Growth traits are one of the focuses of sheep breeding, and growth curve is an effective method to describe growth traits. The body weight of Yiling sheep at 0, 120, 180, 360 and 540 days of age were fitted with five common nonlinear growth models: Logistic, Gompertz, Von Bertalanffy, Brody and Negative exponential, and the growth models were evaluated by goodness of fit standard. The results showed that the Von Bertalanffy model was suitable for characterizing the growth of Yiling sheep. The estimated values of parameters A(mature weight), B(scale parameter related to the initial body weight) and K(maturity rate) in Von Bertalanffy model were 82.88 ± 7.47, 0.64 ± 0.05 and 0.0048 ± 0.0010, respectively. The parameters of the growth curve of the Von Bertalanffy model were further utilized to estimate the inflection point body weight of Yiling sheep as 24.56 kg, and the inflection point age was 135 days old. The absolute growth rate(AGR) first increased and then decreased, reaching the maximum value of 0.1766 kg/day at 135 days of age. The relative growth rate (RGR) of Yiling sheep decreased with age. The mature weight of Yiling sheep was the closest to that of common meat breeds. The Least squares estimation showed that sex had a significant (p < 0.05) effect on the growth curve parameters of Yiling sheep, with rams having a greater mature weight than ewes, while ewes had a higher maturity rate. The heritability estimates of parameters A, B and K were 0.09, 0.04 and 0.01, respectively, and the negative correlation between A and K indicated that lower maturity rate could be selected to increase mature weight.
OBJECTIVE:To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS:From May 2017 to October 2023, among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS:Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION:The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Objective: This study aimed to evaluate the efficacy and safety of venetoclax (VEN) combined with hypomethylating agents (HMA) in the treatment of higher-risk myelodysplastic syndromes (HR-MDS) and analyze the factors influencing their therapeutic effect. Methods: The clinical data of 83 patients with HR-MDS who were diagnosed at the First Affiliated Hospital of Zhengzhou University between November 2019 and May 2023 were retrospectively analyzed. All patients were treated with VEN combined with HMA. The Kaplan-Meier method was used to depict the survival curves, and the log-rank test was used to compare survival between the groups. Results: The median age was 57 (15-82) years old, and 51 patients (61.4%) were male. Forty-five patients (54.2%) were initially treated with HMA, 23 (27.7%) received ≤4 cycles of HMA, and 15 (18.1%) demonstrated HMA failure. At the median follow-up of 10.3 (0.6-34.4) months, the overall response rate (ORR) was 62.7% (52/83), including 18 patients (21.7%) with a complete response (CR), 14 (16.9%) with a bone marrow CR (mCR) with hematological improvement, and 20 (24.1%) with a mCR. The ORR of patients with initial treatment, ≤4 HMA cycles, and HMA failure were 66.7%, 60.9%, and 53.3%, respectively (P=0.641). The median overall survival time was 14.6 (95% CI 7.2-22.0) months, and the median progression-free survival time was 8.9 (95% CI 6.7-11.1) months. The multivariate analysis showed that serum alkaline phosphatase (ALP) ≥90 U/L (OR=14.574, 95% CI 3.036-69.951, P=0.001), TP53 mutation (OR=13.052, 95% CI 1.982-85.932, P=0.008), and U2AF1 mutation (OR=7.720, 95% CI 1.540-38.698, P=0.013) were independent risk factors for poor efficacy of VEN combined with HMA. Hematological toxicity occurred in all patients, and the incidence of treatment-induced grade 3-4 leukopenia was 48.2% (40/83). Infection was the most common non-hematological adverse event, mainly pulmonary infection (31.3%) . Conclusion: VEN combined with HMA had a high response rate in patients with HR-MDS, both at initial treatment and with HMA failure. ALP ≥ 90 U/L, TP53 mutation, and U2AF1 mutation were independent risk factors for non-response to treatment.
