Objective To do analysis of sequence and identify a novel HLA-A allele in Chinese hematopoietic stem cell do-nors.Methods A rare HLA-A allele was initially detected by Luminex PCR-SSO typing,then the sample was sequenced by sequence-based typing (SBT)and the group-specific sequencing primer (GSSP)to confirm the mutation allele and locus.Re-sults The sequence of the sample results showed that the allele compared with the highest homologous allele HLA-A*24∶02∶01∶01 was the difference in the exon 3 at position 544 G>A,resulting in an amino acid sequence of HLA-A*24∶02∶01∶01 at position 158 change Ala to Thr.Conclusion This allele is a new HLA-A allele and has been designated as HLA-A*24∶327 by the HLA Nomenclature Committee of World Health Organization (WHO).

Objective To investigate the survival and recurrence data after treatment in neuroendocrine carcinoma of the uterine cervix(NECUC)with stageⅠb-Ⅱa, and to analyse its prognostic factors. Methods Thirty-two cases of primary NECUC in early-stage disease treated from Jan. 2005 to Dec. 2013 at Cancer Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences were reviewed, and their data of clinicopathologic characteristics were collected and analysed. The median age was 37 years (range, 23-57 years). The distribution by International Federation of Gynecology and Obstetrics (FIGO) clinical stage:19 cases stageⅠb1, 10 cases stageⅠb2, 1 case stageⅡa1, 2 cases stageⅡa2. Pathologic types: 22 cases of small cell carcinoma, 1 case of atypical carcinoid, 9 cases of mixed carcinoma. The diameter of cervical tumor:12 cases≥4 cm, 20 cases<4 cm. All patients underwent radical hysterectomy and pelvic ± para-aortic lymphadenectomy, and 15 cases of them were preserved unilateral or bilateral ovaries. Pathologic examination showed that 25 cases with cervical deep stromal invasion thickness ≥1/2, 21 cases with lymph-vascular space invasion (LVSI), and 18 cases with pelvic and (or) para-aortic lymph nodes involvement. Ten cases were performed neoadjuvant chemotherapy (range,1-3 cycles), all patients received postoperative chemotherapy (range,3-6 cycles), and 15 patients were treated with radiotherapy after surgery. The follow-up data were updated on Jul. 2014. The median follow-up time was 18 months (range, 7-71 months). A retrospective analysis was conducted to analyse the survival and recurrence data,and to explore the prognostic factors of NECUC. Results Thirteen patients died during the follow-up period. The cumulative progression-free survival (PFS) of 2 and 5 years were respectively 54.2%and 38.1%, and the estimated median PFS was 29 months. The cumulative overall survival (OS) of 2 and 5 years were respectively 56.1%and 44.9%, and the estimated median OS was 31 months. Fourteen cases had recurrence, and the median recurrence time was 9 months (range, 3-30 months). Recurrent or metastatic sites:2 cases in pelvis, 4 cases in liver, 3 cases in lung, 3 cases in adrenal glands, 3 cases in bones, 2 cases in brain, 1 case in pancreas, 1 case in lymph nodes of para-aorta and neck, and 3 cases had metastasis in two or more organs. Thirteen cases with recurrence died of disease, and another one is alive with disease. The univariate analysis showed that lesion size of the cervix and FIGO stage were significant prognostic factors (P<0.01), while age, tumor components, deep invasion in cervical stromal, LVSI, pelvic and (or) para-aortic lymph nodes involvement, neoadjuvant chemotherapy, adjuvant radiotherapy and preserving ovaries were not significantly associated with prognosis(all P>0.05). Conclusion The prognosis of NECUC in early-stage is poor and the lesion size of the cervix and FIGO stage are prognostic factors.

OBJECTIVETo investigate the molecular basis of an individual featuring weak A phenotype of ABO blood group system.

METHODSSerologic investigations, serum transferases activity assay and absorption-elution test were carried out to identify the ABO blood group. The 7 exons and flanking introns of ABO glycosyltransferase gene were amplified with polymerase chain reaction (PCR). The products were sequenced bidirectinally following enzyme digestion. Haplotypes of exons 6 and 7 of the ABO gene were analyzed.

RESULTSA weak A antigen was identified on red blood cells of the proband. Eight heterozygous sites in exons 6 and 7 (261delG 297A/G, 421C/T, 467C/T, 646T/A, 681G/A, 771C/T, 829G/A) of the ABO gene were identified. Based on haplotype analysis, one allele was determined as O02, while a novel mutation 421T>C was identified in another allele, which resulted in the amino acid change Ser141Pro of the A glycosyltransferase.

