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Echinococcosis, one of the most serious and life-threatening parasitic forms of zoonosis worldwide, is caused by the larvae of Echinococcus granulosus (E. granulosus) and Echinococcus multilocularis (E. multilocularis). Various drugs are being applied clinically to treat zoonosis; however, their therapeutic efficacy remains a great challenge, especially with albendazole as the preferred drug of choice. Receptor tyrosine kinase (RTK) signaling controls normal cellular proliferation, differentiation, and metabolism in humans and mammals, which are intermediate hosts of E. granulosus and E. multilocularis. Disruption of RTK signaling can cause various forms of carcinogenesis and exacerbate the progression of certain forms of parasitic disease. As a result, a significant number of studies on tyrosine kinase inhibitors (TKIs) have been conducted for the treatment of cancer and parasitic infection, with some TKIs already approved for clinical use for cancer. Notably, RTK signaling has been identified in the parasites E. granulosus and E. multilocularis; however, the mechanisms of RTK signaling response in Echinococcus-host intercommunication are not fully understood. Thus, understanding the RTK signaling response in Echinococcus-host intercommunication and the potential effect of RTK signaling is crucial for identifying new drug targets for echinococcosis. The present review illustrates that RTK signaling in the host is over-activated following infection by E. granulosus or E. multilocularis and can further facilitate the development of metacestodes in vitro. In addition, some TKIs exert strong parasitostatic effects on E. granulosus or E. multilocularis, both in vitro and/or in vivo, through downregulation of RTK signaling molecules. The summarized findings suggest that RTK signaling may be a promising drug target and that TKIs could be potential anti-Echinococcus drugs warranting further research.
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BACKGROUND: This study aimed to explore the diagnostic value of serum adenosine deaminase (ADA) in patients with myelodysplastic syndromes (MDS) and identify potential risk factors for MDS. METHODS: Eighty patients with MDS and 80 healthy individuals were included. The serum ADA level was found to be significantly higher in patients with MDS compared with that of healthy controls (p = 0.014). RESULTS: The receiver operator characteristic curve (ROC) for ADA had an area under curve (AUC) of 0.807 (p = 0.0018). Serum ADA level of 4.5 U/L had a sensitivity of 71.43% and specificity of 80% for MDS diagnosis. The multivariate analysis showed hemoglobin (Hb, OR = 1.322, 95% CI: 1.035 - 2.323, p = 0.039), prothrombin time (PT, OR = 1.524, 95% CI: 1.156 - 3.280, p = 0.042), fibrinogen (OR = 1.335, 95% CI: 1.022 - 2.775, p = 0.027), calculated international normalized ration (INR, OR = 2.212, 95% CI: 1.320 - 3.085, p = 0.038), D-dimer (OR = 2.043, 95% CI: 1.623 - 4.293, p = 0.038), fibrin degradation product (FDP, OR = 2.525, 95% CI: 1.129 - 3.340, p = 0.029), and serum ADA (OR = 2.057, 95% CI: 1.248 - 3.572, p = 0.033) were independently associated with MDS. CONCLUSIONS: Serum ADA might be a potential biomarker in the diagnosis of MDS. Serum ADA level, Hb level, PT, fibrinogen level, INR, D-dimer, and FDPs were independent risk factors of MDS.
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Adenosina Desaminasa , Síndromes Mielodisplásicos , Humanos , Curva ROC , Biomarcadores , Síndromes Mielodisplásicos/diagnóstico , Fibrinógeno , Estudios RetrospectivosRESUMEN
OBJECTIVE: To determine the relationship between coagulation system markers and hyperbilirubinaemia in full-term neonates. METHODS: This retrospective case-control study enrolled full-term neonates with hyperbilirubinaemia and healthy control full-term neonates. Prothrombin time (PT), thrombin time (TT), fibrinogen (Fbg), activated partial thromboplastin time (APTT) and international normalized ratio (INR) were recorded. The correlation between INR and total bilirubin and between INR and indirect bilirubin was analysed by linear regression analysis. Receiver operating characteristic curve analysis was used to assess the efficacy of INR to identify neonates with hyperbilirubinaemia. RESULTS: This study enrolled 40 full-term neonates with hyperbilirubinaemia and 30 healthy controls. PT, INR and APTT were significantly higher in the neonates with hyperbilirubinaemia compared with the healthy controls. There was a significant positive correlation between INR and the level of total bilirubin in neonates with hyperbilirubinaemia (R = 0.3327). There was also a significant positive correlation between INR and the level of indirect bilirubin in neonates with hyperbilirubinaemia (R = 0.3406). INR in neonates with hyperbilirubinaemia significantly achieved an area under the curve of 0.800 (95% confidence interval, 0.6288, 0.9712; cut-off value, 1.060; specificity, 71.43%; sensitivity, 80.00%). CONCLUSION: These findings suggest that INR is a novel biomarker for the diagnosis of neonatal hyperbilirubinaemia in full-term neonates.
