In the study, we used Con A affinity chromatography, 1-D gel electrophoresis, and nano-LC–MS/MS to screen biomarker candidates in plasma samples obtained from 30 patients with gastric cancer and 30 ...healthy volunteers. First, we pooled plasma samples matched by age and sex. We identified 17 differentially expressed Con A-bound glycoproteins, including 10 upregulated proteins and 7 downregulated proteins; these differences were significant (Student's t-test, p-value<0.05). Furthermore, 2 of the upregulated proteins displayed expression levels that were increased by 2-fold or more in gastric cancer samples when compared with normal control samples. These proteins included leucine-rich alpha-2-glycoprotein (LRG1) and inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3), and the expression levels were validated by Western blot analysis. Pathway and network analysis of the differentially expressed proteins by Ingenuity Pathway Analysis revealed vital canonical pathways involving acute phase response signaling, the complement system, LXR/RXR activation, hematopoiesis from pluripotent stem cells, and primary immunodeficiency signaling. Our results suggest that Con A-bound LRG1 and ITIH3 may not be practically applicable as a robust biomarker for the early detection of gastric cancer. Additionally, three novel PTMs in ITIH3 were identified and include hexose-N-acetyl-hexosamine at asparagine-41, trimethylation at aspartic acid-290, and flavin adenine dinucleotide at histidine-335.
Our study was to describe a combinatorial approach of Con A affinity chromatography, 1-D SDS-PAGE, and nano-LC/MS/MS that provides a label-free, comparative glycoproteomic quantification strategy for the investigation of glycoprotein profiles in plasma from gastric cancer patients versus healthy volunteers and to identify glycoprotein biomarkers for the early clinical detection of gastric cancer. Three novel PTMs, HexHexNAc, trimethylation and FAD, in Con A-bound ITIH3 were identified and built in molecular modeling. The aspartic acid-290 trimethylation site was located in a metal ion-dependent adhesion site (MIDAS motif; 290-DXSXS…T…D-313) that may influence important function for binding protein ligands.
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•Comparative glycoproteomic including Con A enrichment and 1D-LC/MS/MS is proposed.•Con A-bound LRG1 and ITIH3 could not be biomarkers to early detect gastric cancer.•Networks analysis included acute phase response signaling.•Three novel PTMs in ITIH3 were identified: HexHexNAc, trimethylation and FAD.
Summary
Dehydropeptidase‐1 (DPEP1) is a zinc‐dependent metalloproteinase abnormally expressed in many cancers. However, its potential role in adults with B cell acute lymphoblastic leukaemia (ALL) is ...unknown. We found that in adults with common B cell ALL high DPEP1, transcript levels at diagnosis were independently associated with an increased cumulative incidence of relapse (CIR) and worse relapse‐free survival (RFS) compared with subjects with low transcript levels. We show an increased proliferation and prosurvival role of DPEP1 in B cell ALL cells via regulation of phosphCREB and p53, which may be the biological basis of the clinical correlation we report. Our data implicate DPEP1 expression in the biology of common B cell ALL in adults. We report clinical correlates and provide a potential biological basis for these correlations. If confirmed, analysing DPEP1 transcript levels at diagnosis could help predict therapy outcomes. Moreover, regulation of DPEP1 expression could be a therapy target in B cell ALL.
Article Note: Funding information Ministry of Health and Welfare of Taiwan, Grant/Award Number: MOHW109-TDU-B-211-114003; International Center for Wound Repair and Regeneration at National Cheng Kung ...University Byline: Jia-Horung Hung, Ping-Chen Hou, Fu-Chin Huang, Chao-Kai Hsu
Remimazolam is a novel, ultrashort-acting benzodiazepine. This study aimed to compare the efficacy and safety of remimazolam and propofol for hysteroscopic examination, to determine the optimal dose ...of remimazolam combined with alfentanil for painless hysteroscopy, and to calculate its median effective dose (ED50).
Step 1: A total of 208 patients undergoing hysteroscopic examination were prospectively included in this study. Patients were randomized into 4 groups: 0.2 mg/kg remimazolam (group A), 0.25 mg/kg remimazolam besylate (group B), 0.3 mg/kg remimazolam (group C), and 2 mg/kg propofol (group D), with 52 patients in each group. One minute after losing consciousness, patients received an intravenous injection of alfentanil at 5 µg/kg, followed by a continuous infusion of alfentanil at 0.5 µg/kg/min. If patients showed frowning, movement, or MOAA/S > 1, sedatives were added: 0.05 mg/kg/dose of remimazolam for groups A, B, and C, and 0.5 mg/kg/dose of propofol for group D. Step 2: Dixon's up-and-down method was used to calculate the ED50 of remimazolam combined with alfentanil during hysteroscopic examination.
