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【Objective】 To investigate the effect of immunoglobulin G (IgG) dimer concentration of intravenous immunoglobulin (IVIG) on the binding ability of IgG Fc fragment to THP-1 cell surface receptors. 【Methods】 Firstly, protein purification and high performance liquid chromatography (HPLC) were used to prepare different concentrations of IgG dimers. After that, IgG dimer was added to IVIG to prepare IVIG containing different concentrations of IgG dimer. Finally, based on the method established in our laboratory, we analyzed the effect of IgG dimer concentration in IVIG on the binding ability of IgG Fc fragment to THP-1 cell surface receptors. 【Results】 When the concentration of IgG dimer in IVIG was 1.11%-10.30%, its binding ability to Fc receptors on the surface of THP-1 cell was 97.67%-135.33%, and this binding ability was positively correlated with the concentration of IgG dimer. When the IgG dimer concentration exceeded 13.22%, the binding ability had no correlation with the IgG dimer concentration. 【Conclusion】 A certain concentration of IgG dimer can promote the binding ability of the IgG Fc fragment in IVIG to receptors on the surface of THP-1 cells, which needs further verification from animal experiments and clinical data.
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【Objective】 To establish a method for determinating the antigen-dependent cell-mediated cytotoxicity (ADCC) of human immunoglobulin (pH4)for intravenous injection (IVIG) on luciferase reporter gene-modified cell assay. 【Methods】 As effector cells, Jurkat-NFAT-Luc-CD16 cells were used in the assay, and PLC/PRF/5 cells were used as target cells. After incubation of effector cells and target cells with IVIG, the method for determinating ADCC biological activity of IVIG was established by detecting luciferase released by activated T nuclear factor after binding of IVIG Fc fragment to effector cells. Meanwhile, the experimental assay conditions were optimized, and the methodology was verified subsequently. 【Results】 IVIG had a dose-response relationship in this method, which was consistent with four parameter logistic model. And the PLC/PRF/5 cells were finally determined as the target cells. The initial dilution concentration of antibody was 20 mg/mL, and the ratio dilution was 1∶2, and the effector to target ratio was 1∶3, and co-incubation time of two cells and IVIG was 24 hours. Within-run and between-run analysis including three independent tests, initial working concentration relative light unit (RLU) and the relative standard deviation (RSD) of the concentration for 50% of maximal effect(EC50) were less than 11%. The relative titers of the recovery samples of the two different dilution groups were (23.50±1.69)% and (49.30±2.97)%, respectively, and the corresponding recovery rates were (93.50±6.30)% and (96.24±5.43)%, respectively, with RSD less than 11%. 【Conclusion】 The method for determinating ADCC biological activity of IVIG based on luciferase reporter gene-modified cell assay was successfully established. It could be applied in determinating the ADCC biological activity of IVIG, and has the advantages of satisfactory linearity, accuracy, precision and specificity.
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【Objective】 To explore the risk of Alzheimer′s disease (AD) transmitted by blood transfusion. 【Methods】 There were 10 APP/PS1 mice of 3, 6 and 9 months old, half female and half male, and the cognitive and behavioral abilities of C57 mice of the same age were measured, and the blood of the oldest APP/PS1 mice with no behavioral changes were collected to detect the contents of Aβ40 and Aβ42. The polymers Aβ40 and Aβ42 were prepared and Western blotting analysis was conducted. Kunming mice aged from 6 to 7 months were randomly divided into 6 groups (10 mice/ group, half male and half female). The blood of APP/PS1 mice was injected intravenously in experimental group 1-2(100 μL/mouse) with high frequency injection (3 times/week) and low frequency injection (1 time/week), respectively. In experimental group 3-4, Aβ40 and Aβ42 polymerized mixture (100 μL/mouse) were injected in high frequency and low frequency, respectively. The control group 1-2 was injected with the same amount of normal saline, with high frequency and low frequency, respectively. The above groups were injected for 4 weeks, and the cognitive and behavioral abilities were tested and analyzed one week after injection. Finally, the contents of Aβ40 and Aβ42 in blood of Kunming mice were detected. 【Results】 Change in cognitive and behavioral ability showed in 9 months old APP/PS1 mice, but not in 3 and 6 months old APP/PS1 mice. The contents of Aβ40 and Aβ42 (pg/mL) in blood of 6-7 months old APP/PS1 mice were 418.40±2.18 and 15.68±0.20, respectively. Except for monomers, most of the polymerized mixtures of Aβ40 and Aβ42 were dimers and trimers. In both high frequency and low frequency, Kunming mice transfused with blood of APP/PS1 mice (experimental group 1-2) showed a certain degree of anxiety-like behavior and short-term memory shortening in open-field test and conditioned fear test, but without significant difference. There was no significant difference in open field test, new object recognition, Barnes maze and cognitive behavior analysis of conditioned fear between experimental group 3-4 and the control group. The levels of blood Aβ40 and Aβ42(pg/mL) of Kunming mice detected by ELISA were 10.30±0.08 and 3.360±0.005, respectively, and there was no significant difference between the two groups. 【Conclusion】 Blood transfusion of APP/PS1 mice and the mixture of Aβ40 and Aβ42 have no significant effect on the cognitive function of healthy Kunming mice in a short time, and the risk of AD transmission is relatively low.
