Objective:To translate and revise the Arteriovenous Fistula Assessment Scale (AVF-AS), test the reliability and validity of the Chinese version of AVF-AS.Methods:The modified Brislin translation model was used to translate, back translate and cross culture adjust AVF-AS, forming the Chinese version of AVF-AS. Using the convenient sampling method, 220 hemodialysis patients from the First Affiliated Hospital of Zhengzhou University were selected for investigation from July to September 2022. Two weeks later, 30 patients were randomly selected for retesting. The valid data were used for project analysis and reliability and validity evaluation.Results:The Chinese version of AVF-AS consisted of 3 factors and 18 items. Consistency level between evaluators was 0.94, the item level content validity index was 0.83-1.00, average scale level content validity index was 0.94, and the calibration validity was 0.68.Three common factors(autogenous arteriovenous fistula blood flow, stenosis and ischemia, puncture location) were extracted from exploratory factors, and the cumulative variance contribution rate was 75.255%. The total scale's Cronbach α was 0.946, the half reliability of each dimension was 0.826 - 0.898, and the test-retest reliability was 0.907.Conclusions:The Chinese version of AVF-AS has good reliability and validity, and can be used as an effective tool to evaluate the autogenous arteriovenous fistula functional status of hemodialysis patients in China.

Objective:To explore the clinical efficacy of adult donor dual kidney transplantation.Methods:Retrospective analysis of case data of 13 adult donor kidney dual kidney transplantation (DKT) performed in the The Second Xiangya Hospital of Central South University from September 2016 to December 2020. For 13 donors, the average age and BMI were (53.5±12.4)years and (24.3±2.8) kg/m 2, respectively. Their mean Serum creatinine (SCr) at admission and before procurement was (132.9±54.1)and (228.7±112.4)μmol/L, respectively. 3 of them had diabetes mellitus history, and 8 had hypertension history. 11 met the United Network for Organ Sharing (UNOS) DKT criteria and 6 met Remuzzi score DKT criteria. For 13 recipients, the average age and BMI were (39.3±8.9)years and (20.2±2.4)kg/m 2, respectively. All of them received ABO blood type-matched kidney transplants. 2 of them had their grafts transplanted in the bilateral iliac. In 12 cases, the grafts filled rapidly and urinated immediately when opening blood flow. In 1 case, the grafts were dark in color and vascular showed weak pulsation after opening blood flow. The time to recovery of perioperative graft function (from the day of surgery to the natural reduction of SCr to the normal range 44-133μmol/L), the occurrence of delayed graft function (DGF), acute rejection (AR), ureteral and surgical incision complications, as well as the recipients’ final follow-up SCr, eGFR, urinary protein, and grafts outcome were observed. Risk factors affecting outcomes were assessed by univariate logistic regression analysis. Results:The SCr dropped to the normal range at discharge in 10 recipients, and the average recovery time was (13.8±13.0) days. In other 3 cases SCr at discharge were 300.0, 149.0, 152.5μmol/L. 4 cases had DGF, 4 had AR, 1 experienced urinary fistula, and 1 experienced incisional dehiscence, which were treated with anti-rejection, J-tube implantation, continuous catheterization to maintain bladder void, secondary suturing, respectively. The follow-up time ranged from 4 to 54 months, with a median of 28(15.5, 31.0) months. At the final follow-up time, 10 cases had good graft function, 2 suffered impaired kidney function, and 1 experienced graft failure. The average SCr and eGFR except for graft failure patient were (144.2±101.3)μmol/L and (52.9±21.2)ml/min, respectively. 4 had positive urine protein. Univariate logistic regression analysis showed that donor age, BMI, history of diabetes mellitus and hypertension, and SCr were not significantly correlated with recipients’ DGF and graft impairment ( P>0.05), and due to the small sample size, multifactorial logistic regression analysis was not performed. Conclusion:The short to medium-term effects of adult donor DKT coule be safe and feasible.

