Objective:To investigate the efficacy and safety of combining venetoclax (VEN) with hypomethylated drugs (HMA) in the treatment of higher-risk (IPSS-R score >3.5) myelodysplastic syndromes (MDS) .Methods:From March 2021 to December 2022, forty-five MDS patients with intermediate and high risk were treated with VEN in combination with HMAs. Clinical data were collected and analyzed retrospectively, including gender, age, MDS subtype, IPSS-R score, treatment regimen, and efficacy, etc. Kaplan-Meier method and Cox regression model were used to analyze univariate and multivariate of survival prognosis.Results:①Forty-five patients with MDS, including ninety-one percent were classified as high or very high risk. According to the 2023 consensus proposal for revised International Working Group response criteria for higher-risk MDS, the overall response rate (ORR) was 62.2% (28/45), with the complete response rate (CR) was 33.3% (15/45). For twenty-five na?ve MDS, the ORR was 68% (17/25) and the CR rate was 32% (8/25). In nonfirst-line patients, the ORR and CR were 55% (11/20) and 35% (7/20) respectively. The median cycle to best response was 1 (1-4). ②With a median followup of 189 days, the median overall survival (OS) time was 499 (95% confidence interval, 287-711) days, and most patients died from disease progression. Responders had a significantly better median OS time than nonresponders (499 days vs 228 days, P<0.001). Multifactor analysis revealed that IPSS-R score and response to treatment were independent prognostic factors for OS; the presence of SETBP1 gene mutations was associated with a longer hospital stay (51.5 days vs 27 days, P=0.017) . Conclusions:There is clinical benefit of venetoclax in combination with hypomethylated agents in patients with higher-risk MDS, but adverse events such as severe hypocytopenia during treatment should be avoided.

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.

Abstract: Objective　To investigate the antimicrobial activity of omadacycline (OMC) against clinical Streptococcus agalactiae (GBS) isolates, as well as its relationship with biofilm formation, resistance genes and virulence genes. Methods　A total of 136 strains of Streptococcus agalactiae isolated from Shenzhen Nanshan People's Hospital between 2015 to 2020. The minimum inhibitory concentration (MIC) of OMC against Streptococcus agalactiae was determined by broth microdilution. Crystal violet staining was used to detect the biofilm formation ability of GBS. Resistance genes (tetM, tetO, tetK, ermB, OptrA) and virulence genes (cpsⅢ, bca, fbsA, cpsA, scpB) were investigated by polymerase chain reaction (PCR). Results　Among the 136 clinical isolates of GBS, 20 strains (14.7%) were resistant to OMC, 64 (47.1%) were intermediate, and 52 (38.2%) were sensitive. Fifty-seven strains (41.9%) were biofilm-positive, 20 of which (35.1%) were sensitive to OMC. Seventy-nine strains (58.1%) were biofilm-negative, 32 of which (40.5%) were susceptible to OMC. There was a statistically significant difference in the sensitivity rates between the two groups of strains (χ2=63.062, P<0.001), but there was no significant difference in the sensitivity of OMC among the biofilm-positive strains (Fisher's exact test, P=0.824). The resistance rates of tetM, tetO, ermB and OptrA positive strains were higher than those of negative strains, while tetK was opposite. The presence of tetM (Z=0.815, P=0.415), tetO (Z=0.151, P=0.88), tetK (Z=0.567, P=0.571), ermB (Z=1.198, P=0.231) resistance genes in Streptococcus agalactiae had no significant impact on the sensitivity of OMC. However, the presence of the OptrA resistance gene showed a statistically significant effect on the sensitivity of OMC (Z=2.913, P=0.004). The virulence factors cpsⅢ, bca, fbsA, cpsA and scpB were all detected at a rate higher than 50%. The presence of the virulence genes cpsⅢ (Z=0.222, P=0.824), bca (Z=0.141, P=0.888), fbsA (Z=0.813, P=0.416), and cpsA (Z=1.615, P=0.106) in Streptococcus agalactiae had no significant impact on the sensitivity of OMC. However, there was a significant inter-group difference in the scpB virulence gene (Z=2.844, P=0.004), but the rank mean values and resistance rates of scpB-positive strains were lower than those of the negative strains. Conclusions　The formation of biofilm in Streptococcus agalactiae reduces its sensitivity to OMC, but there was no significant difference in the sensitivity to OMC among the biofilm-positive strains. The presence of resistance genes tetM, tetO, tetK, ermB, and virulence genes cpsⅢ, bca, fbsA, cpsA, scpB in Streptococcus agalactiae is not associated with OMC resistance, but the presence of the resistance gene OptrA is correlated with OMC resistance..