The sedation success rates of the remimazolam groups were 88.46%, 94.23%, and 98.08%, respectively, compared to 96.15% in the propofol group, with no significant difference (P = .175). MAP in groups A and B was higher than in group D (P < .05), and significantly higher in group C than in group D (P = .0016). SpO2 values in groups A, B, and C were higher than in group D at T2 to T3 (P < .001). HR in groups A, B, and C was significantly higher than in group D (P < .001). The ED50 of remimazolam combined with alfentanil in hysteroscopy was 0.244 mg/kg, 95%CI (0.195-0.22) and ED95 was 0.282 mg/kg, 95%CI (0.261-1.619).
In hysteroscopy, the sedative effect of remimazolam is like that of propofol, with 0.25 mg/kg remimazolam showing better safety and efficacy, and less impact on the respiratory and circulatory systems. Additionally, under the influence of alfentanil, the ED50 of remimazolam in hysteroscopy is 0.244 mg/kg, with no severe adverse reactions observed.
Background: Attention deficit hyperactivity disorder (ADHD) and tic disorder usually co‐occur in the same individuals, but the underlying mechanisms remain unclear. Previous evidence has shown that ...a frequent coexistence of allergic diseases was noted in patients with ADHD or tic disorder. We attempted to investigate the possible link among ADHD, tic disorder, and various allergic diseases.
Methods: Utilizing the Taiwan National Health Insurance Research Database from 1996 to 2010, 5,811 patients with ADHD alone, 1,816 patients with tic disorder alone, and 349 patients with dual diagnoses of ADHD and tic disorder were identified and compared with age‐/gender‐matched controls (1:4) in an investigation of the association among ADHD, tic disorder, and allergic diseases.
Results: Patients with dual diagnoses of ADHD and tic disorder had a significantly higher prevalence of allergic diseases and psychiatric comorbidities, including allergic rhinitis (43% vs. 28.4% vs. 33.6% vs. 19.7%, p < 0.001), asthma (27.5% vs. 17.2% vs. 18.2% vs. 11.9%, p < 0.001), atopic dermatitis (10.6% vs. 8.4% vs. 7.0 vs. 5.9%, p < 0.001), allergic conjunctivitis (55.6% vs. 34.7% vs. 43.5% vs. 26.3%, p < 0.001), obsessive compulsive disorder (4.0% vs. 1.3% vs. 2.0% vs. 0.1%, p < 0.001), and anxiety disorder (22.1% vs. 18.0% vs. 6.0% vs. 0.5%, p < 0.001) than the ADHD alone group, the tic alone group, and the control group. Furthermore, ADHD patients with more allergic diseases (≥3 comorbidities: OR: 3.73, 95% CI: 2.65∼5.25; 2 comorbidities: OR: 2.52, 95% CI: 1.82∼3.47; 1 comorbidity: OR: 1.87, 95% CI: 1.41∼2.49) exhibited an increased risk of tic disorder compared with ADHD patients without allergic disease.
Conclusion: A significant association among ADHD, tic disorder, and allergic diseases was noted in our study. The results may inspire further studies to clarify the underlying mechanisms and help us understand more about the complex etiology of ADHD, tic disorder, and their co‐occurrence.
Summary Background On March 30, a novel influenza A subtype H7N9 virus (A/H7N9) was detected in patients with severe respiratory disease in eastern China. Virological factors associated with a poor ...clinical outcome for this virus remain unclear. We quantified the viral load and analysed antiviral resistance mutations in specimens from patients with A/H7N9. Methods We studied 14 patients with A/H7N9 disease admitted to the Shanghai Public Health Clinical Centre (SPHCC), China, between April 4, and April 20, 2013, who were given antiviral treatment (oseltamivir or peramivir) for less than 2 days before admission. We investigated the viral load in throat, stool, serum, and urine specimens obtained sequentially from these patients. We also sequenced viral RNA from these specimens to study the mutations associated with resistance to neuraminidase inhibitors and their association with disease outcome. Findings All patients developed pneumonia, seven of them required mechanical ventilation, and three of them further deteriorated to become dependent on extracorporeal membrane oxygenation (ECMO), two of whom died. Antiviral treatment was associated with a reduction of viral load in throat swab specimens in 11 surviving patients. Three patients with persistently high viral load in the throat in spite of antiviral therapy became ECMO dependent. An Arg292Lys mutation in the virus neuraminidase (NA) gene known to confer resistance to both zanamivir and oseltamivir was identified in two of these patients, both also received corticosteroid treatment. In one of them, wild-type sequence Arg292 was noted 2 days after start of antiviral treatment, and the resistant mutant Lys292 dominated 9 days after start of treatment. Interpretation Reduction of viral load following antiviral treatment correlated with improved outcome. Emergence of NA Arg292Lys mutation in two patients who also received corticosteroid treatment led to treatment failure and a poor clinical outcome. The emergence of antiviral resistance in A/H7N9 viruses, especially in patients receiving corticosteroid therapy, is concerning, needs to be closely monitored, and considered in pandemic preparedness planning. Funding National Megaprojects of China for Infectious Diseases, Shanghai Municipal Health and Family Planning Commission, the National Key Basic Research Program of China, Ministry of Science and Technology, and National Natural Science Foundation of China.
