Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.

Objective:To investigate the clinical features and multimodal imaging features of eyes with perifoveal exudative vascular anomalous complex (PEVAC).Methods:A retrospective case study. From February 2014 to November 2020, 7 eyes of 7 patients with PEVAC diagnosed by ophthalmology examination in Department of Ophthalmologyof Peking University People's Hospital were included in this study. There were 6 males and 1 female. The age was 60.1±9.1 years. All were monocular. The chief complaints of visual deformation and vision loss were 3 and 1 cases, respectively. All patients underwent best corrected visual acuity (BCVA), fundus color photography, optical coherence tomography (OCT), fundus fluorescein angiography (FFA). BCVA examination was performed using the standard logarithmic visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity. OCT angiography (OCTA) and indocyanine green angiography (ICGA) were performed in 4 and 2 eyes, respectively. Three eyes were treated with intravitreal injection of anti-vascular endothelial growth factor (VEGF) combined with local laser photocoagulation. Two eyes were treated with laser photocoagulation alone. The follow-up time was 16.7±19.1 months. During follow-up, relevant examinations were performed with the same equipment and methods as at the initial diagnosis. The multimodal imaging characteristics and treatment response of the affected eyes were observed.Results:The baseline logMAR BCVA was 0.33±0.19 (0.20-0.80). All eyes showed isolated hemangiomatous lesions in the macular fovea with rigid retinal exudation, and 2 adjacent isolated hemangiomatous lesions were observed in 1 eye. FFA and ICGA examination showed that all eyes with macular hemangiomatous lesions showed clear boundary and strong fluorescence in the early stage. No other retinal or choroidal vascular abnormalities were observed. On OCT examination, circular lumen-like structures with strong reflective wall near the fovea were observed in the macular region of all eyes, accompanied by intraretinal cystic lumen. The macular central retinal thickness (CMT) was 326±125 (207-479) μm. In the four eyes examined by OCTA, blood flow signals were observed in the circular lumenoid structures with strong reflective walls adjacent to the fovea. Blood flow signals were observed in the superficial capillary layer (SCP) and deep capillary layer (DCP) of the retina in 3 eyes. SCP showed blood flow signal in 1 eye. In 4 eyes treated with intravitreal injection of anti-VEGF drugs, there was no significant improvement in the intraretinal capsule space after treatment. Subretinal fluid absorption, retinal cystoid edema persisted, and rigid exudation decreased in 1 eye. CMT decreased and BCVA increased in 5 eyes treated with laser photocoagulation or laser photocoagulation alone. At last follow-up, logMAR BCVA was 0.16±0.06 (0.10-0.20) and CMT was 212±34 (154-252) μm. Compared with baseline, the difference of BCVA was statistically significant ( t=2.661, P=0.037). Conclusions:The fundus of PEVAC patients is characterized by solitary or multiple solitary hemangiomatous lesions in the macular fovea. Round lumenoid structures with strong reflective walls, with or without intraretinal cystic lumen, rigid exudate, and subretinal fluid, in which blood flow signals can be seen in OCT.

Objective:To explore the risk factors in leukemia transformation (LT) in those with myelodysplastic syndromes (MDS) .Methods:From January 2012 to December 2020,data on 320 patients with newly diagnosed primary MDS were gathered from the MDS center. The clinical features and molecular characteristics are explored. Additionally, a retrospective analysis of risk factors for the development of acute leukemia from MDS was done.Results:The median follow-up was13.6 (0.4-107.3) months. 23.4% (75/320) of the MDS patients had LT group. Significant differences between the LT group and non-LT group can be seen in age ( P<0.001) , bone marrow blast percentage ( P<0.001) , bone marrow fibrosis ( P=0.046) , WHO classification ( P<0.001) , IPSS-R ( P<0.001) and IPSS-R karyotype group ( P=0.001) . The median number of mutation of LT group was 1 (1, 3) , that in non-LT group was 1 (0, 2) ,which had a statistical difference ( P=0.003) .At the time of the initial diagnosis of MDS, the LT group had higher rates of the TP53 mutation ( P=0.034) , DNMT3A mutation ( P=0.026) , NRAS mutation ( P=0.027) and NPM1 mutation ( P=0.017) . Compared with the mutations at first diagnosis and LT of six patients, the number of mutations increased and the variant allele frequencies (VAF) increased significantly in LT patients. Higher bone marrow blast percentage (Refer to <5% , 5% -10% : HR=4.587, 95% CI 2.214 to 9.504, P<0.001, >10% : HR=9.352, 95% CI 4.049 to 21.600, P<0.001) , IPSS-R cytogenetic risk groups ( HR=2.603, 95% CI 1.229-5.511, P=0.012) , DNMT3A mutation ( HR=4.507, 95% CI 1.889-10.753, P=0.001) , and NPM1 mutation ( HR=3.341, 95% CI 1.164-9.591, P=0.025) were all independently associated with LT in MDS patients, according to results of multivariate Cox regression. Conclusion:Bone marrow blast percentage, IPSS-R cytogenetic risk groups, DNMT3A mutation, and NPM1 mutation are independent risk factors in LT for MDS patients.

