Objective: To screen the frequency of CD36 antigen expression in platelet donor database in Shaanxi province and analyze the molecular genetic characteristics of samples with CD36 antigen deficiency and low expression. Methods: A total of 525 platelet donors samples were randomly collected during May 2023. CD36-FITC monoclonal antibody was used for immunofluorescence labeling, and flow cytometry was applied to detect the expression of CD36 antigen on platelets. For samples with CD36 antigen deficiency on platelets, the expression of CD36 on monocytes was further detected. Samples with CD36 antigen deficiency and low expression were sequenced and analyzed. Results: Among the 525 blood samples, 99.24% (521/525) showed positive expression of CD36 antigen. There were differences in the expression intensity of CD36 antigen, with low expression accounting for 3.43% (18/525) and CD36 antigen deficiency accounting for 0.76% (4/525), all of which were type Ⅱ deficiency. The exon mutation frequency of CD36 type Ⅱ deficiency and low expression samples was 31.82% (7/22), and the exon mutation types were 121-1_126delGCAAGTT, 329-330delAC, 1142T>G, 1204-1246dupl 43bp, 1221G>A, and 1228-1239delATTGTGCCTATT. All four cases of CD36 type Ⅱ deficiency had a 121-6 T>C mutation in intron 3. All CD36 low expression samples had a mutation of 282-10A>G, and 121-6T>C mutation rate was 61.1%(11/18). Conclusion: There were differences in the expression of CD36 antigen in the platelet donor database in Shaanxi province, which may be caused by multiple molecular genetic variations. The frequency of CD36 antigen deficiency in Shaanxi was lower than that of Han, Zhuang and Yao populations in southern China. This study provides references for solving the CD36 antibody mediated transfusion reaction and auxiliary treatment of diseases caused by CD36 antigen deficiency in the future. It also provides a basis for investigating the molecular mechanisms of CD36 deficiency and low expression.

Objective:To analyze a Chinese pedigree with a recombination occurring between the HLA- A/ C loci in both parents. Methods:A patient who was planning to undergo hematopoietic stem cell transplantation due to "aplastic anemia" in February 2022 was selected as the study subject. Peripheral blood samples were collected from the patient, his parents and brother. HLA- A/ C/ B/ DRB1/ DQB1 high-resolution typing was carried out by using sequence-based typing and sequence-specific oligonucleotides. The recombination was identified by pedigree analysis. The HLA haplotype of each individual was identified by genealogical analysis. The parentage possibility was determined by short tandem repeat analysis. HLA- A/ C/ B/ DRB1/ DRB345/ DQA1/ DQB1/ DPA1/ DPB1 were determined with next-generation high-throughput sequence-based typing. The recombination sites were analyzed by family study. Results:The high parentage possibilities of the family was confirmed by short tandem repeat analysis. Recombination was found between the HLA- A* 24: 02 A* 33: 03/ C* 14: 03 in the paternally transmitted haplotype, whilst HLA- A* 01: 01 A* 03: 01/ C* 08: 02 was found in the maternally transmitted haplotype, which had resulted in two novel HLA haplotypes in the proband. Conclusion:A rare case with simultaneous recombination of the paternal and maternal HLA- A/ C loci has been discovered, which may facilitate further study of the mechanisms of the HLA recombination.

Cancer remains a major global health challenge, with conventional treatments like chemotherapy and radiotherapy often hindered by significant side effects, lack of specificity, and limited efficacy in advanced cases. Among emerging therapeutic strategies, mRNA vaccines have shown remarkable potential due to their adaptability, rapid production, and capability for personalized cancer treatment. This review provides an in-depth analysis of messenger RNA (mRNA) vaccines as a therapeutic approach for cancer immunotherapy, focusing on their molecular biology, classification, mechanisms, and clinical studies. Derived from reported literature and data on clinicaltrials.gov, it examines studies on mRNA vaccines encoding tumor-specific antigens (TSAs), tumor-associated antigens (TAAs), immunomodulators, and chimeric antigen receptors (CARs) across various cancer types. The review highlights the ability of mRNA vaccines to encode TSAs and TAAs, enabling personalized cancer treatments, and classifies these vaccines into non-replicating and self-amplifying types. It further explores their mechanisms of action, including antigen presentation and immune activation, while emphasizing findings from clinical studies that demonstrate the potential of mRNA vaccines in cancer therapy. Despite their promise, challenges remain in enhancing delivery systems, improving immunogenicity, and addressing tumor heterogeneity. Overcoming these obstacles will require further investigation to fully harness the potential of mRNA vaccines in personalized cancer treatment.
Humans ; Cancer Vaccines/immunology* ; Neoplasms/immunology* ; mRNA Vaccines/therapeutic use* ; Immunotherapy/methods* ; Antigens, Neoplasm/genetics* ; RNA, Messenger/therapeutic use*