In this study, an acidic polysaccharide from
Nannf. var.
(Nannf.) L. T. Shen (WCP-I) and its main fragment, WCP-Ia, obtained after pectinase digestion, were structurally elucidated and found to ...consist of a rhamnogalacturonan I (RG-I) region containing both arabinogalactan type I (AG-I) and type II (AG-II) as sidechains. They both expressed immunomodulating activity against Peyer's patch cells. Endo-1,4-β-galactanase degradation gave a decrease of interleukine 6 (IL-6) production compared with native WCP-I and WCP-Ia, but exo-α-l-arabinofuranosidase digestion showed no changes in activity. This demonstrated that the stimulation activity partly disappeared with removal of β-d-(1→4)-galactan chains, proving that the AG-I side chain plays an important role in immunoregulation activity. WCP-Ia had a better promotion effect than WCP-I in vivo, shown through an increased spleen index, higher concentrations of IL-6, transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α) in serum, and a slight increment in the secretory immunoglobulin A (sIgA) and CD4
/CD8
T lymphocyte ratio. These results suggest that β-d-(1→4)-galactan-containing chains in WCP-I play an essential role in the expression of immunomodulating activity. Combining all the results in this and previous studies, the intestinal immune system might be the target site of WCP-Ia.
Background
Previous cross‐sectional studies have suggested an association between asthma and attention‐deficit/hyperactivity disorder (ADHD), but the temporal relationship was not determined. Using a ...nationwide population‐based prospective case–control cohort study (1:4, age‐/gender‐matched), we hypothesized that asthma in infanthood or early childhood would increase the risk of ADHD in later life.
Methods
In all, 2,294 children with asthma and 9,176 controls aged between 0 and 3 years in 2000 were included in our study. Cases of ADHD that occurred to the end of follow‐up (31 December 2010) were identified.
Results
Children with asthma had a higher incidence of developing ADHD (7% vs. 4.6%, p < .001) than control cohort during the follow‐up period. After adjusting for age at enrollment, gender, level of urbanization, and comorbid allergic diseases (allergic rhinitis and atopic dermatitis), children with asthma had an elevated risk (HR: 1.31, 95% CI: 1.07–1.59) of developing ADHD compared with control group.
Discussion
Our prospective study supported a temporal relationship between asthma and ADHD. Asthma in very early life increased the risk of developing ADHD during the school years. Further studies are required to investigate whether the prompt treatment of asthma and comorbid allergic diseases could prevent the development of ADHD or decrease ADHD symptoms.
Background In bone marrow transplant patients, the microenvironment in bone marrow is damaged after chemotherapy or radiotherapy. Subsequent to allogenic hematopoietic stem cell transplantation in ...patients with clinically successful engraftments, the source of mesenchymal stem cells （MSCs） remains controversial. To further verify the stimulatory effect of the simultaneous transplantation of cells from second donors on engraftment success for hematopoietic stem cell transplantation in support of donor MSCs engraftments, the aim of this study is to monitor the dynamics of the engraftment of bone marrow-derived MSCs in patients after transplantation with mismatched-sex hematopoietic stem and third-party cells. Methods In this study, the hematopoietic stem cells from 32 clinical donors of different sexes that resulted in successful engraftments were selected for transplantation and were classified into three groups for research purposes： group A consisted of 14 cases of transplantation with bone marrow and recruited peripheral hematopoietic stem cell transplantation, group B contained 8 cases of simultaneous re-transfusion of MSCs from the second donor, and group C contained 10 cases of simultaneous re-transfusion of umbilical blood from the second donor. The bone marrow from 32 patients with successful engraftments of hematopoietic transplantation were selected and sub-cultured with MSCs. Flow cytometry （FCM） was used to measure the expression of surface antigens on MSCs. Denaturing high-performance liquid chromatography （DHPLC） in combination with polymerase chain reaction amplification of short tandem repeats （STR- PCR） was used to measure the engraftment status of fifth-generation MSCs in patients. Fluorescence in situ hybridization （FISH） revealed the sex origin of the fifth-generation MSCs in 32 patients. Dynamic examinations were performed on patients receiving donor transplantations. Results The progenies of fifth-generation MSCs were successfully cultured in 32 cases. The results of FCM demonstrated that the expression levels of CD14＋ and CD45＋ cells were lower than 0.04% in the fifth-generation MSCs. The analysis using DHPLC and FISH showed similar results. One patient from group B also received a temporary transplantation of MSCs from the donor. The MSCs in the remaining 31 patients all originated from the patients themselves. Conclusions After transplantation, the MSCs present in patients originated from the host. In patients transplanted with MSCs from a second donor, the phenomenon of temporary chimerization of MSCs was observed.
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