Diagnosis, Differential ; Humans ; Medicine, Chinese Traditional

In the last twenty years, using all-trans retinoic acid (ATRA) as a differentiation inducer, Shanghai Institute of Hematology has achieved an important breakthrough in the treatment of acute promyelocytic leukemia (APL), which realized the theory of reversing phenotype of cells and provided a successful model of differentiation therapy in cancers. Our group first discovered in the world the variant chromosome translocation t(11;17)(q23;q21) of APL, and cloned the PML-RAR alpha, PLZF-RAR alpha and NPM-RAR alpha fusion genes corresponding to the characterized chromosome translocations t(15;17); t(11;17) and t(5;17) in APL. Moreover, establishment of transgenic mice model of APL proved their effects on leukemogenesis. The ability of ATRA to modify the recruitment of nuclear receptor co-repressor with PML-RAR alpha but not PLZF-RAR alpha caused by the variant chromosome translocation elucidated the therapeutic mechanism of ATRA from the molecular level and provides new insight into transcription-modulating therapy. Since 1994, our group has successfully applied arsenic trioxide (As(2)O(3)) in treating relapsed APL patients, with the complete remission rate of 70% - 80%. The molecular mechanism study revealed that As(2)O(3) exerts a dose-dependent dual effect on APL. Low-dose As(2)O(3) induced partial differentiation of APL cells, while the higher dose induced apoptosis. As(2)O(3) binds ubiquitin like SUMO-1 through the lysine 160 of PML, resulting in the degradation of PML-RAR alpha. Taken together, ATRA and As(2)O(3) target the transcription factor PML-RAR alpha, the former by retinoic acid receptor and the latter by PML sumolization, both induce PML-RAR alpha degradation and APL cells differentiation and apoptosis. Because of the different acting pathways, ATRA and As(2)O(3) have no cross-resistance and can be used as combination therapy. Clinical trial in newly diagnosed APL patients showed that ATRA/As(2)O(3) in combination yields a longer disease-free survival time. With the median survival of 18 months, none of the 20 cases in combination treatment relapsed, whereas 7 relapsed in 37 cases in mono-treatment. This is the best clinical effect achieved in treating adult acute leukemia to this day, possibly making APL the first adult curable leukemia. Based on the great success of the pathogenetic gene target therapy in APL, this strategy may extend to other leukemias. Combination of Gleevec and arsenic agents in treating chronic myeloid leukemia has already make a figure both in clinical and laboratory research, aiming at counteracting the abnormal tyrosine kinase activity of ABL and the degradating BCR-ABL fusion protein. In acute myeloid leukemia M(2b), using new target therapy degradating AML1-ETO fusion protein and reducing the abnormal tyrosine kinase activity of c-kit will also lead to new therapeutic management in acute leukemias.
Antineoplastic Agents ; therapeutic use ; Benzamides ; Fusion Proteins, bcr-abl ; genetics ; metabolism ; Humans ; Imatinib Mesylate ; Leukemia, Promyelocytic, Acute ; drug therapy ; genetics ; metabolism ; Oncogene Proteins, Fusion ; genetics ; metabolism ; Piperazines ; therapeutic use ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; metabolism ; Pyrimidines ; therapeutic use ; Receptors, Retinoic Acid ; genetics ; metabolism ; Tretinoin ; therapeutic use

This article summarizes the progress of hematology in the recent tens years to show that experimental hematology used to pick up the 'hints' from clinical problems as the renewal of research directions and targets in experimental studies continuously. As the feedback, the results from lab investigations inserted into clinical practice and eventually made a quick modernization of hematology, which was actually a good model for the "translational research". The past few decades have witnessed tremendous advances in our understanding of normal hematopoiesis where genes dictate, epigenetics regulate, transcription factors mediate, and stem cells self-renew and differentiate. Dissection of disease pathogenesis not only elucidates molecular basis of disorders including hemoglobinopathy, aplastic anemia, hemophilia, hematopoietic malignancies such as leukemia and myeloproliferative disorders, but also provides therapeutic targets for drug development. Introduction of targeted therapies and combinatory targeting therapies greatly benefits hundreds of thousands of patients, and even turns acute promyelocytic leukemia from highly fatal to highly curable. In the 21st century the experimental hematology is entering the era of genomics and system biomedicine, and the pace of progress extrapolates to a prediction of hematologic neoplasms control in this century.
Animals ; Clinical Laboratory Techniques ; trends ; Hematologic Diseases ; genetics ; metabolism ; physiopathology ; Hematologic Neoplasms ; genetics ; metabolism ; physiopathology ; Hematology ; trends ; Humans

Objective To study the operative strategy of congenital atlantoaxial dislocation(CAAD)-induced Chiari malformation and (or) syringomyelia. Methods The operation in reported 23cases of CAAD-induced Chiari malformation and (or) syringomyelia was composed with the transoral resection of odontoid process to achieve anterior decompression at first stage and occipito-cervical bone grafting fusion at second stage. Results MRI examination revealed the tonsils ascent and (or) syrinx reduction in 19 cases after first-stage operation. Compared with their preoperative manifestations, 14cases were obviously improved and 5 improved to some extent after operation, while 4 were unchanged. Conclusions CAAD is the main cause of tonsils descent and (or) syringomyelia in the series of patients. After anterior decompression by transoral resection of odontoid process, most patients will get recovered in tonsils descent and (or) syringomyelia reduction. The main aim of posterior operation is to reconstruct the stability of craniovertebral junction.

