Correlation between Serum miR-34a Level and Thrombocytopenia after Chemotherapy in Patients with Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To analyze the relationship between serum miR-34a level and thrombocytopenia after chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#A total of 69 eligible DLBCL patients who received chemotherapy in our hospital from January 2018 to January 2020 were prospectively included as the research subjects, all patients received R-CHOP 21 regimen (rituximab + cyclophosphamide + adriamycin + vincristine + prednisone) for chemotherapy, 3 weeks was 1 cycle, and 2 cycles of chemotherapy were used. The patients were divided into a reduction group and a non reduction group according to whether there was thrombocytopenia after chemotherapy, the general data and laboratory indexes of the two groups were investigated and compared, the relationship between serum miR-34a before chemotherapy and thrombocytopenia after chemotherapy in patients was analyzed.@*RESULTS@#Among the 69 DLBCL patients, 36 patients developed thrombocytopenia after 2 cycles of R-CHOP 21 regimen for chemotherapy, the incidence was 52.17%; the level of serum IL-11 and the relative expression of miR-34a mRNA in the reduction group were significantly lower than the non reduction group (P<0.05), compared other data between groups, there was no statistical significant difference (P>0.05); after Logistic regression analysis, the results showed that the level of serum IL-11 and the relative expression of miR-34a mRNA were related to thrombocytopenia after chemotherapy in DLBCL patients, low expression of each index may be a risk factor of thrombocytopenia after chemotherapy in DLBCL patients (OR>1, P<0.05); ROC curve was drawn, and the results showed that the AUC of serum IL-11 level and miR-34a mRNA relative expression before chemotherapy alone and in combination predicted the risk of thrombocytopenia after chemotherapy in DLBCL patients were all >0.80, and the predictive value was ideal, when the cut-off value of serum IL-11 level before chemotherapy was 42.094 pg/ml, and the cut-off value of miR-34a mRNA relative expression was 3.894, the combined prediction value was the best.@*CONCLUSION@#The relative expression of miR-34a mRNA is associated with thrombocytopenia after chemotherapy in DLBCL patients, which may be a risk factor for thrombocytopenia in patients after chemotherapy, has certain value in predicting the risk of thrombocytopenia of patients after chemotherapy.

Ultrasound- and Electrical Stimulation-guided Botulinum Toxin Injection for Cricopharyngeal Achalasia Dysphagia: A Case Report / 中国康复理论与实践

Objective:To apply Botulinum toxin type A (BTX-A) injection for cricopharyngeal achalasia dysphagia guided by ultrasound and electrical stimulation. Methods:A case with cricopharyngeal achalasia dysphagia was reviewed. Results:He ate food almost in normal way six days after injection, and cricopharyngeus was open seven days after injection. Conclusion:BTX-A injection under ultrasound- and electrical stimulation-guide is effective on cricopharyngeal achalasia dysphagia.

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.

Angiotensin 1-7 attenuates angiotensin Ⅱ-induced human glomerular en-dothelial cell injury via Mas receptor / 中国病理生理杂志

