Chinese Donors Research Articles

Sustentaculum tali in Chinese population: anatomy and clinical significance.

Previous studies lacked adequate quantitative data on sustentaculum tali (ST), especially in Chinese population. The aims of this study are to explore the quantitative morphology of ST in dried bone specimens, and to discuss its implications related to ST screw fixation, talar articular facet variation, as well as subtalar coalitions. A total of 965 dried intact calcanei from Chinese adult donors were evaluated. All linear parameters were measured by two observers with a digital sliding vernier caliper. Most parts of ST body can accommodate a commonly-used 4-mm-diameter screw, but the minimum height of anterior ST is only 4.02mm. The shapes of the STs are slightly affected by left-right, subtalar facet, but the subtalar coalition may potentially increase the sizes of STs. The incidence of tarsal coalition is 14.09%. Among the osseous connection, there are 58.8% of type A articular surface and 76.5% of middle and posterior talar facet (MTF and PTF) involvement. ROC curve shows that subtalar coalition will be detected when ST length is greater than 16.815mm. Theoretically, all the STs can accommodate 4mm diameter screw, but a 3.5mm diameter screw is recommended to be placed in the middle or posterior of the small ST for safety. The shapes of the STs are greatly influenced by the subtalar coalition, while they are less affected by left-right, subtalar facet. The osseous connection is common in type A articular surface and always involved in the MTF and PTF. The cut-off value of the length of STs was confirmed as 16.815mm for predicting subtalar coalition.

The impact of the COVID-19 pandemic on semen quality of uninfected men

BackgroundCoronavirus disease 2019 (COVID-19) has spread rapidly worldwide since its discovery in December 2019. Research published since the COVID-19 outbreak has focused on whether semen quality and reproductive hormone levels are affected by COVID-19. However, there is limited evidence on semen quality of uninfected men. This study aimed to compare semen parameters among uninfected Chinese sperm donors before and after the COVID-19 pandemic to determine the impact of the COVID-19 pandemic-related stress and lifestyle changes on uninfected men.ResultsAll semen parameters were non-significant except semen volume. The average age of sperm donors was higher after the COVID-19 (all P < 0.05). The average age of qualified sperm donors increased from 25.9 (SD: 5.3) to 27.6 (SD: 6.0) years. Before the COVID-19, 45.0% qualified sperm donors were students, but after the COVID-19, 52.9% were physical laborers (P < 0.05). The proportion of qualified sperm donors with a college education dropped from 80.8 to 64.4% after the COVID-19 (P < 0.05).ConclusionAlthough the sociodemographic characteristics of sperm donors changed after the COVID-19 pandemic, no decline in semen quality was found. There is no concern about the quality of cryopreserved semen in human sperm banks after the COVID-19 pandemic.

Using Next-Generation Sequencing Technology to Confirm the HLA Rare Alleles Detected by PCR-SSOP

To confirm the HLA genotypes of the samples including 4 cases of magnetic bead probe HLA genotyping result pattern abnormality and 3 cases of ambiguous result detected by PCR sequence-specific oligonudeotide probe (SSOP) method. All samples derived from HLA high-resolution typing laboratory were detected by PCR-SSOP. A total of 4 samples of magnetic bead probe HLA genotyping result pattern abnormality and 3 samples of ambiguous result were further confirmed by PCR sequence-based typing (SBT) technology and next-generation sequencing (NGS) technology. A total of 4 samples of magnetic bead probe HLA genotyping result pattern abnormality were detected by PCR-SSOP method. The results of SBT and NGS showed that the HLA-A genotype of sample 1 did not match any known genotypes. NGS analysis revealed that the novel allele was different from the closest matching allele A*31:01:02:01at position 154 with G>A in exon 2, which resulting in one amino acid substitution at codon 28 from Valine to Methionine (p.Val28Met). The HLA-C genotype of sample 2 was C*03:119, 06:02, sample 3 was C*03:03, 07:137, and sample 4 was B*55:02, 55:12. A total of 3 samples with ambiguous result were initially detected by PCR-SSOP method. The re-examination results of SBT and NGS showed that the HLA-B genotype of sample 5 was B*15:58, 38:02, sample 6 was DRB1*04:05, 14:101, and sample 7 was DQB1*03:34, 05:02. Among them, alleles C*03:119, C*07:137 and DRB1*14:101 were not included in the Common and Well-documented Alleles (CWD) v2.4 of the Chinese Hematopoietic Stem Cell Donor Database. The abnormal pattern of HLA genotyping results of magnetic probe by PCR-SSOP method suggests that it may be a rare allele or a novel allele, which needs to be verified by sequencing.

