Imaging of lung cancer with molecular beacons delivered by octreotide-modified chitosan nanoparticles / 天津医药

Objective To investigate the identification of octreotide(OCT)modified chitosan(CS)miR-155 molecular beacon nanoparticles(CS-miR-155-MB-OCT)and imaging of lung cancer cells for the early screening of lung cancer.Methods A nude mouse model of lung transplantation tumor was established by injecting A549 lung cancer cells into tail veins to establish lung xenograft models.Cre adenovirus was injected through nasal cavity,and mice were killed at 4,6,8 and 12 weeks after adenovirus injection to establish lung cancer models of atypical hyperplasia,adenoma,carcinoma in situ and adenocarcinoma of lung in LSL K-ras G12D transgenic mice at different pathological stages.Lung tissue samples were taken and observed by HE staining.Immunohistochemistry were used to detect the expression of somatostatin receptor 2(SSTR2).Real-time fluorescence quantitative PCR was used to detect miR-155 expression levels in lung xenograft models and transgenic mice at different stages of lung cancer.Then CS-miR-155-MB and CS-miR-155-MB-OCT were injected via tail vein in lung xenograft models.CS-miR-155-MB-OCT was injected via tail vein in transgenic mice models.The fluorescence signals of lung in nude mice and transgenic mice at different disease stages were imaged by living imaging system.Frozen slices of lung tissue were made.The source of fluorescence signal was detected by laser confocal scanning microscope(CLSM).Results HE staining showed that lung transplantation tumor models and lung cancer models of atypical hyperplasia,adenoma,carcinoma in situ and lung adenocarcinoma at different pathological stages were successfully constructed.Immunohistochemical analysis showed somatostatin receptor 2(SSTR2)was expressed in transplanted lung tumor and tissue at different pathological stages.In transgenic mouse models,the expression of miR-155 was gradually increased as the disease progressed(P＜0.05).In lung xenograft models,the fluorescence signals were significantly higher in the CS-miR-155-MB-OCT group than those of the CS-miR-155-MB group(P＜0.05).In transgenic mouse models,the fluorescence signals gradually increased with the gradual progression of lesions(P＜0.05).After re-imaging the lung tissue,it was found that the fluorescence signal came from lung,and CLSM showed that the fluorescence signal came from cancer cells and some normal alveolar epithelial cells.Conclusion CS-miR-155-MB-OCT can dynamically reflect the occurrence and development of lung cancer according to changes of different fluorescence intensity,thus providing a new technology for the early diagnosis of lung cancer.

Inhibition of RhoA/ROCK signalling pathway activity improves neural damage and cognitive deficits in the fluorosis model.

Excessive fluoride intake poses health risks to humans and animals. Many studies have indicated that fluoride exposure can damage the cytoskeleton and synapses, which has negative effects on the intellectual development of humans and animals. Our previous study suggested that the RhoA/ROCK signalling pathway is activated by NaF exposure in HT-22 cells and plays a vital role in cytoskeletal assembly and synaptogenesis. However, the mechanism underlying RhoA/ROCK-mediated cytoskeletal injury induced by fluoride remains unclear. In this study, Neuro-2A cells and ICR mice were used to investigate the effects of RhoA/ROCK activation inhibition on NaF-induced synaptic dysfunction and cognitive impairment. We detected the expression of GAP, RhoA, ROCK1/2, and (p)-MLC in vivo and in vitro model. The results showed that NaF exposure activated the RhoA/ROCK/MLC signalling pathway. We measured the effects of RhoA/ROCK inhibition on synaptic injury and intellectual impairment induced by NaF exposure. In vitro, Y-27632 suppressed activated RhoA/ROCK, attenuated morphological and ultrastructural damage, and decreased the survival rate and synapse-functional protein expression caused by NaF. In vivo, the results showed that the RhoA/ROCK/MLC pathway was inhibited by fasudil and improved pathological damage in the hippocampus, cognitive impairment, and decreased expression of neurofunctional proteins induced by NaF. Overall, these results suggest that fasudil and Y-27632 can reverse neurotoxicity caused by fluoride exposure. Furthermore, inhibition of RhoA/ROCK may be a future treatment for CNS injury, and more detailed studies on other neurodegenerative disease models are required to confirm its effectiveness.

