ABSTRACT
BACKGROUND: This study aims to investigate the clinical characteristics associated with concurrent Klebsiella pneu-moniae (K. pneumoniae) infection in hospitalized patients with severe pulmonary tuberculosis. METHODS: A retrospective study was conducted on hospitalized severe pulmonary tuberculosis patients between January 2019 and December 2020. Among the 487 patients with severe pulmonary tuberculosis, a positive sputum culture for K. pneumoniae was reported in 76 patients (15.6%, 61 males and 15 females). RESULTS: Among these patients, 27 (35.5%) and 49 (64.5%) patients were with and without K. pneumoniae infection, respectively. Compared to patients without K. pneumoniae infection, patients with K. pneumoniae infection had higher mortality (16.3% vs. 40.7%, p = 0.02), and lower inhibitory/cytotoxic CD8 count (24.2 ± 9.9 vs. 17.8 ± 8.0, p = 0.02), complement C4 (0.3 ± 0.1 vs. 0.2 ± 0.1, p = 0.01), and retinol-binding protein level (32.2 ± 22.2 vs. 22.4 ± 11.8, p = 0.02). Furthermore, the acute Physiology and Chronic Health Evaluation II score was associated with the K. pneumoniae infection in severe pulmonary tuberculosis patients. CONCLUSIONS: It can be concluded that a significant number of severe pulmonary tuberculosis patients can have concurrent K. pneumoniae infection. Immunity, nutritional status, and disease severity are associated with the concurrent infection of K. pneumoniae in these patients.
Subject(s)
Klebsiella Infections , Tuberculosis, Pulmonary , Male , Female , Humans , Klebsiella pneumoniae , Retrospective Studies , Klebsiella Infections/complications , Klebsiella Infections/diagnosis , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/diagnosis , Anti-Bacterial AgentsABSTRACT
Schistosomiasis, a parasite infectious disease caused by Schistosoma japonicum, often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released in the host liver. This study focuses on the role of the egg antigens CP1412 protein of S. japonicum (SjCP1412) with RNase activity in promoting liver fibrosis. In this study, the recombinant egg ribonuclease SjCP1412, which had RNase activity, was successfully prepared. By analysing the serum of the population, it has been proven that the anti-SjCP1412 IgG in the serum of patients with advanced schistosomiasis was moderately correlated with liver fibrosis, and SjCP1412 may be an important antigen associated with liver fibrosis in schistosomiasis. In vitro, the rSjCP1412 protein induced the human liver cancer cell line Hep G2 and liver sinusoidal endothelial cells apoptosis and necrosis and the release of proinflammatory damage-associated molecular patterns (DAMPs). In mice infected with schistosomes, rSjCP1412 immunization or antibody neutralization of SjCP1412 activity significantly reduced cell apoptosis and necroptosis in liver tissue, thereby reducing inflammation and liver fibrosis. In summary, the SjCP1412 protein plays a crucial role in promoting liver fibrosis during schistosomiasis through mediating the liver cells apoptosis and necroptosis to release DAMPs inducing an inflammatory reaction. Blocking SjCP1412 activity could inhibit its proapoptotic and necrotic effects and alleviate hepatic fibrosis. These findings suggest that SjCP1412 may be served as a promising drug target for managing liver fibrosis in schistosomiasis japonica.
Subject(s)
Schistosoma japonicum , Schistosomiasis japonica , Humans , Mice , Animals , Schistosomiasis japonica/complications , Schistosomiasis japonica/parasitology , Ribonucleases/metabolism , Ribonucleases/pharmacology , Endothelial Cells , Liver Cirrhosis/parasitology , Liver Cirrhosis/pathology , Liver/pathology , Inflammation/pathologyABSTRACT
The initiation, development and resolution of hepatic fibrosis are influenced by various cytokines, chemokines, damage-associated molecular patterns (DAMPs) and signaling pathways. A significant number of studies in recent years have indicated that the progression of hepatic fibrosis is closely linked to programmed cell death processes such as apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, cuproptosis, and PANoptosis. Inducement of hepatic stellate cells (HSCs) death or preventing death in other liver cells can delay or even reverse hepatic fibrosis. Nevertheless, the roles of programmed cell death in hepatic fibrosis have not been reviewed. Therefore, this review summarizes the characteristics of various of hepatic fibrosis and programmed cell death, focuses on the latest progress of programmed cell death in the promotion and regression of hepatic fibrosis, and highlights the different roles of the programmed cell death of HSCs and other liver cells in hepatic fibrosis. In the end, the possible therapeutic approaches targeting programmed cell death for treating hepatic fibrosis are discussed and prospected.