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Bilirrubina , Hiperbilirrubinemia , Recién Nacido , Humanos , Estudios de Casos y Controles , Estudios Retrospectivos , Pruebas de Coagulación SanguíneaRESUMEN
BACKGROUND: Our aim was to evaluate the cutoff values of RHE and MRV as markers to diagnose IDA in healthy Han ethnic adults of Chengdu. METHODS: A total of 263 Han adults who needed bone marrow aspiration for diagnosis were enrolled according to the inclusive and exclusive criteria. The cutoff values of RHE and MRV were determined by receiver operating curves. RESULTS: According to statistical analysis, the cutoff values of RHE and MRV in male and female groups were 26.75 pg, 89.60 fL and 26.65 pg, 88.55 fL respectively. The areas under the curve (AUC) of RHE and MRV were 0.941, 0.939 and 0.925, 0.909 in male and female groups, respectively. CONCLUSIONS: In our study, we explored the cutoff values of RHE and MRV to diagnose IDA in the Han ethnic population in Chengdu for the first time.
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Anemia Ferropénica , Adulto , Femenino , Humanos , Masculino , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/epidemiología , Área Bajo la Curva , Pueblos del Este de Asia , Índices de EritrocitosRESUMEN
This study explored the correlation between interleukins (IL)-12, IL-18, and IL-21 and the viral load in patients with chronic hepatitis B virus (HBV). A total of 142 patients were consecutively enrolled. All were hepatitis B surface antigen (HBsAg)-positive for >6 months and did not receive drug therapy. An ELISA kit was used to test the IL-12, IL-18, IL-21, and acetylcholinesterase (AchE) levels in serum samples from chronic HBV patients and healthy control groups. The amounts of IL-12 and IL-18 were highest in the 5-6log10 (high viral load) group, while IL-21 was highest in the 3-4log10 (low viral load) group. Also, the IL-21 amount was decreased in the HBsAg+/HBeAg/HBcAb+ group, and IL-12, IL-18, and IL-21 were decreased in the normal alanine aminotransferase (ALT) group compared to the abnormal ALT group. These data suggested that IL-12, IL-18, and IL-21 serum levels were positively correlated with disease progression and could reflect disease severity for different HBV-DNA loads. Detection of IL-12, IL-18, and IL-21 levels was found to be helpful for evaluating the degree of liver cell damage and predicting the progression of hepatitis.
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Hepatitis B Crónica , Interleucinas , Carga Viral , Humanos , Acetilcolinesterasa , Alanina Transaminasa , ADN Viral , Antígenos de Superficie de la Hepatitis B/uso terapéutico , Virus de la Hepatitis B/genética , Hepatitis B Crónica/diagnóstico , Interleucina-12/sangre , Interleucina-18/sangre , Interleucinas/sangreRESUMEN
This study explored the correlation between interleukins (IL)-12, IL-18, and IL-21 and the viral load in patients with chronic hepatitis B virus (HBV). A total of 142 patients were consecutively enrolled. All were hepatitis B surface antigen (HBsAg)-positive for >6 months and did not receive drug therapy. An ELISA kit was used to test the IL-12, IL-18, IL-21, and acetylcholinesterase (AchE) levels in serum samples from chronic HBV patients and healthy control groups. The amounts of IL-12 and IL-18 were highest in the 5-6log10 (high viral load) group, while IL-21 was highest in the 3-4log10 (low viral load) group. Also, the IL-21 amount was decreased in the HBsAg+/HBeAg/HBcAb+ group, and IL-12, IL-18, and IL-21 were decreased in the normal alanine aminotransferase (ALT) group compared to the abnormal ALT group. These data suggested that IL-12, IL-18, and IL-21 serum levels were positively correlated with disease progression and could reflect disease severity for different HBV-DNA loads. Detection of IL-12, IL-18, and IL-21 levels was found to be helpful for evaluating the degree of liver cell damage and predicting the progression of hepatitis.