Catalpol improves non-alcoholic fatty liver and lipid-lowering mechanism through endoplasmic reticulum stress-mediated PERK-eIF2α signaling pathway / 中华内分泌代谢杂志

Objective:To investigate effect and underlying lipid-lowering mechanisms of catalpol in non-alcoholic fatty liver disease(NAFLD).Methods:In vivo model of NAFLD was established with high-fat diet-fed ICR mice for 8 weeks. Low(50 mg/kg), medium(150 mg/kg), and high(300 mg/kg) doses of catalpol were administered, and the body weight, liver weight, hepatic index, and biochemical parameters of the mice were analyzed. Free fatty acid-induced LO2 in human hepatocytes to establish NAFLD cell model. Quantitative realtime PCR reaction to detect fatty acid synthesis-related gene levels. Western blotting assay was adopted to analyze proteins in the endoplasmic reticulum stress(ERS)-mediated protein kinase RNA-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α) signaling pathway. Results:Compared with model mice, body weight [(39.43±1.84)g, (34.01±1.83)g, (32.28±1.11)g vs(42.17±1.37)g, all P<0.001], liver weight [(1.03±0.06)g, (0.79±0.05)g, (0.64±0.04)g vs(1.30±0.13)g, P<0.01 or P<0.001], and liver index [(2.60±0.09)%, (2.32±0.09)%, (1.99±0.11)% vs(3.07±0.30)%, P<0.05 or P<0.001] were reduced in low, medium, and high doses of catapol model. Medium and high doses of catalpol diminished total cholesterol, triglyceride, low density lipoprotein-cholesterol, aspartate aminotransferase, and alanine aminotransferase( P<0.01 or P<0.001), increased high density lipoprotein-cholesterol( P<0.01 or P<0.001). In the cell model, elevated levels of both fatty acid synthesis genes and PERK-eIF2α pathway proteins were attenuated by catalase, and this attenuation was reversed by signaling pathway agonists. Conclusion:The Chinese herb catalpol may play a role in improving NALFD by regulating the ERS-mediated PERK-eIF2α signaling pathway.

Joint effect of alcohol drinking and tobacco smoking on all-cause mortality and premature death in China: A cohort study.

BACKGROUND: Tobacco smoking and alcohol drinking are associated with several diseases, and studies on the joint effects of smoking and drinking are rare. OBJECTIVE: This study investigates the joint effects of tobacco smoking and alcohol drinking on all-cause and premature mortality in a contemporary cohort. METHODS: The China Health and Retirement Longitudinal Study (CHARLS) is an ongoing nationally representative survey of subjects aged over 45 years in China that was performed every two years for a total of three waves from 2011 to 2015 in China. We used weighted logistic regression models to estimate the joint effects of tobacco smoking and alcohol drinking on all-cause and premature mortality. RESULTS: After adjusting for prespecified confounders, the odds ratios (ORs) of all-cause mortality were 1.51 (95% CI: 1.09-2.10) and 1.47 (95% CI: 1.03-2.08) in smokers and smokers/drinkers, respectively. Compared with nonsmokers/nondrinkers, the OR of smokers/drinkers for premature death was 3.14 (95% CI: 1.56-6.34). In the female subgroup, there was an approximately 5-fold (OR = 4.95; 95% CI: 2.00-12.27) odds of premature mortality for smokers/drinkers compared to nonsmokers/nondrinkers. CONCLUSION: This study found a joint effect of tobacco smoking and alcohol drinking on all-cause and premature mortality among a contemporary and nationally representative cohort in China. Our results suggested that the joint effects were more pronounced in women, but further research is needed.

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, 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.

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<50×109/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.

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)×109/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.

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.