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【Objective】 To analyze the dynamic relationship between the setting up of plasmapheresis station and the volume of voluntary blood donation collected using panel vector autoregressive model, so as to provide scientific reference for the management policies of blood stations and plasmapheresis stations in China. 【Methods】 The data collected from blood stations in seven administrative regions of Guangyuan, Sichuan Province from 2011 to 2021, as well as plasma collection data from two plasmapheresis stations in the region within two years since their operation, were collected. A panel vector autoregressive model was constructed. Impulse response analysis and variance decomposition analysis were used to analyze the impact and time lag effects of simulated plasmapheresis station settings on the collection volume of voluntary blood donation. Covariance analysis was used to explore whether the establishment of plasmapheresis station had an impact on the volume of voluntary blood donation collected after excluding the impact of initial value differences. 【Results】 The pulse response results showed that after the plasmapheresis station was set up, there was a negative impact effect on the voluntary blood donation collection volume at the first stage, and its impact began to rise after the second stage, reached the highest value in the third stage, and then began to decline. After the seventh stage, it tended to be stable. However, within the 10 stage range, the confidence interval for the response strength of voluntary blood donation collection volume always included 0, indicating that the response of blood collection volume to the plasmapheresis station setting in the region was not statistically significant. The results of variance decomposition showed that the contribution of collection volume of voluntary blood donation to their own impact reached 94.3%. In terms of the contribution of plasmapheresis station factors, the number of plasma donors has a relatively greater impact on the volume of voluntary blood donation collected(2.2%). Covariance analysis showed that after removing the initial confounding factors, whether to establish a plasmapheresis station had no significant impact on blood donation volume in the two groups of regions (P>0.05). 【Conclusion】 The establishment of a new plasmapheresis station will have a certain impact on blood collection volume of blood stations in the region in a short term, but in the long term, it may not directly affect the voluntary blood donation collection in the region.
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【Objective】 To analyze the characteristics and mobility of the overlapping population of voluntary blood donation and plasmapheresis donation, so as to provide a scientific basis for the formulation of recruitment and retention strategies for blood donation and plasmapheresis donation, and to further propose a scientific reference for the decision-making of blood banks and plasmapheresis station management in China. 【Methods】 The basic information of blood donors and plasmapheresis donors in two counties in Guangyuan, Sichuan Province, which carried out whole blood collection and plasmapheresis collection from the establishment of the station to July 31, 2021 was statistically compared and analzed using the chi-square test and Post hoc testing test. 【Results】 As of July 31, 2021, a total of 50 658 people participated in blood donation and 63 375 people participated in plasmapheresis donation in Jiange County and Cangxi County, with a total overlap of 6 189 people. In the two regions, 16 458 (35.2%) people aged 40 to 50, and 35 558 people (56.1%) were over 50 years old. Among the overlapping population, 2 496 (40.3%) were 40 to 50 years old, accounted for the largest proportion, and 3 146 (50.8%) were males. Significant differences were noticed in age (P<0.001) and gender (P<0.001). There was a shift in dontion in 5 183, including 2 072 people from plasma to blood and 3 111 people from blood to plasma, among which 2 671 (51.5%) were men and 3 632 (70.1%) were over 50 years old, with significant differences in gender (P<0.05) and age (P<0.001). 【Conclusion】 There were a small number of donors donating both blood and plasma in Jiange and Cangxi, and men aged 40 to 50 were the majority, and people over 50 years old were more likely to shift the donation goals. The vast majority of donors have a single and fixed donation goal (blood or plasma), and are not easy to change.