ABSTRACT
A novel 3D Eu(iii) metal-organic framework (Eu-MOF-1) formulated as [Eu(L)(H2O)(DMA)] (L = 2-(2-nitro-4-carboxylphenyl)terephthalic acid) has been successfully synthesized under solvothermal conditions and characterized by structural analyses. Eu-MOF-1 displays a new 3D framework containing EuIII ions, ligand L, and coordinated DMA molecules and water molecules. The fluorescence investigations indicate that Eu-MOF-1 emits bright red luminescence, and shows relatively high water stability and outstanding chemical stability under a relatively wide range of pH conditions. It is noteworthy that Eu-MOF-1 can quantitatively detect p-aminophenol (PAP) which is a metabolite of phenylamine in human urine. More significantly, Eu-MOF-1 is the first reported multi-responsive luminescent sensor for detecting the biomarker PAP, and MnVII and CrVI anions with high selectivity, sensitivity, recyclability and relatively low detection limits in aqueous solutions. Furthermore, the possible sensing mechanisms of Eu-MOF-1 for selective sensing have also been explored in detail. Eu-MOF-1 could be an ideal candidate as a multi-responsive luminescent sensor in biological and environmental areas.
Subject(s)
Aminophenols/urine , Chromium/analysis , Europium/chemistry , Fluorescent Dyes/chemistry , Manganese/analysis , Metal-Organic Frameworks/chemistry , Water Pollutants, Chemical/analysis , Anions/analysis , Crystallography, X-Ray , Fluorescent Dyes/chemical synthesis , Humans , Metal-Organic Frameworks/chemical synthesis , Models, Molecular , Solubility , Solutions , Water/chemistryABSTRACT
BACKGROUND: To delineate the clinical characteristics associated with long-term viral shedding (>21 days) in patients with coronavirus disease 2019 (COVID-19). METHODS: In this retrospective study, factors associated with long-term (>21 days) severe acute respiratory coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a conhort of 609 patients from two hospitals in Wuhan. RESULTS: The median duration of SARS-CoV-2 viral shedding was 19 days (interquartile range, 10-28 days) among all patients. There were 42% of patients having prolonged viral shedding time (>21 days), in which the longest viral shedding time was 58 days. When comparing patients with early (≤21 days) and late viral RNA clearance (>21 days), prolonged viral shedding was associated with age <65 (P=0.015), female sex (P=0.028), cough (P=0.025), fatigue (P=0.035), sore throat (P=0.013), aspartate aminotransferase (P=0.038), procalcitonin (P=0.010), albumin (P=0.003), D-dimer (P=0.011), lung involvement (P=0.014), reticular shadow (P<0.001) and lung consolidation (P=0.004). Age range (<65 years) (odds ratio [OR], 1.46 [95% CI, 1.05-2.03]) and female sex (odds ratio [OR], 1.40 [95% CI, 1.00-1.94]) were independent risk factors. CONCLUSIONS: Long-term viral shedding (>21 days) is not a rare phenomenon among COVID-19 infectious patients. Age range (<65) and female sex are independent risk factors for long-term viral shedding. Early antiviral treatment should be considered for COVID-19 patients with such risk factors. Further study should be conducted to know the infectivity of patients with long-term viral shedding in order to develop reasonable control measures.
ABSTRACT
Liver fibrosis can result from various causes and could progress to cirrhosis and cancer; however, there are no effective treatments due to that its molecular mechanism is unclear. liver fibrosis model made by Schistosoma japonicum (S. japonicum) infection or Carbon tetrachloride (CCl4) intraperitoneal injection is a conventional model used in liver fibrosis-related studies for mechanism or pharmaceutical research purposes. But the differences in the pathological progression, immune responses and the underlying mechanism between the two liver fibrosis model have not been carefully compared and characterized, which hinders us from correctly understanding and making better use of the two models. In the present study, the pathological changes to the liver, and the cytokines, inflammatory factors, macrophages, and lymphocytes subsets involved were analyzed in the liver fibrosis model of S. japonicum infection or CCl4 intraperitoneal injection. Additionally, the pathological progression, immune responses and the underlying injury mechanism in these two models were compared and characterized. The results showed that the changing trend of interleukin-13 (IL-13), transforming growth factor beta (TGF-ß), inflammatory factors, and M1, M2 macrophages, were consistent with the development trend of fibrosis regardless of whether liver fibrosis was caused by S. japonicum or CCl4. For lymphocyte subsets, the proportions of CD3+ T cells and CD4+ T cells decreased gradually, while proportion of CD8+ T cells peaked at 6 weeks in mice infected with S. japonicum and at 12 weeks in mice injected with CCl4. With prolonged S. japonicum infection time, Th1 (CD4+IFN-γ+) immunity converted to Th2 (CD4+IL-4+)/Th17 (CD4+IL-17+) with weaker regulatory T cell (Treg) (CD4+CD25+FOXP3+) immunity. However, in liver fibrosis caused by CCl4, Th1 cells occupied the dominant position, while proportions of Th2, Th17, and Treg cells decreased gradually. In conclusion, liver fibrosis was a complex pathological process that was regulated by a series of cytokines and immune cells. The pathological progressions and immune responses to S. japonicum or CCl4 induced liver fibrosis were different, possibly because of their different injury mechanisms. The appropriate animal model should be selected according to the needs of different experiments and the pathogenic factors of liver fibrosis in the study.
