Evolvement of a five-way translocation t(5;9;22;6;17) from a four-way Philadelphia translocation t(5;9;22;6) in a rare case of chronic myeloid leukemia / 中华医学遗传学杂志

OBJECTIVE@#To trace a rare case of chronic myeloid leukemia (CML) with a four-way Philadelphia chromosome variant by cytogenetic analysis in order to provide a basis for the selection of treatment.@*METHODS@#Bone marrow morphology, chromosomal karyotyping, fluorescence in situ hybridization (FISH) and real-time quantitative PCR (RQ-PCR) were used for the diagnosis and staging of the disease. Point mutations in the tyrosine kinase domain of ABL1 gene were detected by Sanger sequencing.@*RESULTS@#The patient was initially diagnosed as CML in chronic phase (CML-CP) with a chromosomal karyotype of 46,XX,t(5;9;22;6)(q13;q34;q11;q25), while FISH revealed presence of a variant Philadelphia chromosome translocation. Clonal evolution has occurred after 38 months of tyrosine kinase inhibitor (TKI) treatment, when cytogenetic analysis revealed coexisting t(5;9;22;6)(q13;q34;q11;q25) and t(5;9;22;6;17)(q13;q34;q11;q25;q11). After 57 months of TKIs treatment, only the t(5;9;22;6;17) clone was detected. Three months later, hyperdiploidy with additional abnormalities were detected in addition to t(5;9;22;6;17). Three mutations, including p.Tyr253Phe, p.Thr315Ile and p.Gly250Glu, were identified in the tyrosine kinase domain of the ABL1 gene during the course of disease. The patient did not attain cytogenetic and molecular response to TKIs.@*CONCLUSION@#The four-way variant translocation may be genetically unstable. Clonal evolution and genetic mutations are likely to occur during TKIs treatment, resulting in poor response to drug therapy. This observation, however, needs to be confirmed by large-scale studies.

Application of CD138 Immunomagnetic Sorting Myeloma Cells Combined with Fluorescence in Situ Hybridization for Detecting Cytogenetic Abnormalities of Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficiency of direct fluorescence in situ hybridization (D-FISH) versus FISH on CD138 immunomagnetic sorting myeloma cells (MACS-FISH) to detect the cytogenetic abnormalities of multiple myeloma.</p><p><b>METHODS</b>Thirty-one patients with multiple myeloma (MM) were detected by D-FISH and MACS-FISH, using 5 probes, including 1q21, D13S319, RB1, IgH, P53. The IgH rearrangement positive patients were further examined by 3 IgH rearrangement subtype FISH probes including IgH/FGFR3, IgH/MAF and IgH/CCND1.</p><p><b>RESULTS</b>Metaphase karyotyping revealed cytogenetic abnormalities in 5 cases (16.1%), clonal aberrations were detected in 13 cases(41.9%) by D-FISH, while 25 case(80.6%) with clonal aberrations by MACS-FISH. The results between these 2 FISH methods were significantly different (P=0.042). The detection frequency of clonal aberration by each probes of D-FISH was 22.6%,25.8%,29%,38.7% and 9.7% respectively for 1q21 amplification, D13S319 deletion,RB1 deletion, IgH rearrangement and P53 deletion, compared with 48.4%,45.2%,48.4%,67.7% and 16.1% respectively by MACS-FISH. The 2 FISH methods were well consistent when the percentage of plasma cells was ≥20% in bone marrow smears. When the percentage of plasma cells was<20% in bone marrow smears, the difference between these 2 methods was very statistically significant (P=0.00).</p><p><b>CONCLUSION</b>MACS-FISH can obviously improve the detection efficiency of cytogenetic abnormalities in patients with MM. Conventional cytogenetics combined with MACS-FISH is an ideal efficient method to detect the cytogenetic abnormalities in MM patients, and should be applied widely, especially for those patients with the plasma cells <20% in bone marrow smears.</p>

Voltage sensitive optical mapping used to observe effects of late Na and rapidly activating delayed rectifier K currents on the right and left ventricular electrophysiological heterogeneity / 西安交通大学学报(医学版)

