The Role of Long Noncoding RNA Negative Regulator of Interferon Response in the Regulation of Hantaan Virus Infection.

Hantaan virus (HTNV) is prevalent in Eurasia. It causes hemorrhagic fever with renal syndrome (HFRS). Long noncoding RNAs (lncRNAs) play key roles in regulating innate immunity. Among these, lncRNA negative regulator of interferon response (NRIR) was reported as an inhibitor of several interferon (IFN)-stimulated genes. Our results showed that: NRIR expression was upregulated by HTNV infection in a type I IFN-dependent manner. The expression of NRIR in CD14+ monocytes from HFRS patients in acute phase was significantly higher than that in convalescent phase and healthy controls. HTNV infection in some HTNV-compatible cells was promoted by NRIR. NRIR negatively regulated innate immunity, especially IFITM3 expression. Localized in the nucleus, NRIR bound with HNRNPC, and knockdown of HNRNPC significantly weakened the effect of NRIR in promoting HTNV infection and restored IFITM3 expression. These results indicated that NRIR regulates the innate immune response against HTNV infection possibly through its interaction with HNRNPC and its influence on IFITM3.

Levels of peripheral blood routine, biochemical and coagulation parameters in patients with hemorrhagic fever with renal syndrome and their relationship with prognosis: an observational cohort study.

BACKGROUND: Hantaan virus (HTNV), Seoul virus (SEOV) and Puumala virus (PUUV) are major serotypes of the Hantavirus, which can cause hemorrhagic fever with renal syndrome (HFRS). The pathophysiology of HFRS in humans is complex and the determinants associated with mortality, especially the coagulation and fibrinolysis disorders, are still not been fully elucidated. Severe patients usually manifest multiple complications except for acute kidney injury (AKI). The aim of this study was to observe the levels of peripheral blood routine, biochemical and coagulation parameters during the early stage, so as to find independent risk factors closely related to the prognosis, which may provide theoretical basis for targeted treatment and evaluation. METHODS: A total of 395 HFRS patients from December 2015 to December 2018 were retrospectively enrolled. According to prognosis, they were divided into a survival group (n = 368) and a death group (n = 27). The peripheral blood routine, biochemical and coagulation parameters were compared between the two groups on admission. The relationship between the parameters mentioned above and prognosis was analyzed, and the dynamic changes of the coagulation and fibrinolysis parameters during the first week after admission were further observed. RESULTS: In addition to AKI, liver injury was also common among the enrolled patients. Patients in the death group manifested higher levels of white blood cell counts (WBC) on admission. 27.30% (107/392) of the patients enrolled presented with disseminated intravascular coagulation (DIC) on admission and DIC is more common in the death group; The death patients manifested longer prothrombin time (PT) and activated partial thromboplastin time (APTT), higher D-dimer and fibrinogen degradation product (FDP), and lower levels of platelets (PLT) and fibrinogen (Fib) compared with those of the survival patients. The proportion of D-dimer and FDP abnormalities are higher than PT, APTT and Fib. Prolonged PT, low level of Fib and elevated total bilirubin (TBIL) on admission were considered as independent risk factors for prognosis (death). CONCLUSIONS: Detection of PT, Fib and TBIL on admission is necessary, which might be benefit to early predicting prognosis. It is also important to pay attention to the dynamic coagulation disorders and hyperfibrinolysis during the early stage in the severe HFRS patients.

High levels of exfoliated fragments following glycocalyx destruction in hemorrhagic fever with the renal syndrome are associated with mortality risk.

