The differences in cytokine signatures between severe fever with thrombocytopenia syndrome (SFTS) and hemorrhagic fever with renal syndrome (HFRS).

Severe fever with thrombocytopenia syndrome (SFTS) virus and hantavirus are categorized under the Bunyavirales order. The severe disease progression in both SFTS and hemorrhagic fever with renal syndrome (HFRS) is associated with cytokine storms. This study aimed to explore the differences in cytokine profiles and immune responses between the two diseases. A cross-sectional, single-center study involved 100 participants, comprising 46 SFTS patients, 48 HFRS patients, and 6 healthy controls. The study employed the Luminex cytokine detection platform to measure 48 cytokines. The differences in cytokine profiles and immune characteristics between the two diseases were further analyzed using multiple linear regression, principal component analysis, and random forest method. Among the 48 cytokines tested, 30 showed elevated levels in SFTS and/or HFRS compared to the healthy control group. Furthermore, there were 19 cytokines that exhibited significant differences between SFTS and HFRS. Random forest analysis suggested that TRAIL and CTACK were predictive of SFTS, while IL2Ralpha, MIG, IL-8, IFNalpha2, HGF, SCF, MCP-3, and PDGFBB were more common with HFRS. It was further verified by the receiver operating characteristic with area under the curve >0.8 and P-values <0.05, except for TRAIL. Significant differences were observed in the cytokine profiles of SFTS and HFRS, with TRAIL, IL2Ralpha, MIG, and IL-8 being the top 4 cytokines that most clearly distinguished the two diseases. IMPORTANCE: SFTS and HFRS differ in terms of cytokine immune characteristics. TRAIL, IL-2Ralpha, MIG, and IL-8 were the top 4 that differed markedly between SFTS and HFRS.

Identification of CCL20 as a prognostic predictor for severe fever with thrombocytopenia syndrome based on plasma proteomics.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), a lethal tick-borne hemorrhagic fever, prompted our investigation into prognostic predictors and potential drug targets using plasma Olink Proteomics. METHODS: Employing the Olink assay, we analyzed 184 plasma proteins in 30 survivors and 8 non-survivors of SFTS. Validation was performed in a cohort of 154 SFTS patients using enzyme-linked immunosorbent assay. We utilized the Drug Gene Interaction database to identify protein-drug interactions. RESULTS: Non-survivors exhibited 110 differentially expressed proteins (DEPs) compared to survivors, with functional enrichment in the cell chemotaxis-related pathway. Thirteen DEPs, including C-C motif chemokine 20 (CCL20), calcitonin gene-related peptide alpha and Pleiotrophin, were associated with multiple organ dysfunction syndrome. CCL20 emerged as the top predictor of death, demonstrating an area under the curve of 1 (P = .0004) and 0.9033 (P < .0001) in the discovery and validation cohort, respectively. Patients with CCL20 levels exceeding 45.74 pg/mL exhibited a fatality rate of 45.65%, while no deaths occurred in those with lower CCL20 levels. Furthermore, we identified 202 FDA-approved drugs targeting 37 death-related plasma proteins. CONCLUSIONS: Distinct plasma proteomic profiles characterize SFTS patients with different outcomes, with CCL20 emerging as a novel, sensitive, accurate, and specific biomarker for predicting SFTS prognosis.

High levels of C-reactive protein-to-albumin ratio (CAR) are associated with a poor prognosis in patients with severe fever with thrombocytopenia syndrome in early stage.

C-reactive protein-to-albumin ratio (CAR) can be used to assess the prognosis of various diseases. This study aimed to evaluate the relationship between CAR on the prognosis of patients with severe fever with thrombocytopenia syndrome (SFTS). This study included 155 SFTS patients from the Public Health Clinical Center of Dalian from January to December 2021. They were divided into survival and deceased groups based on the clinical prognosis. The independent risk factors for poor prognosis of SFTS patients at an early stage were determined by Cox regression. The efficacy of CAR prediction was assessed by the receiver operating characteristic (ROC) curve. A total of 155 patients were included in this study, with an average age of 61.98± 11.70 years, including 77 males and 65 females. The mortality rate of the patients enrolled in this study was 14.19%. Multivariate Cox regression indicated that CAR (hazard ratio = 2.585, 95% confidence interval [CI] 1.405-4.753, p = 0.002) could be an independent predictor for prognosis in SFTS patients at an early stage. CAR had an AUC of 0.781 (95% CI, 0.665-0.898, p = 0.000), a cutoff value of 0.57, a sensitivity of 0.77, and a specificity of 0.80, with better predictive efficacy, compared to neutrophil-to-lymphocyte ratio (NLR). High levels of CAR are associated with poor prognosis in SFTS patients, and CAR can be used as an independent predictor for SFTS patients.

