Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center / 中华血液学杂志

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.

Clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm accelerated/blast phase / 中华血液学杂志

Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.

Research progress on the antitumor activity of costunolide / 中国临床药理学与治疗学

In recent years, the research on the anti-tumor effect of traditional Chinese medicine has been increasing year by year. Both the effective extracted ingredients of Chinese medicine and its compound preparations have significant efficacy and advantages in tumor treatment. Costunolide, the active ingredient of Aucklandia lappa (a traditional Chinese medicine), is a natural sesquiterpene lactone, which has a variety of pharmacological effects, such as anti-oxidation, anti-inflammation, hypoglycemic effect, anti-microbial effect etc. In recent years, more and more experimental studies in vivo and in vitro have shown that this component has anti-tumor activity, which can inhibit the growth of breast cancer, gastric cancer, melanoma cancer, prostate cancer, leukemia, liver cancer, lung cancer, ovarian cancer, esophageal cancer, colorectal cancer, osteosarcoma and other tumors. Its antitumor mechanism mainly lies in the regulation of PI3K/AKT/mTOR, AKT-MDM 2-p53, ROS-AKT/GSK-3β, Bcr / Abl, Stat5 and other signaling pathways, which affects reactive oxygen species, apoptosis-related proteins, autophagy-related proteins, and cyclin, and thus induces apoptosis, causes autophagy and arrests cell cycle in G2 / M phase, G1 phase, and S phase. In addition, the combination of costunolide with imatinib and doxorubicin can attenuate toxicity and enhance anti-tumor effect, and also reverse tumor drug resistance. By consulting and sorting out the relevant research literature at home and abroad, the author summarized the research progress of costunolide on the antitumor effect and mechanism, the combined drug use and the reversal of tumor drug resistance in order to provide theoretical basis for the development and utilization of new drugs of this ingredient.

Clinical and laboratory features compared between JAK2 exon12 and JAK2 V617F mutated polycythemia vera / 中华血液学杂志

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.

Effect of sodium-glucose cotransporter 2 inhibitor on serum Chemerin, blood lipid level and insulin dosage in patients with type 2 diabetes and coronary heart disease / 中国医师杂志

Objective:To study the effect of sodium-glucose cotransporter 2 inhibitor (SGLT2i) on serum Chemerin, blood lipid levels and insulin dosage in patients with type 2 diabetes and coronary heart disease.Methods:The clinical data of 96 patients with type 2 diabetes mellitus and coronary heart disease admitted in Xianyang Central Hospital from June 2019 to June 2020 were retrospectively analyzed. According to different treatment methods, they were divided into control group and observation group, with 48 cases in each group. The control group was treated with insulin combined with metformin, and the observation group was treated with insulin combined with SGLT2i (this study mainly used dagglitazone). The blood glucose, serum Chemerin, blood lipid level and insulin dosage of the two groups were observed before and after treatment. The incidence of cardiovascular adverse events and adverse reactions were compared between the two groups.Results:After treatment, the levels of fasting blood glucose (FBG), 2 h PG (plasma glucose), glycosylated hemoglobin (HbA 1c), and Chemerin in the two groups were better than those before treatment ( P<0.05). The decrease in the levels of FBG, 2 h PG, HbA 1c and insulin dosage in the observation group were greater than those in the control group ( P<0.05). However, there was no difference in the decline of Chemerin levels between the two groups ( P>0.05). After treatment, the levels of total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) in the two groups were lower than before treatment, and the levels of high density lipoprotein cholesterol (HDL-C) were higher than before treatment (all P<0.05). The decrease of TG in the observation group was greater than that in the control group, the decrease of TC and LDL-C was samller than that in the control group, and the increase of HDL-C was greater than that in the control group (all P<0.05). The incidence of cardiovascular adverse events in the observation group was 4.17%(2/48), which was lower than that in the control group [16.67%(8/48), P<0.05]. Conclusions:SGLT2i has a significant therapeutic effect on patients with type 2 diabetes complicated with coronary heart disease. It can better control blood glucose and lipid levels and reduce insulin dosage, which is worthy of clinical application.