Background: The glycocalyx is a gel-like structure that covers the luminal side of vascular endothelial cells. It plays an important role in maintaining the integrity of the vascular endothelial barrier structure. However, the presence or absence of glycocalyx destruction in hemorrhagic fever with renal syndrome (HFRS) and its specific mechanism and role is still unclear. Methods: In this study, we detected the levels of exfoliated glycocalyx fragments, namely, heparan sulfate (HS), hyaluronic acid (HA), and chondroitin sulfate (CS), in HFRS patients and investigated their clinical application value on the evaluation of disease severity and prognosis prediction. Results: The expression of exfoliated glycocalyx fragments in plasma was significantly increased during the acute stage of HFRS. The levels of HS, HA, and CS in HFRS patients during the acute stage were significantly higher than in healthy controls and convalescent stages of the same type. HS and CS during the acute stage gradually increased with the aggravation of HFRS, and both fragments showed a significant association with disease severity. In addition, exfoliated glycocalyx fragments (especially HS and CS) showed a significant correlation with conventional laboratory parameters and hospitalization days. High levels of HS and CS during the acute phase were significantly associated with patient mortality and demonstrated an obvious predictive value for the mortality risk of HFRS. Conclusion: Glycocalyx destruction and shedding may be closely associated with endothelial hyperpermeability and microvascular leakage in HFRS. The dynamic detection of the exfoliated glycocalyx fragments may be beneficial for the evaluation of disease severity and prognosis prediction in HFRS.

A retrospective study to evaluate the CT and MR imaging findings of non-Hodgkin's lymphoma affecting the jaw bones.

OBJECTIVE: To explore the CT and MR imaging findings of non-Hodgkin's lymphoma (NHL) involving the jaw bones. METHODS: Gnathic NHLs were retrospectively analyzed in 52 patients. The imaging findings were observed from the lesion number, location, size, shape, margin, density and signal intensity, CT value, bone structure change, and soft tissue mass. RESULTS: Of the 52 subjects, there were 43 with solitary gnathic NHL, and 9 with multicentric gnathic NHLs. The maximum diameter of all the 72 lesions ranged from 1.5 to 9.5 cm (mean 4.6 ± 1.67 cm). Of the 72 lesions, 90.3% were identified as irregular shapes, 87.5% as ill-defined margins, and 76.4% as homogeneous densities and signal intensities. The osteolytic destruction was found in 84.7% lesions, cortical disruption in 84.7%, and no periosteal reaction in 93.1%. The soft tissue masses surrounding the gnathic lesions were shown in 93.1% lesions. On MR imaging, the gnathic NHLs (18 lesions) showed as iso-signal intensity on T1WI, slightly higher signal intensity on T2WI, and high signal intensity on DWI. After contrast media administration, 83.3% lesions showed slightly homogeneous enhancement on T1WI. CONCLUSIONS: On CT and MR imaging, gnathic NHLs usually reveal as osteolytic lesions with irregular shapes, ill-defined margins, homogeneous densities and signal intensities, and surrounded by soft tissue mass. Some gnathic NHLs are characterized by multicentricity, which is important for indicating the condition.

Carcinoma ex pleomorphic adenoma of major salivary glands: CT and MR imaging findings.

OBJECTIVES: To describe the CT and MR imaging characteristics of primary carcinoma ex pleomorphic adenoma (Ca-ex-PA) in major salivary glands and present more information for recognizing this malignancy. METHODS: 212 patients with primary Ca-ex-PA in major salivary glands (169 in the parotid gland, 36 in the submandibular gland, 7 in the sublingual gland) underwent CT and MR imaging (plain and contrast-enhanced scans) prior to surgical management and histopathological examination. The CT and MR imaging findings of this condition were retrospectively reviewed and correlated with their pathological types: non-invasive carcinoma (Type I, 37 cases), minimally invasive carcinoma (Type II, 18 cases), and widely invasive carcinoma (TypeIII, 157 cases). The binary logistic regression analysis was used to analyze the independent influencing factors of morphology and boundary for differentiating between Type I/II and Type III of Ca-ex-PA, and the sensitivity, specificity and positive predictive value were calculated. Differences in apparent diffusion coefficient (ADC) values between Type I/II and Type III of Ca-ex-PA were calculated by independent sample t-tests. RESULTS: On CT and MR imaging, there were 190/212 cases (89.6%) identified as lobular, 203/212 cases (95.8%) with enhancement, and 173/212 cases (81.6%) with inhomogeneous after contrast administration.Calcification within the mass was shown in 76 of 192 cases (39.6%) on plain CT examination. Of 55 neoplasms with Type I and II, 38 (69.1%) were presented as round or oval and 42 (76.4%) as well-defined margins. Of 157 neoplasms with Type III, 103 (65.6%) were presented as irregular form and 110 (70.1%) as uneven margins or with partial uneven margins.The sensitivity, specificity and positive predictive value for distinguishing Type I/II and Type III tumors according to the morphology and boundary were 78.34%, 63.64% and 86.01%, respectively. The mean ADC value of Ca-ex-PA (22 cases) in major salivary glands was about 0.93 × 10-3 mm2 s-1, and there was no significant difference in mean ADC value between Type I/II and Type III of this neoplasm. Cervical lymph node metastasis and distance metastasis were found in 67 patients (31.6%, Type III) and 32 patients (15.1%, Type I in 1; Type II in 1; and Type III in 30), respectively. CONCLUSIONS: Most Ca-ex-PA is characterized by an irregular, lobular, and inhomogeneous enhanced neoplasm with uneven margin or partial uneven margin on CT and MR imaging, which is frequently corresponding with Type III. And a round or oval mass with well-defined margin usually correlates with Type I and II. Morphology and boundary are important basis for distinguishing Type I/II and Type III tumors. Calcification within the neoplasm shown on CT may be regarded as a specific sign for indicating this malignancy. Low ADC value is an important manifestation of this neoplasm.Ca-ex-PA with Type III is more likely to have cervical lymph node metastasis and distant metastasis.