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【Objective】 To develop methods to display the IgG autoantibody repertoire of intravenous immunoglobulin (IVIG) products, analyze the different types of antibodies and study the diversity of IgG autoantibody in 4 IVIG preparations from different Chinese manufacturers. 【Methods】 Two-dimensional gel electrophoresis and immunoblotting with human umbilical vein endothelial cell (HUVEC) proteins were used to demonstrate the IgG autoantibody repertoire and the human protein microarray with bioinformatics analysis was employed to profile the immune reactive autoantigens of the 4 IVIG preparations. 【Results】 The methods to showcase the autoantibody repertoire and study the antibody diversity of IVIG were successfully established. High-quality repertoires of IVIG autoantibodies and biological information about self-proteins that can be recognized were obtained. There was a significant difference in the recognition of the quantity and variety of the self-antigens by different IVIG products. The number of antibodies against HUVEC proteins in four products ranged from 241-386. The number of proteins recognized on the human protein chip ranged from 292-435, with 172 human self-proteins recognized by all four products. 【Conclusion】 Demonstration of antibody repertoire and protein chip technology can be used to analyze IVIG products′ IgG autoantibody repertoire. All four preparations tested in this study exhibited a broad spectrum of antibodies against HUVEC proteins and human proteome microarray, each product had its unique antibody repertoire characteristics.
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ObjectiveTo investigate the inhibitory effects and mechanism of the compound Phyllanthus urinaria Ⅱ （CPU Ⅱ）on the growth of transplanted hepatocellular carcinoma Hep3B2.1-7 （Short for Hep3R） cells in nude mice. MethodAfter the establishment of a xenograft model of hepatocellular carcinoma Hep3B cells in mice， the model mice were randomly divided into a model group， a high-dose CPU Ⅱ group （57.5 g·kg-1）， a low-dose CPU Ⅱ group （28.75 g·kg-1）， and a 5-fluorouracil （5-FU） group （0.025 g·kg-1）， with eight mice in each group. The mice in the high- and low-dose CPU Ⅱ groups were treated with drugs by gavage， once per day， and those in the model group were treated with the same volume of normal saline. The mice in the 5-FU group were treated by 5-FU by intraperitoneal injection， once every other day. After 28 days of administration， mice were sacrificed， and transplanted tumors were collected. Immunohistochemistry （IHC） was used to detect the expression of proliferating cell nuclear antigen （PCNA） of tumor tissues. Terminal-deoxynucleotidyl transferase-mediated nick end labeling （TUNEL） was used to detect cell apoptosis of tumor tissues. The mRNA expression of miR-122 and insulin-like growth factor 1 receptor （IGF-1R） in tumor tissues was detected by Real-time quantitative PCR （Real-time PCR）. The protein expression of CCAAT/enhancer-binding protein α （C/EBPα）， hepatocyte nuclear factor-4α （HNF-4α）， and IGF-1R in tumor tissues was detected by Western blot. ResultThe tumor suppression rates of the high- and low-dose CPU Ⅱ groups and the 5-FU group were 74.90%， 63.62%， and 64.15%， respectively. Compared with the model group， the CPU Ⅱ groups and the 5-FU group showed reduced weight （P<0.01） and volume of tumors （P<0.01）， decreased PCNA positive cells， shallow staining， increased apoptosis cells of transplanted tumor tissues （P<0.05， P<0.01）， increased expression of mRNA expression of miR-122 （P<0.01）， down-regulated mRNA expression of IGF-1R （P<0.01）， and up-regulated protein expression of C/EBPα and HNF-4α in nude mouse transplanted tumor tissues （P<0.01）. The expression of IGF-1R protein in the high-dose CPU Ⅱ group was down-regulated （P<0.05）. Compared with the low-dose CPU Ⅱ group， the high-dose CPU Ⅱ group showed increased apoptotic cells （P<0.01）， up-regulated mRNA expression of miR-122 （P<0.01）， and increased expression of C/EBPα and HNF-4α proteins （P<0.01）. ConclusionCPU Ⅱ has an obvious inhibitory effect on the growth of transplanted hepatocellular carcinoma Hep3B cells in nude mice. The mechanism of action is related to enhancing the expression of transcription factors HNF-4α and C/EBPα， thereby promoting the expression of miR-122 and inhibiting the expression of its target gene IGF-1R.
