indicated. Results Of 72 patients with COVID-19, lymphopenia and leukopenia occurred in 39 (54.2%) and 20 (27.8%) patients with COVID-19, respectively. Fifteen (20.8%) patients were defined as severe cases and 57 (79.2%) were non-severe cases. Compared to non-severe patients, leukocyte count, neutrophil count and neutrophil-to-lymphocyte ratio (NLR) were significantly higher, whereas lymphocyte count was declined in severe patients at each time point. A growing trend in platelet count was found in non-severe patients over the follow-up period. In addition, a positive correlation of NLR with hospitalization time was detected from day 5 after admission. Conclusions Dynamic changes in vital hematological parameters from severe and non-severe patients had been characterized in the course of hospitalization. During hospitalization, NLR was found to have certain relevance to the hospitalization days and a role in forecasting disease prognosis for patients with COVID-19.

Causative agents and outcome of spontaneous bacterial peritonitis in cirrhotic patients: community-acquired versus nosocomial infections.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a serious complication and common cause of death in patients with liver cirrhosis. This study was conducted to compare the microbiological characteristics, drug resistance, and treatment outcomes for nosocomial SBP and community-acquired SBP. METHODS: A retrospective study was performed on 334 patients with culture-positive SBP at Beijing Youan Hospital, China, between January 2012 and December 2016. The medical records for these patients were reviewed, and their clinical and laboratory data were analyzed. RESULTS: A total of 155 (46.4%) patients with nosocomial SBP and 179 (53.6%) with community-acquired SBP were included in this study. From the patients' ascitic fluids, 334 pathogenic strains, including 178 Gram-negative bacterial strains, 138 Gram-positive bacterial strains and 18 other microbial strains were isolated. E. coli was the major pathogen (24.3%), followed by Klebsiella pneumoniae (12.0%) and Enterococcus faecium (10.5%). The proportion of Enterococcus was significantly higher in the patients with nosocomial SBP (6.1% vs. 27.7%, P < 0.001) than in the patients with community-acquired SBP. The main pathogens isolated from the nosocomial infections were significantly more resistant to the first-line recommended drug. Compared with community-acquired SBP, nosocomial SBP had a poorer outcome (36.8% vs. 24.6%; P = 0.016). The independent predictors for 30-day mortality included nosocomial infection, Child-Pugh classification, hepatocellular carcinoma, renal failure and hepatic encephalopathy. CONCLUSION: Gram-negative bacteria were the major pathogens involved in SBP in the cirrhotic patients. The strains isolated from the patients with nosocomial SBP displayed higher drug resistance than those isolated from patients with community-acquired SBP. Compared with community-acquired SBP, nosocomial SBP had a poorer outcome. When choosing drug treatments, the acquisition site of infection and the local epidemiological situation should be taken into account.

Bacteremia due to Gordonia polyisoprenivorans: case report and review of literature.

BACKGROUND: Gordonia polyisoprenivorans is a ubiquitous aerobic actinomycetes bacterium that rarely cause infections in humans. Here, we report a case of G. polyisoprenivorans catheter-related bacteremia in an AIDS patient. CASE PRESENTATION: A 37-year-old man with a past medical history of AIDS-related lymphoma suffered bacteremia caused by a Gram-positive corynebacterium. The strain was identified as a Gordonia species by matrix-assisted laser desorption ionization-time of flight mass spectrometry and confirmed to G. polyisoprenivorans by 16S rRNA combined with gyrB gene sequencing analyses. The patient was treated with imipenem and had a good outcome. CONCLUSIONS: The findings from our case and previously reported cases indicate that malignant hematologic disease, immunosuppression, and indwelling catheter heighten the risk for G. polyisoprenivorans infection. Molecular methods should be employed for proper identification of G. polyisoprenivorans to the species level.

Epidemiology and risk factors for nosocomial Non-Candida albicans candidemia in adult patients at a tertiary care hospital in North China.