AIM:To investigate the effect of angiotensin 1-7(Ang1-7)on the human glomerular endothelial cells(HGECs)injury induced by angiotensin Ⅱ(Ang Ⅱ)and its possible mechanism.METHODS: Cultured HGECs were divided into 6 groups randomly: control group, Ang Ⅱ group, Ang1-7 group, Ang Ⅱ +Ang1-7 group, Ang Ⅱ +Ang1-7+A779(an inhibitor of Mas receptor)group and A779 group.The apoptotic rate and reactive oxygen species (ROS)of HGECs were analyzed by flow cytometry and photographed by fluorescence microscopy.The levels of lactate de-hydrogenase(LDH),nitric oxide(NO),endothelin-1(ET-1),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α), transforming growth factor-β(TGF-β),monocyte chemoattractant protein-1(MCP-1)and intercellular adhesion molecule-1(ICAM-1)in the supernatant of cell cultures were measured.RESULTS:Compared with the control group,the apoptot-ic rate and the average fluorescence intensity of ROS were increased in the Ang Ⅱ group,IL-6,TNF-α,TGF-β,ICAM-1 and MCP-1 in cell supernatants were also increased in the Ang Ⅱ group(P<0.05).Compared with the Ang Ⅱ group,the apoptotic rate,ROS level, and the above inflammatory factors were decreased in Ang Ⅱ +Ang1-7 group(P<0.05). Compared with the Ang Ⅱ +Ang1-7 group,adding A779 increased the cell apoptotic rate,ROS production and the releases of the above inflammatory factors in cell supernatants(P<0.05).Compared with the Ang Ⅱ group,adding Ang1-7 inhibi-ted the LDH leakage, ET-1 secretion and promoted the release of NO in a dose-dependent manner(P<0.05).CON-CLUSION:Ang1-7 attenuates the HGECs injury induced by Ang Ⅱ by inhibiting the Mas receptor.

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.

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>

Relationship between polymorphisms of tumor necrosis factor alpha gene and primary myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the association of single nucleus polymorphisms(SNP)of tumor necrosis factor alpha (TNF-α) gene (-308 G>A and -238 G>A genotypes) with susceptibility to primary myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>Two SNPs (TNF-α-308 G>A,TNF-α-238 G>A) of TNF-α gene were detected by Taqman probes in 341 MDS patients and 365 unrelated-healthy controls.</p><p><b>RESULTS</b>Compared to healthy controls, the frequency of TNF-α-308 AA+AG genotype and A allele increased (18% vs 10%, P=0.015, 9% vs 5%, P=0.021, respectively) in refractory cytopenia with multilineage dysplasia (RCMD) patients. There was no correlation of TNF-α-308 G>A genotype and allele frequency between MDS and controls. No difference in the genotype and allele frequency of TNF-α-238 G>A were found between controls and MDS or the subtypes of MDS (P>0.05). We did not find any linkage between plasma level of TNF-α and TNF-α-308 G>A or TNF-α-238 G>A genotype. Statistic differences were observed between platelet count[58(1-611)×10⁹/L vs 90(7-352)×10⁹/L]and bone marrow blasts in MDS patients carrying TNF-α-308 G>A GG and AA+AG genotype (P=0.024, 0.019, respectively).</p><p><b>CONCLUSION</b>TNF-α-308 G>A polymorphism was correlated with susceptibility to MDS-RCMD.</p>

Analysis of clinical features and prognosis of primary myelodysplastic syndromes with myelofibrosis patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical features and prognosis of the primary myelodysplastic syndrome with myelofibrosis (MDS-MF) patients and to improve the cognition of MDS-MF.</p><p><b>METHODS</b>Four hundred and sixty-six primary MDS patients with bone marrow (BM) biopsy were divided into two groups according to whether BM associated with fibrosis, the clinical features and prognosis of the two groups were analyzed retrospectively.</p><p><b>RESULTS</b>167 (35.8%) MDS cases revealed myelofibrosis, of which MF-1 123 cases (26.4%), MF-2 40 cases (8.6%), MF-3 4 cases (0.9%). The proportion of hepatosplenomegaly in MDS-MF group was significantly higher than in MDS without MF group, the difference had statistical significance (P = 0.031). The proliferation of BM biopsy in MDS-MF group was significantly more active than in MDS without MF group. The number of blasts, megakaryocytes and abnormal megakaryocytes in MDS-MF group were significantly higher than in MDS without MF group, the differences had statistical significance (P < 0.05). Among the 345 patients who had available results of cytogenetic analysis, 121 cases were MDS-MF patients, the proportion of middle and high-risk prognostic group according to IPSS karyotype prognosis groups in MDS-MF group were significantly higher than in MDS without MF group, the differences had statistical significance (P = 0.047). The median survival was 17 (1 - 60) months in MDS-MF group, and was 32 (1 - 62) months in MDS without MF group. The difference had statistical significance (P = 0.001). Myelofibrosis had independent prognostic significance by multi-variable analysis (P = 0.019).</p><p><b>CONCLUSION</b>The myelofibrosis in MDS is main the proliferation of reticular fiber. The proliferation of reticular fiber is closely related with the number of blast cells, the proliferation and developmental abnormalities of megakaryocytes and the karyotype. The prognosis of MDS-MF patients is poor.</p>