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【Objective】 To investigate the effect of intravenous immunoglobulin(IVIG) with different Aβ antibody content on the cognitive function of Alzheimer′s disease model mice. 【Methods】 IVIG from 8 domestic blood products companies were selected. Enzyme-linked immunosorbent assay(ELISA) was used to detect the content of Aβ40/42 antibody. Three kinds of IVIG with high, middle and low Aβ42/40 antibody levels were selected to treat 3xTg-AD mice. Forty 3-month-old 3xTg-AD mice were randomly divided into 4 groups with 10 mice in each group(half male and half female). Three treat groups were intraperitoneally injected with three kinds of IVIG with 1g·kg-1 for 12 weeks(twice a week). The controls were injected with the same volume of saline. Behavioral tests were performed immediately by using the mouse behavior analysis system after a total of 24 injections. 【Results】 The concentrations of antibodies(μg/mL) against Aβ40 monomer in IVIG ranged 0.7±0.05 to 3.1±0.05, concentrations of antibodies against Aβ40 oligomer ranged 11.7±0.7 to 32.0±2.2, concentrations of antibodies against Aβ42 monomer ranged 1.8±0.1 to 27.9±0.3, and concentrations of antibodies against Aβ42 oligomeric ranged 2.3±0.1 to 49.4±2. High(IVIG-1), medium(IVIG-8) and low(IVIG-6) IVIG were selected for mice study. In the open field test, the time of four groups of mice entering the central area(s) was 0.5±0.9, 23.4±6.1(P<0.0001), 4.6±2.8 and 2.6±2.3, respectively; the number of feces(grains) was 1.6±0.7(P<0.0001), 1.2±0.4(P<0.0001), 2.4±0.5(P<0.001) and 3.8±0.8, respectively. In the novel object recognition test, the scores of exploring new objects were 71.3±29.5(P<0.05), 71.8±20.5(P<0.05), 75.9±26.9(P<0.01) and 25.6±23.7, respectively. In the Barnes maze test, the time of exploring the target hole in the IVIG-8 group was significantly longer than that in the control on the 6th day(50.3±19.3 vs 21±14.6, P<0.05) and the 13th day(58.2±20.9 vs 19.2±15.9, P<0.005), but there was no significant difference between the IVIG-1, 6 groups and the control. 【Conclusion】 There is a significant difference in the level of Aβ40/42 antibody among 8 kinds of domestic IVIG. Domestic IVIG could improve the cognitive function of 3-month-old 3xTg-AD mice after continuous intervention for 3 months. The improvement effect, however, was related to the Aβ antibody in IVIG, but not to the antibody concentration.
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【Objective】 To research the effect of the Fc, Fab and F(ab′)2 fragments of immunoglobulin G, the main components of Human Immunoglobulin(pH4) for Intravenous Injection(IVIG), on the phagocytic function of macrophages derived from THP-1 cells. 【Methods】 First of all, IVIG was digested with papain and pepsin to obtain Fc, Fab and F(ab′)2, and these components were then identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Afterwards, propylene glycol monomethyl ether acetate (PMA) was used to induce THP-1 cells to differentiate into M0 macrophages. Finally, the sensitized erythrocytes were labeled with carboxy fluorescein succinimidyl ester (CFSE), and the effect of the above components on the phagocytic ability of M0 macrophages to engulf sensitized erythrocytes was detected by flow cytometry. 【Results】 The identification results of SDS-PAGE showed that the prepared IgG fragments met the requirements of subsequent experiments. Flow cytometry performs showed that the phagocytosis model of M0 macrophages had been successfully established. When the concentration of Fc increased from 0.1μg/ mL to 10μg/ mL, the phagocytosis rate of erythrocytes sensitized by M0 macrophages decreased from (24.21±0.58) % to (12.27±0.19) %. When the concentration of IVIG protein increased from 0.1 μg/ml to 10 μg/ml, the phagocytosis rate decreased from (20.57±0.39) % to (0.20±0.03) %. Meanwhile, at the same protein concentration (10 μg/ml), the inhibitory effect of Fc on phagocytosis was only half that of IVIG. In addition, Fab, F(ab′)2, and human serum albumin could not inhibit phagocytosis of M0 macrophages. 【Conclusion】 IVIG can effectively inhibit the phagocytosis of THP-1 derived M0 macrophages, which is mainly dependent on the Fc, but not related to the Fab of IgG and F (ab′)2.