Background: Recent miRNA profiling studies have implicated the potential use of miRNAs as as diagnostic and prognostic indicators in acute myeloid leukemia (AML), which has been reportedly implicated in the interplay with certain mRNAs. Herein this study, we intend to characterize the functional relevance of SPOP/miR-183/METAP2 axis in AML in vivo and in vitro. Methods: Differentially expressed mRNAs and downstream regulatory miRNA were predicted by in silico analysis. We induced SPOP/miR-183/METAP2 overexpression or inhibition to examine their effects on AML cell proliferation and apoptosis in vitro and tumor growth in vivo , along with their interaction with β-catenin. Results: SPOP and miR-183 were highly expressed, while METAP2 was poorly expressed in patient peripheral blood samples and cell lines of AML. SPOP accelerated the proliferation of AML cells and repressed apoptosis. Mechanistically, SPOP enhanced β-catenin protein stability and nuclear translocation leading to upregulated expression of miR-183. MiR-183 facilitated proliferation and inhibited apoptosis of AML cells by targeting METAP2. Furthermore, miR-183 inhibition and METAP2 overexpression reversed SPOP-induced AML cell malignancy. Besides, in vitro findings were reproduced by in vivo findings. Conclusion: SPOP stimulated AML malignant progression by inducing β-catenin stability and miR-183/METAP2 axis activation, highlighting a potential therapeutic target against AML recurrence and metastasis.
Acute myeloid leukemia (AML) is a heterogeneous disease with a poor prognosis. The current risk stratification system is essential but remains insufficient to select the best schedules. Cysteine-rich protein 1 (CSRP1) is a member of the CSRP family and associated with poor clinicopathological features in many tumors. This study aimed to explore the clinical significance and molecular mechanisms of cysteine- and glycine-rich protein 1 (CSRP1) in AML. RT-qPCR was used to detect the relative expression of CSRP1 in our clinical cohort. Functional enrichment analysis of CSRP1-related differentially expressed genes was carried out by GO/KEGG enrichment analysis, immune cell infiltration analysis, and protein-protein interaction (PPI) network. The OncoPredict algorithm was implemented to explore correlations between CSRP1 and drug resistance. CSRP1 was highly expressed in AML compared with normal samples. High CSRP1 expression was an independent poor prognostic factor. Functional enrichment analysis showed neutrophil activation and apoptosis were associated with CSRP1. In the PPI network, 19 genes were present in the most significant module, and 9 of them were correlated with AML prognosis. The high CSRP1 patients showed higher sensitivity to 5-fluorouracil, gemcitabine, rapamycin, cisplatin and lower sensitivity to fludarabine. CSRP1 may serve as a potential prognostic marker and a therapeutic target for AML in the future.
Rectal temperature is widely used as an indicator of animal health. However, rectal temperature is conventionally measured by an invasive method, which may reduce animal welfare. So, this study aimed to determine the relationships between the deep-body (core) temperature and body surface temperatures in goats and develop a linear regression equation to establish the core temperature based on body surface temperatures. Body surface temperatures (head, eye, muzzle, horn, back, scrotum and groin) of goats were measured by infrared thermography (IRT). Ambient temperatures were measured by digital thermometer. Core temperatures were measured by a digital vet thermometer. Pearson correlation analysis was used to analyze the relationship between body surface temperatures, ambient temperature, and core temperature. Simple linear regression analysis was used to develop core temperature assessment equations. Correlation analysis showed that groin temperature was highly correlated with core temperature, and low correlated with ambient temperature. The body surface temperature of other region was low correlated with core temperature, and highly correlated with ambient temperature. Regression analysis showed that the determination coefficient of core temperature assessment equation based on groin temperature was the highest (P < 0.0001, R2 = 0.55), and those based on surface temperature of other regions were low (P < 0.01, R2 ≤ 0.16). We concluded that body surface temperatures obtained by IRT could be used for the assessment of goat core temperature. The core temperature assessment equations developed by the temperature of the body surface, which is less affected by ambient temperature, was found to have a higher determination coefficient than the equations developed using body surface temperature that is more affected by ambient temperature.