Subject(s)
Hepatitis/immunology , Liver/immunology , Schistosoma japonicum/physiology , Schistosomiasis japonica/immunology , T-Lymphocyte Subsets/immunology , Th1 Cells/immunology , Animals , Carbon Tetrachloride/metabolism , Cells, Cultured , Cytokines/metabolism , Disease Models, Animal , Disease Progression , Female , Fibrosis , Humans , Liver/parasitology , Liver/pathology , Mice , Mice, Inbred C57BLABSTRACT
Candida albicans is a common fungal pathogen in humans that colonizes the skin and mucosal surfaces of the majority healthy individuals. How C. albicans disseminates into the bloodstream and causes life-threatening systemic infections in immunocompromised patients remains unclear. Plasminogen system activation can degrade a variety of structural proteins in vivo and is involved in several homeostatic processes. Here, for the first time, we characterized that C. albicans could capture and "subvert" host plasminogen to invade host epithelial cell surface barriers through cell-wall localized Eno1 protein. We found that the "subverted" plasminogen system plays an important role in development of invasive infection caused by C. albicans in mice. Base on this finding, we discovered a mouse monoclonal antibody (mAb) 12D9 targeting C. albicans Eno1, with high affinity to the 254FYKDGKYDL262 motif in α-helices 6, ß-sheet 6 (H6S6) loop and direct blocking activity for C. albicans capture host plasminogen. mAb 12D9 could prevent C. albicans from invading human epithelial and endothelial cells, and displayed antifungal activity and synergistic effect with anidulafungin or fluconazole in proof-of-concept in vivo studies, suggesting that blocking the function of cell surface Eno1 was effective for controlling invasive infection caused by Candida spp. In summary, our study provides the evidence of C. albicans invading host by "subverting" plasminogen system, suggesting a potential novel treatment strategy for invasive fungal infections.
Subject(s)
Antibodies, Monoclonal/administration & dosage , Antifungal Agents/administration & dosage , Candida albicans/pathogenicity , Candidemia/prevention & control , Phosphopyruvate Hydratase/metabolism , Plasminogen/metabolism , Anidulafungin/administration & dosage , Anidulafungin/pharmacology , Animals , Antibodies, Monoclonal/pharmacology , Antifungal Agents/pharmacology , Caco-2 Cells , Candidemia/metabolism , Disease Models, Animal , Drug Synergism , Endothelial Cells/cytology , Endothelial Cells/drug effects , Endothelial Cells/microbiology , Epithelial Cells/cytology , Epithelial Cells/drug effects , Epithelial Cells/microbiology , Female , Fluconazole/administration & dosage , Fluconazole/pharmacology , Fungal Proteins/chemistry , Fungal Proteins/metabolism , Human Umbilical Vein Endothelial Cells , Humans , Mice , Phosphopyruvate Hydratase/chemistry , Protein Binding/drug effects , Protein Structure, SecondaryABSTRACT
The aim of this retrospective study was to examine how a low estradiol/follicle (E2/fol) may be related to in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI)-embryo transfer outcomes in polycystic ovary syndrome (PCOS) and non-PCOS patients, respectively. Between 2013 and 2017, 516 IVF/ICSI cycles (146 cycles in PCOS patients and 370 cycles in non-PCOS patients) with a long gonadotrophin releasing hormone receptor agonist protocol-including 338 involved fresh transfer cycles (89 cycles in PCOS patients and 249 cycles in non-PCOS patients)-were conducted. Outcomes were compared between 5 groups of PCOS patients defined by E2/fol (pg/mL) as follows: A, <140; B, 140 to 210; C, 210 to 280; D, 280 to 350; and E, >350. Non-PCOS patients' outcomes are grouped as well. Whether in PCOS or non-PCOS patients, those in the lowest E2/fol group (<140âpg/mL) tended to be younger, and with a greater body mass index (BMI) and antral follicle count (AFC), than the patients in the other groups. Relative to the other groups, Group A showed a lower number and rate of oocytes, higher single pronucleus (1PN) and triple pronucleus (3PN) formation rate, early and advanced abortion rates, but these did not differ significantly from those of the other groups, it perhaps due to the limited sample size. Group A have a higher incidence of moderate or severe ovarian hyperstimulation syndrome than the other groups in non-PCOS patients (Pâ>â.05). Whether in PCOS or non-PCOS patients, greater BMI, greater AFC, and younger age may favor the phenomenon of low E2/fol. In turn, low E2/fol may reduce the oocyte retrieval rate and increase the risk of 1PN and 3PN formation and abortion.