【Objective】 To analyze the commonality and characteristics between voluntary blood donors and hematopoietic stem cell donors in this region, and explore the potential for integration and development between China Marrow Donors Program (CMDP) and voluntary blood donors, especially platelet donor databases, so as to improve recruitment success rate and inventory rate. 【Methods】 The database modeling and comparison methods were used to screen and stratify the matching and integration degree between the voluntary blood donors in recent 10 years and the marrow donors in the Shaanxi Branch of CMDP. The frequencies of HLA-A,-B alleles, HPA alleles and haplotypes were calculated with Arlequin 3. 5. 2. 2 software, and the matching probability of different platelet donor reserve pools was conducted according to the phenotypic frequencies. 【Results】 Among the voluntary donors with known HLA genotypes in this region, according to their blood donation behavior,the active blood donors excavated were divided into the first, second, third and fourth echelons of platelet donor reserve pools, with 696, 2 752, 9 092 and 12 028 donors, respectively. The first echelon had the highest proportion of 10-50 times of platelet donations and 10-20 times of whole blood donations, with 13.65% and 26.01%, respectively. The second echelon had 10-20 times of whole blood donations and 10-50 times of platelet donations, accounted for 15.04% and 1.38%, respectively, which were significantly different from other echelons' blood donation characteristics (P<0.05). With a database size of the existing platelet donor bank adding the first and second echelons (n=4 955), there was a 69.02% probability of matching at least one donor with matching HLA-A-B phenotype. When considering the matching ABO and HPA phenotypes, the probability of finding at least one donor with fully matching HLA, HPA and ABO isotype (type B as an example) was 48. 73%. 【Conclusion】 The three groups of whole blood donation, apheresis platelet donation and marrow donation in Xi'an area have a large cross-distribution. Compared with expanding the storage capacity from scratch, the active blood donors in CMDP database are the largest back-up force of platelet donors. While expanding the effective storage capacity, it can minimize the cost of building platelet donor bank and the demand for resources.

Objective:To monitor the cerebral vascular blood flow parameters in the early stage of simulated acute exposure to high altitude hypoxia by transcranial color Doppler (TCCD), and to evaluate the change trend of cerebral hemodynamics and cerebrovascular reactivity.Methods:Sixty-four healthy volunteers were selected to observe the changes of peak systolic flow velocity(Vs), end diastolic flow velocity(Vd), mean flow velocity(Vm), resistance index (RI) and pulsatility index (PI) of middle cerebral artery (MCA) 30 minutes after they quickly entered the simulated altitude of 4 500 meters. Combined with breath holding test, breath holding index (BHI) was used to evaluate cerebrovascular reactivity (CVR), and subjects were divided into ≤30 years old group and >30 years old group, and the changes of CVR after hypoxia of the two groups were compared.Results:In the early stage of hypoxic environment, compared with baseline, SpO 2 decreased, heart rate increased, and blood flow velocity of middle cerebral artery(Vs, Vd, Vm) increased significantly, BHI showed a decreasing trend (all P<0.01). After hypoxia, the BHI rate of change in >30 years old was lower than that of the subjects ≤30 years old ( P<0.05). After breath holding, cerebral blood flow velocity increased significantly, PI and RI decreased significantly (all P<0.01). Conclusions:Cerebral blood flow is very sensitive to hypoxia. The application of TCCD technology can evaluate the trend of cerebral blood flow dynamics and cerebrovascular reserve capacity in real time and accurately, which is helpful to provide objective basis and research basis for the prevention and treatment of high altitude hypoxia.