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ObjectiveTo observe the effects of Fuzitang （FZT） on the proliferation of MH7A cells， the human rheumatoid arthritis synovial fibroblasts， and the expression of miR-155 and explore its anti-rheumatoid arthritis mechanism. MethodMH7A cells were cultured in vitro and divided into a blank group， high- （25 g·L-1） and low-dose （12.5 g·L-1） FZT groups， and a positive drug group （hydroxychloroquine， 0.006 25 g·L-1）. The cell proliferation was detected by cell counting kit-8（CCK-8） method， and the change in the MH7A cell cycle was detected by flow cytometry. The mRNA expression of miR-155 and its downstream genes， including SH2 domain-containing inositol 5-phosphatase-1（SHIP-1）， protein kinase B 3（Akt3）， and mammalian target of rapamycin（mTOR）， was detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression of phosphatidylinositol 3-kinase （PI3K）， Akt3， and mTOR was detected by Western blot. ResultFZT in vitro in a concentration of 6.25 g·L-1 above could inhibit the proliferation of MH7A cells in the significant dose- and time-effect manner. Compared with the blank group， the FZT groups showed increased proportions of cells in the G2/M phase （P<0.05）， and the high-dose FZT group showed a decreased proportion of cells in the G0/G1 phase （P<0.05）. The arresting effect of FZT on the cell cycle was in a significant dose-effect manner. Compared with the blank group， the FZT groups showed down-regulated miR-155 and mTOR mRNA expression （P<0.05）， and the high-dose FZT group showed up-regulated SHIP1 mRNA expression and down-regulated Akt3 mRNA expression （P<0.05）. Compared with the blank group， the FZT groups showed reduced protein expression of PI3K， Akt3， and mTOR （P<0.05）. ConclusionFZT can significantly inhibit the proliferation of MH7A cells， and the mechanism is related to the promotion of the expression of SHIP-1 and down-regulation of the gene expression of the PI3K/Akt3/mTOR signaling pathway by down-regulating the expression of miR-155.
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COVID-19 has brought huge damage and impact to the economy, society and healthy systems of China and the world. As a blood product prepared from healthy human blood, human intravenous immunoglobulin have played an active role in the fight against the epidemic. This article summarized the treatment plans, expert consensus and clinical reports in China concerning immunoglobulin in the treatment of COVID-19, and discussed the related possible mechanism of action, aiming at providing references for the drugs screening of COVID-19.
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【Objective】 Tostudy the effect of sex-differentiated human IgG samples on Dendritic cells (DC) secretion of inflammation-related factors and explore the effect of residual sex hormones in IgG products (such as IVIg) on the secretion of IL-6 by DC. 【Methods】 According to the standard IVIg production process, the company was entrustedto prepare sex-differentiated plasma purified IgG samples, and two sex-differentiated IgG samples with different sex ratios (male to female ratio1: 0, 0: 1) were obtained. The samples and referenceswere treated with human DC (induced by THP-1 cells) respectively. After 24 h of culture, the chemokines (CCL2, CCL3, CCL4), adhesion molecule (ICAM-1) and inflammatory cytokines (IL-1, IL-6, IL-10, IL-12p70, IFN-) in the cell supernatant were detected, The effects of different samples on the secretion of inflammation-related factors by DC were compared. The effect of sex hormone residues on the anti-inflammatory ability of IgG products was preliminarily explored uing sex hormones and sex hormone receptor blockers. 【Results】 The samples in each group significantly inhibitedthe secretion of chemokines (CCL2, CCL3, CCL4) and the adhesion molecule (ICAM-1) by mature DC (compared with the PBS group, P<0.05), but significantly promoted the secretion of inflammatory cytokines (IL-1a/b, IL-6, IL-10, IL-12p70), compared with the PBS group(P<0.05). The results of sex hormone residues showed that therewere residues of estradiol (E2) and testosterone (TSTO) in sex-differentiated IgG samples and IVIg products. The experimental results of IVIg and sex hormone/sex hormone receptor blockers showed that residual E2 may promote the secretion of IL-6 by DC, which may be achieved through the E2 receptor ERb. 【Conclusion】 There are differences in the effect of IgG samples prepared from combined plasma with different sex ratios on the secretion of cytokines by DC, which may be related to the residual E2 in the products. The residual sex hormones in IVIg may promote the production and secretion of IL-6 through the sex hormone receptor ERb expressed in DC, and TSTO may have a collaboration effect to enhance the secretion-promoting effect of IL-6 by E2. This study provides a theoretical basis for whether sex hormone residues need to be considered in the quality control indicators of IVIg products.