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:Diagnostic value assessment of sternal bone marrow cell morphology in patients with acquired hypocellular bone marrow failure syndromes (BMFS) characterized by normal cytogenetics.Methods:A total of 194 eligible patients with an acquired hypocellular BMFS pre-sternum diagnosis in Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College from June 2014 to January 2019 were reviewed. Sternal bone marrow evaluation was performed, and a post-sternum diagnosis was made. Clinical characteristics and overall survival (OS) were then compared among patients with different post-sternum diagnosis. Binary logistic regression was used to develop a predictive scoring system.Results:In 152 patients with pre-sternum AA diagnosis, 29 patients with a pre-sternum idiopathic cytopenia of undetermined significance (ICUS) diagnosis, and 13 patients with a pre-sternum clonal cytopenia of undetermined significance (CCUS) diagnosis, sternal bone marrow evaluation resulted in a change of diagnosis to hypocellular myelodysplastic syndrome (hypo-MDS) in 42.8% (65/152) , 24.1% (7/29) , and 30.8% (4/13) , respectively. Patients with a post-sternum hypo-MDS diagnosis showed a significant difference in OS compared with patients with a post-sternum AA diagnosis ( P=0.005) . Patients with ICUS/CCUS showed no difference in OS compared with AA and hypo-MDS ( P=0.095 and P=0.480, respectively) . A 4-item predictive scoring system to identify hypocellular BMFS patients that need sternal bone marrow evaluation was developed, including age > 60 years old ( OR=6.647, 95% CI 1.954-22.611, P=0.002, 2 points) , neutrophil alkaline phosphatase score ≤ 160 ( OR=2.654, 95% CI 1.214-5.804, P=0.014, 1 point) , abnormal erythroid markers evaluated by flow cytometry on iliac bone marrow ( OR=6.200, 95% CI 1.165-32.988, P=0.032, 2 points) , and DAT (DNMT3A, ASXL1, TET2) genes mutation ( OR=4.809, 95% CI 1.587-14.572, P=0.005, 1 point) . The Akaike information criterin (AIC) was 186.1. Conclusion:Patients with a pre-sternum acquired hypocellular BMFS diagnosis characterized by normal cytogenetics may not reach accurate diagnostic categorization without sternal bone marrow cell morphology evaluation, which could be considered a diagnostic tool for this patient population. A predictive scoring system was developed, and when the total score is ≥ 2 points, sternal bone marrow evaluation should be performed for accurate diagnostic categorization that is critical to optimal patient care.

Objective:To investigate the clinical features, the key point of diagnosis and treatment methods of X-linked hyper-IgM syndrome (XHIGM).Methods:The clinical characteristics and laboratory data of a patient aged 23 years who was diagnosed as XHIGM complicated with T-cell large granular lymphocytic leukemia (TLGLL) in Institute of Hematology & Blood Diseases Hospital in March 2020 were analyzed retrospectively, and the literatures were reviewed.Results:This male patient presented with recurrent infection when he was 17 years old, and was found neutropenia, anemia accompanied by obvious splenomegaly, lower level of IgG and IgA after the visit. The level of IgM was lower than the normal level and the typical XHIGM was manifested with the normal or increased level of IgM, however CD40L homozygous mutation (chromosome: chrX; location: 135730438; variation of amino acid: NM_000074:exon1:c.31C>T:p.R11X; nonsense mutation) was confirmed by next generation sequencing. CD40L heterozygous mutation was detected in his mother, but it was not in his father. The patient was diagnosed as XHIGM. Anemia and neutropenia were alleviated after splenectomy in the patient, who was diagnosed as T-cell large granular lymphocyte elevation and clonal proliferation by flow cytometry, TCR gene rearrangement positive and bone marrow histopathological immunohistochemistry results because of the increasing leukocyte. The patient was eventually diagnosed as XHIGM complicated with T-LGLL.Conclusions:A small number of patients with XHIGM may develop symptoms in adulthood and may present with atypical clinical features of significant reduction in IgG, IgA, and IgM. The confirmed diagnosis of XHIGM is established by identification of CD40L gene mutation. XHIGM gene screening is required in male patients with recurrent infection, IgG level lower than normal and neutropenia. A few XHIGM patients are complicated with T-LGLL.