Subject(s)
Estradiol/blood , Fertilization in Vitro/adverse effects , Infertility, Female/therapy , Ovarian Follicle , Polycystic Ovary Syndrome/blood , Adult , Embryo Transfer/methods , Female , Fertilization in Vitro/methods , Humans , Infertility, Female/blood , Infertility, Female/etiology , Ovarian Hyperstimulation Syndrome/epidemiology , Ovarian Hyperstimulation Syndrome/etiology , Ovulation Induction/adverse effects , Polycystic Ovary Syndrome/complications , Pregnancy , Retrospective Studies , Sperm Injections, Intracytoplasmic/adverse effects , Sperm Injections, Intracytoplasmic/methods , Treatment Outcome , Young AdultABSTRACT
Schistosomiasis is one of the world's major public health problems. Praziquantel is currently the only effective drug against schistosomiasis. As resistance of praziquantel has emerged in some endemic areas, development of new antischistosomal agents should be a high priority. In this study, a phage display peptide library was used for screening for peptide antagonists of thioredoxin glutathione reductase of Schistosoma japonicum (SjTGR), which has been identified as an alternative drug target. Three rounds of panning produced four different fusion phages. ELISA proved that all four phages could bind to SjTGR. One peptide, JIPDys1 (aa, WPHNWWPHFKVK), reduced enzyme activity of SjTGR by more than 50%. 2 µM of the synthesized peptide of JIPDys1 inhibited the activity of TrxR, GR, and Grx of SjTGR by 32.5%, 100%, and 100%, respectively. The IC50 values of the synthetic peptide JIPDys1 for TrxR, GR, and Grx were 3.67 µM, 0.11 µM, and 0.97 µM, respectively. Based on computer simulation, it appeared that JIPDys1 binds to the substrate binding sites of glutathione reductase (GR) and glutaredoxin (Grx). Our data show that the peptide, JIPDys1 (aa, WPHNWWPHFKVK), is a promising candidate to develop novel drugs against S. japonicum which acts by binding with SjTGR and reduces enzyme activity of SjTGR.
Subject(s)
Computer Simulation , Multienzyme Complexes/antagonists & inhibitors , NADH, NADPH Oxidoreductases/antagonists & inhibitors , Peptides , Schistosoma japonicum/enzymology , Animals , Glutathione ReductaseABSTRACT
BACKGROUND: Truly anatomic coracoclavicular ligament reconstruction (TACCR) according to the original insertions is a creative new method for the treatment of severe acromioclavicular separation. This research analyzed the clinical and radiologic results of TACCR in 25 patients with at least 2-year follow-up. METHODS: The study enrolled 25 patients with Rockwood type V acromioclavicular joint dislocations who underwent TACCR using 2 Endobutton (Smith & Nephew Inc., Andover, MA, USA) devices from May 2013 to October 2015. Patients were assessed with clinical and radiologic follow-up at 3, 6, 12, 18, and 24 months postoperatively. The clinical assessments consisted of the visual analog scale and the Constant score. The radiographic evaluations were performed by measurements of the coracoclavicular distance. RESULTS: The mean follow-up was 34 ± 6.8 months (range, 24-48 months). The visual analog scale and Constant scores revealed significant advancements from 5 ± 0.9 (range, 4-7) and 45 ± 5.6 (range, 30-54) scores preoperatively to 0 ± 0.5 (range, 0-2) and 95 ± 2.9 (range, 91-98) scores at 24 months postoperatively, respectively. The coracoclavicular distance significantly decreased from 23 ± 5.4 mm (range, 16-34 mm) preoperatively to 8 ± 0.9 mm (range, 7-10 mm) at the final follow-up. CONCLUSIONS: TACCR represents a safe, reliable and creative surgical technique that yields good to excellent clinical and radiologic outcomes in the treatment of severe acromioclavicular separation.