Influence of NNT mutation on glucose homeostasis in C57BL/6 mice / 中华内分泌代谢杂志

Objective To explore the effect of nicotinaide nucleotide transhydrogenase(NNT) mutation on glucose homeostasis in C57BL/6 mice with mix background. Methods We generated wild type NNT homozygous, mutant NNT homozygous and heterozygous by mating the C57BL/6J (with NNT mutation) and 6N (without NNT mutation). At the age of 4 weeks, those mice were randomly assigned to normal control diet(NCD) or high-fat diet(HFD) for 4 weeks. The body weight was measured every week. At the age of 8 weeks, an intraperitoneal glucose tolerance test(IPGTT) and an intraperitoneal insulin tolerance test (ITT) were performed. Results The body weight growth was not affected by NNT mutation during an HFD fed. NNT mutant mice showed significant glucose intolerance. After 4 weeks of high fat diet, the NNT mutant mice showed a decreased insulin sensitivity, while the glucose excursion curve was not elevated in the heterozygous mice. Conclusion NNT mutation had a significant influence on the phenotype of glucose metabolism and insulin resistance of mice, in particular under a metabolic stress. The phenotypes of heterozygous and homozygous mutant ones differed from each other. When using mice with C57BL/6J and C57BL/6N mixed background in research, NNT mutation should be carefully screened in all metabolic studies.

Shenshao decoction improves myocardial inflammatory injury in diabetic rats by regulation of TLR4/MyD88 pathway / 中国比较医学杂志

Objective To investigate the improving effects of Shenshao decoction on myocardial structure and function in diabetic cardiomyopathy,and its effect on expression of TLR4/MyD88-dependent pathway signal in diabetic cardiomyopathy.Methods Diabetes mellitus was induced in 8-week-old male Wistar rats by a single intraperitoneal injection of streptozotocin.The changes of plasma myocardial enzyme (CK, LDH) and high sensitive C reactive protein (hsCRP) were measured.Cardiac function was measured by left ventricular intubation.Hematoxylin and eosin staining and electron microscopy were used to observe the changes of myocardial morphology and ultrastructure in rats.Expression of Toll-like receptor 4(TLR4), myeloid differentiation protein 88(MyD88), and nuclear factor-κB P65(NF-κB P65) were tested by immunohistochemistry.Results After 6 weeks of treatment, the left ventricular diastolic and systolic functions were obviously improved;the degrees of myocardial fibers and mitochondrial damage were obviously relieved;the content of CK, LDH and hsCRP decreased (P 0.05).Conclusions Shenshao decoction can reduce the myocardial injury in diabetic cardiomyopathy and improve cardiac diastolic and systolic functions.The mechanism may be related to attenuated inflammation by TLR4/MyD88 dependent signaling pathway.

Reasons for misdiagnosis of contrast-enhanced ultrasound in identifying thyroid nodules / 中华内分泌外科杂志

Objective To investigate the reason for misdiagnosis of real-time contrast-enhanced ultrasound (CEUS) in identifying benign and malignant thyroid nodules and the impact of nodule size and calcification on CEUS result.Methods Retrospective analysis were carried out in 331 cases of thyroid disease patients with 421 nodules.All the nodules were performed CEUS and confirmed by pathology.Results In the total of 421 nodules,33 nodular goiters were misdiagnosed as thyroid carcinoma.8 nodular goiters were misdiagnosed as thyroid adenoma.8 thyroid carcinomas were misdiagnosed as nodular goiter,2 thyroid carcinomas were misdiagnosed as thyroid adenoma.The accuracy of diagnosis for thyroid benign and malignant lesions by CEUS was 87.89％,and the misdiagnosis rate was 12.11％.The size of the thyroid nodule and the form of calcification had influence on diagnosis.In the group with diameter of the nodule less than 10 mm,the misdiagnosis rate was higher compared with the other two groups,and the difference was statistically significant (P＜0.05).In addition,the misdiagnosis rate in the group with bulky calcification was higher than microcalcifications group,and the difference was statistically significant (P＜0.05).Conclusion The size of the thyroid nodule and the form of calcification have some impact on diagnosis of CEUS.To make clear the reason for misdiagnosis is beneficial to improve the diagnostic level of thyroid diseases.

