[Analysis of Plasma Metabolic Profile in Children with Transfusion-Dependent Thalassemia].

OBJECTIVE: To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia (TDT), and reveal the changes of metabolic pattern in children with TDT. METHODS: 23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected, and 11 healthy children who underwent physical examination during the same period were selected as the control group. The routine indexes between children with TDT and the control group were compared, and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry. An OPLS-DA model was established to perform differential analysis on the detected metabolites, and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites. RESULTS: The results of routine testing showed that the indexes of ferritin, bilirubin, total bile acid, glucose and triglycerides in children with TDT were significantly higher than those in healthy controls, while hemoglobin and total cholesterol were significantly lower (all P <0.05). However there was no significant difference in lactate dehydrogenase between the two groups (P >0.05). Compared with the control group, 190 differential metabolites (VIP>1) were identified in TDT children. Among them, 168 compounds such as arginine, proline and glycocholic acid were significantly increased, while the other 22 compounds such as myristic acid, eleostearic acid, palmitic acid and linoleic acid were significantly decreased. The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism. CONCLUSION: The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group. This finding is helpful to optimize the treatment choice for children with TDT, and provides a new idea for clinical treatment.

Mechanism of TLR4 mediated immune effect in transfusion-induced acute lung injury based on Slit2/Robo4 signaling pathway.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is the infusion of blood or blood system. OBJECTIVE: To explore the mechanism of TLR4-mediated T cell immune effect in TRALI. METHODS: In this animal study, a mouse model of LPS-induced TRALI was established. Sixty adult C57/BL6 mice (wild-type, WT) were randomly divided into 5 groups: 1) normal WT type, 2) LPS control group of WT type lipopolysaccharide, 3) WT type TRALI group (LPS + MHC-I mAb), 4) (TLR4 antibody) lipopolysaccharide LPS control group, 5) (TLR4 antibody) TRALI group (LPS + MHC-I mAb). Mice were injected with LPS (0.1 mg/kg) and MHC-I mAb (2 mg/kg) into the tail vein. H&E staining was performed to detect pathological features. The myeloperoxidase (MPO) activity and the level of inflammatory cytokines in lung tissue homogenate supernatant were measured. Blood, spleen single-cell suspension, and bronchoalveolar lavage fluid were collected to detect the ratio of Treg and Th17 cells by flow cytometry. RT-PCR and WB were used to detect mRNA or protein expression. RESULTS: TLR4 mAb treatment alleviated the pathogenesis of LPS-induced TRALI in vivo, the MPO activity, and the level of proinflammatory factors in lung tissues. TLR4 exerted its function by changing of Treg/Th17 ratio via the SLIT2/ROBO4 signaling pathway and downregulating CDH5 and SETSIP. CONCLUSION: TLR4 mediates immune response in the LPS-induced TRALI model through the SLIT2/ROBO4 signaling pathway.

Prevalence and clinical characteristics of T2DM patients with OTUD3 gene rs78466831 SNP at a single academic center in China.

Background: A novel, rare OTUD3 c.863G>A (rs78466831) in humans has been reported associated with diabetes, but the prevalence and clinical characteristics of T2DM patients with rs78466831 have not been reported before. Objective: To investigate the prevalence and clinical characteristics of T2DM patients with rs78466831 and provide a basis for clinical diagnosis and treatment. Methods: OTUD3 gene rs78466831 SNP was detected by Sanger sequencing in all the collected specimens of laboratory-confirmed T2DM patients and healthy people. Clinical characteristics indexes inconsisting of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and a body mass index (BMI), T2DM-associated chronic complications (myocardial infarction, cerebrovascular disease, retinopathy, arterial plaque, peripheral neuropathy and nephropathy) were obtained from the clinical laboratory information systems and electronic medical record system. Clinical characteristic indicators were compared between the wild-type and variant (rs78466831) patients with T2DM. Results: The prevalence of rs78466831 in the T2DM patients group was significantly higher than the healthy control in our academic center. The general characteristic indicators were not significantly different between the wild-type and rs78466831 patients with T2DM, except the family history of diabetes. Clinical laboratory indicators including HbA1c, FBG, OGTT, TC, HDL-C, LDL-C and CP had no significant difference between the two groups. The therapeutic drug and target achievement rates were not significantly different between the two groups. The incidence of diabetic retinopathy in the variant group was significantly higher than the wild-type group. Conclusions: The OTUD3 gene rs78466831 was associated with T2DM and may be a biological risk factor of diabetes retinopathy.