Clinical features and survival analysis in primary myelodysplastic syndromes patients with immunological abnormalities / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical features and survival time in primary myelodysplastic syndromes (MDS) patients accompanied with immunological abnormalities.</p><p><b>METHODS</b>The clinical information, laboratory findings and survival time in 194 untreated primary MDS patients with complete immunological laboratory tests or a past history of autoimmune disease were analyzed retrospectively.</p><p><b>RESULTS</b>There were 37/194 cases (19.07%) with autoimmune abnormalities, including 16/194 (8.25%) with autoimmune disease and 21/194 asymptomatic cases (10.82%) with serologic immunological abnormalities only. There was significant differences in the distribution of age < 60 years old, female, CD4(+)T-cell/CD8(+)T-cell ration < 1 and trisomy 8 (P < 0.05) between the cases with autoimmune disease and without autoimmune abnormalities. The former had a higher 2-year OS, but there was no significance (P = 0.065). There was no significant differences in the distribution of age, MDS-subtype, IPSS risk groups, haemoglobin, absolute neutrophil count, platelets count, the severity of anemia and neutropenia, high level of serologic TNF, chromosomal abnormalities, cytogenetic risk groups and bone marrow cellularity (P > 0.05).</p><p><b>CONCLUSION</b>MDS patients with autoimmune disease are mainly female and younger than 60 years old, with high proportion of trisomy 8 and better prognosis.</p>

A preliminary study of prognostic value of thrombocytopenia in patients with primary myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the prognostic value of thrombocytopenia in patients with primary myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>Four hundred and nineteen primary MDS patients were retrospectively analyzed. Kaplan-Meier method, Log-rank test and COX regression model were used to evaluate factors that influence the prognosis.</p><p><b>RESULTS</b>Two hundred and fifty-six cases (61.1%) had thrombocytopenia (PLT < 100×10(9)/L), one hundred and three cases (24.6%) had severe thrombocytopenia (PLT < 30×10(9)/L). Overall survival (OS) tended to shorten along with the decreasing of platelet count. Univariate analysis indicated that PL < 30×10(9)/L, MCV ≤ 95 fl, LDH ≥ 300 U/L, lymphocyte-like micromegakaryocyte, nucleated RBC PAS positive, IPSS cytogenetic intermediate- and poor-risk were all related with poor prognosis. Moreover, the prognosis of patients with RCMD, RAEB-Ior RAEB-IIwas poorer than that of the other subgroups. Among these parameters, PLT < 30×10(9)/L, MCV ≤ 95 fl, IPSS cytogenetic intermediate- and poor-risk group and RCMD, RAEB-I and RAEB-II had independent prognostic significance in multivariate analysis. Modified WPSS prognostic model was proposed by adopting PLT, MCV, chromosomal karyotype and WHO classification. The OS of patients with low risk, intermediate-1 risk, intermediate-2 risk and high risk were 59, 28, 14 and 4 months, respectively, and there was a statistically significant difference between the groups (P < 0.05).</p><p><b>CONCLUSION</b>Severe thrombocytopenia indicated unfavorable prognosis, in combination with MCV, chromosomal karyotype and WHO classification, a modified WPSS prognostic model was proposed and worked well for prognostic indication in patients with MDS.</p>