Objective:To investigate the current practice environment of male nurses in Qinghai province, and understand the professional environment and turnover intention of male nurses, provide ideas and theoretical basis for continuous improvement of the working environment of male nurses in hospitals.Methods:From September to October 2020, the practice environment and turnover intention of male nurses in Qinghai Province were investigated by using the method of convenience sampling and using the general data questionnaire, the Nurse Practice Environment Assessment Scale and the turnover intention table.Results:A total of 155 registered male nurses in Qinghai Province participated in this survey, and the overall evaluation score of the practicing environment of nurses in Qinghai Province was (74.38±22.63) points, among which the highest score was that nurses could write nursing records in time (85.24±20.99) points, and the lowest score was that nurses had the opportunity to participate in the internal management of the hospital (55.03±30.55) points. The total score of resignation intention was (14.34±4.35) points.Conclusion:The overall evaluation of the practicing environment of male nurses in Qinghai Province is fair, and their turnover intention is high. Nursing managers should attach importance to the cultivation of male nurses' feelings towards hospitals and professions, so as to reduce their turnover intention and stabilize the nursing team of male nurses.

Objective:To evaluate the prognostic value of MIPSS70-plus in Chinese patients with primary myelofibrosis (PMF) .Methods:A total of 113 Chinese patients with PMF were retrospectively analyzed. The Kaplan-Meier method, Log-rank test, and Cox proportional hazard regression model were performed to evaluate the prognostic factors. The likelihood ratio test was used to evaluate the predictive power between MIPSS70-plus and DIPSS systems.Results:The median age of the Chinese patients was 55 (range: 20-70) years, including 71 males and 42 females. According to the standard of MIPSS70-plus system, 99 patients (79.6% ) had a favorable karyotype and 23 patients (20.4% ) had an unfavorable karyotype. JAK2V617F in 55.8% ( n=63) , CALR exon9 in 17.7% (including 15 CALR type 1 and 5 CALR type 2, n=20) , MPLW515 in 4.4% ( n=5) , and triple negative (no detectable JAK2, MPL, and CALR mutations) in 22.1% of patients in our cohort were found by target-specific next-generation sequencing approach. At least one high-molecular risk mutations were presented in 45.1% ( n=51) of patients, with ASXL1 in 38.9% ( n=44) , SRSF2 in 7.1% ( n=8) , IDH1/2 in 4.4% ( n=5) , and EZH2 in 3.5% ( n=4) of patients. A total of 28 patients (26.7% ) were in low risk, 20 (19.0% ) in intermediate risk, 41 (39.0% ) in high risk, and 16 (15.3% ) in very-high risk categories, which were delineated for the MIPSS70-plus model. A 2-year OS was 100% in low risk, 89.7% (95% CI 76.2% -100.0% ) in intermediate risk, 64.8% (95% CI 47.0% -82.6% ) in high risk, and 35.0% (95% CI 10.3% -59.7% ) in very-high risk categories, which had a significant difference ( P<0.001) . A significantly higher predictive power for survival of the MIPSS70-plus group was observed compared with the DIPSS group ( P=0.001, -2 log-likelihood ratios of 86.355 vs 95.990 for the MIPSS70-plus and DIPSS systems, respectively) . Conclusion:The MIPSS70-plus had significantly higher predictive power than the DIPSS.