Clinicopathological analysis of 3 cases of trichoblastoma / 重庆医学

Objective To summarize and study the clinicopathologic features,diagnosis and differential diagnosis of tricho-blastoma (TB).Methods The clinicopathological characteristics,histomorphology features and immunophenotype features of TB and differential diagnosis with multiple diseases in 3 cases of TB were retrospectively analyzed;moreover,5 cases of basal cell carci-noma were selected and performed the immunophenotype detection,which focused on the differential diagnosis with TB.Results The masses in 3 cases were located under the skin without connecting with the epidermis and were composed of basal-like cells with palisade arrangement of peripheral cells.The case 1 showed unequal-sized multiple cyst cavities and pigment deposition and was di-agnosed as pigmented TB.The papillary mesenchymal bodies were found in case 2,which was diagnosed as TB.The basal cells of tumor in case 3 distributed as palisade arrangement and formed the wave structure,which was diagnosed as rippled-pattern TB.AR in 3 cases and Bcl-2 in 2 cases were negative expression,CK20 in 1 case was sporadically positive,CD10 stroma and papillary struc-ture in 3 cases were positive,paliform-like arrange tumor cells CD10 around basal cell carcinomas in 5 cases were positive,AR in 4 cases was positive,Bcl-2 in 3 cases was positive and CK20 in 5 cases was negative.Conclusion TB is a benign tumor derived from the hair follicle germinal epithelium with a good prognosis after complete resection and the differential diagnosis focuses on basal cell carcinomas.

The demand analysis and plan design for the maintenance management system of medical equipment / 中国医学装备

Objective:To analyze the demands of maintenance management system of medical equipment, and realize the scientization and normalization of plan design for maintenance management system of medical equipment.Methods: On the basis of current status of maintenance management system of medical equipment, the demands of various department during management process were analyzed, and then a systematic maintenance management plan was designed to face to all of medical equipment in hospital.Results: The preponderances of this system were discussed from three aspects: equipment maintenance, equipment archive and equipment benefit.Conclusion: The application of this system can accelerate the progress of maintenance for medical equipment, enhance maintenance awareness of clinical medical staffs for medical equipment, improve the transparency of equipment scrapping and disposal, and provide effective references for demonstration and purchase of medical equipment.

Observations on the Efficacy of Dog Days' Acupoint Application in Treating Allergic Rhinitis / 上海针灸杂志

Objective To investigate the clinical efficacy of dog days' acupoint application in treating allergic rhinitis and assess its safety.Methods Two hundred and forty-nine patients were randomly allocated to a dog days' acupoint application group of 166 cases and a placebo group of 83 cases. The two groups were received treatment at the first day of the first, second and last periods of the hot season The dog days' acupoint application group received acupoint application of Chinese herbal medicine and the placebo group, acupoint application of non-medicinal placebo. In the two groups, the symptoms and signs were scored and the VAS score was recorded before and after treatment and during the follow-up period, and adverse reactions and relapses were observed and the clinical therapeutic effect of acupoint application and its safety were assessed after treatment and during the follow-up period.Results The total efficacy rate was 69.8% in the dog days' acupoint application group and 44.4% in the placebo group. The therapeutic effect was significantly better in the dog days' acupoint application group than in the placebo group (P0.05). The relapse rate was 46,6% at the 6-month follow-up and 62.1% at the 12-month follow-up in the dog days' acupoint application group and 85.2% and 95.1% in the placebo group; there were statistically significant differences between the two groups (P<0.01).Conclusions Dog days' acupoint application has better short-term and long-term therapeutic effect on allergic rhinitis with a low relapse rate and high safety.