Nosocomial candidemia extends the length of hospital stay, increases the costs of medical care, and is associated with a high mortality rate. Epidemiological data that assist in the choice of initial therapy may help to improve the prognosis. The present study was undertaken to investigate the epidemiology of nosocomial candidemia and identify risk factors for nosocomial candidemia caused by C. albicans and non-albicans Candida species (NAC). A retrospective chart review was undertaken to analyze cases of nosocomial candidemia treated at the Beijing Friendship Hospital between January 2008 and December 2012. All cases of candidemia were identified using the previously published criteria. Among 106 patients analyzed, 53.8% had nosocomial candidemia caused by NAC. Candida albicans was the most common causative agent, accounting for 46.2% of all cases, followed by C. glabrata (25.5%), C. tropicalis (15.1%), C. parapsilosis (10.4%) and C. Krusei (0.9%). Comparison of nosocomial C. albicans and NAC candidemia by multivariate logistic regression showed that factors independently associated with nosocomial NAC candidemia included exposure to azole agents (odds ratio [OR]: 3.359; 95% confidence interval [CI]: 1.136-10.154; P = .031) and artificial surgical implants (OR: 37.519; 95% CI: 2.5-562.998; P = .009). A significant risk factor for nosocomial C. albicans candidemia was cancer surgery (OR: 0.075; 95% CI: 0.013-0.437; P = .004). Clinical and epidemiological differences in the risk factors between nosocomial candidemia caused by C. albicans and NAC should be considered when selecting an initial antifungal regimen for the treatment of adult patients. This should be undertaken before the availability of species identification and/or antifungal susceptibility results.

Human serum inhibits adhesion and biofilm formation in Candida albicans.

BACKGROUND: Candida albicans can form biofilms on intravenous catheters; this process plays a key role in the pathogenesis of catheter infections. This study evaluated the effect of human serum (HS) on C. albicans biofilm formation and the expression of adhesion-related genes in vitro. A C. albicans laboratory strain (ATCC90028) and three clinical strains were grown for 24 h in RPMI 1640 supplemented with HS or RPMI 1640 alone (as a control). The growth of biofilm cells of four strains was monitored by a Live Cell Movie Analyzer, and by XTT reduction assay. The expression of the adhesion-related genes BCR1, ALS1, ALS3, HWP1 and ECE1 was analyzed by RT-PCR at three time points (60 min, 90 min, and 24 h). RESULTS: In the adhesion phase, C. albicans cells kept a Brownian movement in RPMI medium containing HS until a large number of germ tubes were formed. In the control group, C. albicans cells quickly adhered to the bottom of the reaction plate. Compared with RPMI 1640, medium supplemented with 3-50% HS caused a significant decrease in biofilm development (all p < 0.001). However, the presence of HS had no significant inhibitory effect on the pre-adhered biofilms (all p > 0.05). Biofilm formation was also inhibited by heat-inactivated and proteinase K pre-treated HS. The presence of 50% HS did not significantly affect the planktonic growth of C. albicans (p > 0.05). At three time points, HS inhibited expression of the ALS1 and ALS3 genes and promoted expression of the HWP1 and ECE1 genes. Significant up-regulation of BCR1 was observed only at the 90-min point. CONCLUSIONS: Human serum reduces biofilm formation by inhibiting the adhesion of C. albicans cells. This response may be associated with the down-regulation of adhesion-related genes ALS1, ALS3 and BCR1. The inhibitory serum component is protease-resistant and heat stable.

Human papillomavirus type-specific prevalence in women referred for colposcopic examination in Beijing.

Human papillomavirus (HPV) is associated with several disorders of the genital tract, skin, and oropharynx. This study investigated the prevalence of infection by 37 HPV genotypes among women of the Beijing area in China. Cervical specimens from 1,082 patients and 165 healthy controls were tested for HPV genotypes using a chip hybridization assay. Based on the local pathology, patients were divided into cervicitis and cervical lesion groups. Overall HPV infection rates were 30.5% for the cervicitis group and 78.4% for the cervical lesion group; whereas infection rates for high-risk HPV types (i.e., those associated with cervical cancers) were 24.0% and 73.4%, respectively. The most common HPV genotypes were HPV 52, 16, 81, 58, and 18 in healthy controls, HPV 52, 61, 55, 16, and 53 in those with cervicitis, HPV 52, 16, 33, 39, and 58 in cervical intraepithelial neoplasia grade 1, HPV 16, 58, 31, 52, and 33 in cervical intraepithelial neoplasia grade 2 or grade 3, and HPV 16, 33, 18, 52, and 58 in cervical cancer. Established high-risk HPV showed two peaks, in patients aged 30-34 and 55-79 years. In Beijing, HPV 16, 52, 58, and 33 are the most prevalent HPV types in women with cervical lesions, which should affect development of a cervical cancer vaccination for local use.

