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.

【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 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

【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.

Objective:To analyze the clinicopathological features and prognostic factors of patients with uterine clear cell carcinoma (UCCC).Methods:UCCC patients who underwent surgery and complete follow-up at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 1, 2004 and December 31, 2014 were retrospectively reviewed. The Kaplan-Meier method and Cox regression analysis were used for survival analysis.Results:The study included 34 patients. Only 18 patients (52.9%) were diagnosed with UCCC preoperatively and 8 patients (23.5%) underwent UCCC standard comprehensive staging surgery. Among the 34 patients, stage ⅠA was 17 cases (50.0%), stage ⅠB was 1 case (2.9%), stage Ⅱ was 4 cases (11.8%), stage ⅢA was 2 cases (5.9%), stage ⅢB was 1 case (2.9%), stage ⅢC1 was 5 cases (14.7%) and stage ⅣB was 4 cases (11.8%). The median follow-up period was 72 months, 5-years disease-free survival (DFS) rate and overall survival (OS) rates for all patients were 79.1% and 81.3%, respectively. Univariate analysis result showed that preoperative CA125 level, range of lymphadenectomy, tumor stage and peritoneal cytology were significantly associated with DFS ( P<0.05). Preoperative CA125 level, range of lymphadenectomy, tumor stage, peritoneal cytology and lymph vascular space invasion were significantly associated with OS ( P<0.05). Multivariate analysis result showed that peritoneal cytology was the only independent prognostic factor for DFS, the relapse risk of peritoneal cytology positive patients was 11.47 folds higher than that of the negative patients ( P=0.009). Tumor stage was the only independent prognostic factor for OS, the death risk of ⅣB stage patients was 25.29 folds higher than that of theⅠA stage ( P=0.009). Conclusions:The preoperative pathological diagnosis of UCCC is difficult, which results in incomplete surgical staging. Peritoneal cytology and tumor stage are independent prognostic factors for DFS and OS of UCCC patients, which deserve much more attention in clinical practice.

Objective:To analyze the clinicopathological features and prognostic factors of patients with uterine clear cell carcinoma (UCCC).Methods:UCCC patients who underwent surgery and complete follow-up at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 1, 2004 and December 31, 2014 were retrospectively reviewed. The Kaplan-Meier method and Cox regression analysis were used for survival analysis.Results:The study included 34 patients. Only 18 patients (52.9%) were diagnosed with UCCC preoperatively and 8 patients (23.5%) underwent UCCC standard comprehensive staging surgery. Among the 34 patients, stage ⅠA was 17 cases (50.0%), stage ⅠB was 1 case (2.9%), stage Ⅱ was 4 cases (11.8%), stage ⅢA was 2 cases (5.9%), stage ⅢB was 1 case (2.9%), stage ⅢC1 was 5 cases (14.7%) and stage ⅣB was 4 cases (11.8%). The median follow-up period was 72 months, 5-years disease-free survival (DFS) rate and overall survival (OS) rates for all patients were 79.1% and 81.3%, respectively. Univariate analysis result showed that preoperative CA125 level, range of lymphadenectomy, tumor stage and peritoneal cytology were significantly associated with DFS ( P<0.05). Preoperative CA125 level, range of lymphadenectomy, tumor stage, peritoneal cytology and lymph vascular space invasion were significantly associated with OS ( P<0.05). Multivariate analysis result showed that peritoneal cytology was the only independent prognostic factor for DFS, the relapse risk of peritoneal cytology positive patients was 11.47 folds higher than that of the negative patients ( P=0.009). Tumor stage was the only independent prognostic factor for OS, the death risk of ⅣB stage patients was 25.29 folds higher than that of theⅠA stage ( P=0.009). Conclusions:The preoperative pathological diagnosis of UCCC is difficult, which results in incomplete surgical staging. Peritoneal cytology and tumor stage are independent prognostic factors for DFS and OS of UCCC patients, which deserve much more attention in clinical practice.