Anemia is the most common manifestation in myelodysplastic syndrome (MDS) patients, but the cause of ineffective hematopoiesis is not fully understood. Enucleation is an important event in the maturation process of erythroblasts. According to a series of morphological phenotypes of the pathological development of MDS erythroblasts, we speculate that there may be enucleation disorders. To verify this hypothesis, we cultured MDS bone marrow CD34+ cells in vitro and induced erythroblast development. The results showed that erythroblast enucleation in MDS was significantly lower than that in the normal group, and the rate of enucleation was positively correlated with hemoglobin concentration. Risk stratification of MDS was performed to further analyze the differences in enucleation among the normal group, low-middle risk group and high-risk group. The results showed that the enucleation rate of the high risk group was higher than that of the low-middle risk group but still lower than that of the normal group. Moreover, the expression of pERK and pAKT in MDS erythroblasts in the high risk group was higher than that in the normal group, while the expression of pERK and pAKT in the low-middle risk group was lower than that in the normal group. Furthermore, the enucleation of MDS was positively correlated with the phosphorylation degree of ERK and AKT. In conclusion, this study reveals that the enucleation of erythroblasts is one of the possible causes of anemia in MDS.
Aspermatogenesis has been induced in rats by intratesticular administration of heterologous antitesticular and antisperm antisera. The extent of lesion of the germinal epithelium, reversibility of the aspermatogenesis and regaining of the fertilizing ability were correlated with the dose of the antibody administered. Determination of the lysosomal stability of the aspermatogenic testes indicated that the degenerative changes of the seminiferous tubules were not due to any autolytic activity consequent to physical injury. The aspermatogenesis was observed to be associated with increased activity of the testicular enzyme 3-beta hydroxysteroid dehydrogenase and depletion of testicular ascorbic acid which suggested increase steroidogenesis in the testis.
Background: Animal reproduction performance is crucial in husbandry. Immunocastrated animals serve as an ideal animal model for studying testicular function. During androgen suppression, the testis undergoes dramatic developmental and structural changes, including the inhibition of hormone secretion and spermatogenesis. Methods: To characterize this process, we investigated the effects of castration using a recombinant B2L and KISS1 DNA vaccine, and then identified functional genes in the testes of Yiling goats using RNA-seq and WGS. The experimental animals were divided into three groups: the PVAX-asd group (control), PBK-asd-immunized group, and surgically castrated group. Results: The results demonstrated that the administration of the recombinant PBK-asd vaccine in goats elicited a significant antibody response, and reduced serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH), resulting in smaller scrotal circumferences and decreased sexual desire compared to the control group. In addition, RNA transcriptome sequencing (RNA-seq) analysis of the testes revealed that the biological processes after immunocastration mainly focused on the regulation of cell matrix adhesion, histone acetylation, negative regulation of developmental processes, apoptosis, and activation of the complement system and the thrombin cascade reaction system. Then, we integrated the whole-genome sequencing and testis transcriptome, and identified several candidate genes (FGF9, FST, KIT, TH, TCP1, PLEKHA1, TMEM119, ESR1, TIPARP, LEP) that influence steroidogenesis secretion and spermatogenesis. Conclusions: Multiple pathways and polygenic co-expression participate in the response to castration vaccines, altering hormone secretion and spermatogenesis. Taken together, our atlas of the immunocastration goat testis provides multiple insights into the developmental changes and key factors accompanying androgen suppression, and thus may contribute to understanding the genetic mechanism of testis function. Joint analysis of whole genome sequencing and RNA-seq enables reliable screening of candidate genes, benefiting future genome-assisted breeding of goats.