Characterization of a VRC01-like antibody lineage with immature VL from an HIV-1 infected Chinese donor

Because of the broadly neutralizing activity, VRC01-class antibodies are attractive templates for HIV-1 vaccine development and suitable candidates for HIV-1 therapy. Although we previously revealed that glycans in gp120 may have a role in the uneven evolution of the VH and the VL of a VRC01-class antibody, DRVIA7, which was isolated from an elite neutralizer, it is unknown whether the immature VH or VL of VRC01-class antibodies are also present in the non-neutralizer. We identified a CD4bs-directed antibody – 263A9 – with low neutralizing activity from a donor whose plasma had a moderate neutralizing spectrum in this study. The 263A9 antibody, in particular, was a VRC01-like antibody whose VH and VL were derived from IGHV1–2 * 04 and IGKV1–33 * 01, respectively, and both had significant SHM rates. Surprisingly, we discovered that the VL of 263A9 hindered the neutralizing activity of the antibody, and that replacing its LCDR1 and LCDR3 with VRC01 increased the neutralizing breadth of the chimeric antibodies. Following that, an antibodyomics research revealed that the VL of 263A9 lineage was remote from VRC01-class antibodies. We also looked at the envelope sequence characteristics of donor CBJC263 and discovered that N276 in the D loop and N460/N463 glycans in the V5 region of gp120 potentially interact with VL of 263A9 at the structural level. This study will provide valuable information for immunogen screening and vaccine development for eliciting VRC01-class antibodies. Data availability statementThe original data presented in the study are included in the article or Supplementary materials. Further inquiries can be directed to the corresponding author. HIV Env sequences in the manuscript had been deposited into the GenBank with the accession numbers from OL466822 to OL466859.

Cytomegalovirus seroprevalence, infection, and disease in Chinese thoracic organ transplant recipients: a retrospective cohort study

BackgroundCytomegalovirus (CMV) infection is a leading cause of morbidity and mortality after transplantation. This study aimed to investigate CMV seroprevalence, infection, and disease in Chinese thoracic organ transplant recipients.MethodsThe clinical data of the patients who underwent lung and/or heart transplantation between January 2015 and October 2020 were retrospectively collected from four transplantation centers in China.ResultsA total of 308 patients were analyzed. The CMV serostatus was donor positive (D+) recipient negative (R−) in 19 (6.17%) patients, D+/R+ in 233 (75.65%), D−/R+ in 36 (11.69%), and D−/R− in 20 (6.50%). CMV DNAemia was detected in 52.3% of the patients and tissue-invasive CMV disease was diagnosed in 16.2% of the patients. Only 31.8% of the patients adhered to the postdischarge valganciclovir therapy. The D+/R− serostatus (odds ratio [OR]: 18.32; 95% confidence interval [CI]:1.80-188.68), no valganciclovir prophylaxis (OR: 2.64; 95% CI: 1.05–6.64), and higher doses of rabbit anti-human thymocyte globulin (> 2 mg/kg) (OR: 4.25; 95% CI: 1.92–9.42) were risk factors of CMV disease.ConclusionCMV seroprevalence was high in Chinese thoracic organ transplant donors and recipients. The low adherence rate to the postdischarge CMV prophylaxis therapy in Chinese patients is still an unresolved issue.

Identification of the novel HLA-DRB1*04:316 allele by next-generation sequencing in a Chinese bone marrow donor.