CONCLUSIONAbove results suggested that amino acid substitutions resulted from a novel mutation 421T>C of the ABO gene may decrease the enzymatic activity and result in the weak A phenotype.

ABO Blood-Group System ; genetics ; Adult ; Alleles ; Female ; Humans ; Mutation ; N-Acetylgalactosaminyltransferases ; genetics

OBJECTIVETo determine the frequency of RHD1227A allele in Chinese Hans.

METHODSFor a total of 890403 ethnic Han blood donors, the D antigen was determined with a saline method and indirect antiglobulin test. The RHD1227A allele and number and type of zygosity of RHD gene were determined with PCR sequence specific primer (PCR-SSP). Allelic frequency was calculated through statistics.

RESULTSIn total 2385 donors were found to be Rh-negative, 108 individuals were found to be weakly positive for D antigen (including weak D and partial D phenotypes). The remaining 887 910 individuals were Rh-positive. Among the Rh-negative individuals, 516 were found with RHD1227A. Among these, 467 were RHD1227A/d and 49 were RHD1227A/RHD1227A. Two of 108 D antigen weak-positive individuals were found as RHD1227A/RHD+. In addition, 8 of 1073 random Rh-positive samples were found to be RHD1227A/RHD+. The allele frequency of RHD1227A in the population was calculated as 0.004 036. The figure should be 0.006 682 if calculated based on the detected rate of the allele in Rh-negative individuals, and 0.007 884 if calculated based on the reported average phenotype rate of DEL in Rh-negative individuals.

CONCLUSIONBy taking main influencing factors such as the RHD zygosity, the rate of RHD1227A and DEL phenotype may be determined. The allele frequency of RHD1227A in Chinese Hans is between 0.004 036 and 0.007 884.

Adolescent ; Adult ; Asian Continental Ancestry Group ; ethnology ; genetics ; China ; ethnology ; Exons ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Mutation, Missense ; Rh-Hr Blood-Group System ; genetics ; Young Adult

OBJECTIVETo assess the association of polymorphisms of human leukocyte antigen (HLA)-A, -B, -DRB1 alleles and haplotypes with acute lymphoblastic leukemia (ALL) among ethnic Hans from northern China.

METHODSA total of 170 ALL patients (patient group) and 1241 unrelated healthy bone marrow donors (control group) were genotyped at a high-resolution level using polymerase chain reaction-sequence-based typing (PCR-SBT), sequence specific oligonucleotide probes (SSO) and sequence specific primer (SSP) typing methods. Frequencies of HLA alleles and haplotypes were calculated with Arlequin 3.5.2 software. The distribution of genes and haplotypes were analyzed through a case-control study, and the odd ratio (OR) of ALL was also calculated.

RESULTSBy cha-square test and correction, an increased frequency of B*13:01 and B*40:02 among ALL patients was discovered in comparison with the controls (7.35% vs. 4.63%, P=0.030; 2.94% vs. 1.45%, P=0.042), whereas B*35:03 and B*46:01 were less frequent compared with the controls (0.29% vs. 1.69%, P=0.048; 4.41% vs. 7.82%, P=0.025). Although the above discrepancies were not statistically significant by Bonferroni correction, within DRB1*15 group, the frequency of DRB1*15:01 in ALL patients was significantly greater than that of the controls (16.18% vs. 10.19%, Pc'=0.041) and was correlated with ALL (OR=1.70, 95% CI:1.24-2.33). Nineteen haplotypes identified in the ALL patients had a frequency greater than those of the controls. Of these, 11 were absent from the control group and were correlated with ALL.

CONCLUSIONThe association of HLA-A, -B, -DRB1 polymorphisms with ALL was determined among patients from northern Chinese Hans. The correlation between DRB1*15:01 and ALL suggested that DRB1*15:01 may be a susceptibility gene for ALL with its particular haplotypes.

Adolescent ; Adult ; Alleles ; Case-Control Studies ; Child ; Child, Preschool ; Female ; HLA-A Antigens ; genetics ; HLA-B Antigens ; genetics ; HLA-DRB1 Chains ; genetics ; Haplotypes ; Humans ; Infant ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Young Adult

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 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 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 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.

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