Objective:To exploring the clinical features of SF3B1-mutated myelodysplastic syndrome with excess blasts (MDS-EB) and analyzing the association between SF3B1 mutation, and efficacy and prognostic significance for patients with MDS-EB.Methods:This was a retrospective case series study. The clinical data of 266 patients with MDS-EB diagnosed in the First Affiliated Hospital of Zhengzhou University between April 2016 and November 2021 were analyzed. The observed indicators included blood routine counts, mutated genes, overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and leukemia-free survival (LFS). The Kaplan-Meier method was used to depict the survival curves. The Log-rank test method was equally used to compare survival across groups and performed the Cox proportional hazard regression model for prognostic analysis.Results:In 266 patients with MDS-EB, 166 (62.4%) were men, and the median age was 57 (17-81) years. Moreover, there were included 26 and 240 patients in the SF3B1-mutated and SF3B1 wild-type groups. Patients in the SF3B1-mutated group were older [median age 65 (51, 69) years vs. 56 (46, 66) years, P=0.033], had higher white blood cell (WBC) counts [3.08 (2.35, 4.78) × 10 9/L vs. 2.13 (1.40, 3.77) × 10 9/L], platelet (PLT) counts [122.5 (50.5, 215.0) ×10 9/L vs. 49.0 (24.3, 100.8) × 10 9/L], absolute neutrophil counts (ANC) [1.83 (1.01, 2.88) × 10 9/L vs. 0.80 (0.41, 1.99) × 10 9/L]and occurrence of DNMT3A mutation [23.1% (6/26) vs. 6.7% (16/240)] (all P<0.05). The ORR were similar in both groups after 2 and 4 cycles of therapy ( P=0.348, P=1.000). Moreover, the LFS ( P=0.218), PFS ( P=0.179) and OS ( P=0.188) were similar across the groups. Univariate Cox analysis revealed that SF3B1 mutation did not affect the prognosis of patients with MDS-EB (OS: P=0.193; PFS: P=0.184). Conclusions:Patients with SF3B1 mutation were older, with greater WBC, PLT, and ANC, and SF3B1 mutation easily co-occurred with DNMT3A mutation. From this model, there were no significant differences in efficacy and survival of MDS-EB with or without SF3B1 mutation.
This study aimed to calculate the economic value (EV) of reproductive and growth traits for Yiling sheep. A bio-economic model was developed to assess the economic value of litter size (LS), litter size at weaning (LSW), age at first lambing (AFL), lambing interval (LI), birth weight (BW), weaning weight (WW), and 6-month body weight (6MW). The sensitivity of the economic value of traits to changes in market prices was also analyzed. In this study, the trait with the highest EV was LSW (427.97 ¥), followed by LS (419.96 ¥), BW (52.13 ¥), 6MW (14.46 ¥), WW (11.03 ¥), AFL (−0.51 ¥), and LI (−9.09 ¥). LS was the most important trait in the production system with a relative economic weight of 22.81
With the demand for standardized large-scale livestock farming and the development of artificial intelligence technology, a lot of research in the area of animal face detection and face identification was conducted. However, there are no specialized studies on livestock face normalization, which may significantly reduce the performance of face identification. The keypoint detection technology, which has been widely applied in human face normalization, is not suitable for animal face normalization due to the arbitrary directions of animal face images captured from uncooperative animals. It is necessary to develop a livestock face normalization method that can handle arbitrary face directions. In this study, a lightweight angle detection and region-based convolutional network (LAD-RCNN) was developed, which contains a new rotation angle coding method that can detect the rotation angle and the location of the animal's face in one stage. LAD-RCNN also includes a series of image enhancement methods to improve its performance. LAD-RCNN has been evaluated on multiple datasets, including a goat dataset and infrared images of goats. Evaluation results show that the average precision of face detection was more than 97%, and the deviations between the detected rotation angle and the ground-truth rotation angle were less than 6.42° on all the test datasets. LAD-RCNN runs very fast and only takes 13.7 ms to process a picture on a single RTX 2080Ti GPU. This shows that LAD-RCNN has an excellent performance in livestock face recognition and direction detection, and therefore it is very suitable for livestock face detection and normalization.