ABSTRACT:Objective To observe the effects of late Na current (INa‐L ) and rapidly activating delayed rectifier K current (IKr ) on ventricular heterogeneity and frequency dependency by using high resolution voltage sensitive optical mapping technology .Methods The model of 12 isolated hearts was constructed in rabbits . Voltage sensitive dye Di‐4‐ANEPPS were perfused into the isolated hearts by Langendorff method .LED source with the wave length of 532 nm was used to record APD80 and APD50 of the left and right ventricles .Experimental groups were divided into 3 groups by perfusion drugs dofetillide (30 nmol/L) ,dofetillide+ATX‐Ⅱ(1 nmol/L) ,and dofetillide +ATX‐Ⅱ +mexiletine (10μmol/L) .The subjects were intervened by the above drugs in order ,and they were self‐compared before dosing .After each drug administration ,the hearts were stimulated respectively with the BCL of 2 000 ms ,1 000 ms ,500 ms ,and 300 ms .Then we observed the changes of APD80 and APD50 in the left and right ventricles before and after the interventions .Results ① In the control group ,APD80 and APD50 of the right ventricle were longer than those of the left ventricle in response to different stimulation , and the differences increased with the decrease of stimulating frequency .② When BCL was 1000 ms ,APD80 and APD50 of the left and right ventricles were prolonged respectively after administration of dofetillide , but the differences in APD80 and APD50 were insignificant between the left and right ventricles (P>0 .05) .ΔAPD80 of the two ventricles increased significantly with the decrease of stimulating frequency . ③ After administration of ATX‐Ⅱ , when BCL was 1000 ms ,APD80 and APD50 of the left and right ventricles increased significantly compared with those in the control group and dofetillide intervention group (P0 .05) .The increase of ΔAPD80 of the two ventricles became milder when the stimulating frequency decreased . Conclusion ① IKr blocked by dofetillide did not affect the heterogeneity between the two ventricles , which showed reverse‐frequency dependence . ② In the context of blocking IKr , ATX‐Ⅱ increased the heterogeneity between the left and right ventricles and enhanced the reverse‐frequency dependence .In contrast ,mexiletine ,the blocker of INa‐L ,decreased the heterogeneity between the two ventricles and reverse‐frequency dependence .

Effects of high extracellular K[+] in atrium on pacemaker activity of sinoatrial node

Sinoatrial node [SAN] plays a significant role in rhythmic firing in hearts. Little is known about the pacemaker activity of SAN when the extracellular K[+] concentration [K[+]][o] is accumulated in the atrium at the tissue level. In this paper, a gradient model of the intact SAN and its surrounding atrial muscle was developed by considering details of the SAN heterogeneous electrophysiology. The operator splitting method was used to solve the computer model. A factor k was introduced to [K[+]][o] of the atrial cell to simulate the accumulation of [K[+]][o]. The results showed that with the elevation of [K[+]][o] in the atrium, the maximum diastolic depolarization of the peripheral SANCs became less negative while their action potential amplitude became smaller than that of the control condition, but little effect was found on the central SANCs. The conduction block occurred in the atrium after [K[+]][o] was elevated to greater than 2.5 times of its control condition. The larger the [K[+]][o] was, the earlier the conduction block occurred. The elevation of [K[+]][o] in the atrium shifted the leading pacemaker site from the center to the periphery, together with a slightly increased sinus rate. Coupling conductance within the SAN had effects on the excitation propagation in the high [K[+]][o] setting. For a same [K[+]][o], the more the conductance was enhanced, the shorter the excitation propagated away from the center. In conclusion, the high [K[+]][o] in the atrium was shown to modulate the pacemaker activity of SAN and impair its ability to pace and drive the atrium

Testosterone-induced spermatogenic impairment is associated with looser arrangement of spermatogenic cells in rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To determine whether testosterone-induced intra-testicular testosterone withdrawal and therefore spermatogenic impairment is associated with looser arrangement of spermatogenic cells in rats.</p><p><b>METHODS</b>Adult male SD rats received intramuscular injection of testosterone undecanoate at 19 mg/(kg x 15 d) for 130 days, and then testicular tissue blocks were obtained for the preparation of methacrylate resin-embedded sections and observation of the changes in testicular histology.</p><p><b>RESULTS</b>Apart from such changes as impaired spermiogenesis and spermiation, apparently looser arrangement of spermatogenic cells was seen in 11.5% of the seminiferous tubule profiles, with radial cracks (empty spaces) running towards the tubule lumen being formed between lines, bundles or groups of spermatogenic cells (mainly spermatids and spermatocytes).</p><p><b>CONCLUSION</b>Looser arrangement of spermatogenic cells is one of the key histological changes resulting from intra-testicular testosterone withdrawal in rats.</p>