Study on the implications of erythroblasts periodic acid-Schiff stain in myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the implications of erythroblasts periodic acid-Schiff (PAS) stain for myelodysplastic syndromes (MDS) dyserythropoiesis, diagnosis and differential diagnosis.</p><p><b>METHODS</b>PAS stain of bone marrow (BM) erythroblasts in 406 MDS patients, 207 non-severe aplastic anemia (NSAA), 144 immune thrombocytopenic purpura (ITP), 67 megaloblastic anemia (MegA), 76 iron deficiency anemia (IDA), 50 paroxysmal nocturnal hemoglobinuria (PNH), and 50 acute erythroid leukemia (AEL) as well as some related laboratory parameters in MDS patients were analyzed retrospectively.</p><p><b>RESULTS</b>PAS-positive detection rate was significantly higher in MDS (53.0%) than in NSAA (14.5%), ITP (27.1%) and PNH (16.0%), but was significantly lower in MDS than in AEL (84.0%) (all P = 0.000). There was no significant difference in PAS-positive detection between MDS and MegA (46.3%), or MDS and IDA (40.8%) (P = 0.310, 0.052, respectively). Erythroblasts PAS-positive rate (Median, M = 1%) and PAS-positive scores (M' = 2) was significantly lower in MDS than in AEL (M = 8%; M' = 17), and significantly higher than in NSAA (M = 0%; M' = 0), ITP (M = 0%; M' = 0), PNH (M = 0%; M' = 0), MegA (M = 0%; M' = 0), and IDA (M = 0%; M' = 0) (all P < 0.05). The cut-off value of PAS-positive rate and score for distinguishing MDS from the other groups except AEL were 0.5% and 0.5, with a sensitivity and specificity of 60.8% and 74.4%, respectively. For MDS patients, the percentage of BM erythroid cells was significantly higher in PAS-positive group than in PAS-negative group (P < 0.05), and so were megakaryocyte count, lymphocyte-like micromegakaryocytes count and percentage of micromegakaryocyte (P = 0.002, 0.000, 0.000, respectively). HGB, MCV, MCH and MCHC were significantly lower in PAS-positive group (all P < 0.05), and so was the neutrophil alkaling phosphatase (NALP) (P = 0.000). PAS-positive detection rate, positive rate and score were higher in MDS patients with abnormal karyotype than with normal karyotype, and were also higher in IPSS high/intermediate-risk 2 group than in low/intermidiate-risk 1 group.</p><p><b>CONCLUSION</b>The positive reaction of erythroblasts PAS stain is an indicator of dyserythropoiesis. It is helpful to the diagnosis of MDS patients.</p>

Effects of ethanol on action potential of rat myocardium and human Kv1.5 channel / 生理学报

The purpose of the present study was to investigate the effects of different concentrations of ethanol on action potential (AP) in the isolated rat myocardium and the possible mechanism of electric-physiological changes. Standard microelectrode technique was used to record AP in isolated rat myocardium, and whole cell patch clamp technique was used to record the human Kv1.5 (hKv1.5) channel currents in HEK293 cells. The effects of different concentrations of ethanol (6.25, 12.5, 25.0, 50.0, 100.0 and 200.0 mmol/L) on AP parameters in rat atrium and papillary and Kv1.5 channel currents in HEK293 cells were analyzed. The results showed that in isolated atrium, action potential amplitude (APA), action potential duration (APD), action potential duration of 50% repolarization (APD(50)) and action potential duration of 90% repolarization (APD(90)) were not affected by 6.25 and 12.5 mmol/L ethanol, while APD, APD(50) and APD(90) were prolonged significantly by 25.0-200.0 mmol/L ethanol (P < 0.05 or P < 0.01), and APA was reduced with 100.0 and 200.0 mmol/L ethanol (P < 0.05 or P < 0.01). In isolated papillary, APA, APD, APD(50) and APD(90) were not affected by 6.25-25.0 mmol/L ethanol, while APD, APD(50) and APD(90) were prolonged significantly with 50.0-200.0 mmol/L ethanol (P < 0.05 or P < 0.01), and APA was reduced with 200.0 mmol/L ethanol (P < 0.05). The Kv1.5 channel currents were inhibited by ethanol in a concentration dependent manner in HEK293 cells. These findings suggest that 6.25 and 12.5 mmol/L ethanol produce no effects on AP parameters, and 50.0-200.0 mmol/L ethanol prolong APD significantly in isolated rat atrium and papillary. The prolonged effect on APD in isolated myocardium may be due to the inhibition of the Kv1.5 channel currents.