Mesenchymal Stem Cells with Enhanced Bcl-2 Expression Promote Liver Recovery in a Rat Model of Hepatic Cirrhosis.

BACKGROUND/AIMS: Mesenchymal stem cell (MSC) transplantation has emerged as an option for the treatment of chronic hepatic cirrhosis, while its therapeutic efficacy could be improved. The bcl-2 gene is anti-apoptotic and can help cell survival and proliferation. Therefore, we explored whether transplanted MSCs with enhanced bcl-2 expression may be beneficial in the treatment of experimental cirrhosis in rats. METHODS: MSCs were isolated from rat bone marrow, expanded in vitro and transfected with adeno-associated virus (AAV) engineered the bcl-2 gene (AAV-bcl-2). Rats with cirrhosis induced by carbon tetrachloride (CCl4) were treated with AAV-bcl-2 infected BMSCs-AAV-bcl-2, with the cells traced in vivo post transplantation. Liver pathology and function were evaluated 7, 14, 21, and 28 days post transplantation, respectively. RESULTS: On day 7 post transplantation, the infused AAV-bcl-2 had integrated into the hepatocyte-like cells (HLCs) that expressed albumin (ALB), Cytokeratin 18 (CK18), and hepatocytes nuclear factor 4a (HNF4a). On day 28 post transplantation, rats in the cirrhosis + BMSCs-AAV-bcl-2 group showed the most dense HLCs, highest mRNA and protein levels of ALB, CK18, and HNF4a, compared to the other groups. Their liver function recovered most rapidly in 4 week observation, while histological sign of cirrhosis remained at the end of this period. CONCLUSION: BMSCs over expressing bcl-2 gene showed better survival, and enhanced the differentiation into hepatocytes-like cells, and appeared to promote the recovery of liver function in rats with experimental cirrhosis.

Development and validation of the PLNA score to predict cytokine storm in acute-phase SFTS patients: A single-center cohort study.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease known for its high mortality rate and its correlation with Cytokine Storms (CS). Timely detection of CS is crucial for improving the prognosis of the disease. The objective of this investigation was to develop a model for identifying cytokine storms in the acute phase of SFTS. METHODS: A total of 245 patients diagnosed with SFTS were included in this study between January 2020 and July 2022. Among them, 184 patients were part of the training set, while 61 patients were part of the validation set. Variables identified by LASSO were subsequently included in a multivariate logistic regression analysis to determine independent predictors. Subsequently, a nomogram was then developed to predict the likelihood of CS in SFTS patients. The predictive efficacy and clinical applicability of the nomogram model were further assessed through ROC analysis and the DCA curve. RESULTS: Following LASSO analysis, a total of 11 indicators were included in multivariate logistic regression analysis. The findings indicated that PLT (OR 0.865, P < 0.001), LDH (OR 1.002, P < 0.001), Na+ (OR 1.155, P = 0.005), and ALT (OR 1.019, P < 0.001) serve as independently predictors of CS in the acute phase of SFTS. Furthermore, a nomogram named the PLNA was constructed by integrating these four factors. The PLNA model exhibited favorable predictive accuracy with an AUC of 0.958. Moreover, the PLNA model exhibited excellent clinical applicability in both the training and validation sets, as evidenced by the DCA curve. CONCLUSIONS: The PLNA model, constructed using clinical indicators, can predict the probability of cytokine storm in the acute phase of SFTS patients.

MCP-3 as a prognostic biomarker for severe fever with thrombocytopenia syndrome: a longitudinal cytokine profile study.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is characterized by a high mortality rate and is associated with immune dysregulation. Cytokine storms may play an important role in adverse disease regression, this study aimed to assess the validity of MCP-3 in predicting adverse outcomes in SFTS patients and to investigate the longitudinal cytokine profile in SFTS patients. Methods: The prospective study was conducted at Yantai Qishan Hospital from May to November 2022. We collected clinical data and serial blood samples during hospitalization, patients with SFTS were divided into survival and non-survival groups based on the clinical prognosis. Results: The levels of serum 48 cytokines were measured using Luminex assays. Compared to healthy controls, SFTS patients exhibited higher levels of most cytokines. The non-survival group had significantly higher levels of 32 cytokines compared to the survival group. Among these cytokines, MCP-3 was ranked as the most significant variable by the random forest (RF) model in predicting the poor prognosis of SFTS patients. Additionally, we validated the predictive effects of MCP-3 through receiver operating characteristic (ROC) curve analysis with an AUC of 0.882 (95% CI, 0.787-0.978, P <0.001), and the clinical applicability of MCP-3 was assessed favorably based on decision curve analysis (DCA). The Spearman correlation analysis indicated that the level of MCP-3 was positively correlated with ALT, AST, LDH, α-HBDH, APTT, D-dimer, and viral load (P<0.01). Discussion: For the first time, our study identified and validated that MCP-3 could serve as a meaningful biomarker for predicting the fatal outcome of SFTS patients. The longitudinal cytokine profile analyzed that abnormally increased cytokines were associated with the poor prognosis of SFTS patients. Our study provides new insights into exploring the pathogenesis of cytokines with organ damage and leading to adverse effects.