Analysis of the occurrence of interstitial pneumonia and its related factors in patients with diffuse large B-cell lymphoma after the treatment of CHOP-like regimens containing liposomal doxorubicin / 肿瘤研究与临床

Objective:To explore the occurrence and risk factors of interstitial pneumonia (IP) in patients with diffuse large B-cell lymphoma (DLBCL) after the treatment of CHOP-like regimens containing liposomal doxorubicin.Methods:The clinical data of 145 newly diagnosed and newly treated DLBCL patients who were admitted to the Affiliated Tumor Hospital of Xinjiang Medical University from January 2013 to June 2020 were retrospectively analyzed, of which 73 cases were treated with RCDOP regimen containing liposomal doxorubicin, and 72 cases were treated with RCHOP regimen. The incidence of IP was compared between the two groups, and the risk factors of IP were analyzed by multivariate logistic regression.Results:In 145 patients, 34 patients (23.4%) developed IP; most cases of IP occurred during 3 to 5 cycles of chemotherapy, accounting for 79.4% (27/34); when IP occurred, the median cycles of chemotherapy was 4 cycles. The incidence of IP in RCDOP regimen group and RCHOP regimen group were 31.5% (23/73) and 15.3% (11/72), and the difference was statistically significant ( χ2 = 5.319, P < 0.05). Multivariate logistic regression analysis showed that the application of liposomal doxorubicin ( OR = 2.416, 95% CI 1.059-5.509, P = 0.036) and age ≥60 years old ( OR = 2.505, 95% CI 1.127-5.567, P = 0.024) were independent risk factors for the occurrence of IP. Conclusions:The application of liposomal doxorubicin is a risk factor for the occurrence of IP in DLBCL patients. The prevention and monitoring of IP should be strengthened after 4 cycles of treatment with RCDOP regimen, especially for patient ≥ 60 years of age.

Temporal trend in energy and macronutrients for pilot schools involved in the Nutrition Improvement Program for Rural Compulsory Education Students in 2012-2017 / 中国学校卫生

Objective@#To evaluate temporal trend in food supply among pilot schools involved in the National Nutrition Improvement Program for Rural Compulsory Education Students (NNIPRCES).@*Methods@#Ten percent of pilot schools were randomly selected and asked to report the information on food supplies. Daily intake of energy, carbohydrates and protein for each student were calculated and compared with the reference value in Nutrition Guidelines of School Meals (WS/T 554-2017).@*Results@#Energy and protein supply increased among those pilot schools. The supply of energy increased from 1 566.5 kcal in 2012 to 1 927.4 kcal in 2017, protein increased from 49.0 g to 61.0 g. The energy ratio of fat increased from 31.9% to 34.9%, while energy ratio of carbohydrate decreased significantly (F=83.38, 128.36, 20.27 and 17.28, all P<0.05). The proportion of reasonable energy supply from carbohydrate and fat in 2017 were 17.5% and 26.8%, respectively.@*Conclusion@#The supply of energy and macronutrients in the pilot areas were unreasonable, more measures including dietary guide and monitoring need to be adopted to improve students nutrition status among rural areas.

School canteen construction and canteen meal provision from 2012 to 2017 in schools under the National Nutrition Improvement Program for Rural Compulsory Eudcation Students / 中国学校卫生

Objective@#To analyze changes of school canteen construction and canteen meal provision in surveilled schools after the initiation of the National Nutrition Improvement Program for Rural Compulsory Education Student (NNIPRCES), therefore to provide data basis for improving efficacy of school canteen meals.@*Methods@#From 2012 to 2017, among the 699 trial counties in 22 provinces under NNIPRCES, at least 10% of elementary schools and middle schools with each food supply model (canteen meals, enterprise meals, and family meals) were randomly selected in each county in each year. Questionnaire survey was conducted to collect school canteen construction and meal provision information. The sample size were around 8 000 to 11 000 schools every year.@*Results@#From 2012 to 2017, the proportion of schools that have canteens only, have both canteen and dining room, as well as those have canteen and dining room with tables and chairs significantly increased with years(χ 2=3 043.95, 6 383.85, 6 731.17, P<0.01). The proportion of schools having canteen increased from 59.5% in 2012 to 87.0% in 2017. The proportion of schools with canteen providing breakfast, lunch or dinner varied across years(χ 2=51.85, 144.96, 189.19, P<0.01). The varieties of food groups of three meals all significantly increased during 2012, 2014 and 2017(χ 2=702.30, 892.38, 550.55, P<0.01). The canteen construction indicators, proportion of canteens providing three meals, and food groups included in three meals all significantly differed between elementary schools and middle schools, also between schools of central area and western area(P<0.05). The changing patterns with year were significantly different in elementary schools and middle schools, and in schools of central area and western area(P<0.05).@*Conclusion@#After the implementation of NNIPRCES, canteen construction and food variety in canteen meals significantly improved during 2012 to 2017. However, there are still gaps between changes of canteen construction and canteen meal provision. It is necessary to overcome obstacles to further increase the proportion of schools with canteen offering meals and the variety of food of meals.