HLA-DRB1*04:316 differs from HLA-DRB1*04:03:01:01 by one nucleotide substitution at position 161 in exon 2.

A novel HLA allele, HLA-B*07:248, detected in a Chinese hematopoietic stem cell donor and platelet donor.

HLA-B*07:248 has one nucleotide change from HLA-B*07:18:01 where Tyrosine (Y) is changed to Serine (S).

Immune repertoire analysis of normal Chinese donors at different ages.

This study investigated the characteristics of the immune repertoire in normal Chinese individuals of different ages. In this study, all seven receptor chains from both B and T cells in peripheral blood of 16 normal Chinese individuals from two age groups were analyzed using high-throughput sequencing and dimer-avoided multiplex PCR amplification. Normal in this study is defined as no chronic, infectious or autoimmune disease within 6months prior to blood draw. We found that compared with the younger group, the clonal expression of T-cell receptor repertoire increased in the older group, while diversity decreased. In addition, we found that the T-cell receptor repertoire was more significantly affected by age than the B-cell receptor repertoire, including significant differences in the use of the unique TCR-alpha and TCR-beta V-J gene combinations, in the two groups of normal participants. We further analyzed the degree of complementarity determining region 3 sequence sharing between the two groups, and found shared TCR-alpha, TCR-gamma, immunoglobulin-kappa and immunoglobulin-lambda chain complementarity determining region 3 sequences in all subjects. Taken together, our study gives us a better understanding of the immune repertoire of different normal Chinese people, and these results can be applied to the treatment of age-related diseases. Immune repertoire analysis also allows us to observe participant's wellness, aiding in early-stage diagnosis.

Cationic Mechanosensitive Channels Mediate Trabecular Meshwork Responses to Cyclic Mechanical Stretch.

The trabecular meshwork (TM) is responsible for intraocular pressure (IOP) homeostasis in the eye. The tissue senses IOP fluctuations and dynamically adapts to the mechanical changes to either increase or decrease aqueous humor outflow. Cationic mechanosensitive channels (CMCs) have been reported to play critical roles in mediating the TM responses to mechanical forces. However, how CMCs influence TM cellular function affect aqueous humor drainage is still elusive. In this study, human TM (HTM) cells were collected from a Chinese donor and subjected to cyclically equiaxial stretching with an amplitude of 20% at 1 Hz GsMTx4, a non-selective inhibitor for CMCs, was added to investigate the proteomic changes induced by CMCs in response to mechanical stretch of HTM. Gene ontology enrichment analysis demonstrated that inhibition of CMCs significantly influenced several biochemical pathways, including store-operated calcium channel activity, microtubule cytoskeleton polarity, toll-like receptor signaling pathway, and neuron cell fate specification. Through heatmap analysis, we grouped 148 differentially expressed proteins (DEPs) into 21 clusters and focused on four specific patterns associated with Ca2+ homeostasis, autophagy, cell cycle, and cell fate. Our results indicated that they might be the critical downstream signals of CMCs adapting to mechanical forces and mediating AH outflow.

Comparison of twelve human milk oligosaccharides in mature milk from different areas in China in the Chinese Human Milk Project (CHMP) study

Human milk oligosaccharides (HMOs) act as a vital role in the development of infant’s gut microbiome and immune function. This study aimed to measure 12 oligosaccharides in milk from Chinese donors (n = 203), and evaluated the influences of multiple factors on the HMOs profiles. The results indicated that concentrations of 6′-sialyllactose were the highest among 12 oligosaccharides (2.31 ± 0.81 g/L). HMOs concentrations varied depending on geographical location. Latitude was observed to be related to concentrations of Lacto-N-neohexaose, lacto-N-fucopentaose III, 3′-sialyllactose (r = -0.67, r = +0.63 and r = +0.50, respectively). Environmental factors like seasons correlated with lacto-N-difucohexaose Ⅱ, Lacto-N-neohexaose and 2′-fucosyllactose (r = -0.47, r = -0.4, r = -0.35, respectively). Several HMOs concentrations were correlated with maternal diet. As a consequence, the HMOs profiles measured were influenced by geographical, environmental, maternal anthropometric as well as dietary factors.