Study on the activity--heart rate prediction system for motion sensed rate responsive pacemakers / 中国医疗器械杂志

Focusing on the heart rate control mode of acceleration sensor based rate responsive pacemakers, this paper implemented the design of activity--heart rate prediction system. Bluetooth module was used as communication means in activity--heart rate prediction system, and the slave computer was used to complete the acceleration signal acquisition and processing, map from acceleration signal to the pacing rate signal, and achieve real-time transmission of acceleration signal and heart rate signal. The master computer fulfilled real-time display and recording of acceleration signal and heart rate signal, moreover, it achieved control function to the slave computer algorithm through classification of 6 parameters. The results of verification experiment showed that there was a significant relation between mapping heart rate and actual heart rate using linear mapping algorithm (R2 = 0.787, P < 0.001).

Cultivation and karyotype analysis of the human embryonic stem cells HUES4 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To establish a protocol for culturing of human embryonic stem cells (HUES4) without any animal-derived feeder cells and to investigate the karyotype stabilities of HUES4 cells after long-term cultivation.</p><p><b>METHODS</b>HUES4 cells were cultured on mitomycin C treated MEFs or human foreskin fibroblast feeder cells. The pluripotency of the ES cells was analyzed by immunocytochemistry staining to detect the expression of pluripotent marker, karyotype of the ES cells at passage 27, 34, 41, 44 and short tandem repeat (STR) at passage 27 were analyzed.</p><p><b>RESULTS</b>The HUES4 cells cultured on human feeder cells were positive for alkaline phosphatase activity, SSEA-4, TRA-1-60 and TRA-1-81 staining, but negative for SSEA-1. Analysis of karyotype at different passages suggested an abnormal karyotype 46, XY, t(9;15)(q22;q26) mosaicism occurred in HUES4, and the ratios of abnormal increased with passage.</p><p><b>CONCLUSION</b>HUES4 could be cultured without animal-derived feeder cells and the incidence of abnormal karyotype might be increased with long-term culture.</p>

Histological changes of the testis and epididymis in adult rats as a result of Leydig cell destruction after ethane dimethane sulfonate treatment: a morphometric study / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To quantitatively study the histological changes of the testis and epididymis as a result of a drastic reduction of testosterone secretion.</p><p><b>METHODS</b>Fourteen adult Sprague-Dawley rats were injected intraperitoneally with ethane dimethane sulfonate (EDS, 75 mg/kg) and the same number of animals were injected with normal saline as a control. At days 7 and 12 (after treatment), respectively, half of the animals from each group were killed. The testes and epididymides were removed and tissue blocks embedded in methacrylate resin. The cell number per testis was estimated using the stereological optical disector and some other parameters were obtained using other morphometric methods.</p><p><b>RESULTS</b>The EDS treatment resulted in an almost complete elimination of Leydig cells but had no effect on the numbers of Sertoli cells per testis. At day 7 after EDS treatment, many elongated spermatids were retained in the seminiferous epithelium and many round spermatids could be seen in the epididymal ducts. At day 12, a looser arrangement of spermatids and spermatocytes became evident, with apparent narrow empty spaces being formed between germ cells in an approximately radial direction towards the tubule lumen; the numbers (per testis) of non-type B spermatogonia and spermatocytes were similar to controls, whereas that of type B spermatogonia increased by 59%, and that of early round, elongating and late elongated spermatids decreased by 37%, 72% and 52%, respectively.</p><p><b>CONCLUSION</b>The primary spermatogenic lesions following EDS administration were (i) spermiation failure and (ii) detachment of spermatids and spermatocytes associated with impairment in spermiogenesis and meiosis.</p>

Ethic Consideration on the Responsibility of the Scientific Research Morality of Medical Students / 中国医学伦理学

There are many medical students who make artificial data in their scientific research and scientific paper.Therefore,it's very urgent to carry on the ethical education of scientific research to medical students.This article tries to make some ethical discussion on the responsibility of the scientific research monality of medical students.