Predictive value of pentraxin-3 on disease severity and mortality risk in patients with hemorrhagic fever with renal syndrome.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus is characterized by systemic immunopathological injury. Pentraxin-3 is an acute-phase reactant involved in the processes of inflammation and infection. This study aimed to investigate the levels of plasma pentraxin-3 and evaluate its predictive value on disease severity and mortality risk in patients with HFRS. METHODS: This was a prospective real-world observational study. The concentrations of plasma pentraxin-3 were measured by enzyme linked immunosorbent assay (ELISA) in 105 HFRS patients and 27 healthy controls. We analyzed the clinical relevance between pentraxin-3 and clinical subtyping, hospital stay and conventional laboratory parameters of HFRS patients. Considering the prognosis (death) as the primary endpoint, the levels of pentraxin-3 between survivors and non-survivors were compared, and its association with mortality was assessed by Kaplan-Meier survival analysis. The predictive potency of pentraxin-3 for mortality risk in HFRS patients was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: The levels of pentraxin-3 during the acute phase were increased with the aggravation of the disease, and showed the highest expression in critical-type patients (P < 0.05). Pentraxin-3 demonstrated significant correlations with conventional laboratory parameters (WBC, PLT, AST, ALB, APTT, Fib) and the length of hospital stay. Compared with the survivors, non-survivors showed higher levels of pentraxin-3 and worse expressions of conventional laboratory parameters during the acute phase. The Kaplan-Meier survival curves showed that high levels of pentraxin-3 during the acute phase were significantly associated with the death in HFRS patients. Pentraxin-3 demonstrated significant predictive value for the mortality risk of HFRS patients, with the area under ROC curve (AUC) of 0.753 (95%CI: 0.593 ~ 0.914, P = 0.003). CONCLUSIONS: The detection of plasma pentraxin-3 might be beneficial to the evaluation of disease severity and to the prediction of mortality risk in HFRS patients.

The histogram analysis of apparent diffusion coefficient in differential diagnosis of parotid tumor.

OBJECTIVES: Use apparent diffusion coefficient (ADC) histogram to investigate whether the parameters of ADC histogram can distinguish between benign and malignant tumors and further differentiate the tumor subgroups. METHODS AND MATERIALS: This study retrospectively enrolls 161 patients with parotid gland tumors. Histogram parameters including mean, inhomogeneity, skewness, kurtosis and 10th, 25th, 50th, 75th, 90th percentiles are derived from ADC mono-exponential model. Mann-Whitney U test is used to compare the differences between benign and malignant groups. Kruskal-Wallis test with post-hoc Dunn-Bonferroni method is used for subgroup classification, then receiver operating characteristic curve analysis is performed in mean ADC value to obtain the appropriate cutoff values. RESULTS: Except for kurtosis and 90th percentile, there are significant differences in all other ADC parameters between benign and malignant groups. In subgroup classification of benign tumors, there are significant differences in all ADC parameters between pleomorphic adenoma and Warthin's tumor (area under curve 0.988; sensitivity 93.8%; specificity 94.7%; all ps < 0.05). Pleomorphic adenoma has high value in mean than basal cell adenoma (area under curve 0.819; sensitivity 76.9%; specificity 76.9%; p < 0.05). Basal cell adenoma has high values in mean (area under curve 0.897; sensitivity 92.3%; specificity 78.9%; all ps < 0.05) and 10th, 25th, 50th percentiles than Warthin's tumor. In subgroup classification of malignant tumors, low-risk parotid carcinomas have higher values than hematolymphoid tumors in mean (area under curve 0.912; sensitivity 84.6%; specificity 100%, all ps < 0.05) and 10th, 25th percentiles. CONCLUSION: ADC histogram parameters, especially mean and 10th, 25th percentiles, can potentially be an effective indicator for identifying and classifying parotid tumors.