Reduction of Pre-Existing Adaptive Immune Responses Against SaCas9 in Humans Using Epitope Mapping and Identification.

The CRISPR-Cas9 system is increasingly being used as a gene editing therapeutic technique in complex diseases but concerns remain regarding the clinical risks of Cas9 immunogenicity. In this study, we detected antibodies against Staphylococcus aureus Cas9 (SaCas9) and anti-SaCas9 T cells in 4.8% and 70% of Chinese donors, respectively. We predicted 135 SaCas9-derived B cell epitopes and 50 SaCas9-derived CD8+ T cell epitopes for HLA-A*24:02, HLA-A*11:01, and HLA-A*02:01. We identified R338 as an immunodominant SaCas9 B cell epitope and SaCas9_200-208 as an immunodominant CD8+ T cell epitope for the three human leukocyte antigen allotypes through immunological assays using sera positive for SaCas9-specific antibodies and peripheral blood mononuclear cells positive for SaCas9-reactive T cells, respectively. We also demonstrated that an SaCas9 variant bearing an R338G substitution reduces B cell immunogenicity and retains its gene-editing function. Our study highlights the immunological risks of the CRISPR-Cas9 system and provides a solution to mitigate pre-existing adaptive immune responses against Cas9 in humans.

Chinese aid and local political attitudes

This paper investigates whether and how foreign aid generates pro-authority attitudes in recipient regions. With a retrospection to the literature on the soft-power implications of aid, through which donors seek to cultivate specific values, this paper contributes to the investigation of the mechanisms behind the correlation. Combining a geo-referenced dataset on Chinese aid projects obtained from AidData with the political attitudes of residents from four World Value Survey waves across 526 sub-national regions in 47 developing countries, we use a difference-in-difference-in-differences (DDD) type of approach and an instrumental variable (IV) method to address the endogeneity issues. We show that Chinese infrastructure aid significantly motivated a positive attitude toward several organs of government in the regions where the aid was implemented. The main channels of this effect are improved welfare and increased affinity for the values espoused by Chinese donors, occurring through the interaction between residents in the aid-receiving regions and Chinese enterprises and their employees dispatched to these regions.

Generation of an induced pluripotent stem cell line (ZZUi034-A) from a 65 year old Chinese female donor with sendai virus reprogramming protocol

Peripheral blood was extracted from a 65 year old Chinese female health donor. Induced pluripotent stem cells (iPSC) were reprogrammed with the 4 reprogramming factors: Klf-4, c-Myc, Oct-4, Sox-2, using sendai virus reprogramming protocol. The iPSC line showed pluripotency which was confirmed by immunofluorescent staining; the iPSC line was also able to form embryoid bodies in vitro and differentiate into the 3 germ layers in vivo. The iPSC line also showed normal karyotype. This healthy iPSC line can be served as healthy control for disease mechanism and disease modeling study.

The MDM2 Single-Nucleotide Polymorphism T309G Is Associated With the Development of Epimacular Membranes.