The effectiveness of wechat-based transitional care in patients with Myasthenia gravis / 中国实用护理杂志

Objective To evaluate the effectiveness of wechat-based transitional care in patients with Myasthenia gravis. Methods Choose 60 patients with Myasthenia gravis from August 2013 to August 2014 were divided into two groups,30 cases in each group.The patients in the two groups recevied routine dischared education.In addition,the patients in the experimental group received wechat-based transitional care for three months. The patients, anxiety, depression, self-care and health behavior at 3 months after discharge were compared between the two groups. Results There was no statistical significance between the experimental group and the control group in anxiety, depression, self-care ability and health behavior scale (P > 0.05). In the experimental group, the SAS evaluation results of normal, mild anxiety, moderate anxiety, severe anxiety respectively is 8、19、2、1. However, in the control group the result is 3、15、8、4 respectively. There was statistically difference (χ2=2.732, P < 0.01). In the experimental group, the SDS evaluation results of normal, mild depression, moderate depression, major depression respectively is 9、15、5、11. However, in the control group the result is 3、13、8、6 respectively. There was significant difference (χ2=2.626, P<0.01). Patients self-care ability and health behavior scale assessment results in the experimental group is (134.2±14.1)、(151.9±14.3) respectively and the results in the control group is (123.3±18.8)、(142.8±17.5) respectively. There was a statistically significant difference (t=2.541、2.294, P < 0.05). Conlusion Wechat-based transitional care acieves good effectiveness in patients with Myasthenia gravis and is worthy of promotion.

The clinical characteristics, gene mutations and prognosis of chronic neutrophilic leukemia / 中华血液学杂志

Objective@#To investigate the clinical manifestation, cytogenetics, gene mutations and prognostic factors of chronic neutrophilic leukemia (CNL) .@*Methods@#16 CNL cases, according to WHO (2016) -definition, were reviewed retrospectively. Identifications of the CSF3R, ASXL1, SETBP1, CALR and MPL mutations were performed by direct sequencing. JAK2 V617F mutation was detected by AS-PCR.@*Results@#Of the 16 CNL patients, the median age was 64 (43-80) years with a male predominance of 75% (12/16) . The median hemoglobin was 114 (81-154) g/L, with median WBC of 41.20 (26.05-167.70) (109/L and median PLT of 238 (91-394) ×109/L.The median level of marrow fibrosis (MF) was 1 (0-3) degree. There was no other cytogenetic abnormalities except t (1;7) (p32;q11) , +21 and 14ps+ for each. All the 16 CNL patients harbored CSF3R T618I mutation. ASXL1 mutations were identified in 81% (13/16) , while SETBP1 mutations were confirmed in 63% (10/16) . The CALR K385fs*47 mutation was found. There was no mutation in JAK2 V617F or MPL in the above 16 patients. The median overall survival (OS) of patients presented with WBC≥50×109/L at diagnosis (11 months) was significantly shorter than of WBC<50×109/L (39 months, P=0.005) .@*Conclusion@#CSF3R T618I mutation was specific for CNL. The median OS of CNL patients was 24 months, and WBC≥50×109/L at diagnosis was an unfavorable prognostic factor.

The efficacy and safety of the patients of myelodysplastic syndromes-refractory anemia with excess blasts treated with decitabine alone or CAG/HAG regimen / 中华血液学杂志