Synthesis and Evaluation of Highly Inhibitory Oil Well Cement Retarders with Branched-Chain Structures.

Cementing at medium temperature and high temperature (90-150 °C) is facing challenges on account of the properties of the retarders. Except for the thermal stability, abnormal gelation, such as "bulging" and "stepping", often takes place and results in safety problems. In this article, the synthesis of a new retarder DRH-150 was introduced. First, a main chain with thermal-resistant groups, 2-acrylamido-2-methylpropanesulfonic acid-acrylic acid (AMPS-IA-AA) was prepared by free radical polymerization. Second, the retarder with a branched structure was synthesized by the grafting reaction. Evaluation of the construction performance showed that, within the temperature range from 90 to 150 °C, the initial viscosity of the cement slurry with DRH-150 was less than 15 Bc, exhibiting an adjustable thickening time and a dosage sensitivity of less than 20%. Meanwhile, no abnormal gelation phenomenon was observed. Referring to the static gelation, both the transition time and the starting strength time (1 MPa) were short. The overall results proved that the retarder DRH-150 might ensure the safety of well cementing and improve the wellbore sealing effect in deep wells, ultradeep wells, and complex wells.

A model based on meta-analysis to evaluate poor prognosis of patients with severe fever with thrombocytopenia syndrome.

Background: Early identification of risk factors associated with poor prognosis in Severe fever with thrombocytopenia syndrome (SFTS) patients is crucial to improving patient survival. Method: Retrieve literature related to fatal risk factors in SFTS patients in the database, extract the risk factors and corresponding RRs and 95% CIs, and merge them. Statistically significant factors were included in the model, and stratified and assigned a corresponding score. Finally, a validation cohort from Yantai Qishan Hospital in 2021 was used to verify its predictive ability. Result: A total of 24 articles were included in the meta-analysis. The model includes six risk factors: age, hemorrhagic manifestations, encephalopathy, Scr and BUN. The analysis of lasso regression and multivariate logistic regression shows that model score is an independent risk factor (OR = 1.032, 95% CI 1.002-1.063, p = 0.034). The model had an area under the curve (AUC) of 0.779 (95% CI 0.669-0.889, P<0.001). The validation cohort was divided into four risk groups with cut-off values. Compared with the low-medium risk group, the mortality rate of high-risk and very high-risk patients was more significant (RR =5.677, 95% CI 4.961-6.496, P<0.001). Conclusion: The prediction model for the fatal outcome of SFTS patients has shown positive outcomes.Systematic review registration:https://www.crd.york.ac.uk/prospero/ (CRD42023453157).

Eosinophils and basophils in severe fever with thrombocytopenia syndrome patients: Risk factors for predicting the prognosis on admission.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne phlebovirus with a high fatality rate. Previous studies have demonstrated the poor prognostic role of eosinophils (EOS) and basophils (BAS) in predicting multiple viral infections. This study aimed to explore the role of EOS and BAS in predicting prognosis of patients with SFTS. METHODOLOGY: A total of 194 patients with SFTS who were admitted to Yantai City Hospital from November 2019 to November 2021 were included. Patients' demographic and clinical data were collected. According to the clinical prognosis, they were divided into survival and non-survival groups. Independent risk factors were determined by univariate and multivariate logistic regression analyses. FINDINGS: There were 171 (88.14%) patients in the survived group and 23 (11.86%) patients in the non-survived group. Patients' mean age was 62.39 ± 11.85 years old, and the proportion of males was 52.1%. Older age, neurological manifestations, hemorrhage, chemosis, and increased levels of laboratory variables, such as EOS% and BAS% on admission, were found in the non-survival group compared with the survival group. EOS%, BAS%, aspartate aminotransferase (AST), direct bilirubin (DBIL), and older age on admission were noted as independent risk factors for poor prognosis of SFTS patients. The combination of the EOS% and BAS% had an area under the curve (AUC) of (0.82; 95% CI: 0.725, 0.932, P = 0.000), which showed an excellent performance in predicting prognosis of patients with SFTS compared with neutrophil-to-lymphocyte ratio (NLR), and both exhibited a satisfactory performance in predicting poor prognosis compared with De-Ritis ratio (AST/alanine aminotransferase (ALT) ratio). EOS% and BAS% were positively correlated with various biomarkers of tissue damage and the incidence of neurological complications in SFTS patients. CONCLUSION: EOS% and BAS% are effective predictors of poor prognosis of patients with early-stage SFTS. The combination of EOS% and BAS% was found as the most effective approach.