Purpose: To investigate the role of the mouse double minute 2 (MDM2) gene single-nucleotide polymorphism (SNP) T309G in the development of epimacular membranes (EMMs) by analyzing the genotype distribution and consistency of the polymorphism in paired membrane-blood samples. Methods: This was a cross–sectional genetic association study of patients with proliferative vitreoretinopathy (PVR) or EMMs. PVR membranes (PVRMs), internal limiting membranes (ILMs) (PVR-ILMs) and blood samples (PVR-blood) from patients with PVR, and EMMs, EMM-ILMs and EMM-blood from patients with EMMs were collected. The genotype of all samples was determined by Sanger sequencing. Sex composition, mean age, the genotype distribution of MDM2 T309G, the allelic frequency of the MDM2 SNP309 G allele (% G) and the somatic mutation rate at the MDM2 T309G locus (% M) were analyzed and compared. The PVR and healthy Chinese donor groups were used as controls for different comparisons. Results: The EMM group of 62 patients was older than the PVR group of 61 patients by an average of 8.87 years (p < 0.0001), but the two groups were statistically similar in the sex composition (p = 0.1754). Importantly, G allele carriers were at a higher risk of developing EMMs than non-G allele carriers (p = 0.0479; OR = 2.047). Moreover, EMM-blood exhibited a significantly higher % G than blood samples from healthy Chinese donors (EMM-blood: 56.78%, donors: 45.61%; p = 0.0256; OR = 1.567). Regarding membrane-blood consistency, % M was significantly different between PVRMs and EMMs (PVRMs: 2.63%, EMMs: 21.57%; p = 0.0097; OR = 10.18) but not between different types of ILMs (PVR-ILMs: 18.18%, EMM-ILMs: 29.17%; p = 0.6855). Furthermore, EMMs (p = 0.0053; OR = 8.250) and EMM-ILMs (p = 0.0233; OR = 14.40) from patients with preoperative macular holes were more predisposed toward somatic mutations at the MDM2 T309G locus than those from patients without preoperative macular holes. Conclusions: MDM2 T309G is associated with the development of EMMs. Herein, the MDM2 SNP309 G allele is first reported as an associated factor of EMMs in a Chinese population. In addition, EMMs and ILMs are genetically unstable at the MDM2 T309G locus, especially when complicated with preoperative macular holes.

Generation of induced pluripotent stem cell line (FMCPGHi001-A) from a 25-year-old Chinese Han healthy male donor

Peripheral blood mononuclear cells (PBMC) were donated by a healthy 25-year-old Han Chinese man and reprogrammed with human transcription factors (Oct4, Sox2, Klf4, and c-Myc) using CytoTune™-iPS 2.0 Sendai Reprogramming Kit. The pluripotency was confirmed by pluripotency markers. The iPSC lines could be differentiated into three germ layers and be used as a control in drug development and studies on pathological mechanisms.

The novel HLA-DRB1*12:02:11 allele identified by next-generation sequencing in a Chinese bone marrow donor.

HLA-DRB1*12:02:11 differs from HLA-DRB1*12:02:01:01 by a single nucleotide substitution at position 579 T > G.

Human leukocyte antigen allele and haplotype frequencies in Singapore bone marrow donors and cord blood units.

We describe the allele and haplotype frequencies seen in a volunteer unrelated bone marrow donor registry, a public cord blood bank, and donor/recipient samples processed by the Health Sciences Authority (HSA) in Singapore. Historical human leukocyte antigen (HLA) typing reports were anonymized and combined. They were checked for HLA typing nomenclature discrepancies or ambiguities using the HLA-net UNIFORMATE tool, and for analysis, the validated data were subsequently separated into Chinese, Malay, Indian, and "Others," according to the race classification system used in Singapore. Individual ethnic allele and haplotype frequencies were calculated with the HLA-net GENE[RATE] pipeline using basic statistics. The Basic Statistics Tool of HLA-net was used to estimate haplotype frequency using an expectation maximization algorithm, given a set of multi-allelic data pairs for a given HLA locus. The outputs downloaded from the site comprised plain text files with haplotype frequency estimates, results of a global linkage disequilibrium test, and standardized residuals (stdres) corresponding to deviations from expected frequencies. HLA typing results from 59,186 individuals met the inclusion criteria, yielding 118,372 analyzable alleles. In our study population, the haplotype A*33:03-B*58:01-C*03:02-DRB1*03:01～DQB1*02:01:01G with a frequency of 4.91% was the most common. This haplotype was also the most common among Singaporean Chinese donors. Consistent with the predominant Chinese population, haplotypes with a frequency greater than 1% were also the most frequently observed haplotypes in the Singaporean population. In the Malay donor population, the most common haplotype was A*33:03～B*44:03～C*07:01:01G～ DRB1*07:01-DQB1*02:01:01G, with a frequency of 3.41%, whereas within the Indian donor population, the most common haplotype was A*01:01-B*57:01-C*06:02～DRB1*07:01-DQB1*03:03, with a frequency of 3.42%. Haplotype diversity and composition statistics within donor pools provide HLA background data required for the targeted recruitment of donors to support the hematopoietic stem cell donor requirements of the country. These data may be used in the future to devise donor recruitment strategies for optimizing the donor pool through targeted publicity and accruals.