OBJECTIVE To understand the future development trend of dispensing and use for preparations of medical institutions，and to provide countermeasures and suggestions for promoting the high-quality development of application and dispensing use for preparations of medical institutions . METHODS The development history of dispensing and use for preparations of medical institutions of China was reviewed as a whole ，and then the differences of domestic dispensing and use institutions for preparations of medical institutions over the years were compared from different perspectives ；and the differences between domestic institutions and Japan ’s hospital preparation dispensing and use institutions were compared. The development trend of dispensing and use for preparations of medical institutions of China was summarized to put forward countermeasures and suggestions. RESULTS & CONCLUSIONS The development process of dispensing and use for preparations of medical institutions of China could be roughly divided into the initial stage （2001-2004），the forming stage （2005-2018） and the development stage （2019-present）. Year by year ，the dispensing and use institutions of preparations of medical institutions had shown that the scope of dispensing and use had been expanded ；the approval process had been accelerated ，and the responsibilities of all parties had been clearly defined. Compared with Japan ，regulatory model for preparations of medical institutions was relatively simple in China. In the future ，the large-scale promotion and application of preparations of medical institutions will be normalized ，the time limit for dispensing approval will be shortened ，the approval process will be simplified ，the access threshold for dispensing and use will be gradually lowered ，and the supervision of dispensing and use will be strengthened during and after the event. It is recommended to strictly control the quality and safety of preparations of medical institutions ，implement classified management of use for preparations of medical institutions ，and further improve the supervision mechanism during and after the event.

【Objective】 To evaluate the appropriate optimal capacity and matching probability of the platelet donor database with known HLA/HPA genotype in Shaanxi aera, and provide data support for subsequent construction, maintenance and application of the local platelet donor database. 【Methods】 A total of 11 755 individuals from the Shaanxi Branch of China Marrow Donor Program, 401 and 249 unrelated random platelet donors in Shaanxi aera were enrolled to the population study of HLA-A, -B polymorphisms, HPA genotyping and CD36 antigen expression, respectively. The frequencies of HLA-A, -B alleles, HPA alleles and haplotypes were calculated with Arlequin 3. 5. 2. 2 software; matching probability and capacity evaluation of platelet donor database was conducted according to the phenotypic frequencies. 【Results】 The population genetic and phenotypic polymorphisms data of HLA-A, -B and HPA1-6, 10, 15, 21 in Shaanxi aera were obtained. The frequency of CD36 type Ⅰ or Ⅱ deficiency was 0.40%(1/249). According to the subsequent calculating and deriving, with a database size of 194 donors, the patient having approximate 95% probability could achieve matching of HPA1-6, 10, 15, 21 genotype. With a database size of 1500 donors, there is a 95% probability of matching at least one donor with HLA-A-B phenotype frequency >0.002 or haplotype frequency >0.001; meanwhile, the probability of matching a cross-reactive group donor should be 44.95%-97.57%. Based on database size of 8 856 and 15 033, the probabilities of matching HLA-A, -B phenotype were about 80% and 90%, respectively. 【Conclusion】 The differences in the distribution of HLA/HPA polymorphism in different regions make the establishment mode and optimal capacity of platelet donor database different. It is necessary to apply a variety of platelet matching transfusion strategies to expand the range of donor selection, thereby effectively reducing the database construction cost and resource requirements.