Objective:To explore the psychological resilience of adolescent leukemia survivors and analyze its influencing factors.Methods:From October 2018 to August 2020, convenience sampling was used to select adolescent leukemia survivors in the routine follow-up group and follow-up group for children with leukemia who stopped taking medication in Beijing Children's Hospital affiliated to Capital Medical University as the research object. The General Information Questionnaire, Resilience Scale for Chinese Adolescents, and the General Self-Efficacy Scale were used to investigate adolescent leukemia survivors. A total of 110 questionnaires were issued, and 106 valid questionnaires were returned, with the effective response rate of 96.36%.Results:Among 106 adolescent leukemia survivors, the total score of psychological resilience was (97.83±14.93) . The results of multiple linear regression analysis showed that disease risk, duration of drug withdrawal, and general self-efficacy were the influencing factors of psychological resilience in adolescent leukemia survivors, and the difference was statistically significant ( P<0.05) . Conclusions:The psychological resilience level of adolescent leukemia survivors is at an upper-middle level. Medical and nursing staff, the family and friends of adolescent leukemia survivors should pay active attention to survivors whose disease risk is medium or high risk or whose duration of drug withdrawal is less than 5 years, and provide them with a lot of support and help. At the same time, pay attention to the general self-efficacy of survivors, provide targeted self-care guidance or substantive help for the survivors to return to school and society so as to improve their psychological resilience.

Objective: To explore the prognostic effects of mean corpuscular volume (MCV) in patients with myelodysplastic syndromes (MDS) . Methods: 321 newly diagnosed, untransfused primary MDS patients who administered from December 2009 to December 2017 were enrolled. The association of MCV with prognosis and several clinical features and genetic mutations were analyzed. Results: Patients were divided into MCV≤100 fl (n=148) and MCV>100 fl (n=173) cohorts. Median overall survival of patients with MCV≤100 fl was shorter than their counterparts (27 months vs 72 months, P<0.001) . In subgroup analysis, MCV≤100 fl patients had worse survivals in bone marrow blast <5% cohort (34 months vs not reached, P=0.002) , but not so in ≥5 % cohort (17 months vs 20 months, P=0.078) . MCV≤100 fl was still an independent adverse variable (HR=1.890, 95%CI 1.007-3.548, P=0.048) after adjusting for clinical and laboratory variables and mutation topography in bone marrow blasts<5% cohort. In bone marrow blasts<5% cohort, patients with MCV≤100 fl had higher hemoglobin levels [90 (42-153) g/L vs 78.5 (28-146) g/L, P=0.015].The proportions of Revised International Prognostic Scoring System (IPSS-R) high/very high risks and poor/very poor IPSS-R karyotypes were higher in MCV≤100 fl cohort (28.8% vs 10.8%, P=0.003; 24.7% vs 12.9%, P=0.049) . MCV≤100 fl cohort had more genetic mutations than those with MCV>100 fl though without significance (0.988 vs 0.769, P=0.064) . Mutated SF3B1 was less frequently in MCV≤100 fl cohort (4.7% vs 15.4%, P=0.018) . Conclusion MCV≤100 fl was an independent adverse variable after adjusting for clinical and laboratory variables and mutation topography in MDS patients with bone marrow blasts<5%.