Study on expression of plasma sCD138 in patients with hemorrhagic fever with renal syndrome.

BACKGROUND: Until now, there is non-specific treatment, and exploring early and novel biomarkers to determine the disease severity and prognosis of hemorrhagic fever with renal syndrome (HFRS) would be of importance for clinician to take systematic and timely intervention. This study observed the expression of plasma sCD138, a soluble component shedding from the glycocalyx (GCX) to the circulating blood, and evaluated its predictive value on disease severity and prognosis of HFRS. METHODS: One hundred and seventy-six patients with HFRS who were treated at our center between January 2011 and December 2013 were randomly enrolled in this study. The patients were divided into a mild-type group, a moderate-type group, a severe-type group and a critical-type group according to the HFRS criteria for clinical classification. Thirty-five blood samples from healthy subjects were obtained as the controls. The concentrations of sCD138 were detected using enzyme linked immunosorbent assay (ELISA). The levels of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), white blood cells (WBC), platelets (PLT), glucose (GLU), blood urea nitrogen (BUN) and serum creatinine (Scr) in the samples were routinely tested. The levels of sCD138 among the different types were compared; the correlation among sCD138 and the laboratory parameters mentioned above were analyzed. The predictive effectiveness for prognosis of sCD138 was evaluated using the receiver operating characteristic (ROC) curve analysis. RESULTS: Except for the mild-type, the levels of sCD138 in the moderate-, severe- and critical-type patients during the acute stage were significantly higher than that of the convalescent stage and the control (P<0.05). With the aggravation of the disease, the levels of sCD138 during the acute stage had an increasing tendency, while demonstrated no significant difference among the moderate-, severe- and critical-type patients (P>0.05). sCD138 was negatively correlated with Fib, PLT and ALB, and was positively correlated with WBC and AST (P<0.05). sCD138 demonstrated predictive effectiveness for prognosis with the area under the curve (AUC) of 0.778 (P<0.001). CONCLUSION: Dynamic detection of plasma sCD138 might be benefit to evaluating the disease severity and prognosis of the patients with HFRS.

[Diagnostic value of diffusion-weighted magnetic resonance imaging for solid tumors affecting the base of tongue and glossopharynx].

PURPOSE: The objective of the present study was to evaluate the potential application value of diffusion-weighted magnetic resonance imaging (DW-MRI) to differentiate solid benign from malignant tumors affecting the base of tongue and glossopharynx. METHODS: Sixty-one patients who presented with solid tumors affecting the base of tongue and glossopharynx underwent conventional MRI and DW-MRI before pathologic verification. Based on pathologic findings, the tumors were classified into 4 groups: Group 1, solid benign tumor (n=10); Group 2, epithelial carcinoma (n=35); Group 3: non- epithelial malignant tumor (n=16); and Group 4: malignant tumor (n=51, a combination of Group 2 and 3). The mean apparent diffusion coefficients (ADCs) were computed from DW-MRI scans obtained with b factors of 0 and 1000 s/mm2. SAS 9.1 software package was used for Wilcoxon test. RESULTS: The mean ADCs were significantly different (P<0.05) between group 1 and the other 3 groups, and between group 2 and group 3, respectively. Among all kinds of pathological types of lesions, non-Hodgkin lymphoma had a lowest mean ADC value, and schwannoma had a highest mean ADC value. In addition, the mean ADCs among epithelial carcinoma subtypes were not significantly different(P>0.05). CONCLUSIONS: DW-MRI has differential diagnostic value of solid tumors affecting the base of tongue and glossopharynx, especially in distinguishing between benign solid tumors and malignant tumors, and between epithelial carcinomas and non-epithelial malignant tumors.