OBJECTIVE: To verify a rare allele of human leukocyte antigen (HLA) and analyze its inheritance and 3D molecular structure. METHODS: PCR-sequence-based typing, PCR-single strand oligonucleotide polymorphism and single allele-specific sequencing were carried out to characterize the rare HLA-C allele and its transmission in the family. Its protein structure was modeled by using SWISS-MODEL, Phyre2 and FATCAT software. RESULTS: Analysis indicated that the rare allele (HLA-C*08:84) has transmitted from the proband's mother and has differed from HLA-C*08:01 by a single base (g.512G>C), resulting in substitution of an amino acid (p.Trp147Ser). Modeling of the 3D structure of the encoded protein indicated that the amino acid residue variation is located at the alpha 2 helix, which participates the formation of pocket F. Modeling of the structures of C*08:84, C*08:01, C*08:02, C*08:03 and C*08:22 has suggested significant variation in the peptide binding regions of the backbone, with root mean square errors being 1.70 nm, 1.79 nm, 0.71 nm and 1.70 nm, respectively. CONCLUSION A rare HLA-C*08:84 allele has been identified, and its clinical significance has been analyzed.
Alleles ; Base Sequence ; HLA-B Antigens/genetics* ; HLA-C Antigens/genetics* ; Humans ; Molecular Structure ; Sequence Analysis, DNA

A significant proportion of non-small cell lung cancer (NSCLC) patients experience accumulating chemotherapy-related adverse events, motivating the design of chemosensitizating strategies. The main cytotoxic damage induced by chemotherapeutic agents is DNA double-strand breaks (DSB). It is thus conceivable that DNA-dependent protein kinase (DNA-PK) inhibitors which attenuate DNA repair would enhance the anti-tumor effect of chemotherapy. The present study aims to systematically evaluate the efficacy and safety of a novel DNA-PK inhibitor M3814 in synergy with chemotherapies on NSCLC. We identified increased expression of DNA-PK in human NSCLC tissues which was associated with poor prognosis. M3814 potentiated the anti-tumor effect of paclitaxel and etoposide in A549, H460 and H1703 NSCLC cell lines. In the four combinations based on two NSCLC xenograft models and two chemotherapy, we also observed tumor regression at tolerated doses

【Objective】 To explore the association of HLAII(-DRB1, -DQB1, -DPB1) alleles and haplotypes polymorphisms with acute myeloid leukemia (AML) in northern Han population. 【Methods】 A total of 308 AML (non-M3) patients (patient group) and 824 unrelated healthy bone marrow donors (control group) were genotyped at a high-resolution level using polymerase chain reaction-sequence-based typing (PCR-SBT), next-generation sequencing (NGS) with Ion Torrent S5 platform and sequence specific oligonueleotide probes (SSO) with LABScan^® 3D platform. Frequencies of HLA II alleles and haplotypes were calculated with Arlequin 3.5.2.2 software. The odds ratio (OR) of AML was also calculated for case-control study. 【Results】 By χ² test and correction, an increased frequency of HLA-DRB1^*07∶01(14.61% vs 9.53%, P<0.01), HLA-DQB1^*02∶02(12.82% vs 8.31%, P<0.01), HLA-DQB1^*06∶02(11.53% vs 8.74%, P<0.05) and HLA-DPB1^*17∶01(5.84% vs 3.16%, P<0.01) among AML patients was discovered in significant comparison with the control group. After Bonferroni correction, the frequency of HLA-DRB1^*07∶01(Pc<0.05), HLA-DQB1^*02: 02(Pc<0.05) and HLA-DPB1^*17∶01(Pc<0.05) in AML patients were still higher than those in the control group, which had a strong positive correlation with AML (OR=1.62 (95% CI=1.23~2.14), 1.62(95% CI=1.21~2.18) and 1.91(95% CI=1.23~2.94), respectively. The frequency of two loci haplotype HLA-DRB1^*07∶01-DQB1^*02∶02 in AML patients was still higher than that of the control group after Bonferroni correction (12.66% vs 8.19%, Pc<0.05). The frequency of the 3 loci haplotype HLA-DRB1^*07∶01-DQB1^*02∶02-DPB1^*17∶01, as a susceptible haplotype of AML, was higher than that of the control group and was strongly correlated with AML. 【Conclusion】 The data on the association of HLA II (-DRB1, -DQB1, -DPB1) alleles and haplotype polymorphisms with AML in northern Han populations was obtained in this study. HLA-DRB1^*07∶01, HLA-DQB1^*02∶02, HLA-DPB1^*17∶01 and the HLA-DRB1^*07∶01-DQB1^*02∶02-DPB1^*17∶01 haplotype are the risk genes and susceptible extended haplotype for AML. The risk prediction based on HLA haplotype might be more accurate than that based on single allele.