Objective:To explore the features and clinical significance of gene mutations in patients with myelodysplastic syndromes with ring sideroblasts (MDS-RS) .Methods:A total of 255 newly diagnosed primary MDS-RS patients were retrospectively reviewed from our center from January2001 to June 2019. SF3B1 gene mutations were detected by Sanger sequencing in 129 patients, and next generation sequencing (NGS) was performed in the other 126 patients using a set of selected 112-genes.Results:A total of 193 (75.7%) patients presented with SF3B1 mutation, predominantly mutant at amino acid position 700 (K700E) ( n=147, 76.2%) . Non-SF3B1 gene mutations were TET2 (16.7%) , ASXL1 (14.3%) , U2AF1 (11.1%) , TP53 (7.9%) , SETBP1 (6.3%) , and RUNX1 (6.3%) . RS 5%-<15% patients had a higher SETBP1 mutation frequency than RS≥15% patients (21.4% vs 4.5%, P=0.044) . Mutation frequencies of other genes were similar in both groups (all P>0.05) . SF3B1 variant allele frequencies (VAF) had positive correlation with marrow RS percentage but without statistical significance in RS 5%-<15% group ( P=0.078, r=0.486) . SF3B1 mutant patients presented with higher marrow RS percentage compared with wild-type patients[40.0% (15.0%-80.0%) vs 25.5% (15.0%-82.0%) , P<0.001], and SF3B1 VAF positively correlated with RS percentage ( P=0.009, rs=0.261) in RS≥15% group. Age, ANC, PLT, mean RBC corpuscular volume, RS percentage, IPSS-R cytogenetics, and IPSS-R risk score were significantly different between patients with SF3B1 mutations and wild-type SF3B1 (all P<0.05) . Multivariable survival analyses adjusted by age and IPSS-R cytogenetics revealed that SF3B1 mutation was an independent favorable prognostic factor ( HR=0.265, 95% CI 0.077-0.917, P=0.036) , and TP53 mutation was an adverse variable independent of SF3B1 mutation ( HR=6.272, 95% CI 1.725-22.809, P=0.005) . According to the mutant status of SF3B1 and TP53, MDS-RS patients were categorized into 4 groups, namely, with SF3B1 and TP53 mutation, with wild-type SF3B1 and TP53, with wild-type SF3B1 but TP53 mutation, and with SF3B1 mutation but wild-type TP53. There was a significant difference for OS among these 4 groups ( P<0.001) . The former 3 groups showed no significant difference in OS in multiple comparisons. However, the SF3B1 mutation but wild-type TP53 group had a better OS than wild-type SF3B1 but TP53 mutation group and wild-type SF3B1 and TP53 group, whereas a similar OS compared with SF3B1 and TP53 mutation group. Conclusion:SF3B1 mutations were prevalent in MDS-RS patients with the most common mutation at amino acid position 700 (K700E) . SF3B1 mutation was an independent favorable prognostic variable, whereas TP53 mutation was an independent adverse variable. SF3B1 mutation could coordinate with TP53 mutation for more sophisticated prognosis stratification in MDS-RS patients.

Objective:To explore the molecular features and prognostic value of RAS mutations in patients with myelodysplastic syndromes (MDS) .Methods:112-gene targeted sequencing was conducted to detect RAS mutations in 776 patients with newly diagnosed primary MDS from December 2011 to December 2018. The mutual exclusivity and co-occurrence in gene mutations and clonal architecture were explored. Moreover, the prognostic significance of RAS mutations in MDS was analyzed.Results:RAS gene mutations were found in 52 (6.7% ) cases, 38 (4.9% ) of whom harbored NRAS mutation, 18 (2.3% ) KRAS mutation, and 4 (0.5% ) both NRAS and KRAS mutations. All the NRAS mutations and 65% of the KRAS mutations were located in codons 12, 13, and 61. PTPN11, FLT3, U2AF1, RUNX1, WT1, ETV6, and NPM1 mutations were enriched in patients with RAS mutations ( Q<0.05) . Around 80% of RAS mutations represented subclonal lesions in patients who harbored at least two different mutations. Patients with RAS mutations were more frequently diagnosed with MDS with excess blast (MDS-EB) (82.7% vs. 35.2% , P<0.001) and had higher levels of white blood cell count (4.33×10 9/L vs. 2.71×10 9/L, P<0.001) , neutrophil absolute count (2.13×10 9/L vs. 1.12×10 9/L, P<0.001) , and bone marrow blast percentage (7% vs. 2% , P<0.001) but lower levels of platelet count (48×10 9/L vs. 62×10 9/L, P=0.048) . RAS mutations were correlated with higher-risk categories in the Revised International Prognostic Scoring System (IPSS-R) (71.1% vs. 37.9% , P<0.001) . The median overall survival of patients with NRAS mutations was shorter than the others ( P=0.011) , while the significance was lost in the multivariable model. Conclusion:RAS gene mutations always occurred in the late-stage MDS and co-occurred with other signal transduction- and transcription factor-related gene mutations. PTPN11, a RAS pathway-related gene, is an independent poor prognostic factor in MDS patients.