Higher numbers of circulating endothelial progenitor cells in stroke patients with intracranial arterial stenosis.

BACKGROUND: Bone marrow-derived endothelial stem cells participate in vascular repairs. Numbers of circulating endothelial progenitor cells (cEPCs) are associated with atherosclerosis. Fibrinogen plays a key role in atherosclerosis. Objective was to assess if cEPC counts were associated with atherosclerotic intracranial artery stenosis (IAS). METHODS: Three hundred subjects (108 patients with stroke and IAS (IAS), 120 control patients with stroke without IAS (CP), and 72 healthy controls (HC)) were retrospectively analyzed. cEPCs were identified and counted by flow cytometry using CD34, CD133 and KDR. Plasma fibrinogen was measured by immunoturbidimetry. cEPC counts were compared between the three groups. RESULTS: cEPC numbers were significantly higher in IAS (0.059 ± 0.031%) than in CP (0.026 ± 0.012%) (P < 0.001) and HC (0.021 ± 0.011%) (P < 0.001), but without difference between CP and HC (P = 0.401). Multiple logistic regression analysis showed that cEPC levels (OR 3.31, 95%CI 1.26-8.87, P = 0.025; IAS vs. CP) were independent markers of IAS after adjustment for hypertension, diabetes and smoking. No significant correlation between cEPC counts and plasma fibrinogen levels was observed (P > 0.05). CONCLUSION: cEPC numbers were associated with degrees of IAS. This measurement may be useful for non-invasive evaluation of atherosclerotic IAS.

Inhibition of PRMT1 alleviates sepsis-induced acute kidney injury in mice by blocking the TGF-ß1 and IL-6 trans-signaling pathways.

Sepsis-induced acute kidney injury (SI-AKI) causes renal dysfunction and has a high mortality rate. Protein arginine methyltransferase-1 (PRMT1) is a key regulator of renal insufficiency. In the present study, we explored the potential involvement of PRMT1 in SI-AKI. A murine model of SI-AKI was induced by cecal ligation and perforation. The expression and localization of PRMT1 and molecules involved in the transforming growth factor (TGF)-ß1/Smad3 and interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) signaling pathways were detected in mouse kidney tissues by western blot analysis, immunofluorescence, and immunohistochemistry. The association of PRMT1 with downstream molecules of the TGF-ß1/Smad3 and IL-6/STAT3 signaling pathways was further verified in vitro in mouse renal tubular epithelial cells. Cecal ligation and perforation caused epithelial-mesenchymal transition, apoptosis, and inflammation in renal tissues, and this was alleviated by inhibition of PRMT1. Inhibition of PRMT1 in SI-AKI mice decreased the expression of TGF-ß1 and phosphorylation of Smad3 in the renal cortex, and downregulated the expression of soluble IL-6R and phosphorylation of STAT3 in the medulla. Knockdown of PRMT1 in mouse renal tubular epithelial cells restricted the expression of Cox-2, E-cadherin, Pro-caspase3, and phosphorylated Smad3 (involved in the TGF-ß1-mediated signaling pathway), and also blocked IL-6/soluble IL-6R, inducing the expression of Cox-2 and phosphorylated-STAT3. In conclusion, our findings suggest that inhibition of PRMT1 mitigates SI-AKI by inactivating the TGF-ß1/Smad3 pathway in the cortex and the IL-6/STAT3 pathway in the medulla. Our findings may aid in the identification of potential therapeutic target molecules for SI-AKI.