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【Objective】 To investigate the level of atherosclerotic cardiovascular disease (ASCVD) related indexes in plasma donors from longevity area, and explore its influencing factors. 【Methods】 1 027 plasma donors from longevity hotspot (Bama, Guangxi province) and 1 816 donors from non-longevity region (Shimen, Hunan province) who donated plasma during June to November 2018 were randomly selected. Triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B), and fructosamine (FUN) of the two groups were measured and statistically analyzed. 【Results】 Compared with the non-longevity region group, the TG, TC and FUN levels of longevity hotspot group were lower (1.41±0.96 vs 2.31±1.28, 3.89±0.92 vs 4.04±0.82, 176.65±26.60 vs 200.33±34.19; all P<0.05), but HDLC, LDLC, Apo-A1 and Apo-B levels were higher (1.11±0.32 vs 0.96±0.25, 2.53±0.70 vs 2.29±0.56, 1.56±0.28 vs 1.23±0.18, 0.80±0.27 vs 0.72±0.19; all P<0.05). The yield (%) of high TG(12.0 vs 40.01) and FUN(0.58 vs 2.48), low HDLC(24.63 vs 43.90) and Apo-A1(1.66 vs 22.56) were lower in longevity area than those in non-longevity region (all P<0.05), but high LDLC(2.73 vs 0.28) and Apo-B(4.09 vs 0.22) yield(%) were higher in longevity area group ( P<0.05). The levels of TC, HDLC, LDLC, Apo-A1 and Apo-B were significantly different by ages (all P < 0.01), presenting positively correlated with age, significantly by gender and nationality, and slightly by blood type. 【Conclusion】 The ASCVD indexes of plasma donors from Bama were different from those from Shimen. Age, nationality, gender and blood type of donors from Bama all had a certain influence on these indexes levels.
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【Objective】 To obtain the quality information of von Willebrand factor (vWF) in coagulation factor Ⅷ (FⅧ) concentrates in China. 【Methods】 FⅧ concentrates produced by 7 domestic blood product manufactures and 1 foreign manufacture were collected, then FⅧ and vWF contained in FⅧ concentrates were evaluated. 【Results】 The activity loss of vWF was more than 25% in 2 of the 7 domestic FⅧ concentrates. The ratio of vWF activity to FⅧ activity in FⅧ concentrates from different domestic manufactures was significantly different (P<0.05). The ratio in FⅧ concentrates prepared by C, D, F manufacturer was greater than 1, which was similar to that in willate@ approved abroad for the treatment of vWD. The ratio in FⅧ concentrates prepared by E manufacturer was greater than 0.7 and less than 1, and by A, B, G manufacturers was less than 0.5. In addition, the specific activities of FⅧ and vWF were significantly different among different FⅧ concentrates in China (P<0.05), and the specific activities of FⅧ and vWF were much lower than that of willate@. 【Conclusion】 The variation of vWF quality between domestic FⅧ concentrates and willate@ is mainly due to the different in vWF content. After the comprehensive consideration of various indicators, the FⅧ concentrates made by C and D manufacturers may be used in the treatment of vWD.
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Growth differentiation factor 11 (GDF11), a member of the transforming growth factor β superfamily, is widely expressed in multiple species such as human, mouse, rat, horse and sheep. Moreover, GDF11 is implicated in diverse biological functions and plays an important role in regulating anterior/posterior patterning, skeletal muscle regeneration, bone formation, vascular remodeling and neurogenesis. Recent studies have revealed that GDF11 in blood reverses age-related cardiac hypertrophy, skeletal muscle dysfunction and age-related cognitive decline, suggesting the potential value of GDF11 on anti-ageing. However, some other studies questioned the effects of GDF11 on anti-ageing. Herein, we highlighted structural characteristics of GDF11, advances in effects of GDF11 on anti-ageing, and the controversies of GDF11, to provide new insights for future studies on anti-ageing.
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Objective@#To understand the current situation and associated factors of unintentional injury among preschool children in Shunyi District, and to provide reference for the development of unintentional injury intervention measures.@*Methods@#Three kindergartens in Shunyi district were selected through stratified cluster sampling method, and all the parents were surveyed online by self-designed questionnaire.@*Results@#The proportion of low, medium and high risk assessment of unintentional injury in preschool children were 59.5%, 37.5% and 3.0%, respectively. Risk of unintentional injury increased significantly with age and grade(χ 2=12.35, 12.70, P<0.05). The risk of unintentional injury in inter-generational care (3.7%) was higher than that in parental care(2.4%). The higher the education level of the primary caretaker and family income, the higher level of unintentional injury risk(χ 2=11.23, 14.10, P<0.05).There were significant differences in the risk for burning, poisoning, other accidental injury, prevention of accidental injury and total score of unintentional injury among children of different ages and classes(F=8.26，5.61，4.95，6.15，7.86；9.88，8.39，4.25，6.27，7.55，P<0.05). There was statistical significance in burning risk between boys and girls(t=-4.27, P<0.05). There was statistical significance in unintentional injury prevention between children of different residence(t=9.11, P<0.05). There were significant differences in behavior supervision among risk among children of different ages and grades(P<0.05). Multiple linear regression analysis showed that education level of primary caregivers (college:B=-2.66, 95%CI=-4.69--0.63; bachelor degree or higher:B=-3.80, 95%CI=-5.90--1.70), annual family income (B=-2.82, 95%CI=-4.80--0.84) were associated with unintentional injury risk of preschool children(P<0.05).@*Conclusion@#Health education of unintentional injury prevention among preschool children should focus on the primary caretaker with low education and low family income, which is crucial for prevention of children s injury.