Objective@#To observe the clinical efficacy and safety of the patients of myelodysplastic syndromes-refractory anemia with excess blasts (MDS-REAB) treated with decitabine alone or based on low dose cytarabine (Ara-C) regimen CAG/HAG [aclarubrci (ACR) /homoharring-tonine (HHT) +cytarabine+granulocyte colony stimulating factor (G-CSF) ].@*Methods@#Totally 121 patients with MDS-REAB were retrospectively analyzed, including 59 patients treated with decitabine alone (20 mg·m-2·d-1 for 5 days) , the rest 62 ones treated with low-dose Ara-C-based regimen CAG/HAG. Overall response rate (ORR) , overall survival (OS) and adverse events of the two groups were analyzed and compared retrospectively.@*Results@#The ORR of decitabine alone or CAG/HAG were 66.2% and 56.4% respectively, with no statistically significant differences (χ2=1.185, P=0.276) . Initial response rate detected by the end of first cycle of CAG/HAG was higher than that of decitabine alone (94.3% vs 69.2%) , there was statistically significant difference in the overall comparison of two groups (χ2=7.612, P=0.009) . The median OS of decitabine alone was 19.5 (95% CI 10.5-28.4) months, the median OS of CAG/HAG was 20.3 (95% CI 10.7-29.9) months, with no statistically significant differences (χ2=0.004, P=0.947) . Grade 3-4 cytopenia and infection were the most prevalent adverses of two group patients. Grade 3-4 cytopenia rate of CAG/HAG was higher than that of decitabine alone (100.0% vs 64.4%, P<0.001) . The infection rate detected at third cycle of CAG/HAG was higher than that of decitabine alone (52.9% vs 15.2%, P=0.008) .@*Conclusion@#The efficacy of treating MDS-RAEB with decitabine alone or CAG/HAG was equivalent. CAG/HAG treatment came into effect faster, but decitabine alone treatment was safer.

Gene mutations from 511 myelodysplastic syndromes patients performed by targeted gene sequencing / 中华血液学杂志

Objective@#To study the characteristics of gene mutations in Chinese myelodysplastic syndromes (MDS) patients.@*Methods@#A total of 511 Chinese patients with MDS performed 112-gene targeted sequencing were retrospectively analyzed.@*Results@#Eighty-three distinct mutant genes were found in 511 patients with MDS. Amongst these, the most frequent mutations was associated with epigenetics (50%) , followed by spliceosome (37%) , signal transduction (34%) , transcription factors (24%) and cell cycle/apoptosis (17%) . 439 subjects (86%) had at least one gene mutation. The mean number of mutations in refractory anemia with unilineage dysplasia (RCUD) was 1.25, refractory anemia with multilineage dysplasia (RCMD) was 1.73, refractory anemia with ring sideroblasts (RARS) was 2.79, refractory anemia with excess blasts-1 (RAEB-1) was 2.22, RAEB-2 was 2.34, MDS with isolated 5q- was 2.67, MDS, unclassified (MDS-U) was 2.00. U2AF1 mutant subjects were more likely to have isolated+8[Q<0.001, OR=4.42 (95% CI 2.23-8.68) ]and less likely to have complex karyotypes[Q=0.005, OR=0.22 (95% CI 0.04-0.72) ]. According to the number of gene mutations, all subjects were categorized into three groups, namely group with 0-1 mutation, with 2 mutations and with three or more mutations. There was a significant difference in overall survival (OS) among three groups (P=0.041) .@*Conclusion@#About 90% patients with MDS have at least one gene mutation. Genes associated with epigenetics and spliceosome are most common mutated genes in MDS. The increased numbers of gene mutations accompany with disease evolution and associate with poor prognosis.

Clinical and laboratory characteristics in patients of myelodysplastic syndrome with PNH clones / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical, laboratory characteristics and PIG-A gene mutations in patients of myelodysplastic syndromes (MDS) with PNH clones.</p><p><b>METHODS</b>218 MDS patients diagnosed from August 2013 to August 2015 were analyzed. The PIG-A gene mutations were tested in 13 cases of MDS with PNH clones, 17 cases of AA-PNH and 14 cases of PNH selected contemporaneously by PCR and direct sequencing.</p><p><b>RESULTS</b>13 (5.96%) MDS patients were detected with PNH clones (13/218 cases). 9 patients were treated with cyclosporin A (CsA). Patients showed hematological improvement (HI). There were significant differences between MDS-PNH and PNH patients in terms of granulocyte clone size, red cell clone size and LDH levels [19.2% (1.0%-97.7%) vs 60.2% (3.1%-98.0%), P=0.007; 4.3% (0-67.2%) vs 27.9% (2.5%-83.6%), P=0.026; 246 (89-2014) U/L vs 1137 (195-2239) U/L, P=0.049], while the differences were not statistically significant in patients between MDS-PNH and AA-PNH patients [19.2% (1.0%-97.7%) vs 23.2% (1.5%-96.0%), P=0.843; 4.3% (0-67.2%) vs 14.4% (1.1%-62.8%), P=0.079; 246 (89-2014) U/L vs 406 (192-1148) U/L, P=0.107]. PIG-A gene mutations were detected in 7 MDS-PNH patients, of them, six were missense mutations, one were frameshift mutation and four cases with the same mutation of c.356G>A (R119Q). The PIG-A gene mutations were also detected in 9/11 AA-PNH patients and 11/14 PNH patients, both of them had the mutation of c.356G>A (R119Q). The PIG-A gene mutations of MDS-PNH, AA-PNH, PNH patients were all small mutations, the majority of those (59%) were missense mutation and mainly located in exon 2.</p><p><b>CONCLUSION</b>MDS patients with PNH clones had better response to CsA, smaller PNH clone size. The PIG-A gene mutations of MDS-PNH patients mainly located in exon 2, which could be a mutational hotspot of these patients.</p>