Subject(s)
Acromioclavicular Joint/surgery , Joint Dislocations/surgery , Ligaments, Articular/surgery , Plastic Surgery Procedures/instrumentation , Plastic Surgery Procedures/methods , Acromioclavicular Joint/diagnostic imaging , Acromioclavicular Joint/physiopathology , Adolescent , Adult , Aftercare , Aged , Female , Humans , Joint Dislocations/diagnostic imaging , Joint Dislocations/physiopathology , Male , Middle Aged , Pain Measurement , Postoperative Period , Radiology , Visual Analog Scale , Young AdultABSTRACT
BACKGROUND: Schistosome infection typically induces a polarized Th2 type host immune response. As egg antigen molecules play key roles in this immunoregulatory process, clarifying their functions in schistosomiasis would facilitate the development of vaccine and immunotherapeutic methods. Schistosoma japonicum (Sj) CP1412 (GenBank: AY57074.1) has been identified as a new member of the RNase T2 family with immune regulatory functions. METHODS: The expression plasmid Sj CP1412-pET28a was constructed and transformed into bacteria for production of recombinant Sj CP1412 protein (rSj CP1412) via IPTG induction. The RNase activity of Sj CP1412 was predicted by bioinformatic analysis and confirmed by digesting the yeast tRNA with rSj CP1412.C57BL/6j mice were immunized with rSj CP1412, and its immune regulatory effects in vivo and in vitro were investigated. Meanwhile, the relationship between the RNase activity of Sj CP1412 and its immune regulation was observed. RESULTS: Sj CP1412 was confirmed as a novel RNase T2 family protein with RNase activity. Immunoblotting and RT-PCR analyses demonstrated Sj CP1412 as a protein exclusively secreted/excreted from eggs, but not cercariae and adult worms. Stimulating RAW264.7 macrophages with rSj CP1412 raised the expression of CD206, Arg-1 and IL-10, which are related to M2 type macrophage differentiation. Stimulating dendritic cells (DCs) with rSjCP1412 failed to induce their maturation, and the recombinant protein also inhibited LPS-stimulated DC maturation. Depletion of Sj CP1412 from soluble egg antigen (SEA) impaired the ability of SEA to induce M2 type polarization of RAW264.7 macrophages. Immunizing mice with rSj CP1412 induced high antibody titers, increased serum IL-4 and TGF-ß levels and splenic CD4 + CD25 + Foxp3 + T cells, downregulated serum IFN-γ levels and alleviated the egg granuloma pathology of schistosome infection. In vitro stimulation by rSj CP1412 significantly increased CD4 + CD25 + Foxp3 + T cell numbers in splenocytes of healthy mice. The rSj CP1412 protein with RNase activity inactivated by DEPC failed to induce M2 surface marker CD206 expression in RAW264.7 macrophages. CONCLUSIONS: The Sj CP1412 protein expressed specifically in S. japonicum eggs is a novel member of the RNase T2 family. Similar to Omega-1 of Schistosoma mansoni, the Sj CP1412 protein drives polarization of the host Th2 immune response, which is dependent on its RNase activity. These data provide new evidence towards understanding the immune regulatory role of RNase T2 family proteins during schistosome infection.
Subject(s)
Antigens, Helminth/immunology , Endoribonucleases/immunology , Endoribonucleases/metabolism , Immunologic Factors , Schistosoma japonicum/immunology , Th2 Cells/immunology , Animals , Antigens, Helminth/isolation & purification , Computational Biology , Dendritic Cells/immunology , Endoribonucleases/genetics , Female , Gene Expression Regulation , Immunization , Immunologic Factors/metabolism , Interleukin-10/biosynthesis , Interleukin-10/immunology , Interleukin-4/biosynthesis , Interleukin-4/immunology , Macrophage Activation , Macrophages/immunology , Mice , Mice, Inbred C57BL , Schistosoma japonicum/chemistry , Schistosomiasis japonica/immunologyABSTRACT
OBJECTIVE: To establish a novel convenient loop-mediated isothermal amplification (LAMP) method with the unique genes coding Plasmodium helical interspersed sub-telomeric superfamily (PHIST) for the rapid molecular diagnosis of P. falciparum. METHODS: The unique genes coding PHIST with high expression mRNA profile during the ring form or schizont period of P. falciparum were screened and selected from the PlasmoDB database. The LAMP primers of targeted genes were designed by the online software (PrimerExplorer V4). The LAMP assay was executed by the color-displaying method with SYBR Green. The dried blood spots of P. falciparum from clinical isolates were collected and the genomic DNA (gDNA) was extracted. For evaluation of sensitivity, the gDNA was diluted to four gradients (10⻹, 10⻲, 10⻳, and 10â»4). For assessment of specificity, the gDNA (s) of P. vivax, P. yoelii, Taenia saginata, and Schistosoma japonicum were also extracted. RESULTS: Totally, 61 P. falciparum unique genes coding PHIST were found. The PF3D7_1372300 with high expression value during the ring form and PF3D7_1401600 with high expression value during the schizont period were selected for LAMP assay. The lowest detectable limits of PF3D7_1372300 and PF3D7_1401600 were 130.5 parasite/µl and 1305.3 parasite/µL, respectively. Specific tests showed the amplified products of P. falciparum was positive and all the others including P. vivax, P. yoelii, T. saginata, and S. japonicum were negative. CONCLUSIONS: The established LAMP method with PF3D7_1372300 gene is sensitive, specific, simple and useful. It can be applied to the field investigation and clinical diagnosis for falciparum malaria.