Objective: To evaluate clinical characteristics and prognosis of primary myelofibrosis (PMF) patients with thrombocytopenia in varied degrees. Methods: Clinical features and survival data of 1 305 Chinese patients with PMF were retrospectively analyzed. The prognostic value of thrombocytopenia in patients with PMF was evaluated. Results: 320 subjects (47%) presented severe thrombocytopenia (PLT<50×10⁹/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×10⁹/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×10⁹/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×10⁹/L, circulating blasts ≥ 3%, abnormal karyotype and unfavourable cytogenetics (P<0.001, P<0.001, P=0.004, P<0.001 and P<0.001, respectively) were observed in this cohort of patients. The more severe the thrombocytopenia, the lower the proportion of JAK2V617F positive (P<0.001) was also noticed. Platelet count was positively correlated with splenomegaly, HGB and WBC (P<0.001, correlation coefficients were 0.131, 0.445 and 0.156, respectively). Platelet count was negative correlated with constitutional symptoms and circulating blasts (P=0.009, P=0.045, respectively; correlation coefficients were -0.096 and -0.056, respectively). The median survival of patients with severe thrombocytopenia, mild thrombocytopenia and without thrombocytopenia were 32, 67 and 89 months, respectively (P<0.001). Multivariate analysis identified thrombocytopenia in varied degrees (HR=1.693, 95%CI 1.320-2.173, P<0.001) and Dynamic Internation Prognostic Scoring System(DIPSS) prognostic model (HR=2.051, 95%CI 1.511-2.784, P<0.001) as independent risk factors for survival. Conclusion PMF patients with severe thrombocytopenia frequently displayed anemia, leucopenia, circulating blasts and short survival, so active treatment measures should be taken especially in these patients.

Objective: To explore the clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes (MDS) . Methods: 112-gene targeted sequencing and interphase fluorescence in situ hybridization (FISH) were used to detect TP53 mutation and deletion in 584 patients with newly diagnosed primary MDS who were admitted from October 2009 to December 2017. The association of TP53 mutation and deletion with several clinical features and their prognostic significance were analyzed. Results: Alterations in TP53 were found in 42 (7.2%) cases. Of these, 31 (5.3%) cases showed TP53 mutation only, 8 (1.4%) cases in TP53 deletion only, 3 (0.5%) cases harboring both mutation and deletion. A total of 37 mutations were detected in 34 patients, most of them (94.6%) were located in the DNA binding domain (exon5-8) , the remaining 2 were located in exon 10 and splice site respectively. Patients with TP53 alterations harbored significantly more mutations than whom without alterations (z=-2.418, P=0.016) . The median age of patients with TP53 alterations was higher than their counterparts[60 (21-78) years old vs 52 (14-83) years old, z=-2.188, P=0.029]. TP53 alterations correlated with complex karyotype and International prognostic scoring system intermediate-2/high significantly (P<0.001) . Median overall survival of patients with TP53 alterations was shorter than the others[13 (95%CI 7.57-18.43) months vs not reached, χ²=12.342, P<0.001], while the significance was lost during complex karyotype adjusted analysis in multivariable model. Conclusion TP53 mutation was more common than deletion in MDS patients. The majority of mutations were located in the DNA binding domain. TP53 alterations were strongly associated with complex karyotype and always coexisted with other gene mutations. TP53 alteration was no longer an independent prognostic factor when complex karyotype were occurred in MDS.

OBJECTIVE:To evaluate the effect and role of Pharmaceutical Care Network Europe (PCNE) classification system (8.0 edition) on drug-related problems (DRPs) in respiration department.METHODS:Clinical pharmacists provided pharmaceutical care for DRPs in a patient with acute exacerbation of chronic obstructive pulmonary disease of respiration department by using PCNE classification system (8.0 edition).Type,cause,intervention measure,intervention acceptability and state of DRPs were analyzed.RESULTS:PCNE classification system (8.0 edition) mainly included 5 aspects as problems,reasons,plan intervention,the acceptance of intervention plan,the situation of DRPs.Clinical pharmacists confirmed the type of DRPs,with the help of the system and solved two items of DRPs.Physicians accepted intervention and fully implemented it.CONCLUSIONS:Clinical pharmacists can provide standardardized pharmaceutical care systematically,discover and solve DRPs in time through PCNE classification system (8.0 edition) so as to guarantee safe,effective and reasonable drug use.