Associations between depression, oxidative stress, and semen quality among 1,000 healthy men screened as potential sperm donors

To explore the association between depression and semen quality and the mediating role of oxidative stress. Cross-sectional study with repeated measures of semen quality. Human Sperm Bank of Hubei Province, People's Republic of China. From April 2017 to July 2018, we recruited 1,000 potential sperm donors who completed the Beck Depression Inventory questionnaire and had measures of oxidative stress biomarkers. None. Severity of depression was evaluated by the Beck Depression Inventory scores (0-4, no depression; 5-13, mild depression; 14-20, moderate depression; and 21 or greater, severe depression). The urinary concentrations of 8-hydroxy-2-deoxyguanosine, 4-hydroxy-2-nonenal-mercapturic acid, and 8-iso-prostaglandin F2α (8-isoPGF2α) were measured to reflect oxidative stress status. Repeated semen quality parameters (n = 5,880) were examined by trained professional technicians according to the World Health Organization laboratory manual. Associations between depression, oxidative stress, and repeated measures of semen quality parameters were evaluated using linear or mixed-effects models with adjustment for potential confounders. Mediation analysis was performed to test the potential mediating role of oxidative stress. A total of 391 (39.1%) men were classified as mild depression, 67 (6.7%) as moderate depression, and 19 (1.9%) as severe depression. Inverse dose-response relationships between severity of depression and semen quality parameters were found. Compared with men without depression (n = 523), those with severe depression had a 25.26% (95% confidence interval, -38.65%, -8.93%) lower semen volume, 37.04% (-55.37%, -11.20%) lower total sperm count, 13.57% (-23.17%, -2.78%) lower total motility, and 15.08% (-25.09%, -3.72%) lower progressive motility; men with moderate depression also had a 12.28% (-21.16%, -2.40%) lower semen volume and 23.56% (-36.50%, -7.97%) lower total sperm count. We found a positive dose-response relationship between severity of depression and urinary 8-isoPGF2α concentrations. However, we found no evidence that the associations between depression status and semen quality were mediated by oxidative stress markers. In the study of Chinese male sperm donors, men with depression had worse semen quality parameters, including semen volume, sperm concentration, total sperm count, total motility, and progressive motility. Although depression was positively associated with urinary 8-isoPGF2α concentrations, depression-semen quality associations were not mediated by oxidative stress.

Identification of the novel HLA-B*55:107 allele in a Chinese bone marrow donor.

HLA-B*55:107 shows two nucleotides substitution when compared to HLA-B*55:02:01:01.

Identification of a CD4-binding site-directed antibody with ADCC activity from a chronic HIV-1B′-infected Chinese donor

Antibody-dependent cell-mediated cytotoxicity (ADCC) plays an important role in controlling HIV-1 invasion and replication in vivo. Isolation and identification of monoclonal antibodies (mAbs) with ADCC activity help design effective vaccines and develop novel treatment strategies. In this study, we first identified a broad neutralizer who had been infected with an HIV-1B’ strain for over 10 years. Next, through probe-specific single-B-cell sorting and PCR amplification, we obtained genes for variable regions of the heavy chain (VHs) and light chain (VLs) of six antibodies and ligated them into expression vectors. After antibody expression and ELISA screening, we obtained a CD4-binding site-directed antibody (451-B4), whose VH and VL originated from the IGHV1-24 and IGLV1-40 germlines, respectively. Although 451-B4 neutralized only the SF162 tier 1 pseudovirus and 398F1 tier 2 pseudovirus, it could mediate comparable ADCC activity to a broadly neutralizing antibody, VRC01. The 451-B4 antibody will be a useful candidate for developing an ADCC-based treatment strategy against HIV-1 replication or latent infection in vivo.