Subject(s)
Nucleic Acid Amplification Techniques/methods , Plasmodium falciparum/genetics , Protozoan Proteins/genetics , Base Sequence , Computational Biology , Molecular Sequence DataABSTRACT
OBJECTIVE: To investigate the early predictors of necrotizing pneumonia in children. METHODS: The clinical data of 43 children with necrotizing pneumonia and 83 children with lobar pneumonia were retrospectively analyzed. Sex, age, the number of days with fever, laboratory examination results, and bronchoscopic findings were compared between the two groups. The multiple logistic regression analysis was used to identify the early predictors of necrotizing pneumonia. RESULTS: The necrotizing pneumonia group had a higher percentage of girls than the lobar pneumonia group (P<0.05). Compared with the lobar pneumonia group, the necrotizing pneumonia group had a larger number of days with fever, a higher peripheral blood white blood cell count (WBC), a higher percentage of neutrophils (NE%), and higher serum levels of high-sensitivity C-reactive protein (hs-CRP), albumin (Alb), and lactate dehydrogenase (LDH) (P<0.05). The necrotizing pneumonia group also had higher percentages of children with a large amount of sputum bolt under a bronchoscope which needed to be removed with biopsy forceps and children with rice-water-like bronchoalveolar lavage fluid (P<0.05). The multiple logistic regression analysis showed that being a female, the presence of sputum bolt under a bronchoscope which needed to be removed with biopsy forceps, the number of days with fever, WBC, hs-CRP, and LDH were independent predictors of necrotizing pneumonia. The receiver operating characteristic curve analysis showed that the cut-off values of the latter 4 predictors were 18.5â d, 15.1×10(9)/L, 121.5 mg/L, and 353.5 U/L, respectively. CONCLUSIONS: Increased WBC (≥15.1×10(9)/L), increased hs-CRP (≥121.5â mg/L), increased serum LDH (≥353.5 U/L), and the presence of sputum bolt under a bronchoscope which needs to be removed with biopsy forceps and rice-water-like bronchoalveolar lavage fluid may be the early predictors of necrotizing pneumonia in children.
Subject(s)
Pneumonia/diagnosis , C-Reactive Protein/analysis , Child , Child, Preschool , Female , Humans , L-Lactate Dehydrogenase/blood , Leukocyte Count , Logistic Models , Male , Necrosis , Pneumonia/bloodABSTRACT
BACKGROUND: Schistosomiasis is one of the world's major public health problems. Besides praziquantel (PZQ), there is currently no other effective treatment against schistosomiasis. The development of new antischistosomal agents to curb the emergence of PZQ resistance should be a high priority. Oxadiazole-2-oxides have been identified as potential antischistosomal reagents, with thioredoxin glutathione reductase (TGR) being one of their molecular targets. METHODS: To develop novel treatment reagents against Schistosoma japonicum, 30 novel oxadiazole-2-oxides were synthesised and their antischistosomal activities on juvenile and adult S. japonicum were evaluated in vitro and in vivo. Their inhibitory activities against S. japonicum thioredoxin glutathione reductase (SjTGR) were also analysed. RESULTS: Most of the oxadiazole-2-oxides showed good juvenile and adult S. japonica killing activities in vitro. However, the antischistosomal effects of these compounds were not positively correlated with either their inhibition of SjTGR, or with nitric oxide (NO) release. Compounds 4a, 4b, 7c, 13, 16 and 20 resulted in 87.7%, 83.1%, 87.1%, 84.6%, 90.8% and 69.5%, respectively, mortality in the adult worms, when used to treat infected mice at schistosomula stage. These mortality rates were similar to or higher than that of artemisinin. Furthermore, compounds 4a and 16 resulted in 66.7% and 69.4% reductions in the worm burdens, respectively, when infected mice were treated at the adult worm stage. These treatment effects were similar to PZQ. No differences in activity of the oxadiazole-2-oxides against female and male adult worms were observed. The toxicity of the oxadiazole-2-oxides on mammalian cells appeared to be similar to, or less than, that of PZQ. CONCLUSIONS: The antischistosomal activity of the oxadiazole-2-oxides does not depend on NO production or the inhibition of SjTGR activity. There may be other functional targets of the oxadiazole-2-oxides in S. japonicum. Several of the novel oxadiazole-2-oxides synthesised in this study could be used to develop novel antischistosomal drugs and explore potential molecular targets.