Lymphoepithelial carcinoma of salivary glands: CT and MR imaging findings.

OBJECTIVES: To depict the CT and MRI characteristics of salivary gland lymphoepithelial carcinoma (LEC) and provide more diagnostic information for this malignancy. METHODS: 103 salivary gland LEC subjects were retrospectively reviewed. The subjects include 35 males with a mean age of 40.8 years and 68 females with a mean age of 49.4 years. Of the 103 subjects, 86 had carcinomas in the parotid gland, 5 in the submandibular gland, 1 in the sublingual gland, 3 in the cheek and 8 in the palate. All subjects underwent routine CT and MRI (plain and contrast-enhanced scans) prior to surgical treatment and histopathological examination. RESULTS: Based on the pathological outcomes, all the salivary gland LECs were classified into two types from CT and MRI scans: solitary LEC (56 cases, 54.4%) and multiple LEC (47 cases, 45.6%). The latter included solitary salivary gland LEC with extraglandular lymph-node metastases (12 cases), parotid gland LEC with ipsilateral intraglandular lymph-node metastases (11 cases), parotid gland LEC with ipsilateral intra- and extraglandular lymph-node metastases (23 cases) and bilateral parotid gland LEC (1 case). The salivary gland LEC was depicted on CT and MRI scans as a lobular mass in 64 of 104 (61.5%), homogeneous mass in 65 of 104 (62.5%) or enhanced neoplasm in 94 of 104 (90.4%). CONCLUSIONS: Salivary gland LEC has a predilection for females in the fourth to fifth decade of life and the parotid gland. CT and MRI findings between solitary and multiple salivary LECs vary. A majority of multiple parotid gland LECs are characterized by metastasis of ipsilateral intraglandular lymph nodes, which may accompany with or without extraglandular lymph-node metastases.

The value of combining conventional, diffusion-weighted and dynamic contrast-enhanced MR imaging for the diagnosis of parotid gland tumours.

OBJECTIVES: The aim of this study was to determine the value of combining conventional MRI, diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE)-MRI in diagnosing solid neoplasms in the parotid gland. METHODS: A total of 148 subjects (101 subjects with benign and 47 subjects with malignant tumours) were evaluated with conventional MRI, DWI and DCE-MRI prior to surgery and pathologic verification. The items observed with conventional MRI included the shape, capsule and signal intensity of parotid masses. The apparent diffusion coefficient (ADC) was calculated from DWI that was obtained with a b-factor of 0 and 1000 s mm-2. A time-intensity curve (TIC) was obtained from DCE-MRI. RESULTS: There were significant differences (p < 0.01) in the shape, capsule, ADC and TIC between benign and malignant parotid tumours. Irregular neoplasms without a capsule, ADC <1.12 × 10-3 mm2 s-1 and a plateau enhancement pattern were valuable parameters for predicting malignant neoplasms. A combination of all of these parameters yielded sensitivity, specificity, accuracy, positive-predictive value and negative-predictive value of 85.1%, 94.1%, 91.2%, 87.0% and 93.1%, respectively. CONCLUSIONS: A combined analysis using conventional MRI, DWI and DCE-MRI is helpful in distinguishing benign from malignant tumours in the parotid gland.

Hantavirus infection: a global zoonotic challenge.

Hantaviruses are comprised of tri-segmented negative sense single-stranded RNA, and are members of the Bunyaviridae family. Hantaviruses are distributed worldwide and are important zoonotic pathogens that can have severe adverse effects in humans. They are naturally maintained in specific reservoir hosts without inducing symptomatic infection. In humans, however, hantaviruses often cause two acute febrile diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). In this paper, we review the epidemiology and epizootiology of hantavirus infections worldwide.

Changes in Plasma Adiponectin Concentrations in Patients With Hemorrhagic Fever With Renal Syndrome: An Observational Prospective Study.