[Experimental Study on Neonatal ABO or RhD Compatible Blood Transfusion].

OBJECTIVE: To investigate the safety and effectiveness of neonatal ABO or Rh(D) by using compatible blood transfusion through retrospective analysis of data from cases received compatible blood transfusion and type matched blood transfusion. METHODS: The clinical data of 26 cases of neonatal compatible blood transfusion in Chinese Nanchang area from January 2014 to October 2016 were collected, and 26 cases of neonatal type-matched blood transfusion were selected according to ratio of 1:1 cases. The efficiency and safety index of 26 patients compatible blood transfusion were compared with that of type-matched blood transfusion. The efficiency indexes included: patients' basic characteristics, red blood cell (RBC) count, hemoglobin (Hb) level, hematocrit (Hct), and the safety indexes contain Hb level and indirect bilirubin (IBiL) value before and after blood transfusion, irregular antibody screening, direct antiglobulin test (DAT) results and the adverse reactions of blood transfusion. RESULTS: The age, sex, days of hospitalization between compatible blood transfusion and type matched blood transfusion were not statistically significantly different (P>0.05). The Hb level before transfusion, blood transfusion volume and the increase of Hb, Hct and RBC were not statistically significantly different between two groups (P>0.05). The values of Hb, Hct and RBC in 2 groups significantly increased at the day 1 after blood transfusion (P<0.05). No blood transfusion adverse reaction occurred in 2 groups. The IBiL value significantly decreased in compatible blood transfusion patients at the day 1 after blood transfusion (P<0.05). No new irregular antibodies had been detected after transfusion in all patients, and the others' DAT and screening for irregular antibodies were negative except 22 patients with neonatal hemolysis. The values of Hb and IBiL statistically significantly differenence were not in 12 patients between 1d, 3d, 7d after blood transfusion (P>0.05). CONCLUSION: The efficiency and safety between compatible blood transfusion and type matched blood transfusion are the same in neonatal blood transfusion. Compatible blood transfusion is a safe and effective in clinical blood transfusion.

Cantharidin inhibits cell proliferation and induces apoptosis through G2/M phase cell cycle arrest in hepatocellular carcinoma stem cells.

The present study was designed to investigate the effect of cantharidin on cell proliferation, ability of selfrenewal, cell cycle arrest and induction of apoptosis in HepG2 hepatocellular carcinoma stem cells (HCSCs). It was observed that cantharidin treatment exhibited dose- and time-dependent inhibitory effect on the viability of HCSCs. The inhibition of cell viability by cantharidin in HepG2 CD133+ and parental cells was significant at the concentration 5 and 15 µM, respectively after 48 h. Cantharidin treatment inhibited the self-renewal ability of the HCSCs and the expression of ß-catenin and cyclin D1. Flow cytometry revealed that cantharidin treatment at 5 µM concentration significantly increased the cell population in G2/M phase and decreased the population in the G1 phase. Cantharidin treatment in the HCSCs for 48 h increased expression of histone H2AX, Myt1, cyclin A2, cyclin B1, p53 and cdc2 (Tyr15) phosphorylation significantly compared to the parental cells. Exposure of the HCSCs to cantharidin for 48 h at a concentration of 5 µM caused a significant increase in the proportion of apoptotic cells. Therefore, cantharidin is a promising agent for the hepatocellular carcinoma treatment.

[Diagnostic value of anti-alpha-fodrin antibody testing for Sjögren's syndrome: a meta-analysis].