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Objective:To explore the correlation between the expression levels of serum estradiol and otolin-1 and the recurrence of postmenopausal benign paroxysmal positional vertigo (BPPV).Methods:A total of 116 postmenopausal female patients who were diagnosed with primary BPPV in the Vertigo Treatment Center of Beijing Geriatric Hospital from January 2018 to December 2019 were selected as the research objects. They were divided into recurrence group (27 cases) and the non-recurrence group (89 cases) according to the recurrence during follow-up. The basic data, laboratory indexes and complications of the two groups were compared. The serum estradiol level was detected by electrochemiluminescence and the serum otolin-1 level was detected by enzyme-linked immunosorbent assay. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum estradiol and otolin-1 in the recurrence of postmenopausal BPPV patients; Multivariate logistic regression was used to analyze the risk factors of recurrence in postmenopausal BPPV patients.Results:The proportion of severe cough in the recurrence group was higher than that in the non-recurrence group ( P<0.05); the level of estradiol in the recurrence group was significantly lower than that in the non-recurrence group ( P<0.05), and the level of otolin-1 was significantly higher ( P<0.05); ROC results showed that the areas under the curve (AUCs) of serum estradiol and otolin-1 for predicting the recurrence of postmenopausal BPPV patients were 0.852 (95% CI: 0.774-0.911) and 0.722 (95% CI: 0.631-0.801) respectively, and the cut-off values were 18.09 pg/ml and 361.79 pg/ml respectively; Multivariate logistic regression analysis showed that severe cough, estradiol ≤18.09 pg/ml, and otolin-1 >361.79 pg/ml were independent risk factors for recurrence in postmenopausal BPPV patients ( P<0.05). Conclusions:The serum estradiol level of patients with postmenopausal BPPV recurrence decreases, and the level of otolin-1 increases. The abnormal level is an independent risk factor affecting the recurrence of patients with postmenopausal BPPV.
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The purpose of early treatment of ischemic stroke is to limit the expansion of the infarct core. However, even after successful recanalization, the infarct may increase and result in poor outcomes. This article reviews other possible factors that may affect early infarct enlargement in addition to vascular recanalization, in order to provide more therapeutic targets for the rescue of ischemic tissues. Understanding these factors may be helpful for clinicians to predict the progress of infarction and adopt individualized treatments to improve the clinical outcomes of patients with ischemic stroke.