Long-term outcomes of homoharringtonine, cytarabine, daunorubicin or idarubicin (HAD/HAI) as induction chemotherapy in de novo acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To estimate the long-term outcomes and the prognostic factors of homoharringtonine, cytarabine, daunorubicin or idarubicin (HAD/HAI) as induction chemotherapy in de novo acute myeloid leukemia (AML).</p><p><b>METHODS</b>The CR rate, overall survival (OS) rate, relapse free survival (RFS) rate were retrospectively assayed in 143 de novo AML patients who received the HAD/HAI induction chemotherapy. The outcomes were compared among prognostic groups according to world health organization (WHO) classification, genetic prognosis and initial white blood cell (WBC) count. The role of consolidation chemotherapy consisting of middle-dosage Ara-C (MD-Ara-C) on long term survival was evaluated.</p><p><b>RESULTS</b>Of 143 patients, 112 (78.3%) achieved CR after the first course of HAD/HAI induction treatment, and early death occurred in only one case. Notably, the CR rate of patients with an initial WBC count ≥100×10(9)/L was not significantly different from those with an initial WBC count<100× 10(9)/L (70.4% vs 80.2%, P=0.266). The CR rate for the patients with favorable, intermediate and unfavorable integrated genetics risk factors was 93.7%, 71.4% and 61.3%, respectively, the difference between groups was statistically significant (P=0.001). Patients with FLT3-ITD mutation obtained similar CR rate (70.6%) to that of patients with FLT3 wild type (79.3%, P=0.528).The estimated 5-year OS rate and 5-year RFS rate for all patients was 40.0% and 37.0%, respectively, with a median follow-up of 24 (range 1-104) months. The median survival time was 30 [95%CI (12, 48)] months. 5-year OS and 5-year RFS of the 96 patients who achieved CR after first course chemotherapy without undergoing allo-HSCT in complete remission was 47.0% and 38.0%, respectively. 5-year OS was significantly higher in MD-Ara-C consolidation group than in no MD-Ara-C consolidation group among CR patients without allo-HSCT (58.0%, 19.0%, respectively, P=0.004). In patients who obtained CR after first course and received MD-Ara-C consolidation without allo-HSCT, the 5-year OS of patients with hyperleukocytosis was not significantly lower than that of patients without hyperleukocytosis (55.5%, 58.8%, respectively,P=0.419). FLT3-ITD mutation patients showed similar 5-year OS to that of wild type FLT3 patients (51.4%, 60.2%, respectively, P=0.482). And furthermore, 5-year OS of favorable, intermediate and unfavorable integrated genetics groups were 59.1%, 62.5%, 51.9%, respectively (P=0.332) in this subgroup.</p><p><b>CONCLUSION</b>HAD/HAI induction chemotherapy with sequential consolidation of MD-Ara-C could obtain satisfactory CR rate and long-term survival rate in de novo AML, especially for patients with hyperleukocytosis or FLT3-ITD mutation. It yet remains to be verified by large sample, prospective studies.</p>