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Hand, foot and mouth disease (HFMD) is an infectious disease caused by a variety of enterovirus infections, and the most common types of virus infections are the newenterovirus71 (EV71) and coxsackievirus A group 16 (CoxA16). A small fraction of HFMD will cause further severe HFMD. A rapid and accurate diagnosis biomarker of severe HFMD is important for the timely treatment. In the study, we conducted a clinical biomarker discovery study using iTRAQ combined with MS. Serum proteome alterations in severe HFMD group (nâ¯=â¯32) and health control group (nâ¯=â¯32) were analyzed. 47 proteins were upregulated (fold changeâ¯>â¯1.5) between the severe HFMD group and HC group. The identified proteins were classified into different groups according to the molecular function, biology processes, cellular component. During the up-regulated proteins, serum amyloid A (SAA) and human ß-actin (ACTB), were confirmed in the serum of the severe HFMD and HC by ELISA assay. SAA and ACTB levels were significantly higher in the sever HFMD patients (Pâ¯<â¯.01), consistent with iTRAQ-LC-MS/MS analysis. In summary, Our results showed that SAA and human ß-actin (ACTB) may be served as a potential biomarker of the clinical diagnosis of severe HFMD.
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Actinas/sangre , Enterovirus Humano A , Enfermedad de Boca, Mano y Pie/sangre , Proteína Amiloide A Sérica/metabolismo , Índice de Severidad de la Enfermedad , Biomarcadores/sangre , Preescolar , Femenino , Enfermedad de Boca, Mano y Pie/patología , Enfermedad de Boca, Mano y Pie/virología , Humanos , Masculino , ProteómicaRESUMEN
The correlation of genetic polymorphisms of GALNT3 and vitamin D receptor (VDR) with osteoporosis in postmenopausal women was investigated. A total of 1,212 cases of postmenopausal patients diagnosed with osteoporosis (observation group) and 404 cases of postmenopausal women without osteoporosis (control group) were selected. Dual-energy X-ray absorptiometry was used for measurement of bone mineral density (BMD) of lumbar vertebrae L2-4, proximal femoral neck and total hip, and classifications were made. TaqMan genotyping technology was employed to examine tag single-nucleotide polymorphism (tagSNP) of GALNT3 and VDR and the correlation of tagSNP with bone turnover markers (BTMs) and serum calcium and phosphorous levels was analyzed. The multiple logistic regression analysis was used to screen risk factors for osteoporosis. A comparison of age and menopause time of the two groups, yielded no statistical significance difference (P>0.05). BMD and T values of the lumbar vertebrae, femoral neck and total hip in the observation group were significantly lower than those in the control group, and the differences were statistically significant (P<0.05). A comparison of the degree of osteoporosis, yielded statistically significant differences (P<0.05). The proportion of tagSNP of 5 loci in GALNT3 and 3 loci in VDR in the observation group was significantly higher than that in the control group, and the differences were of statistical significance (P<0.05). Levels of 25-OHD3, ß-CTX, P1NP and serum calcium in the observation group were lower than those in the control group and the level of serum phosphorus in the observation group was higher than that in the control group, and all of these results were statistically significant (P<0.05). The result of the correlation analysis revealed that rs1425000 and rs757343 were negatively correlated with BTM and serum calcium and phosphorus levels (P<0.05). The result of the regression analysis revealed that 8 tagSNPs were independent risk factors for osteoporosis. Genetic polymorphisms of GALNT3 and VDR were closely associated with osteoporosis in postmenopausal women.
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Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process has been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.