Effects of Temperature on Outpatient Visits for Urticaria among Lanzhou Residents Based on Distributed Lag Non-linear Model / 中国医学科学院学报

Objective To evaluate the influence of temperature on the outpatient visits for urticaria in Lanzhou City and its hysteresis and to find out the sensitive populations by sex and age stratification.Methods We collected the urticaria outpatient data in three grade A class three hospitals as well as the meteorological data and air pollutant data in Lanzhou from January 2011 to December 2017.The distributed lag non-linear model(DLNM)was employed to analyze the influence of daily mean temperature on the outpatient visits for urticaria.Stratification analysis was performed for different age groups(0-14,15-59,≥60 years)and different sex populations.Results Temperature had a non-linear relationship with the outpatient visits for urticaria,and there existed hysteresis.During the research period,the average daily outpatient visits for urticaria at the three hospitals in Lanzhou was 25,ranging from 1 to 76.With the rise in the daily mean temperature within 0-10 ℃,the risk of outpatient visits for urticaria first increased and then decreased.When the daily mean temperature was 2 ℃,hysteresis occurred on the 18th day,and the relative risk(

Mean corpuscular volume ≤100 fl was an independent prognostic factor in patients with myelodysplastic syndrome and bone marrow blast<5 percent / 中华血液学杂志

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%.

Analysis of clinical characteristics, treatment response rate and survival of 77 myelodysplastic syndrome patients with del (5q) syndrome / 中华血液学杂志

Objective: To observe the clinical characteristics, treatment responses and prognosis of patients with myelodysplastic syndrome (MDS) -del (5q) syndrome who met WHO (2016) diagnostic typing criteria. Methods: A total of 77 patients with del (5q) syndrome, according to WHO (2016) classification, were retrospectively analyzed between January 2008 and April 2018 in the Blood Diseases Hospital, Chinese Academy of Medical Sciences. Clinical characteristics, lenalidomide (LEN) efficacy and survivals were compared between the patients with del (5q) alone and those with one additional cytogenetic abnormality (ACA) with the exception of monosomy 7 or del (7q) . Treatment response and overall survival (OS) were compared between patients who were treated with LEN and traditional non-LEN drugs. Results: Of 77 patients, 64 were isolated del (5q) and 13 were del (5q) with ACA. There were significant differences of the median age and percentage of patients who had small megakaryocytes in bone marrow smear by immunohistochemistry (CD41) between the patients with isolated del (5q) and the patients with del (5q) + ACA[58 (29-64) years old vs 63 (31-82) years old, z=2.164, P=0.030; and 91.7%vs 60.0%, P=0.046, respectively]. The overall hematological response rate (78.9%vs 80.0%) , complete hematological remission (CR) rate (57.9% vs 60.0%) , cytogenetic response (CyR) rate[69.2% (9/13) vs 66.7% (4/6) ] and complete cytogenetic response (CCyR) rate [61.5% (8/13) vs 33.3% (2/6) ] of LEN were similar between the patients with isolated del (5q) (n=19) and with del (5q) + ACA (n=10) , as well as the median Overall survival (OS) between these two groups of patients (62 months vs 78 months, P=0.388) . The hematological response rate (79.3% vs 36.0%) , CR rate (58.6% vs 8.0%) , CyR rate [68.4% (13/19) vs 11.1% (1/9) ] and CCyR rate [52.6% (10/19) vs 0 (0/9) ] were higher among patients treated with LEN (n=29) than those treated with non-LEN therapy (n=25) . There was no statistically significant difference in OS between the patients with LEN or non-LEN therapy (78 months vs 62 months, P=0.297) . Conclusion: Comparing del (5q) syndrome patients with isolated del (5q) or with del (5q) + ACA, two groups of patients had similar clinical characteristics, median OS and LEN efficacy. LEN showed better treatment response than traditional drugs in patients with del (5q) syndrome.

Clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes / 中华血液学杂志

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, χ(2)=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.

Ruxolitinib combined with prednisone, thalidomide and danazol for treatment of myelofibrosis: a pilot study / 中华血液学杂志

Objective: To evaluate the efficacy and tolerability of ruxolitinib combined with prednisone, thalidomide and danazol for treatment of in myelofibrosis (MF). Methods: Patients of MF according to the WHO 2016 criteria, received ruxolitinib (RUX) combined with prednisone, thalidomide and danazol (PTD). The response, changes of blood counts and adverse events were evaluated. Results: Six PMF and one post-ET MF patients were enrolled. Four patients presented JAK2V617F mutation, one CALR mutation, one MPL mutation, one triple-negative. Responses per IWG-MRT criteria were clinical improvement in 5 patients, stable disease in 2 ones, spleen response in 6 ones. All of 7 patients were symptomatic responses, four patients achieved at least 50% improvement from baseline on MPN-SAF TSS. Three patients initially treated with RUX alone, all of 3 patients experienced treatment-associated anemia and thrombocytopenia. Then these 3 patients received RUX combined with PTD, both hemoglobin and platelet increased significantly. Four patients initially treated with RUX combined with PTD. Increased levels of hemoglobin and platelet were seen in all of 7 patients received RUX combined with PTD with maximum increased hemoglobin of 30(18-54) g/L and maximum increased platelets of 116(13-369)×10(9)/L, respectively from baseline. The treatment dose of RUX increased due to improved platelet count in 3 patients. The frequent non-hematologic adverse events grade 1-2 were constipation, abdominal distension, crura edema and increased ALT. Conclusions: RUX combined with PTD for treatment of MF may modulate initial hematologic toxicity observed when RUX alone, and may increase response due to improved levels of hemoglobin or platelet.

A study of clinical characteristics and prognosis of primary myelofibrosis patients with thrombocytopenia in varied degrees / 中华血液学杂志

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<50×10(9)/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×10(9)/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×10(9)/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×10(9)/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.

Analysis of Gene Mutation Types in 920 Cases of Thalassemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the gene mutation types and distribution features of α- and β-thalassemia in reproductive population of Xing bin district of Guangxi Lai bin city so as to provide the scientific basis for formulating the preventive and control measures.@*METHODS@#The high risk population with thalassemia in 6 498 people of child-bearing age admited in department of antenatal care of our hospital from January 2017 to December 2017 were screened by blood cell test and hemoglobin electrophoresis. The gene mutation types and mutation frequency in αandβthalassemia positive cases were diagnosed and analyzied by Gap-PCR and PCR-RDB.@*RESULTS@#The inital screening showed that there were 1 432 cases of thalassemia positive accounting for 22.04%; the gene diagnoses showed that there were 920 cases of thalassemia gene positive accounting for 14.16%. Among 920 cases, 593 cases were α-thalassemia accounting for 64.45% (593/920); the gene mutation types were 19 kinds. The α-deletion type gene was mainly -- (47.22%), the α-mutatin type gene was mainly -αα(13.66%); 260 cases were the β-thalassemia accounting for 28.26%, (260/920), the gene mutation types were 9 kinds, out of which the β41-42 βN was main (50.38%), followed by β17/βN (38.08%)，there were 2 kinds of gene mutation types accounted for 88.46%; the αβ-thalassemia numbered 67 cases (7.28%), the mutation types were mainly --/β41-42 (17.91%) and -α3.7/β41-42 (17.91%).@*CONCLUSION@#The α-and β-thalassemia mostly observed in the childbearing population of Laibin city Xinbin district possess the gene comblexity and diversity as well as the significant genetic heterogeneily.The results of this study provide the reference basis for the prevention of thalassemia and eugenic works.