Subject(s)
Oxadiazoles/pharmacology , Oxides/pharmacology , Praziquantel/pharmacology , Schistosoma japonicum/physiology , Schistosomiasis japonica/drug therapy , Schistosomicides/pharmacology , Animals , Female , HeLa Cells , Helminth Proteins/antagonists & inhibitors , Humans , Male , Mice , Mice, Inbred ICR , Multienzyme Complexes/antagonists & inhibitors , NADH, NADPH Oxidoreductases/antagonists & inhibitors , Nitric Oxide/metabolism , Oxadiazoles/chemical synthesis , Oxides/chemical synthesis , Schistosomiasis japonica/parasitology , Schistosomicides/chemical synthesisABSTRACT
OBJECTIVE: To explore the performance of the biotin-avidin complex enzyme linked immunosorbent assay of detecting specific IgG4 for the diagnosis of clonorchiasis. METHODS: The avidin-biotin complex enzyme linked immunosorbent assay of detecting specific IgG4 (IgG4-ABC-ELISA)against Clonorchis sinensis was established, and used to detect the serum samples of patients with clonorchiosis sinensis, schistosomiasis japonica, paragonimiasis, toxoplasmosis, echinococcosis, cysticercosis and sparganosis mansoni. At the same time, these sera were analyzed by the ELISA of detecting IgG4 (IgG4-ELISA) and ELISA of detecting the total IgG (IgG-ELISA) as controls. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the respective diagnostic performance of the three methods were compared. RESULTS: The IgG4-ABC-ELISA for diagnosis of clonorchiasis was established successfully. The sensitivity and specificity of the IgG4-ABC-ELISA for detecting clonorchiasis were 90.0% and 98.2% respectively, and PPV and NPV were 93.8% and 97.0% respectively. Its diagnostic performance was 96.3%. The sensitivity and specificity of the IgG4-ELISA for detecting clonorchiasis were 86.0% and 98.2% respectively, and PPV and NPV were 93.5% and 95.9% respectively. Its diagnostic performance was 95.4%. The sensitivity and specificity of the IgG-ELISA for detecting clonorchiasis were 94.0% and 88.1% respectively, and PPV and NPV were 70.1% and 98.0% respectively. Its diagnostic performance was 89.4%. The sensitivity of IgG4-ABC-ELISA was higher than that of IgG4-ELISA (P < 0.05), and the specificity of IgG4-ABC-ELISA was higher than that of IgG-ELISA (P < 0.05). CONCLUSIONS: IgG4-ABC-ELISA of detecting specific antibody IgG4 against Clonorchis sinensis has high sensitivity and specificity. Therefore, it has a good application value in the diagnosis of clonorchiasis.
Subject(s)
Antibodies, Helminth/blood , Clonorchiasis/diagnosis , Enzyme-Linked Immunosorbent Assay/methods , Immunoglobulin G/blood , Avidin , Biotin , Humans , Sensitivity and SpecificityABSTRACT
OBJECTIVE: To Study the effect of anti-aging and its mechanism of total saponins of Wu-He Dipsacus asper on skin of mice-aging model. METHODS: Forty-eight mice were randomly divided into blank control group, model group, low-Dipsacus group, medium-Dipsacus group, high-Dipsacus group and positive control group( n = 8) . The mouse model of skin aging was established by nape subcutaneous injection of 5% D-galactose (0.025 mL/(g · d)), the mouse of low-Dipsacus group, medium-Dipsacus group, high-Dipsacus group were administered with total saponins of Wu-He Dipsacus asper (50 ml/(kg · d), 100 mL/(kg · d), 200 mL/(kg · d)), the mice of the positive control group were administered with vitamin E(50 mg/(kg · d)) for 42 d. The content of hydroxyproline (HYP) and lipofuscin (LF) were measured in skin of each group mice, the activity of catalase (CAT) glutathione peroxidase ( GSH-Px) superoxide dismutase (SOD) and the content of malondi- aldehyde (MDA) were determined in serum and skin of each group mice. RESULTS: Compared with blank control group, the content of HYP decreased significantly and the content of LF increased significantly in skin, the activities of CAT, GSH-Px and SOD decreased significantly and the content of MDA increased significantly in serum and skin of model group; Compared with model group, the content of HYP increased significantly and the content of LF decreased significantly in skin, the activities of CAT, GSH-Px and SOD enhanced significantly and the con- tent of MDA decreased significantly in serum and skin of low-Dipsacus group, medium-Dipsacus group, high-Dipsacus group and positive control group; Compared with low-Dipsacus group, the content of HYP increased significantly and the content of LF decreased significantly in skin, the activities of CAT, GSH-Px and SOD enhanced significantly and the content of MDA decreased significantly in serum and skin of high-Dipsacus group and positive control group; The activity of SOD in serum and skin had a significant positive correlation with the content of HYP, and a significant negative correlation with LF in skin. CONCLUSION: Total saponins of Wu-He Dipsacus asper have obvious effect of anti-agng on skin of mouse-aging model , its mechanism is closely related to oxidative damage.