ObjectiveTo explore the value of inflammation cytokines for predicting the postoperative occurrence of acute kidney injury (AKI) after surgery for congenital heart disease in children.MethodsFrom February 2018 to November 2020, 139 cases of congenital heart disease undergoing cardiopulmonary bypass surgery were recruited and divided into two groups of AKI and non-AKI. Children in AKI group were further divided into AKI with progression and AKI without progression according to whether or not renal function worsened persistently. The groups were compared with regards to the levels of interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) in sera and liver fatty acid binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL) in urine. Correlation analysis was performed between those factors and AKI and AKI occurring predicated by area under the ROC curve (AUC).ResultsCardiopulmonary bypass (CBP) time [(133.6±31.5) min vs (102.8±19.8) min, 142.6(52.5, 288.6) min vs 115.7(64.8, 69.4) min], aortic cross-clamp time [(68.5±29.7) min vs (52.0±36.5) min, 73(56.5, 93.8) min vs 56(40.5, 72.2) min], PICU stay [9.7(6.4, 17.2) d vs 4.2(2.2, 7.2) d, 11.5(10.6, 15.5) d vs 5.3(4.3, 9.7) d], hospital stay [15.7(11.3, 19.2) d vs 9.5(8.5, 13.5) d, 21.7(15.8, 32.6) d vs 10.2(9.4, 17.6) d], mechanical ventilation time [5.7(1.4, 12.2) d vs 2.8(2.0, 8.9) d, 7.7(5.2, 18.7) d vs 4.8(2.2, 12.2) d] of AKI and AKI with progression groupa were longer than those of non-AKI and AKI without progression groups (P<0.05). The levels of IL-2 [2.4(1.1, 2.7)ng/L vs 0.9(0.5, 2.3) ng/L, 2.9(1.1, 3.6)ng/L vs 1.3(1.1, 1.9) ng/L], IL-6 [41.3(6.1, 86.5)ng/L vs 3.1(1.2, 3.9) ng/L, 56.4(7.7, 108.6)ng/L vs 38.5(6.3, 74.2) ng/L], IL-8 [52.9(16.8, 100.2) ng/L vs 2.9(1.9, 4.3) ng/L, 84.5(43.3, 168.7)ng/L vs 45.2(9.6, 84.3) ng/L], IL-10 [46.8(7.1, 136.4)ng/L vs 1.3(0.8, 7.7) ng/L, 66.7(7.9, 244.8)ng/L vs 38.2(6.8, 106.7) ng/L] in sera and L-FABP [63.2(4.2, 167.3)ng/L vs 4.5(2.4, 6.5) ng/L, 94.6(3.9, 268.7)ng/L vs 25.8(5.6, 103.2) ng/L], NGAL [18.3(10.9, 46.3)ng/L vs 3.6(1.8, 5.2) ng/L, 29.3(16.7, 85.4)ng/L vs 9.6(1.1, 25.6) ng/L] in urine at Day 1 post-operation were higher in AKI and AKI with progression groups than those in non-AKI and AKI without progression groups (P<0.05). ROC analysis revealed that IL-6, IL-8, L-FABP and NGAL could predict the occurrence of AKI with AUC 0.79, 0.81, 0.75 and 0.74 (P<0.05) respectively. Furthermore, serum IL-8 and urinary L-FABP could predict the progression of AKI with AUC 0.82 and 0.81 (P<0.05).ConclusionIL-6, IL-8, L-FABP and NGAL are obviously elevated in AKI so that they have prediction values of AKI. And marked elevations of IL-8 and L-FABP in children with AKI progression offer prediction values for AKI progression.
目的 探讨结肠癌合并糖尿病患者血糖水平与可溶性细胞间黏附分子-1(sICAM-1)、C反应蛋白(CRP)的关系及术后感染的影响因素.方法 根据是否出现术后感染将168例结肠癌合并糖尿病患者分为观察组(n=68,术后感染)和对照组(n=100,术后无感染).比较两组患者的围手术期(术前、术后1天、术后7天)血糖水平,比较术后7天两组患者的外周血辅助性T细胞17(Th17)和调节性T细胞(Treg)水平.分析围手术期血糖水平与sICAM-1、CRP水平的相关性,采用Logistic回归模型分析结肠癌合并糖尿病患者术后感染的影响因素.结果 术后1天和术后7天,两组患者的sICAM-1、CRP水平均高于本组术前,且观察组患者的sICAM-1、CRP水平均高于对照组,差异均有统计学意义(P﹤0.05);术后7天,观察组患者的血糖水平高于对照组,差异有统计学意义(P﹤0.05).术后7天,观察组患者的外周血Th17/CD4+、Th17/Treg均明显高于对照组,Treg/CD4+明显低于对照组,差异均有统计学意义(P﹤0.01).两组患者的围手术期血糖水平均与sICAM-1、CRP水平呈正相关(P﹤0.05).Logistic回归分析结果显示,sICAM-1、CRP水平及血糖控制情况均是结肠癌合并糖尿病患者术后感染的独立影响因素(P﹤0.01).结论 结肠癌合并糖尿病患者的围手术期血糖水平与sICAM-1、CRP水平均呈正相关,sICAM-1、CRP水平及血糖控制情况均是结肠癌合并糖尿病患者术后感染的独立影响因素,控制炎性因子水平及血糖水平有利于降低患者的术后感染风险.