The objective is to observe the changes in plasma adiponectin (APN) and its predictive capacity for disease severity and prognosis of hemorrhagic fever with renal syndrome (HFRS).One hundred and five patients who were treated at our center between October 2011 and December 2012 were randomly enrolled in this study. The patients were divided into a mild-type group, a moderate-type group, a severe-type group, and a critical-type group according to the HFRS criteria for clinical classification. Ninety-three plasma samples from the patients in the acute stage and 78 samples from the patients in the convalescent stage were obtained, and 28 samples from healthy subjects were obtained as controls. The concentrations of APN were detected using the enzyme-linked immunosorbent assay. The levels of white blood cells, platelets, hematocrit, albumin, blood urea nitrogen, serum creatinine, and uric acid in the samples were routinely tested. The levels of APN among the different types were compared; the correlation between APN and the laboratory parameters was analyzed. The predictive effectiveness for prognosis of APN and the laboratory parameters as mentioned above were evaluated using the receiver operating characteristic curve analysis.The levels of APN in the mild- and moderate-type patients in the acute stage were significantly higher than the severe-type and control (P < 0.05) and decreased with the severity of the disease, while there were no obvious difference among severe-, critical-type and control groups. The levels of APN in patients in the convalescent stage were higher than the control group (P < 0.05), and the APN levels of the critical-type group were higher compared with the mild-type groups (P < 0.05). Adiponectin was negatively correlated with white blood cells and hematocrit and positively correlated with platelets, albumin, and uric acid (P < 0.001). Adiponectin showed no statistical significance for predicting prognosis, with the area under the curve equal to 0.609 (95% CI: 0.237-0.745, P = 0.215).Adiponectin can be considered as a novel biomarker for disease severity in patients with HFRS, while it seems to have no predictive capacity for prognosis of HFRS.

HMGB-1 as a novel predictor of disease severity and prognosis in patients with hemorrhagic fever with renal syndrome.

OBJECTIVE: To examine the predictive capacity of the high mobility group box protein-1 (HMGB-1) for disease severity and prognosis of hemorrhagic fever with renal syndrome (HFRS). METHODS: One hundred and five HFRS patients and 28 controls were studied. The concentrations of HMGB-1 in the blood were measured with a commercially available ELISA. The levels of white blood cells (WBC), platelets (PLT), hematocrit (HCT), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (Scr), and uric acid (UA) were routinely tested in the same time frame. RESULTS: The levels of HMGB-1 increased with the severity of the disease (P < 0.001). HMGB-1 was positively correlated with WBC and BUN and negatively correlated with PLT, ALB, and UA (P < 0.001). HMGB-1 showed statistical significance for predicting prognosis (AUC = 0.800, P < 0.001). The sensitivity and specificity of HMGB-1, WBC, PLT, and ALB used in combination for predicting outcome were better than those of single analyses (AUC = 0.892, P < 0.001). CONCLUSIONS: HMGB-1 can be considered a novel biomarker for severity and outcome in patients with HFRS. The use of HMGB-1, WBC, PLT, and ALB in combination to predict the outcome in patients with HFRS exhibited an acceptable level of diagnostic capability.

Elevated soluble CD163 plasma levels are associated with disease severity in patients with hemorrhagic fever with renal syndrome.

BACKGROUND: Hantaan virus is a major zoonotic pathogen that causesing hemorrhagic fever with renal syndrome (HFRS). Although HFRS pathogenesis has not been entirely elucidated, the importance of host-related immune responses in HFRS pathogenesis has been widely recognized. CD163, a monocyte and macrophage-specific scavenger receptor that plays a vital function in the hosts can reduce inflammation, is shed during activation as soluble CD163 (sCD163). The aim of this study was to investigate the pathological significance of sCD163 in patients with HFRS. METHODS: Blood samples were collected from 81 hospitalized patients in Tangdu Hospital from October 2011 to January 2014 and from 15 healthy controls. The sCD163 plasma levels were measured using a sandwich ELISA, and the relationship between sCD163 and disease severity was analyzed. Furthermore, CD163 expression in 3 monocytes subset was analyzed by flow cytometry. RESULTS: The results demonstrated that sCD163 plasma levels during the HFRS acute phase were significantly higher in patients than during the convalescent stage and the levels in the healthy controls (P<0.0001). The sCD163 plasma levels in the severe/critical group were higher than those in the mild/moderate group during the acute (P<0.0001). A Spearman correlation analysis indicated that the sCD163 levels were positively correlated with white blood cell, serum creatine, blood urea nitrogen levels, while they were negatively correlated with blood platelet levels in the HFRS patients. The monocyte subsets were significantly altered during the acute stage. Though the CD163 expression levels within the monocyte subsets were increased during the acute stage, the highest CD163 expression level was observed in the CD14++CD16+ monocytes when compared with the other monocyte subsets. CONCLUSION: sCD163 may be correlated with disease severity and the disease progression in HFRS patients; however, the underlying mechanisms should be explored further.