Subject(s)
Dipsacaceae/chemistry , Saponins/pharmacology , Skin Aging/drug effects , Animals , Disease Models, Animal , Mice , Oxidative StressABSTRACT
BACKGROUND: Both the T cell immunoglobulin domain- and mucin domain-containing molecule-3 (Tim-3) and the death receptor Fas contribute to the pathogenesis of various autoimmune diseases, including systemic lupus erythematosus (SLE). The aim of the present study was to determine whether Tim-3 and Fas are co-expressed on certain peripheral T lymphocyte subsets, and whether this expression is associated with greater disease activity in SLE. METHODS: Peripheral blood mononuclear cells were isolated from 46 patients newly diagnosed with SLE and 28 age- and sex-matched healthy controls (HCs). Expression of Tim-3 and Fas on T subsets was analyzed by flow cytometry, while mRNA levels of the Tim-3 ligand galectin-9 and Fas ligand FasL were assayed using real-time RT-PCR. RESULTS: The proportions of CD3(+)CD4(+) and CD3(+)CD4(-) T cells expressing Tim-3(+) and Tim(+)Fas(+) were significantly higher in patients than in HCs (p < 0.05), while the proportions of these subtypes expressing Fas were similar for the two groups. Patients with active SLE, as defined by their score on the SLE Disease Activity Index, had lower proportions of CD3(+)CD4(+) T cells and higher proportions of CD3(+)CD4(+)Tim-3(+) and CD3(+)CD4(+)Tim-3(+)Fas(+) T cells than did patients with stable SLE. Serum levels of complement C3 and C4 proteins, considered as a marker of SLE activity, correlated negatively with proportions of CD3(+)CD4(+) and CD3(+)CD4(-) T cells expressing Tim-3. CONCLUSIONS: Expression of Tim-3 and co-expression of Tim-3 and Fas on certain peripheral T subsets are associated with disease activity in SLE patients. Future research should examine whether the same is true of other T subsets implicated in SLE, and should explore the potential role(s) of Tim-3 in the disease pathway. VIRTUAL SLIDES: http://www.diagnosticpathology.diagnomx.eu/vs/1855527845145188.
Subject(s)
Lupus Erythematosus, Systemic/blood , Membrane Proteins/blood , T-Lymphocyte Subsets/immunology , Adult , Biomarkers/blood , Case-Control Studies , Complement C3/analysis , Complement C4/analysis , Fas Ligand Protein/genetics , Female , Flow Cytometry , Galectins/genetics , Hepatitis A Virus Cellular Receptor 2 , Humans , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/immunology , Male , Middle Aged , Prognosis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Severity of Illness Index , Up-Regulation , Young Adult , fas Receptor/bloodABSTRACT
BACKGROUND: This study assessed the feasibility of anatomical coracoclavicular (CC) ligaments reconstruction, using three-dimensional (3D) measurement and virtual drilling. METHODS: One-hundred-and-five 3D shoulder models were constructed using SuperImage software, based on computed tomography (CT) scan data. For each model the attachment sites and footprint dimensions of the CC ligaments were defined and adjusted according to constant anatomical ratios and individual measurement results. Different drilling techniques and 3D measurements were carried out separately on each model. RESULTS: The collinear drilling technique with one bundle was used to breach the clavicle and/or coracoid process bone cortex in 38 of 105 models (36.2%); the percentage with two bundles was 90.5% (95/105). No cortical breach was observed using the non-collinear drilling technique. CONCLUSIONS: The non-collinear drilling technique provides the capability to prepare bony tunnels without any risk of cortical breach.