Abstract This study focused on the changes in the composition and immune evolution in milk from birth to 144 h postpartum and the genes associated with the colostrum yield of Hu sheep. Twelve Hu sheep, which were bred carefully under animal health standards and have a litter size of two kids and similar gestation length (149 ± 1 days), were used. Lambs were transferred into their own cots to avoid interference. The compositional content (i.e., fat, protein, and lactose) and some other properties, including daily colostrum yield, DM, and SNF, were determined. In addition, immunity molecules (IgG, IgA, and IgM concentrations) received remarkable attention. The DM, SNF, fat, and protein contents were higher in the first days postpartum and then dropped quickly from the time of birth to 144 h postpartum. However, the lactose content displayed an increasing pattern and reached normal milk percentage at 48 h. The highest IgG (103.17 mg/mL), IgA (352.82 μg/mL), and IgM (2.79 mg/mL) colostrum concentrations were observed at partum, decreased quickly, and finally stabilized. The change law of concentration of IgA and IgM in colostrum are the same with IgG. Furthermore, the whole-genome resequencing was performed, and a missense variant locus in the SRC gene and two missense locus variants in the HIF1A gene were significantly associated with the colostrum yield of sheep by using the whole-genome selection signal detection analysis. In conclusions, colostrum contains abundant nutrients especially immunoglobulin, and the HIF1A gene may be used as candidate genes for colostrum yield, which has important information as a basic knowledge for the Hu sheep breeding program.
目的 构建预测老年高血压患者发生高尿酸血症(HUA)的列线图模型,并评估模型的区分度和一致性.方法 选取2017年12月至2021年5月郑州大学附属郑州中心医院收治的260例原发性高血压患者为研究对象,根据患者是否发生HUA分为发生HUA组(90例)和未发生HUA组(170例),收集患者临床资料,采用logistic回归分析影响老年高血压患者发生HUA的危险因素.采用R软件构建预测老年高血压患者发生HUA风险的列线图模型,并使用受试者工作特征(ROC)曲线及校准曲线分别评估列线图模型的区分度和一致性.结果 260例老年高血压患者中有90例发生HUA,发生率为34.62%.发生HUA组体质量指数、尿酸、空腹血糖(FPG)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)水平高于未发生HUA组,差异有统计学意义(P<0.05).多因素logistic结果显示,体质量指数、尿酸、TG、FPG是影响老年高血压患者发生HUA的危险因素(P<0.05).构建的列线图预测模型具有较好的区分度[ROC曲线下面积为0.917(95%CI:0.883~0.951)]与一致性(Hosmer-Lemeshow拟合优度检验为8.563,P=0.381).结论 本研究构建的预测老年高血压患者发生HUA风险的列线图模型具有较好的区分度和一致性.
Objective To genetically analyze the Del sample from a blood donor in Jiangyin and make clear the molecular basis of the serological phenotype. Methods The EDTA anticoagulant blood were collected: buffy coat were used for nucleic acid extract and cDNA analysis; red blood cells for serological test. Tube method and microcolumn gel were used for serological test. Genotyping kit were used for exon analysis. Gene mutation was analyzed using the sequence analyzer. Results Serological analysis demonstrated the sample′s RhD phenotype was Del. The phenotype of RhCE was CCEe. Real-time fluorescence quota PCR result demonstrated the existence of all exones. Weak D15 and RHD*DEL1 [RHD(1227G>A)], which had a high frequency of occurrence in China, were excluded according to real-time fluorescence quota PCR result. Sequence analyzing result verified RHD(28C>T) SNP mutation in cDNA. The genotype of this sample was RHD*01 W. 61[RHD(28C>T)]. Conclusion A weak D61 was found among blood donors in our city, Jiangyin.