Imbalance of regulatory T cells and T helper type 17 cells in patients with chronic hepatitis C.

Pegylated interferon and ribavirin combination therapy is known to be effective in suppressing viral replication in 50-60% of hepatitis C virus (HCV)-infected patients. However, HCV-infected patients often exhibit varied responses to therapy. Therefore, the identification of immunological markers associated with the clinical outcomes of antiviral treatment is critical for improvement of therapeutic options. In this study, we aimed to investigate the ratio of CD4(+) CD25(+) FoxP3(+) regulatory T (Treg) cells to interleukin-17A (IL-17A) -producing T helper type 17 (Th17) cells, and its association with clinical outcomes in response to anti-HCV treatment. In all, 114 patients with HCV infection received pegylated interferon-α2a and ribavirin therapy for 48 weeks, and the frequency of Treg cells and Th17 cells as well as the levels of secreted cytokines were longitudinally analysed by flow cytometry and ELISA. Treg cell proportions and IL-10 production were significantly elevated in HCV-infected patients, especially for HCV genotype 1b. However, the frequency of Th17 cells as well as the secretion of IL-17, IL-22 and IL-23 did not reveal notable difference between HCV infections and healthy individuals. Inhibition of HCV replication was accompanied by a reduction in Treg cells, but little influence on Th17 cells, which led to a significant decrease in Treg : Th17 ratios. Skewed Treg : Th17 ratios existed in chronic hepatitis C. HCV RNA load is closely associated with Treg : Th17 ratios during pegylated interferon-α2a and ribavirin treatment in HCV-infected patients. The imbalance of Treg cells to Th17 cells might play an important role in persistent HCV infection.

Early indicators of severity and construction of a risk model for prognosis based upon laboratory parameters in patients with hemorrhagic fever with renal syndrome.

BACKGROUND: The objective of this study was to explore the role of laboratory parameters as early indicators of severity and as effective predictors of prognosis in patients with hemorrhagic fever with renal syndrome (HFRS). METHODS: A total of 356 patients were enrolled in this study and were divided into mild, moderate, severe and critical types according to the clinical classification of HFRS. The levels of 12 routinely tested laboratory parameters during the acute stage among the four types were compared. The predictive values of the laboratory parameters for prognosis were analyzed, and a risk model for prognosis based upon the parameters was constructed. RESULTS: The levels of white blood counts (WBC), platelets (PLT), aspartate aminotransferase (AST), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (Scr), prothrombin time (PT) and activated partial thromboplastin time (APTT) demonstrated significant differences among the four types (p<0.001); WBC, AST, PT and fibrinogen (Fib) were major independent risk factors for death; WBC, AST, PT and Fib used in combination were better for predicting prognosis than single parameters used alone (p<0.001). CONCLUSIONS: Some routinely tested laboratory parameters can be beneficial as early indicators of severity of HFRS. Using a combination of WBC, AST, PT and Fib to predict the outcome in patients with HFRS exhibited acceptable diagnostic capability.