Runt-related transcription factor 1 (RUNX1) is an essential regulator of normal hematopoiesis. Its dysfunction, caused by either fusions or mutations, is frequently reported in acute myeloid leukemia (AML). However, RUNX1 mutations have been largely under-explored compared with RUNX1 fusions mainly due to their elusive genetic characteristics. Here, based on 1741 patients with AML, we report a unique expression pattern associated with RUNX1 mutations in AML. This expression pattern was coordinated by target repression and promoter hypermethylation. We first reanalyzed a joint AML cohort that consisted of three public cohorts and found that RUNX1 mutations were mainly distributed in the Runt domain and almost mutually exclusive with NPM1 mutations. Then, based on RNA-seq data from The Cancer Genome Atlas AML cohort, we developed a 300-gene signature that significantly distinguished the patients with RUNX1 mutations from those with other AML subtypes. Furthermore, we explored the mechanisms underlying this signature from the transcriptional and epigenetic levels. Using chromatin immunoprecipitation sequencing data, we found that RUNX1 target genes tended to be repressed in patients with RUNX1 mutations. Through the integration of DNA methylation array data, we illustrated that hypermethylation on the promoter regions of RUNX1-regulated genes also contributed to dysregulation in RUNX1-mutated AML. This study revealed the distinct gene expression pattern of RUNX1 mutations and the underlying mechanisms in AML development.
Core Binding Factor Alpha 2 Subunit/metabolism* ; DNA Methylation ; Gene Expression ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Promoter Regions, Genetic

The morbidity and mortality of myeloproliferative neoplasms (MPNs) are primarily caused by arterial and venous complications, progression to myelofibrosis, and transformation to acute leukemia. However, identifying molecular-based biomarkers for risk stratification of patients with MPNs remains a challenge. We have previously shown that interferon regulatory factor-8 (IRF8) and IRF4 serve as tumor suppressors in myeloid cells. In this study, we evaluated the expression of IRF4 and IRF8 and the JAK2V617F mutant allele burden in patients with MPNs. Patients with decreased IRF4 expression were correlated with a more developed MPN phenotype in myelofibrosis (MF) and secondary AML (sAML) transformed from MPNs versus essential thrombocythemia (ET). Negative correlations between the JAK2V617F allele burden and the expression of IRF8 (P < 0.05) and IRF4 (P < 0.001) and between white blood cell (WBC) count and IRF4 expression (P < 0.05) were found in ET patients. IRF8 expression was negatively correlated with the JAK2V617F allele burden (P < 0.05) in polycythemia vera patients. Complete response (CR), partial response (PR), and no response (NR) were observed in 67.5%,10%, and 22.5% of ET patients treated with hydroxyurea (HU), respectively, in 12 months. At 3 months, patients in the CR group showed high IRF4 and IRF8 expression compared with patients in the PR and NR groups. In the 12-month therapy period, low IRF4 and IRF8 expression were independently associated with the unfavorable response to HU and high WBC count. Our data indicate that the expression of IRF4 and IRF8 was associated with the MPN phenotype, which may serve as biomarkers for the response to HU in ET.
Biomarkers ; Humans ; Hydroxyurea/therapeutic use* ; Interferon Regulatory Factors/genetics* ; Janus Kinase 2/genetics* ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Phenotype ; Primary Myelofibrosis/genetics* ; Thrombocythemia, Essential/genetics*

Objective:To explore the effects of nursing program-based dietary intervention combined with family support in hemodialysis patients.Methods:The clinical data of 180 hemodialysis patients admitted to the First Affiliated Hospital of Zhengzhou University from September 2019 to September 2020 were selected by convenient sampling and retrospectively analyzed. The patients were divided into control group and observation group with 90 cases in each group according to different nursing methods. Patients in the control group received routine dietary care, while patients in the observation group underwent nursing program-based dietary intervention combined with family support on this basis. The nutritional status and dialysis compliance were compared between the two groups at the time of enrollment, 3 months, and 6 months after the intervention.Results:3 and 6 months after the intervention, the levels of body mass index, total protein, albumin, prealbumin, total lymphocyte count, and white blood cell count in the two groups increased, and the observation group was better than the control group, with statistically significant differences ( P<0.05) . At 3 and 6 months after the intervention, the scores of each dimension of compliance in the two groups increased, and the scores of each dimension in the observation group were better than those in the control group, with statistically significant differences ( P<0.05) . Conclusions:Nursing program-based dietary intervention combined with family support can improve the nutritional status and dialysis compliance of hemodialysis patients, which is worth promoting in clinical practice.