Objective To investigate the prevalence of high-risk HPV subtypes in different pathological types of cervical cancer, and analyze the attribution of carcinogenic HPV subtypes in different pathological types. Methods A total of 1 541 patients with cervical cancer were treated between February 2009 and October 2016 in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. The median age at diagnosis was 49 years (ranged 20-82 years old). The numbers of patients with cervical cancer from North China, Northeast China, East China, Central China and other regions (including Northwest, Southwest and South China) were 961, 244, 175, 87 and 74 cases, respectively. Pathological types: 1 337 cases of squamous cell carcinoma (SCC), 87 usual adenocarcinoma (ADC), 23 adenosquamous carcinoma (ASC), 20 mucinous carcinoma (MC), 19 clear cell carcinoma (CCC), 12 endometrioid carcinoma (EC), 25 neuroendocrine carcinoma (NEC), 9 serous carcinoma (SC), 5 villous adenocarcinoma (VADC) and 4 minimal deviation adenocarcinoma (MDAC). The prevalence of high-risk HPV in different regions, age groups at diagnosis and pathological types in cervical cancer were analyzed. The attribution of 13 high-risk HPV subtypes in different pathological types of cervical cancer based on proportional attribution method, and the attribution of high-risk HPV subtypes prevented by 9-valent HPV vaccine in SCC and ADC were calculated. Results (1) The prevalence of high-risk HPV in 1 541 patients with cervical cancer was 86.6% (1 335/1 541). The multiple high-risk HPV infection rate in patients with SCC ≥60 years old (23.0%, 37/161) was significantly higher than those in patients aged 45-59 years old and≤44 years old [11.4% (85/747) vs 11.7% (50/429), P<0.01], and the high-risk HPV infection rates of patients with cervical cancer in North China, Northeast China, East China, Central China and other regions were respectively 86.8% (834/961), 87.7% (214/244), 83.4% (146/175), 83.9% (73/87) and 91.9% (68/74). SCC (86.8%, 1 337/1 541) and ADC (5.6%, 87/1 541) were the most common pathological types in cervical cancer. The high-risk HPV prevalence of SCC, ADC, ASC, MC, NEC and VADC were 90.1% (1 205/1 337), 74.7% (65/87), 87.0% (20/23), 65.0% (13/20), 72.0% (18/25) and 5/5 respectively. The high-risk HPV infection rates of SC, EC, CCC and MDAC were 4/9, 3/12, 2/19 and 0/4 respectively. (2) According to proportional attribution, HPV 16 (69.5%), HPV 18 (5.6%), HPV 58 (2.2%), HPV 31 (1.9%), HPV 52 (1.4%) and HPV 33 (1.3%) were the six common high-risk HPV subtypes in SCC. While, HPV 18 (44.1%), HPV 16 (20.5%), HPV 52 (2.3%), HPV 58 (1.2%) and HPV 51 (1.2%) were the main carcinogenic subtypes in ADC. The main carcinogenic high-risk HPV subtypes of ASC, NEC and MC were HPV 18 and HPV 16. The total attribution of HPV 16, 18, 31, 33, 45, 52 and 58 prevented by 9-valent HPV vaccine in SCC and ADC were 82.6% and 68.1% respectively; the attribution of HPV 45 in SCC and ADC were only 0.8% and 0. Conclusions SCC and ADC are the main pathological types in cervical cancer. SCC, ADC, ASC, MC, NEC and VADC are closely related to high-risk HPV infection. HPV 16 is the main carcinogenic genotypes of SCC. HPV 18 maybe play an important role in the pathogenesis of ADC.

Objective To analyze the prognosis and appropriate treatment modalities of the patients with recurrence of early stage (Ⅰb-Ⅱa) cervical squamous cancer primarily treated with radical hysterectomy. Methods This retrospective study included patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰb and Ⅱa recurrent cervical squamous cancer who underwent radical hysterectomy primarily from January 2007 to July 2015. Kaplan-Meier method and Cox regression analysis were performed to analyze related prognostic factors of overall survival and progression-free survival, which included age, postoperative therapy, the site of recurrence, therapy-free interval (TFI) and treatment modality. The patients who were treated with palliative chemotherapy after recurrence were selected as a subgroup. The responses of palliative chemotherapy were evaluated and analyzed among different factors, included TFI, the site of recurrence and chemotherapy regime. Results Of the 2 071 patients, 116 relapsedⅠb-Ⅱa cervical squamous cancer were included in the study with the average age of (45.6±7.2) years old. 3-year progression-free survival rate and 3-year overall survival rate after recurrence were 30.2% and 42.2%, respectively. Univariate analysis implied that postoperative radiotherapy, recurrence site, TFI and treatment modality were associated with progression-free survival (P<0.05), while postoperative radiotherapy, TFI and treatment modality with overall survival (P<0.05). Multivariate analysis showed that TFI and treatment modality were independent prognostic factors for progression-free survival (P<0.05), while postoperative radiotherapy at initial treatment, TFI and treatment modality were independent prognostic variables for overall survival (P<0.05). In the analysis of treatment modality, 3-year progression-free survival rate and 3-year overall survival rate of 47 patients who were treated with definitive local therapy were significantly higher than that of 69 patients who were treated with palliative chemotherapy (P<0.01). In the subgroup analysis of palliative chemotherapy, 15 patients achieved complete response (21.7%) and 16 displayed partial response (23.2%). The overall response rate (ORR) was 44.9%. TFI (P<0.01) and chemotherapy regime (P<0.05) were significant factors associated with ORR. The ORR of TFI≥12 months was significantly higher than that of TFI <12 months. Besides, the ORR of paclitaxel plus platinum chemotherapy was prominently higher than that of other regimens, while there was no significant difference between the ORR of paclitaxel plus cisplatin and other platinum (P=0.408). Conclusions For recurrent stageⅠb-Ⅱa cervical squamous carcinoma treated with radical hysterectomy, use of definitive local therapy for suitable patients is advised to achieve better prognosis. In terms of palliative chemotherapy, longer TFI may mean better ORR and the combination of paclitaxel plus platinum is preferred.