Bone density and bone metabolism in plasmapheresis donors / 中国输血杂志

【Objective】 To investigate the level of serum bone metabolism and biochemical markers and bone density of plasmapheresis donors, and to provide scientific basis for ensuring the health and safety of plasmapheresis donors in China. 【Methods】 A total of 437 plasmapheresis donors from Linwu plasmapheresis station in Hunan Province from July 1 to September 30, 2022 were recruited to determine the levels of total serum calcium, albumin, serum 25-hydroxyvitamin D (25OHD), serum type I procollagen N-terminal propeptide (P1NP), and collagen type 1 crosslinked carboxyl-terminal peptide (β-CTX). Dual-energy X-ray method was used to measure the bone density of the anteroposterior lumbar spine (L1-L4) and bilateral femoral neck bone density of plasmapheresis donors. Plasmapheresis donors were grouped according to the type of plasma donation (first-time and repeat plasmapheresis donors) and the total number of plasma donations to assess the differences in bone density and serum bone metabolism biochemical markers between groups. The dose-response relationship between the total number of plasmapheresis donations and biochemical indexes was analyzed by limiting cubic spline, and the influencing factors of different indexes were explored by multiple linear regression. 【Results】 A total of 437 plasmapheresis donors were included in this study, including 187 first-time plasmapheresis donors and 250 repeat plasmapheresis donors. There were no significant differences in bone density and prevalence of osteoporosis between first-time donors and repeat donors (P>0.05). There was also no significant difference in bone density levels between groups of total number of plasmapheresis donations. The levels of albumin and 25OHD decreased with the increase of the total number of plasma donations, while the serum P1NP level was positively correlated with the total number of plasma donations. The results of the restriction cubic spline showed that the total number of plasmapheresis donations had a nonlinear dose-response relationship with 25OH and P1NP (P<0.05). The results of multiple linear regression showed that the frequency of plasmapheresis donation was the influencing factor of 25OHD, and the total number of plasmapheresis donation was the influencing factor of P1NP. 【Conclusion】 Plasmapheresis donation does not affect the bone health of donors and increase the risk of osteoporosis due to the use of long-term anticoagulants, but it will increase the osteogenic activity of plasmapheresis donors. It is recommended that middle-aged and elderly plasmapheresis donors supplement vitamin D appropriately.

Desalination effect on FⅧ components: a compartive study among 5 desalination methods / 中国输血杂志

【Objective】 To compare the desalination effects of five desalination methods and their effects on the components for human coagulation factor Ⅷ(FⅧ), and provide reference for selection of protein desalination methods. 【Methods】 Sephadex G-25 Medium gel, Fractogel EMD BioSEC gel, ultrafiltration, room temperature dialysis and 4℃ dialysis were used to desalt human FⅧ. The desalination effect was evaluated by the removal rate of Na +, citrate ion and glycine. FⅧ protein recovery, FⅧ activity (FⅧ∶C), VWF antigen (VWF∶Ag), VWF activity(VWF∶Ac), VWF polymers and SDS-PAGE analysis before and after desalination were compared to evaluate the effect of desalination on FⅧ components. 【Results】 In terms of desalination effect, the removal rate of Na+ was the lowest in ultrafiltration desalination, while that of Fractogel EMD BioSEC gel was the highest [(97.90±0.06) % vs (99.82±0.07) %]. Except that there was no statistical significance between Sephadex G-25 Medium gel desalination and Fractogel EMD BioSEC gel desalination (P=0.90), the removal rates of the other four methods were statistically significant. The removal rate of glycine was the lowest in ultrafiltration desalination, wihle that of Fractogel EMD BioSEC gel desalination was the highest [(95.78±0.42) % vs (99.81±0.08) %]. Significant difference in glycine removal was noticed in ultrafiltration desalination, but not among the other four desalination methods. There was no significant difference in the removal rate of citrate ions among the five methods (P=0.85). For the effect of FⅧ components, FⅧ∶C, VWF∶Ag, VWF∶Ac and protein recovery rates of ultrafiltration desalination were the highest, with (18.34±1.99) IU/mL, (11.81±0.33) IU/mL, (12.26±0.58) IU/mL and (97.13±1.37) %, respectively. There was no significant change in VWF∶Ac/VWF∶Ag before and after desalination by the five methods. SDS-PAGE and VWF polymer analysis showed that different desalination methods had no significant impact on protein composition. 【Conclusion】 Although different desalination methods had no significant effect on the composition of FⅧ protein, the desalination effect was different. Moreover, different desalination methods had significant effects on protein recovery, FⅧ∶C, VWF∶Ag and VWF∶Ac. The selection of desalination methods should be more considered during protein processing,

Binding and carrying role of human serum albumin from various sources to sphingosine-1-phosphate / 中国输血杂志