Analysis of Early-Death and Factors Affecting Prognosis of Patients with Acute Promyelocytic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the factors affecting the early-death, overall survival (OS) and relapse-free survival (RFS) of acute promyelocytic leukemia (APL) patients.</p><p><b>METHODS</b>The clinical and laboratorial charachteristics of 176 APL patients in our center were analyzed retrospectively during January 2002 to Mar 2016. The risk factors of early death and factors affecting OS and RFS of patients were analyzed.</p><p><b>RESULTS</b>Among total of 176 patients, early death occured in 10 patients. Multivariate analysis showed both age ≥60 years and fibrinogen<1.5 g/L (HR=6.4, 95%CI 1.4-28.2) (P=0.015), (HR=12.2, 95%CI 1.5-102.8) (P=0.021), respectively were the independent risk factors for the early death during the induction therapy. Among 154 patients with full follow-up data (median follow-up time was 101(2-262) months), the estimated 5-year OS and RFS rate were (98± 1)% and (77± 4)%, respectively. Cox regression analysis showed relapse during treatment as well as initial WBC count≥30× 10/L were independent prognostic indicators for OS. Accompanied psoriasis indicated higher relapse rate of APL(HR=4.8, 95%CI 1.8-12.5)(P=0.002), while the low-risk APL indicated lower relapse rate (HR=0.4, 95%CI 0.2-0.99)(P=0.048).</p><p><b>CONCLUSION</b>Importance should be attached to the early-death events in elder and low-fibrinogen APL patients. As for patients with psoriasis or non low-risk group, emphasizing the intensified dynamic supervision during the treatment helps to detect the early-relapse events. For relapsed patients and patients with ≥30× 10/L WBC count, seeking more optimized therapy strategy seems allow this cohorts to get better prognosis.</p>

Targeted sequencing analysis of hyper-eosinophilic syndrome and chronic eosinophilic leukemia / 中华血液学杂志

Objective: Analysis of the molecular characteristics of eosinophilia. Methods: Targeting sequence to 24 patients with chronic eosinophilic leukemia (CEL) with rearrangement of PDGFRA, PDGFRB, or FGFR1 and 62 patients with hyper-eosinophilic syndrome (HES). Mutation annotation and analysis of amino acid mutation using authoritative databases to speculate on possible pathogenic mutation. Results: Thirty-seven kinds of clonal variant were detected from 17 patients with CEL, no recurrent mutation site and hot spot region were found. No pathogenic mutation was detected in 19 patients with PDGFRA rearrangement, but pathogenic mutations of ASXL1, RUNX1 and NRAS were detected from 2 patients with FGFR1 rearrangement who progressed to acute myeloid leukemia and 1 patient with PDGFRB rearrangement who progressed to T lymphoblastic lymphoma, respectively. One hundred and two kinds of clonal abnormalities were detected in 49 patients with HES. The main hot spot mutation regions included: CEBPA Exon1, TET2 Exon3, ASXL1 Exon12, IDH1 Y208C, and FGFR3 L164V. CRRLF2 P224L and PDGFRB R370C point mutations were detected separately in 2 patients with HES who treated with imatinib monotherapy and achieved hematologic remission. Conclusion: The pathogenesis of CEL with PDGFRA, PDGFRB or FGFR1 rearrangement is usually single, and the progression of the disease may involve other driver mutation. A variety of genes with hot mutation regions may be involved in the pathogenesis of HES, and some mutation sites are sensitive to tyrosine kinase inhibitors.

Correlation between severity of gastroesophageal reflux cough and degree of gastroesophageal reflux disease / 中华儿科杂志