Objective:To examine the distribution of syphilis antibody in pregnant women and newborns and to explore how to optimize the existing syphilis screening process by setting the diagnostic gray area.Methods:The results of syphilis testing obtained from 119 531 pregnant women and 21 275 newborns from 2015 to 2018 by automatic chemiluminescent immunoassay (CLIA) and the re-examination results determined by Treponema pallidum particle agglutination (TPPA) and the rapid plasma reagin test (RPR) were retrospective analyzed. Data analysis was performed by Chi-square, Fisher′s exact test and Chi-square test for trend. Results:The positive rates of Syphilis specific antibody (TPAb) in clinical specimens from pregnant women and newborns were 0.69% (825/119 531) and 1.24%(264/21 275). The total re-examination positive rates were 0.32% (380/119 531) and 0.90%(191/21 275), and the suspicious syphilis prevalence rates in these specimens were 0.13% (161/119 531) and 0.31%(67/21 275), respectively. The suspicious syphilis prevalence rates in specimens of pregnant women from 2015 to 2018 and newborns increased year by year (χ 2=9.860, P=0.002; χ 2=5.311, P=0.021). With the elevation of the optical density value of samples to cut-off ratio (S/CO) value, positive coincidence rate of TPPA and TPAb in pregnant women and newborns increased significantly (χ 2=614.833, P<0.001; P<0.001). When the S/CO value in newborns exceeded 7.00 or the S/CO value in pregnant women exceeded 15.00, the effectiveness of TPAb results is equivalent to TPPA. The prevalence of suspected syphilis in pregnant women and newborns also increased with the increase of S/CO value (χ 2=323.059, P<0.001; P<0.001). When the S/CO value in newborns bellowed 3.00 or the S/CO value in pregnant women bellowed 5.00, the prevalence rate of suspected syphilis was 0%, which could preliminarily exclude syphilis infection. Conclusions:The prevalence rates of suspected syphilis in pregnant women was increasing during the recent years. It is necessary to further strengthen syphilis screening and intervention treatment in early pregnancy to improve the rate of eugenics. Being a primary screening method for syphilis in pregnant women and newborns, CLIA has high false positive rate. According to the gray area established in this study, the syphilis screening process can be optimized to prevent missed detection, which may reduce the false positive rate and avoid clinical misdiagnosis.

Objective: To predict the prognosis of cervical cancer, we constructed a novel model with 5 specific cell types and identified a potential biomarker. Methods: We employed CIBERSORT and xCell method to evaluate the abundances of 23 cells types in tumor microenvironment. Five specific cell types were filtrated to determine different immunotypes by applying least absolute shrinkage and selection operator (LASSO) Cox regression method. The expression of immune checkpoints (ICPs) and effectors were validated by immunohistochemistry. Correlation analysis was performed to examine the relevance between PIK3CA mutational status and ICPs. Results: Unsupervised clustering of patients on the basis of tumor infiltrating lymphocytes and fibroblasts identified patients with shorter overall survival (OS) (hazard ratio [HR]=3.0729; 95% confidence interval [CI]=1.5103–6.2522; p=0.0118). An immunoscore (IS) signature consisting of 5 immune cell types infiltrating in tumor core (CD8T, activated NK cells, neutrophils, activated mast cells, macrophages) was constructed using LASSO Cox regression analysis. Receiver operating characteristic curves confirmed that the area under the curve of IS was significantly higher to that of International Federation of Gynecology and Obstetrics staging alone (0.637 vs. 0.55). Survival analysis revealed patients in high IS group exhibited a poorer OS (HR=3.0113; 95% CI=1.8746–4.8373; p<0.0001). The multivariate analysis indicated the IS was an independent prognostic factor. In addition, the lower IS related to higher expression of ICPs and neoantigen load. Conclusions The identification of IS in cervical cancer tissues could facilitate patient risk stratification and selection of immunotherapeutic responses, but more prospective studies are needed to assess its reliability.

OBJECTIVE: To detect potential mutations of the coagulation factor Ⅶ (F7) gene in a pedigree affected with hereditary FⅦ deficiency and explore its molecular pathogenesis. METHODS: The FⅦ antigen (FⅦ:Ag) was analyzed by an enzyme-linked immunosorbent assay (ELISA) method. Prothrombin time (PT), FⅦ activity (FⅦ:C) and other coagulant parameters were quantified with an one-stage clotting assay. The F7 gene was amplified by PCR and sequenced. Mutational sites were confirmed by reverse sequencing. Impact of amino acid substitution was assessed using SIFT and PolyPhen-2 software. Structure of the mutant protein was analyzed using Swiss-pdb Viewer software based on the three-dimensional structure in the Protein Data Bank. RESULTS: The propositus had prolonged PT (36.3 s), with FⅦ:C and FⅦ:Ag significantly reduced to 2% and 44%, respectively. Her father, mother, younger sister and daughter had slightly prolonged PT and reduced FⅦ:C (86%-120%). The FⅦ:Ag of her father and younger sister were also reduced. DNA sequencing revealed that the propositus has carried compound heterozygous mutations (Lys341Glu and IVS6-1G>A) of the F7 gene. Her father and younger sister were heterozygous for the IVS6-1G>A mutation, while her mother and daughter were heterozygous for the Lys341Glu mutation. Bioinformatics analysis indicated that Lys341Glu mutation may affect the stability and function of the FⅦ protein. CONCLUSION The Lys341Glu and IVS6-1G>A mutations probably underlie the reduced activity of FⅦ in this pedigree.
Factor VII ; genetics ; Factor VII Deficiency ; genetics ; Female ; Genetic Testing ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree

Objective: To analyze the phenotype and F5 gene variant in a pedigree affected with hereditary coagulation factor Ⅴ (FⅤ) deficiency. Methods: All of the exons, flanking sequences, and 5′ and 3′ untranslated regions of the F5 gene were subjected to PCR and direct sequencing. Suspected variant sites were confirmed by clone sequencing. Influence of the variants was predicted by using software including ClustalX and Mutation Taster. Results: The prothrombin time (PT) and activated partial thromboplastin time (APTT) of the proband were prolonged to 20.3 s and 59.2 s, respectively, while FⅤ activity (FⅤ∶C) and FⅤ antigen (FⅤ∶Ag) were reduced by 13% and 17%, respectively. The FⅤ∶C and FⅤ∶Ag of his father, sister and daughter were decreased to 35%, 37%, 29% and 42%, 46%, 35%, respectively. The proband was found to carry a heterozygous c. 2851delT variant in exon 13 of the F5 gene, which caused a frameshift and resulted in a truncated protein (p.Ser923LeufsX8). In addition, a heterozygous c. 1538G>A (p.Arg485Lys) variant was found in exon 10. The father, sister and daughter of the proband all carried the p. Ser923LeufsX8 variant, while his mother and son carried the heterozygous p. Arg485Lys polymorphism. His younger brother and wife were of the wild type. Bioinformatic analysis showed that p. Ser923 was highly conserved across various species. Mutation Taster scored 1.00 for the p. Ser923LeufsX8 variant, and the result has predicted a corresponding disease. Conclusion A heterozygous deletional mutation c. 2851delT in exon 13 of the F5 gene and a heterozygous c. 1538G>A polymorphism harbored by the proband may be associated with the decreased FⅤ level in this pedigree.

OBJECTIVE: To identify potential mutations of F11 gene in a pedigree affected with hereditary coagulation factor XI (FXI) deficiency and explore its molecular pathogenesis. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), coagulation factor VIII activity (FVIIIC), coagulation factor IX activity (FIXC), coagulation factor XI activity (FXIC), coagulation factor XII activity (FXIIC) and lupus anticoagulation (LA) of the proband and eight family members were determined. FXI antigen (FXIAg) was determined by enzyme-linked immunosorbent assay (ELISA). For the proband, potential mutations in the exons, flanking introns and 5'-, 3'-untranslated regions of the F11 gene were screened by direct DNA sequencing. The results were confirmed by reverse sequencing. Suspected mutations were detected in other family members. ClustalX-2.1-win and four online bioinformatic tools (PolyPhen-2, PROVEAN, SIFT, and Mutation Taster) were used to study the conservation and possible impact of the mutations. The structure of the mutational sites was processed with Swiss-PdbViewer. RESULTS: The propositus had prolonged APTT (69.6 s), whose FXIC and FXIAg were reduced to 6.0% and 10.7%, respectively. Her mother, elder sister, one younger sister, little brother, daughter and son showed slightly prolonged APTT and moderate FXIC and FXIAg levels. Gene sequencing revealed that the propositus carried a heterozygous nonsense mutation c.738G>A (p.Trp228stop) in exon 7 and a heterozygous mutation c.1556G>C (p.Trp501Ser) in exon 13. Her mother, elder sister and daughter were heterozygous for the p.Trp228stop mutation, while one younger sister and little brother and son were heterozygous for p.Trp501Ser. Her husband and the youngest sister were of the wild type. Phylogenetic analysis suggested that Trp501 was highly conserved among all homologous species. The p.Trp501Ser was predicted to be "probably damaging","deleterious", "affect protein function" and "disease causing" corresponding to PolyPhen-2, PROVEAN, SIFT and Mutation Taster. Model analysis demonstrated that the non-polar Trp501 has two benzene rings, forming a hydrogen bond with Gln512 in the wild type. Once substituted by Ser501, the side chain may form another hydrogen bond with the benzene of His396. This may affect the normal space conformation and stability of FXI protein. CONCLUSION The compound heterozygous mutations of the F11 gene probably accounted for the low FXI concentration in this pedigree.
Factor XI ; genetics ; Factor XI Deficiency ; genetics ; Female ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree ; Phylogeny