【Objective】 To investigate the binding and carrying effects of human serum albumin (HSA) from various sources on sphingosine-1-phosphate (S1P). 【Methods】 Utilizing human plasma-derived HSA (pHSA) and recombinant HSA (rHSA) samples as the focal points of our investigation, LC-MS/MS technology was employed to meticulously compare and analyze the disparities in S1P content among the aforementioned samples. Subsequently, under physiological concentration conditions, S1P was directly introduced to HSA samples for loading processing, facilitating a comprehensive comparison of the binding efficacy of HSA from different sources to S1P. Within a serum-free culture setting, HSA samples from various sources were co-cultured with HUVEC cells. The alterations in S1P content within the cell culture supernatant across different treatment groups were meticulously analyzed, allowing for a nuanced comparison of the S1P carry effects exerted by HSA from different sources on cells.The interaction between HSA and S1P molecules from different sources was analyzed and their affinity was calculated using surface plasmon resonance (SPR) technology. Furthermore, leveraging AutoDock Vina software and the Molprophet platform, the molecular docking analysis of HSA and S1P was conducted, aiming to predict the key binding pocket domain of S1P within HSA. 【Results】 All pHSA samples exhibited detectable levels of S1P (ranging from 3.31±0.03 to 30.35±0.07 μg/L), with significant variations observed among pHSA samples from different manufacturers (P<0.001). Conversely, S1P was undetectable in all rHSA samples. Upon load treatment, the binding affinity of HSA from diverse sources to S1P demonstrated significant discrepancies (P<0.001), with rHSA exhibiting approximately double the average S1P loading compared to pHSA (ΔCrHSA=801.75±142.45 μg/L vs ΔCpHSA=461.94±85.73 μg/L; P<0.001, t=5.006). Co-culture treatment outcomes revealed a significant elevation in S1P concentration within the supernatant after 6 hours of co-culture across all HSA sample processing groups with HUVEC cells, while no changes were observed in the supernatant of the blank control group. Notably, significant differences in supernatant S1P concentration were observed among treatment groups at 6 h, 12 h, and 24 h (P<0.001). SPR analysis unveiled a stronger affinity of pHSA for S1P compared to rHSA (KDpHSA-S1P: 2.38E-06, KDrHSA-S1P: 3.72E-06). Molecular docking analysis and binding pocket prediction suggested that the key binding pocket of HSA and S1P may reside in the IB subdomain of the HSA molecule. 【Conclusion】 HSA from various sources exhibits distinct binding and carrying effects on S1P, which appear to be closely associated with the IB subdomain of the HSA molecule.

Development of the method for determinating ADCC biological activity of IVIG / 中国输血杂志

【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.

Effect of Compound Phyllanthus urinaria Ⅱ on Growth and Expression of miR-122 and IGF-1R of Hepatocellular Carcinoma Hep3B Cells in Nude Mice / 中国实验方剂学杂志

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.

Effect of IgG dimer concentration on the binding ability of IgG Fc fragment in IVIG to THP-1 cell surface receptors / 中国输血杂志

【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.

Diversity of IgG autoantibodies of 4 Chinese intravenous immunoglobulins / 中国输血杂志

【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.

Investigation and analysis of characteristics and mobility of the overlapping population of voluntary blood donation and plasmapheresis donation / 中国输血杂志

【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.

Analysis of the impact of setting up plasmapheresis station on the collection volume of voluntary blood donation based on panel vector autoregressive model / 中国输血杂志

【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.

The risk of Alzheimer′s disease transmitted by blood transfusion based on APP/PS1 double transgenic mice / 中国输血杂志

【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.

Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture (version 2023) / 中华创伤杂志

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Effect of IgG fragments in IVIG(pH4)on phagocytosis of sensitized erythrocytes by macrophage / 中国输血杂志

【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.

Preliminary study on the effect of IVIG with different Aβ antibody on cognitive function of Alzheimer′s disease model mice / 中国输血杂志

【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.

Effect of Fuzitang on Proliferation of Human Rheumatoid Arthritis Synovial Fibroblast Cell Line MH7A and Expression of miR-155 / 中国实验方剂学杂志

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.

Advances in the anti-ageing effects of GDF11 in blood / 中国输血杂志

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.

Research progress of human intravenous immunoglobulin in the treatment ofCOVID-19 / 中国输血杂志

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.

Correlation between the expression of serum estradiol and otolin-1 and the recurrence of postmenopausal benign paroxysmal positional vertigo / 中国医师杂志

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.

Effect of residual sex hormones in sex-differentiated human IgG samples on DC secretion of inflammation-related factors / 中国输血杂志

【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.

Efficacy analysis of von Willebrand factor in human coagulation factor FⅧ concentrates in China / 中国输血杂志

【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.

ASCVD indexes in Bama and Shimen area plasma donors, China / 中国输血杂志

【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.