Effect of ischemia/hypoxia on mesenteric vasomotor function in spontaneously hypertensive rats and its possible mechanism / 生理学报

Hypertension is a common cardiovascular disease and can induce many complications, such as stroke and coronary heart disease. The purpose of the present study was to investigate the effect of ischemia/hypoxia on mesenteric artery vasomotor function in spontaneously hypertensive rats (SHR). Rat mesenteric arterial rings were cultured in modified ischemia-mimetic solution in a hypoxia incubator for a certain time period. Isometric tension changes of isolated mesenteric arterial rings were recorded continuously by a myograph system. The results obtained were as follows: In SHR group, the maximum contractions to KCl and phenylephrine (PE) were increased, and the maximum relaxation to acetylcholine (ACh) was decreased, compared to those in Wistar-Kyoto (WKY) rats group. Compared with SHR group and WKY with acute ischemia/hypoxia (WKY+H) group, SHR with acute ischemia/hypoxia (SHR+H) increased the maximum contractions induced by KCl and PE and inhibited the maximum relaxations by ACh. In SHR+H and SHR groups, the vasodilation induced by ACh was unaffected by N(G)-nitro-L-arginine methylester (L-NAME), whereas in WKY group, the relaxation to ACh was attenuated by L-NAME. CaCl2-induced contraction in depolarized rings in SHR+H group significantly shifted to the left compared with SHR group. In Ca(2+)-free K-H solution, the maximum contractions induced by PE and caffeine were increased in SHR+H group compared to those in WKY+H group; the PE- and caffeine-induced contractions were also enhanced in SHR group versus WKY group; the maximum contraction induced by PE was significantly increased in SHR+H group versus SHR group. These findings suggest that acute ischemia/hypoxia aggravates mesenteric artery dysfunction in SHR. The mechanism may be related to the decreased NO generation and increased sarcoplasmic reticulum Ca(2+) release.

Clinical study on combination of homoharringtonine, Ara-C and idarubicin induction for treatment of newly diagnosed acute myeloid leukemia patients / 中国实验血液学杂志

The purpose of this study was to assess the efficacy and toxicity of HAI regimen [(homoharringtonine 2.5 mg/(m(2)×d), days 1 - 7; cytarabine 150 mg/(m(2)×d), days 1 - 7; idarubicin 9 mg/(m(2)×d), days 1 - 7)] for induction treatment of newly diagnosed acute myeloid leukemia (AML) (except acute promyelocytic leukemia). 31 patients with newly diagnosed AML, aged 39 (14 - 58) years, were enrolled in this clinical study. The complete remission (CR) rate, especially after one course, the overall survival (OS) rate and relapse free survival (RFS) rate were estimated. The outcomes were compared between different prognostic groups according to World Health Organization (WHO) classification, genetics and initial WBC count. Safety was evaluated using standard WHO criteria. The results showed that 26 patients (84%) achieved CR after 1 course of induction. The CR rate for the patients with favorable, intermediate and unfavorable cytogenetics was 90%, 88% and 60% respectively. All 7 patients with a high initial WBC count (≥ 100×10(9)/L) obtained CR, while 19 out of 24 without a high initial WBC count obtained CR. With a median follow-up of 15(range 2-56) months, the estimated 3-year OS rate for all patients and the patients with CR was 44% and 52% respectively. The 3-year RFS rate was 51%. The patients receiving induction chemotherapy died of the chemotherapy. Profound myelosuppression was seen in all patients after the HAI induction with the median duration of neutropenia (ANC < 0.2×10(9)/L) of 16 (6 - 24) days. As the most common toxicity, severe infections (grade III-IV) involved in all the patients and the duration of febris was 6 (1 - 36) days. The incidence of septemia and invasive fungus infection were 19.4% and 45.2% respectively. The incidence of non-infection fever, increased glutamic-pyruvic transaminase (GPT), diarrhea, increased bilirubin and oral cavity mucositis were 6.5%, 6.5%, 3.2%, 3.2%, 3.2% respectively, as the more frequent severe non-hematological toxicities. It is concluded that HAI regimen is a high efficient induction schedule for the newly diagnosed AML, and archive the higher CR rate after one course than DNR/Ara-C standard induction regimen. Side effects are acceptable, except severe infection.