Clinical characteristics and outcomes in critical patients with hemorrhagic fever with renal syndrome.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) has become an important public health concern because of the high incidence and mortality rates, and limited treatment and vaccination. Until now, clinical studies on characteristics and outcomes in critical patients with HFRS have been limited. The aim of this study was to observe the clinical characteristics and cumulative proportions surviving and explore the predictive effects and risk factors for prognosis. METHODS: A detailed retrospective analysis of clinical records for critical HFRS patients was conducted. The patients enrolled were treated in the centre for infectious diseases, Tangdu Hospital, between January 2008 and August 2012. The clinical characteristics between the survivors and non-survivors were compared by Student's t-test or Chi-square test. The risk clinical factors for prognosis were explored by logistic regression analysis. The predictive effects of prognosis in clinical and laboratory parameters were analyzed by receiver operating characteristic (ROC) curves. The cumulative proportions surviving at certain intervals in the critical patients were observed by Kaplan-Meier survival analysis. RESULTS: Of the 75 patients enrolled, the cumulative proportion surviving was 70.7% at the second week interval, with a 28-day mortality rate of 36.3%. The non-survivors tended to have higher frequencies of agitation, dyspnea, conjunctival hemorrhage, coma, cardiac failure, acute respiratory distress syndrome (ARDS) and encephalopathy (P < .05). ARDS, conjunctival hemorrhage and coma were risk factors for death in the critical patients with HFRS. The non-survivors were found to have lower serum creatinine (Scr) levels (P < .001) and higher incidences of prolonged prothrombin time (PT) (P = .006), activated partial thromboplastin time (APTT) (P = .003) and elevated white blood cells (WBC) levels (P = .005), and the laboratory parameters mentioned above reached statistical significance for predicting prognosis (P < .05). CONCLUSION: The high fatality in critical patients with HFRS underscores the importance of clinicians' alertness to the occurrence of potentially fatal complications and changes in biochemical status to ensure that timely and systematically supportive treatment can be initiated when necessary.

Involvement of the Akt/NF-κB pathways in the HTNV-mediated increase of IL-6, CCL5, ICAM-1, and VCAM-1 in HUVECs.

BACKGROUND: Hantaan virus (HTNV) infection causes a severe form of HFRS(hemorrhagic fever with renal syndrome)in Asia. Although HTNV has been isolated for nearly forty years, the pathogenesis of HFRS is still unknown, and little is known regarding the signaling pathway that is activated by the virus. METHODOLOGY/PRINCIPAL FINDINGS: Cardamonin was selected as a NF-κB inhibitor, and indirect immunofluorescence assays were used to detect the effect of cardamonin on HTNV-infected HUVECs. The effect of cardamonin on the HTNV-induced phosphorylation of Akt and DNA-binding activity of NF-κB were determined using Western blot analysis and electrophoretic mobility shift assays (EMSAs), respectively. Then, flow cytometric and quantitative real-time PCR analyses were performed to quantify the expression levels of the adhesion molecules ICAM-1 and VCAM-1, and the concentrations of IL-6, IL-8, and CCL5 in HUVEC supernatants were examined using ELISA. The results showed that cardamonin did not effect the proliferation of HUVECs or the replication of HTNV in HUVECs. Instead, cardamonin inhibited the phosphorylation of Akt and nuclear transduction of NF-κB and further reduced the expression of the adhesion molecules ICAM-1 and VCAM-1 in HTNV-infected HUVECs. Cardamonin also inhibited the secretion of IL-6 and CCL5, but not IL-8. CONCLUSION/SIGNIFICANCE: HTNV replication may not be dependent upon the ability of the virus to activate NF-κB in HUVECs. The Akt/NF-κB pathways may be involved in the pathogenesis of HFRS; therefore, cardamonin may serve as a potential beneficial agent for HFRS therapy.

[The radiation-induced jaw osteosarcoma: CT imaging features].

OBJECTIVE: To evaluate the CT features of radiation-induced jaw osteosarcoma(RIJOS) developed after therapeutic irradiation for a variety of nonosseous lesions. METHODS: The demographic and CT findings of thirteen patients with RIJOS were reviewed retrospectively.Observation items included location, bone destruction, mineralized tumor matrix, periosteal reaction, soft tissue extension and calcification.Of the thirteen patients, twelve were male and one was female. The mean age was 48 years (range: 29-68 years).Five patients had tumors in the maxilla and eight in the mandible. All the patients underwent tumor resection. RESULTS: The latent period before development of RIJOS ranged from 3.5 to 14 years (mean, 11 years).In all thirteen patients, eight tumors were osteoblastic, with one osteolytic and four mixed lesions.Osteoid tumor matrix mineralization was present in twelve patients. Periosteal reaction was identified in 11 cases.Soft-tissue extension was present in all patients beyond the area of bone destruction. CONCLUSIONS: The characteristic CT imaging of RIJOS showed the bone destruction associated with a large number of mineralized tumor matrix and significant soft tissue extension in the original radiation field after radiotherapy. CT findings could play an important role in identifying the tumor and pre-operative assessment.