Determination of the optimal volume of ascitic fluid for the precise diagnosis of malignant ascites.

BACKGROUND/AIMS: The aim of this study was to determine the optimal volume of peritoneal effusion required to diagnose malignant ascites. PATIENTS AND METHODS: The authors recruited 123 patients with shifting dullness and obtained 123 peritoneocentesis fluid samples. The samples were divided into seven aliquots of 10, 50, 100, 150, 200, 250, and 300 mL for cytopathological examination. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were calculated for each aliquot. RESULTS: The sensitivity for the diagnosis of malignant ascites gradually increased as the sample volume increased and reached a constant value at a volume of 200 mL. The sensitivity and NPV for the 10-, 100-, and 150-mL volumes were significantly different from those for the 200-mL sample. However, the sensitivity and NPV for the 250- and 300-mL volumes were not significantly different. The sensitivity for the diagnosis of malignant ascites is closely related to the volume of peritoneal fluid that is extracted by peritoneocentesis. CONCLUSION: We suggest a volume of 200 mL as the optimal minimum volume to confirm malignant ascites in patients with shifting dullness.

Therapeutic effect of dental pulp stem cell transplantation on a rat model of radioactivity-induced esophageal injury.

Dental pulp stem cell (DPSC) transplantation has been demonstrated to promote the regeneration and repair of tissues and organs and is a potentially effective treatment for radioactive esophageal injury. In this study, to explore the therapeutic effects of DPSCs on acute radiation-induced esophageal injury, DPSCs were cultured and transplanted into rats with acute radioactive esophageal injuries induced by radioactive 125I seeds in vivo. In the injured esophagus, PKH26-labeled DPSCs co-localized with PCNA, CK14, CD71, and integrin α6, and the expression levels of these four makers of esophageal stem cells were significantly increased. After DPSC transplantation, the injured esophagus exhibited a greater thickness. In addition, the esophageal function and inflammation recovered faster. The results demonstrated that transplanted DPSCs, which trans-differentiated into esophageal stem cells in vivo, could repair the damaged esophageal tissue.

Stem cell transplantation for the treatment of liver diseases: A systematic review and meta-analysis.

BACKGROUND/AIMS: The therapeutic efficacy of stem cell transplantation in liver diseases has not yet been determined. The objective of this study was to conduct a meta-analysis to evaluate changes in liver function and clinical outcome following stem cell transplantation in patients with liver disease. MATERIALS AND METHODS: A literature review of NCBI, Cochrane Library, and MEDLINE was performed. Eligible studies reported liver function indices and prothrombin time (PT) before and after transplantation. The weighted mean difference (WMD) was defined by the distinction before and after stem cell transplantation. Either a fixed-effects model or random-effects model was used to analyze the data. RESULTS: A total of 17 publications involving 21 original studies were included. We found that the levels of serum albumin significantly increased at 4, 8, 12, 24, and 48 weeks after stem cell transplantation compared with that at baseline. Serum alanine aminotransferase levels notably decreased at 1, 3, 4, 12, 24, and 48 weeks after stem cell transplantation. Aspartate aminotransferase levels significantly decreased at 4, 8, 12, and 48 weeks after transplantation. Total bilirubin levels significantly decreased at 4, 12, 24, and 48 weeks after transplantation. PT decreased at 4, 12, 24, and 48 weeks after transplantation. The MELD score significantly decreased at 24 weeks after transplantation. Stem cell infusion through the hepatic artery had better biochemical outcomes than an injection through the portal vein. CONCLUSION: Our meta-analysis verified that there are clinical and biochemical improvements in patients who suffered from liver diseases after stem cell transplantation, suggesting that stem cell transplantation may be a viable clinical solution for treating such patients.