Alterations in aortic vasomotor function in rats with chronic heart failure and its mechanism / 生理学报

The aim of the present study was to investigate the alterations in thoracic aortic vasomotor function in rats with chronic heart failure (CHF) post myocardial infarction (MI), and then explored the possible mechanism of pathological changes. Male Sprague-Dawley rats were divided into sham and CHF groups randomly. The CHF model group of rats was generated by ligating the left anterior descending artery. In sham-operated rats the ligation was placed but not tightened. A total of 20 rats underwent either sham-operated (n=8) or surgery for MI (n=12). All sham-operated rats survived the surgical procedure and the post-surgical period, whereas total mortality among MI-rats was 25% (3 out of 12). Only MI-rats with infarct-size >30% of the left ventricle (LV) were included for analysis (8 out of 9). Ten weeks after surgery, rats were anaesthetized for hemodynamic measurements, which contains systolic pressure, diastolic pressure, left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), LV+dp/dt(max) and LV-dp/dt(max). After that hearts were rapidly excised and weighed. Myocardial infarct size was determined by triphenyltetrazolium chloride (TTC) staining method. Isolated thoracic artery ring preparations were studied in a wire-myograph. The arterial constrictive responses to KCl, CaCl2, phenylephrine (PE), and caffeine and the arterial diastolic responses to acetylcholine (ACh) were recorded by the Multi Myograph System. To explore the possible mechanism, nitric oxide synthase (NOS) inhibitor N-nitrl-L-arginine methylester (L-NAME) and non-selective cyclooxygenase (COX) inhibitor indomethacin (Indo) were used. The results obtained were as follows: (1) CHF group showed an increased contraction response to KCl (5-100 mmol/L) and PE (1x10(-8)-3x10(-4) mol/L), and a reduced endothelium-dependent relaxation response to ACh (1x10(-12)-1x10(-4) mol/L) compared with those observed in sham group (P<0.01, P<0.05); (2) In the presence of L-NAME (1 mmol/L), the endothelium-dependent cumulative contractions to ACh (1x10(-7)-1x 10(-4) mol/L) was significantly enhanced in CHF group (P<0.05), and this effect was reversed by pretreatment with Indo (10 mumol/L); (3) In CHF group, the vessels incubated with Indo (10 mumol/L) showed an increased vasodilation induced by ACh (1x10(-12)-1x10(-4) mol/L) (P<0.05); (4) In the Ca(2+)-free K-H solution, calcium-dependent contraction curves induced by CaCl2 (1x10(-4)-3x10(-2) mol/L) in CHF group significantly shifted to the left compared with sham group (P<0.05); while the vascular contraction induced by caffeine (30 mmol/L) had no significant changes. These findings suggest that thoracic arteries of rats with CHF have endothelial dysfunction, and the contribution of endothelial dilation and contraction was significantly altered in CHF rats. The mechanism could be partly associated with the increased endothelium-dependent contracting factors by COX pathway, or the increased extracellular Ca(2+) influx through voltage-operated channels, thus leading to elevated vasoconstriction.