目的 观察U2AF1基因突变的成人急性髓系白血病(AML)患者的临床特征及预后.方法 对2016年1月至2019年12月就诊于郑州大学第一附属医院的690例AML患者的病历资料进行回顾性分析.按U2AF1突变与否将患者分为U2AF1未突变组(652例)和U2AF1突变组(38例).比较两组临床特征及预后.结果 690例AML患者中,U2 AF1突变率为5.5%,常合并ASXL1、NRAS、SETBP1等基因突变.与U2 AF1未突变组相比,U2 AF1突变组外周血白细胞计数(WBC)、骨髓原始细胞比率低,预后中等及不良染色体核型多见,+8核型较多(P<0.05).在625例可评估疗效的AML患者中,单因素分析发现,U2AF1突变组中位总生存期(OS)、中位无进展生存期(PFS)较U2AF1未突变组短,完全缓解(CR)率、2 a OS率较U2AF1未突变组低(P<0.05).与未突变组相比,U2AF1 S34F突变组CR率较低,中位OS较短(P<0.05);两者中位PFS比较,差异无统计学意义(P>0.05).U2AF1 S34Y突变组中位PFS较未突变组短(P<0.05);两者CR率、中位OS比较,差异无统计学意义(P>0.05).多因素分析发现,U2AF1突变是影响<60岁AML患者OS、PFS的独立危险因素,1~2个疗程内达CR、接受造血干细胞移植、CEBPA双突变是影响<60岁AML患者OS及PFS的有利因素(P<0.05).结论 U2AF1突变在AML患者中发生率低,常与其他基因突变共存,预后中等及不良染色体核型多见.不同突变位点的预后意义不同.U2AF1突变是年轻(<60岁)AML患者的预后不良因素.
目的:探讨维奈克拉对骨髓增生异常综合征(MDS)转化的急性巨核细胞白血病(AML-M 7)老年患者的疗效和安全性。 方法:回顾性分析郑州大学第一附属医院2021年2月收治的1例应用维奈克拉治疗的老年继发性AML-M 7患者的临床资料,并复习相关文献。 结果:患者经老年综合评估(CGA),为不适合组(unfit),应用维奈克拉治疗后临床症状好转,骨髓原始细胞明显降低,但出现严重感染。患者最终死于脓毒性休克、呼吸衰竭。结论:维奈克拉治疗CGA不适合组AML患者疗效明显,但是骨髓抑制期需要做好感染预防,可作为老年AML患者的一种新治疗选择。
Enudeation is a key event in mammalian erythropoiesis responsible for the generation of enucleated reticulocytes. Although progress is being made in developing mechanistic understanding of enucleation, our understanding of mechanisms for enudeation is still incomplete. The MAPK pathway plays diverse roles in biological processes, but its role in erythropoiesis has yet to be fully defined. Analysis of RNA-sequencing data revealed that the MAPK pathway is significantly upregulated during human terminal erythroid differentiation. The MAPK pathway consists of 3 major signaling cassettes: MEK/ERK, p38, and JNK. In the present study, we show that among these 3 cassettes, only ERK was significantly upregulated in late-stage human erythroblasts. The increased expression of ERK along with its increased phosphorylation suggests a potential role for ERK activation in enudeation. To explore this hypothesis, we treated sorted populations of human orthochromatic erythroblasts with the MEK/ERK inhibitor U0126 and found that U0126 inhibited enudeation. In contrast, inhibitors of either p38 or JNK had no effect on enudeation. Mechanistically, U0126 selectively inhibited formation/accumulation of cytoplasmic vesicles and endocytosis of the transferrin receptor without affecting chromatin condensation, nuclear polarization, or enucleosome formation. Treatment with vacuolin-1 that induces vacuole formation partially rescued the blockage of enudeation by U0126. Moreover, phosphoproteomic analysis revealed that inactivation of the ERK pathway led to downregulation of the endocytic recycling pathway. Collectively, our findings uncovered a novel role of ERK activation in human erythroblast enudeation by modulating vesicle formation and have implications for understanding anemia associated with defective enudeation.