Epidemic, risk factors of carbapenem-resistant Klebsiella pneumoniae infection and its effect on the early prognosis of liver transplantation.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection remains a major cause of morbidity and mortality in early-stage post-liver transplantation (LT). Methods: We retrospectively analyzed the demographic and clinical infections characteristics of all LT recipients in our hospital between January 2019 and December 2021. Results: Among the 272 LT recipients who received LT between January 2019 and December 2021, sixty-two patients had at least one infection within 3-months post-LT, with a prevalence of 22.8% (62/272). The prevalence of CRKP infections was 7.0% (19/272), and the 3-months post-LT mortality was 19.4% (12/62). The risk factors independently related to 3-months mortality were age (Odds ratio (OR)= 1.126, 95% Confidence interval (CI): 1.009~1.257; P=0.034), mechanical ventilation (MV) (OR=1.206, 95% CI: 1.039~1.401; P =0.014), and CRKP infection (OR=18.240, 95% CI: 2.206~150.842; P =0.007). In CRKP infection, the length of ICU stay (OR=1.067, 95% CI: 1.015~1.122; P=0.011), pre-operation infection (POI) (OR=6.733, 95% CI: 1.160~39.088; P=0.034), and hepatocellular carcinoma (HCC) (OR=26.772, 95% CI: 1.747~410.187; P=0.018) were the independent risk factors. With COX multivariate regression analysis, the 3-months survival rate of CRKP infected patients was significantly lower than that without CRKP infection post-LT. Conclusions: CRKP infection is closely correlated with poor prognosis in 3-months post-LT.

[Study on the association of the CRP gene +1444C/T polymorphism with symptomatic carotid artery stenosis].

OBJECTIVE: To investigate the potential association of the C-reactive protein (CRP) gene +1444C/T polymorphism with symptomatic carotid artery stenosis. METHODS: Polymerase chain reaction-restriction fragment length polymorphism was used for the detection of CRP +1444C/T genotypes in 192 patients with symptomatic carotid artery stenosis and 197 healthy controls. Serum high sensitivity-CRP (hs-CRP) levels were measured by routine method. RESULTS: No TT genotype was detected in this study. Patients with >70% stenosis had higher CC genotype compared with those with <70% stenosis after adjusting for major cerebrovascular risk factors (OR: 2.958; 95% CI: 1.198 - 7.305; P=0.019). CRP levels were significantly higher in patients than in controls. Subgroup analysis according to clinical characteristics (single or double stenosis; >70% or <70% stenosis) did not show difference in CRP levels. There was no significant difference in the prevalence of CT genotype between patients and controls, or between single and double stenosis (P>0.05). CONCLUSION: The CRP +1444 CC genotype is a risk factor for >70% carotid artery stenosis. The serum CRP level is associated with the presence of carotid stenosis. However, it is not associated with the number and severity of stenosis.

Rapid identification of Candida spp. frequently involved in invasive mycoses by using flow-through hybridization and Gene Chip (FHGC) technology.

The incidence of invasive fungal infections in immunocompromised patients has increased in recent decades. Rapid and accurate identification of these pathogenic fungi is crucial for initiating a timely, safe, and effective antifungal therapy. Here we developed a microarray based on flow-through hybridization gene chip technology. The microarray was tested for its specificity using a panel of reference and blinded clinical isolates. The results proved that this microarray was highly discriminative, leading to the unequivocal identification of each species, including Candida famata and the highly related species Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis. This new system represents a reliable method that is of potential use in clinical laboratories for the simultaneous detection and identification of the most common pathogenic fungi.

[Levels and clinic significance of serum soluble Fas and soluble Fas ligand in coal workers' pneumoconiosis].