Immune tolerance induction in a severe hemophilia A patient with inhibitor / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the immune tolerance induction (ITI) in a severe hemophilia A patient with inhibitor, and to improve the therapeutic efficacy for patient.</p><p><b>METHODS</b>The FVIII:C was assayed by one-stage method and FVIII antibody by Bethesda method. Mutation screening of FVIII gene intron 22 inversion was performed using LD-PCR.</p><p><b>RESULTS</b>FVIII gene intron 22 inversion was detected in this patient. Clinical tolerance to FVIII was successfully induced after administration of the ITI regimen combined with immunosuppression. A fall of inhibitor titer from 8 BU to 0 BU after treatment for 3 months, and in vivo FVIII recovery (> 66%) was normalized. The patient had no bleeding episode in the following 6 months.</p><p><b>CONCLUSION</b>This is the first case report on successful immune tolerance induction therapy in Chinese hemophilia A patient. ITI is the most effective therapy for hemophilia A with inhibitor.</p>

Identification of genes that are differentially expressed in omental fat of normal weight subjects, obese subjects and obese diabetic patients / 中国应用生理学杂志

<p><b>AIM</b>To identify genes that are differentially expressed in omental fat of normal weight subjects, obese subjects and obese type 2 diabetic patients.</p><p><b>METHODS</b>Using a home-made high-density cDNA microarray, we compared gene expression profile of omental fat from normal weigh subjects, obese subjects and obese type 2 diabetic patients, to identify adipose-specific genes associated with obesity and diabetes.</p><p><b>RESULTS</b>119 and 257 genes were up-regulated in obese patients and obese diabetic patients respectively, while 46 and 58 genes were down-regulated in obese patients and obese diabetic patients respectively. 77 genes, including metabolism related genes (PDK4), and caveolin 2, metallo thionein 1B, were up-regulated in both obese and obese diabetic patients, while 8 genes, including key enzymes in lipid synthesis, such as HMG-CoA synthase, fatty acid synthase and stearoyl-CoA desaturase, were down-regulated in both groups. Another interesting finding was that tyrosine-3-monooxygenase/ tryptophan 5-monooxygenase activation protein theta (YWHAZ), a negative regulator for insulin signal transduction, was up-regulated only in obese diabetic patient, but not in normal-glycemic obese subjects.</p><p><b>CONCLUSION</b>Our study demonstrated that decrease of lipogenesis along with increase of fatty acids oxidation of adipose tissue could be a common cause of insulin resistance in obesity and type 2 diabetes, while functional changes of other genes, such as immune regulation genes,might also be involved in the pathogenesis of obesity and type 2 diabetes. Block of insulin signal transduction might trigger the transition from obesity to diabetes. Further exploration of these genes will greatly help us in the understanding of the pathogenesis of obesity and type 2 diabetes.</p>

Effects of hyperglycemia on proliferation,secretion function and expression of endoplasmic reticulum stress related molecules of pancreatic ? cell line / 上海第二医科大学学报

Objective To investigate the effects of chronic hyperglycemia on the proliferation,secretion function and expression of endoplasmic reticulum stress(ERS) related molecules in pancreatic ? cell line MIN6. Methods MIN6 cells were treated with different concentrations of glucose(5.6,25 and 33.3mmol/L) and were harvested at indicated time(24h and 96h) for examinations.Cell proliferation was tested using CCK-8 solution,insulin and proinsulin secretion function was determined by ELISA,and mRNA expression of ERS related molecules(Total XBP-1,Spliced XBP-1) and protein expression of phosphorylated IRE1? were detected by Real-time PCR and Western blotting,respectively. Results After treatment with hyperglycemia for 96h, cell proliferation was significantly lower than that treated for 24h(P