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Objective@#To investigate the value of abnormal expression of HLA-DR on peripheral blood monocytes in evaluating the immune function status, clinical prognosis and severity of patients with hand, foot and mouth disease (HFMD).@*Methods@#From June 2017 to October 2018, 100 cases of mild HFMD, 80 cases of severe HFMD, 32 cases of critical HFMD and 40 healthy children (control group) were recruited in this study. The patients were divided into two groups, lower DR group (DR-L, HLA-DR expression<30%) and normal DR group (DR-N, HLA-DR expression>30%) according to the HLA-DR expression on monocytes. Flow cytometry was used to detect the CD14+ monocytes expressing HLA-DR and the absolute count of lymphocyte subsets. Immunoturbidimetry was used to detect the levels of IgG, IgM and IgA in plasma samples. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of IFN-γ and IL-10 in plasma samples. Pediatric critical illness score (PCIS) and the pediatric risk of mortality Ⅲ (PRISM Ⅲ) were used to estimate the severity of HFMD.@*Results@#① There were significant differences in HLA-DR expression on monocytes among children with mild, severe and critical HFMD (F=47.102, P<0.05). Patients with critical HFMD had the lowest HLA-DR expression (P<0.05). ② The numbers of CD14+ monocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells and NK cells in peripheral blood of the DR-L group were significantly lower than those of the DR-N group and the normal group, especially in patients with severe or critical HFMD (P<0.05). ③ There was no significant difference in the level of IgG, IgA or IgM among the DR-L, DR-N and control groups (P>0.05). ④ Compared with the DR-N group, the DR-L group showed decreased IFN-γ level and increased IL-10 level in plasma (P<0.05). The ratio of IFN-γ/IL-10 of the DR-L group was lower than that of the DR-N group and control group (P<0.05). HLA-DR expression was negatively correlated with the concentration of IL-10 in plasma (r=-0.704, P<0.05), and positively correlated with the IFN-γ/IL-10 ratio (r=0.773, P<0.05). ⑤ Compared with the DR-N group, the DR-L group showed lower PCIS and higher PRISM Ⅲ. HLA-DR expression was positively correlated with PCIS (r=0.715, P=0.00) and negatively correlated with PRISM Ⅲ (r=-0.610, P=0.00). ⑥ The incidence of pulmonary edema, pulmonary hemorrhage and cardiopulmonary failure and the mortality of HFMD patients in the DR-L group were significantly higher than those in the DR-N group (P<0.05).@*Conclusions@#Patients with severe or critical HFMD had cellular immune dysfunction and abnormal HLA-DR expression on CD14+ monocytes. Assessing the expression of HLA-DR on monocytes could be used to evaluate the cellular immunity of patients with severe or critical HFMD. Lower expression of HLA-DR on CD14+ monocytes might be associated with severe HFMD and poor prognosis.
ABSTRACT
Objective To investigate the value of abnormal expression of HLA-DR on peripheral blood monocytes in evaluating the immune function status, clinical prognosis and severity of patients with hand, foot and mouth disease (HFMD). Methods From June 2017 to October 2018, 100 cases of mild HFMD, 80 cases of severe HFMD, 32 cases of critical HFMD and 40 healthy children (control group) were recruited in this study. The patients were divided into two groups, lower DR group (DR-L, HLA-DR expres-sion<30％ ) and normal DR group (DR-N,HLA-DR expression>30％ ) according to the HLA-DR expression on monocytes. Flow cytometry was used to detect the CD14+ monocytes expressing HLA-DR and the absolute count of lymphocyte subsets. Immunoturbidimetry was used to detect the levels of IgG, IgM and IgA in plas-ma samples. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of IFN-γ and IL-10 in plasma samples. Pediatric critical illness score ( PCIS) and the pediatric risk of mortality Ⅲ(PRISM Ⅲ) were used to estimate the severity of HFMD. Results ① There were significant differences in HLA-DR expression on monocytes among children with mild, severe and critical HFMD (F = 47. 102, P<0. 05). Patients with critical HFMD had the lowest HLA-DR expression (P<0. 05). ② The numbers of CD14+ monocytes, CD3+T cells, CD4+T cells, CD8+T cells, B cells and NK cells in peripheral blood of the DR-L group were significantly lower than those of the DR-N group and the normal group, especially in pa-tients with severe or critical HFMD (P<0. 05). ③ There was no significant difference in the level of IgG, IgA or IgM among the DR-L, DR-N and control groups (P>0. 05). ④ Compared with the DR-N group, the DR-L group showed decreased IFN-γ level and increased IL-10 level in plasma (P<0. 05). The ratio of IFN-γ/ IL-10 of the DR-L group was lower than that of the DR-N group and control group (P<0. 05). HLA-DR expression was negatively correlated with the concentration of IL-10 in plasma (r= -0. 704, P<0. 05), and positively correlated with the IFN-γ/ IL-10 ratio (r = 0. 773, P<0. 05). ⑤ Compared with the DR-N group, the DR-L group showed lower PCIS and higher PRISM Ⅲ. HLA-DR expression was positively corre-lated with PCIS (r=0. 715, P=0. 00) and negatively correlated with PRISM Ⅲ (r = -0. 610, P = 0. 00).⑥ The incidence of pulmonary edema, pulmonary hemorrhage and cardiopulmonary failure and the mortality of HFMD patients in the DR-L group were significantly higher than those in the DR-N group (P<0. 05).Conclusions Patients with severe or critical HFMD had cellular immune dysfunction and abnormal HLA-DR expression on CD14+ monocytes. Assessing the expression of HLA-DR on monocytes could be used to evaluate the cellular immunity of patients with severe or critical HFMD. Lower expression of HLA-DR on CD14+ monocytes might be associated with severe HFMD and poor prognosis.