OBJECTIVE: To investigate the changes of levels and clinic significance of serum soluble Fas (sFas) and soluble FasL (sFasL) in coal workers' pneumonoconiosis. METHODS: Serum levels of sFas and sFasL were determined in 52 patients with silicosis, 57 coal workers' pneumonoconiosis, 46 healthy underground coal workers' (the underground control group) and 40 healthy volunteers working on the ground (the ground control group) with a sandwich ELISA. RESULTS: Compared to the underground control and the ground control group, the serum levels of sFas and sFasL in the patients with silicosis and the coal workers' pneumonoconiosis were significantly higher (P < 0.01). Serum levels of sFas and sFasL in the underground control group were significantly higher than those in the ground control group (P < 0.01); Serum sFas levels in coal workers' pneumonoconiosis was significantly higher than those in the patients with silicosis (P < 0.01). Although the serum sFasL levels was also increased, there was no significant difference (P > 0.05). In the patients with silicosis and the coal workers' pneumonoconiosis patients, the serum sFas levels in Phase I patients combined with emphysema and simple Phase II + III patients were significantly higher than those in simple Phase I patients (P < 0.01). There was no significant difference in the serum sFasL levels among various groups with different parameters of pneumonoconiosis. In the patients with silicosis and the coal workers' pneumonoconiosis, serum levels of sFas and sFasL were not significantly altered among different duration of exposure to dusts. There was no correlation between serum levels of sFas and sFasL in the patients with silicosis while there was a slightly positive correlation between sFas and sFasL levels in the coal workers' pneumonoconiosis (r = 0.479, P < 0.05). CONCLUSION: In the patients with silicosis and the coal workers' pneumonoconiosis, the serum levels of sFas and sFasL are abnormal and associated with the development of the pneumonoconiosis. The changes of serum sFas levels may indicate the development and progression of the pneumonoconiosis. The detection of the serum sFas level may be used in the differential diagnosis for the silicosis and the coal worker's pneumonoconiosis.

The Prognostic Significance of Beta2 Microglobulin in Patients with Hemophagocytic Lymphohistiocytosis.

OBJECTIVE: To determine the prognostic significance of beta2 microglobulin (ß2-m) concentrations in patients with hemophagocytic lymphohistiocytosis (HLH), a rare disorder caused by pathologic activation of the immune system. PATIENTS AND METHODS: The study population consisted of 74 patients diagnosed with HLH and 35 healthy controls. Serum ß2-m levels were measured using a latex agglutination photometric immunoassay. RESULTS: Median serum ß2-m levels were significantly higher in HLH patients than in healthy controls (4.05 versus 1.5 mg/L; P < 0.001) and were significantly higher in patients with lymphoma associated hemophagocytic syndrome (LAHS) than in patients with benign disease-associated HLH (4.2 versus 3.3 mg/L; P < 0.001). Higher serum ß2-m levels were positively correlated with LAHS (P = 0.005), abnormal lactate dehydrogenase concentrations (P = 0.009), and hypoalbuminemia (P = 0.003). ROC analysis showed that overall survival (OS) was significantly shorter in LAHS patients with serum ß2-m levels ≥4.03 mg/L compared to <4.03 mg/L (P < 0.001). Moreover, multivariate analysis showed that serum ß2-m level was an independent prognostic of OS (P = 0.034) in patients with LAHS. CONCLUSION: High serum ß2-m levels and LAHS were associated with markedly poorer OS in patients with HLH. Serum ß2-m concentration was a powerful and independent prognostic factor for OS in patients with LAHS.

Modification of Wiener Index and its application.

A novel topological index based on the Wiener Index is proposed as W* = 1/2 sigma (n)(i,j=1) S(*)(ij), the element S(*)(ij) of the distance matrix is defined either as S(*)(ij) = alpha x square root of I(i)I(j)/R(ij) (atoms i and j are adjacent) or as S(*)(ij) = = alpha x (j-i+1)square root of I(i) x x x x x I(j)/R(ij) (atoms i and j are not adjacent), where I(i) and I(j) represent the electronegativity of vertices i or j, respectively, R(ij)() is the sum of the bond length between the vertices i and j in a molecular graph, and alpha = (Z(i)/Z(j))(0.5), where Z(i) and Z(j) are the atomic numbers of the positive valence atom i and the negative valence atom j, respectively. The properties and the interaction of the vertices in a molecule are taken into account in this definition. That is why the application of the index W to heteroatom-containing and multiple bond organic systems and inorganic systems is possible. Correlation coefficients above 0.97 are achieved in the prediction of the retention index of gas chromatography of the hydrocarbons, the standard formation enthalpy of methyl halides, halogen-silicon, and inorganic compounds containing transition metals.