Objective@#To explore the correlation between the severity of gastroesophageal reflux cough and degree of gastroesophageal reflux.@*Methods@#A cross-sectional investigation was carried out. Data of 174 cases of chronic cough were collected in Children's Hospital of Fuzhou from March 2009 to December 2016. The esophageal 24 hours pH value dynamic monitoring was used to detect gastric acid reflux index. Cases with abnomal results were divided into mild, moderate and severe groups according to severity of reflux and that of day and night cough symptoms, respectively. They were also divided into infant (1-3 years old), preschool (4-6 years old), and school age (>7 years old) groups according to age. Comparative analysis between groups by chi-square test and rank sum test were performed. Correlation analysis was used to analyze the correlation between cough severity and gastroesophageal reflux index.@*Results@#A total of 174 patients with chronic cough, including 115 males and 59 females, aged from 1 to 15 years with an average age of (8.5±2.3) years, and (1.6±0.8) years of disease duration were enrolled. Among them, 129 cases (74.1%) were positive for esophageal reflux test and 45 cases (25.9%) with no obvious pathological gastroesophageal reflux. Patients with positive esophageal reflux test were divided into severe (n=37, 28.7%), moderate (n=23, 17.8%), and mild (n=69, 53.5%). There was no significant difference in the distribution of gastroesophageal reflux in each age group. (The proportions of mild, moderate and severe reflux in infants were 45.0% (9/20), 25.0% (5/20), and 30.0% (6/20), respectively. The proportions of mild, moderate and severe reflux in preschool children were 53.3% (32/60), 16.7% (10/60), 30.0% (18/60), respectively. The proportions of mild, moderate and severe reflux in school age children were 57.1% (28/49), 16.3% (8/49), 26.5% (13/49), respectively χ2=1.204, P=0.877). There was no correlation between age group and gastroesophageal reflux (r=-0.065, P=0.489).The severity of nighttime cough was positively correlated with percentages of distal esophagus pH≤4 in time, recumbent pH≤4 in time, and DeMeester score<14.72 (r=0.689, 0.621, and 0.707 respectively, all P<0.05). There was no statistically significant correlation between the severity of nighttime cough symptoms and percentage of standing pH≤4 in time (r=0.113, P>0.05). There were no statistically significant correlation between the severity of daytime cough and all gastroesophageal reflux markers (all P>0.05).@*Conclusion@#The severity of nocturnal symptoms of gastroesophageal reflux cough is related to the degree of gastroesophageal reflux, to which clinical pediatricians should pay attention.

Clinical effect and cost analysis of panretinal photocoagulation combined with Ranibizumab or triamcinolone acetonide for diabetic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To compare clinical effects and cost of panretinal photocoagulation (PRP) combined with Ranibizumab or triamcinolone acetonide (TA) for diabetic macular edema (DME). ·METHODS: Forty-eight patients (48 eyes) with DME and diabetic retinopathy ( DR) receiving PRP were randomly assigned to two groups, which were respectively intravitreally injected ranibizumab (0. 5mg) and TA (4mg). Ranibizumab (0.5mg) was intravitreal injected every 4wk for 3 times. The effects of injection for DME were evaluated using best-corrected visual acuity (BCVA ), central macular thickness ( CMT ) and intraocular pressure (IOP). During the follow-up, other injections were performed to eyes which had CMT greater than 400μ m. The medical costs were calculated at 12wk and 24wk.·RESULTS: BCVA and CMT between 2 groups were not significantly different (P>0.05); BCVA and CMT among different time points were significantly different(P<0.05);the treatments and the time points had significant interaction on BCVA (P<0.05). BCVA was improved in two groups at all the time after injection(P<0.05),except 1wk after injection of TA (P=0.33). There was significant difference between the two groups at 12wk and 16wk on BCVA and that injected with ranibizumab was better (P=0.03,0.045). CMT decreased in two groups at all the time after injection (P<0.05). There was significant difference only between the two groups at 1wk (P< 0. 01). All intraocular pressures were in the normal range, except one needed ocular hypotensive agents. The medical costs (yuan) of the ranibizumab group in 12wk and 24wk were 38 736 and 42 564,which of the TA group were 5 790 and 7 053,respectively. ·CONCLUSION:Both PRP combined with ranibizumab or TA for DME can effectively control disease progression in short time. Therapeutic effect is not significant between two methods, but PRP combined with TA is more economic.

Research of relationship among C-peptide level,coagulation function and microvascular disease in pa-tients with type 2 diabetes mellitus / 心血管康复医学杂志

Diabetic microvascular disease is a severe complication of diabetes mellitus (DM).There are many hypoth-esis for its mechanisms.This overview aimed at effect of C-peptide,coagulant factors,platelet and D-dimer in dia-betic microvascular disease,and provided evidence for its prevention and treatment in clinic.