Objective:To explore the outcome of cyclosporine A (CsA) combined with danazol with or without thalidomide regimen for myelodysplastic syndrome (MDS) with low-percentage bone marrow blasts and predictive factors for treatment response.Methods:Data of 115 subjects who were newly diagnosed with primary MDS with low-percentage bone marrow blasts and were treated with CsA combined with danazol with or without thalidomide from December 2011 to December 2019 in our center were collected. Their clinical features, efficacy, and predictive factors of efficacy were retrospectively analyzed. A model for predicting this response was developed.Results:A total of 55 subjects responded (47.8%) , including 11 complete responses and 44 hematologic improvements. Fifty-two patients (52/105, 49.5%) achieved erythrocyte response; 35 (35/86, 40.7%) , platelet response; and 14 (14/40, 35%) , neutrophil response. Of 29 subjects (24.1%) , 7 who were red blood cell (RBC) transfusion-dependent became independent of transfusion. The median response duration was 20 months (range, 3-84 months) . In the univariate analysis, patients <0 years had a higher response rate than those ≥60 years (52.5% vs 22.2%, P=0.018) . Contrarily, the response rate was substantially decreased in patients with RBC transfusion dependence compared with those without RBC transfusion dependence (24.1% vs 55.8%, P=0.003) , as well as in patients with the mutated U2AF1 compared with those with the wild-type U2AF1 (26.1% vs 53.2%, P=0.020) . In multivariable analyses, age <0 years ( OR=4.302, 95% CI 1.245-14.820, P=0.021) , RBC transfusion dependence ( OR=3.774, 95% CI 1.400-10.177, P=0.009) , and U2AF1 mutation ( OR=3.414, 95% CI 1.168-9.978, P=0.025) were significantly correlated with response. Variables that independently predicted the response were combined to generate the predictive model. According to the model, the overall response rates of patients with 0, 1, 2, and 3 risk factors were 65%, 30%-35%, 10%-15%, and 3%, respectively. Conclusion:CsA combined with danazol with or without thalidomide regimen could improve cytopenia symptoms in patients with MDS with low-percentage bone marrow blasts. At age <60 years, no transfusion dependence of RBC and wild-type U2AF1 mutation is a favorable prognostic factor.

Objective:To explore the relationship between symptom burden and hematologic responses after treatment with interferon and/or hydroxyurea in patients with polycythemia vera (PV) .Methods:Hematologic responses after continuous treatment with interferon and/or hydroxyurea for six months were evaluated in 190 patients with PV using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-10 score) . In all patients, the PV diagnosis was based on the 2016 World Health Organization diagnostic definitions.Results:The study cohort comprised 93 (48.9% ) male and 97 (51.1% ) female patients. The median age at the time of MPN-10 assessment was 60 (32-82) years. The median MPN-10 score of the entire cohort was 9 (range, 0-67) . The median MPN-10 score of patients treated with interferon plus hydroxyurea ( n=27) was 11 (0-67) , which was significantly higher than those of patients treated with interferon only ( n=64) (6[0-56], P=0.019) or hydroxyurea only ( n=99) (9[0-64], P=0.047) , whereas the median MPN-10 score was not significantly different between those treated with interferon only and hydroxyurea only ( P=0.421) . The rate of severe symptom burden (i.e., any single symptom burden score ≥ 7 and/or total score ≥ 44) was 28.9% (55/190) in the entire cohort, whereas the rate of severe symptom burden was not significantly different among the interferon only (23.4% ) , hydroxyurea only (29.3% ) , and interferon plus hydroxyurea (40.7% ) groups ( P>0.05 for all two-group comparisons) . When evaluating MPN-10 score, 37.4% (71/190) of the patients achieved complete hematologic remission (CHR) . Only 28.9% (55/190) patients had adequate disease control, defined as CHR without severe symptom burden. Reasons for inadequate disease control were evaluating blood counts alone, severe symptom burden alone, and evaluating blood counts accompanied with severe symptom burden in 42.1% (80/190) , 8.4% (16/190) , and 20.5% (39/190) of the patients, respectively. Compared to the patients with a platelet count ≤ 400×10 9/L, those with a platelet count > 400×10 9/L had a significantly higher rate of severe symptom burden (40.8% [20/49] vs 24.8% [35/141], P=0.044) and a higher median MPN-10 score (14[0-67] vs 7[0-56], P=0.038) . Platelet count > 400×10 9/L was associated with an increased risk of severe symptom burden (hazard ratio, 2.089; 95% confidence interval, 1.052-4.147, P=0.035) . Conclusions:Symptoms related to disease after treatment with interferon and/or hydroxyurea were rather universal in patients with PV. Some patients still experienced severe symptom burden despite achieving CHR. Platelet count > 400×10 9/L was associated with an increased risk of severe symptom burden in patients with PV treated with interferon and/or hydroxyurea.