OBJECTIVE: To evaluate the diagnostic accuracy of anti-alpha-fodrin antibody for Sjögren's syndrome (SS). METHODS: Qualified literatures on evaluation of anti-alpha-fodrin antibody in diagnosis of SS in English and Chinese published between January 1997 and December 2007 were retrieved from the Cochrane Library, Medline, Embase, and China National Knowledge Infrastructure (CNKI) databases, etc. Two reviewers independently assessed the methodological quality of each study with the tool QUADAS (quality assessment of diagnostic accuracy studies). Statistical analysis was performed by employing MATLAB, Review Manager 4.2 and Meta-Disc1.4. A meta-analysis of the reported sensitivity and specificity of each study and Summary Receiver Operating Characteristic (SROC) curve was performed. RESULTS: Eighteen literatures were included at last. After testing the heterogeneity of the included articles, proper effect model was selected to calculate the pooled weighted sensitivity and specificity with 95% confidence interval: for anti-alpha-fodrin antibody IgG, the sensitivity was 0.40 [95%CI (0.37-0.43)] and the specificity was 0.82 [95%CI (0.79-0.84)], the area under the curve (AUC) of SROC was 0.8029 (SE=0.0580). Eight studies tested anti-alpha-fodrin antibody IgA, the pooled weighted sensitivity and specificity with 95% confidence interval were 0.34 [95%CI (0.30-0.38)] and 0.83 [95%CI (0.79-0.86)] respectively, the AUC of SROC was 0.6374 (SE=0.1841), the synthesis data all showed heterogeneity. The subgroups were analyzed to identify the sources of heterogeneity according to age, race, assay method, agent source, diagnostic criteria, and country. There was homogeneity among the 4 studies from China, and the 6 studies from Japan, the AUC of SROC were 0.7343 (SE=0.0448) and 0.9273 (SE=0.0394), respectively. CONCLUSION: Diagnostic criteria, agent source, assay method, age, race, and country are the important sources of heterogeneity. Anti-alpha-fodrin antibodies IgG and IgA have relatively low pooled sensitivity and relatively high pooled specificity. Negative anti-alpha-fodrin antibody has not important value in excluding SS, but positive anti-alpha-fodrin antibody may be a useful parameter in clinical diagnosis of SS.

[Diagnostic value of anti-cyclic citrullinated peptide antibody for rheumatoid arthritis: a meta-analysis].

OBJECTIVE: To evaluate the diagnostic value of anti-cyclic citrullinated peptide (CCP) antibody for rheumatoid arthritis. METHODS: Data about RA from January 2000 to December 2005 were retrieved through Cochrane Library, Pubmed database, Excerpta Medica Database (EMBASE), OVID database, and China National Knowledge Infrastructure (CNKI), especially through the Annul of the Rheumatic Disease and relevant gray literatures, by entering the words "cyclic citrullinated peptides", "rheumatoid arthritis", "sensitivity", and "specificity". The inclusion of qualified literatures was based on the criteria for diagnostic research recommended by the Cochrane Methods Group on Screening and Diagnostic Test. Statistical analysis wes performed by employing the softwares of MATLAB and Review Manager 4, 2, and summary receiver operation characteristic (SROC) curve method. RESULTS: Twenty-two articles, 15 in English and 7 in Chinese, were extracted. The reported sensitivity of anti-CCP for the diagnosis of RA ranged from 39.2% to 84.6%, and the reported specificity ranged from 90% to 97.9%. The heterogeneity of the included articles was tested, a proper effect model was selected to calculate the pooled weighted sensitivity and specificity with 95% confidence interval for anti-CCP antibody as 77.3% (63.1%, 89.2%) and 93.85% (85.5%, 98.1%), and the positive and negative likelihood ratios as 12.0 and 0.24 respectively. The area under the curve of SROC was 0.8976, and the Q value was 0.87. The sensitivity of the patients with the duration of illness < 1 year was 43%, significantly lower than that of the patients with a duration of illness > 1 year (70.2%, P < 0.01); and the specificity of the patients with the duration of illness < 1 year was 94.2%, not significantly different from that of the patients with the duration of illness > 1 year (95.2%, P = 0.94). CONCLUSION: With relatively high sensitivity and specificity, anti-CCP antibody may be a useful parameter in the clinical diagnosis pf RA.