OBJECTIVETo evaluate the clinical effects of iliolumbar fixation for the sacrum fractures of Denis type II.

METHODSThe clinical data of 86 patients with sacrum fracture of Denis type II treated by iliolumbar fixation from January 2008 to January 2012 were retrospectively analyzed. There were 55 males and 31 females, aged from 17 to 55 years old with an average of 39.1 years. Among them, 73 cases complicated with pelvis fracture and 13 cases with acetabular fracture; 37 cases with sacral neurological symptoms and 49 cases without sacral neurological symptoms. Fracture healing time, nerve function, clinical function and complications were observed in the patients.

RESULTSIn 86 cases, 6 cases were out of followed-up and 80 cases were followed up from 24 to 71 months with an average of 36 months. The mean fracture healing time was 13 weeks (ranged, 10 to 38 weeks). According to Gibbons scoring to evaluate the neurological function, preoperative nerve rehabilitation, lower limbs feeling, lower limbs activity,bladder and rectum function,total score respectively were 0.62 +/- 0.04, 1.54 +/- 0.35, 1.12 +/- 0.18, 0.23 +/- 0.01, 3.46 +/- 0.47 and postoperative respectively were 0.82 +/- 0.12, 0.36 +/- 0.04, 0.05 +/- 0.01, 0.03 +/- 0.01, 1.25 +/- 0.22, there were statistically significant differences between preoperative and postoperative (P < 0.05). According to Majeed scoring to evaluate the clinical function, postoperative pain, standing, sitting, sexual life, work ability, total score respectively were 22.54 +/- 4.02, 27.93 +/- 5.46, 8.47 +/- 3.61, 2.54 +/- 1.33, 16.46 +/- 4.34, 81.32 +/- 8.73, 60 cases got excellent results, 17 good, 3 fair. The main complications including fracture nonunion of 5 cases,deep incision infection of 1 case, and screw prominence resulting uncomfortable of 8 cases.

CONCLUSIONIliolumbar fixation has the advantages of stable fixation, satisfactory functional rehabilitation, less complications, and is a good method in treating sacrum fracture of Denis type II.

Adolescent ; Adult ; Bone Screws ; Female ; Fracture Fixation, Internal ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Sacrum ; injuries ; surgery ; Spinal Fractures ; surgery ; Treatment Outcome ; Young Adult

Objective To explore the morphological changes of the atlantoaxial facet joint and the three-dimensional characteristics of joint dislocation in patients with atlanto-occipital assimilation accompanied by atlantoaxial dislocation. Methods Thirty-six patients with atlanto-occipital assimilation and concurrent atlantoaxial dislocation underwent spiral CT scanning of the craniovertebral junction, and the imaging data in DICOM format were transferred to the three-dimensional visualization workstation to construct the three-dimensional model of the craniovertebral junction. The characteristics of atlantoaxial dislocation in association with the bony malformation were studied in the reconstructed model. Results Multiple anomalies of the atlantoaxiai facet joint were found in these patients, including joint dislocation involving 57 sides in the 36 patients, skeletal deformity in 61 sides, and facet separation in 11 sides. Three-dimensional classification identified 3 types of atlantoaxial dislocation in these patients, namely symmetrical type (14 cases, 39%) representing the approximately symmetrical joint dislocation and/or skeletal distortion, rotational type (13 cases, 36%) representing apparently asymmetrical joint dislocation and/or skeletal deformity, and separate type (9 cases, 25%) with separation of the joint facets. Conclusion In patients with atlanto-occipital assimilation, multiple factors including developmental anomaly, secondary skeletal deformity and ligament extension and fatigue interact as the fundamental causes ofatlantoaxial dislocation. The CT-based three-dimensional model of the craniovertebrai junction allows visualization of the atlantoaxial facet joint and atlantoaxial dislocation to provide important evidence for surgical planning and decision on the internal fixation approaches.

BACKGROUNDA nonsteroidal anti-inflammatory drug, indomethacin, has been shown to have anti-leukemic activity and induce leukemic cell apoptosis. This study was to elucidate the mechanism of indomethacin-induced K562 cell apoptosis.

METHODSK562 cells were grown in RPMI 1640 medium and treated with different doses of indomethacin (0 micromol/L, 100 micromol/L, 200 micromol/L, 400 micromol/L, 800 micromol/L) for 72 hours. The cells were harvested, and cell viability or apoptosis was analyzed using MTT assay and AO/EB stain, combining laser scanning confocal microscopy (LSCM) technique separately. For the localization and distribution of intracellular caspase-3 or caspase-8 protein, immunofluorescence assay was carried out. To reveal the activation of caspase-3 or caspase-8 in indomethacin-treated cells, Western blot detection was used. The change in intracellular free calcium was determined by Fluo-3/Am probe labeling combined with LSCM.

RESULTSIndomethacin could lead to K562 cell apoptosis and inhibit cell viability in a concentration-dependent manner. An increased expression of intracellular caspase-3 or caspase-8 was observed at higher doses of indomethacin (400 - 800 micromol/L). Western blot results showed upregulation and activation in both caspase-3 and caspase-8 protein. Under indomethacin intervention, the levels of intracellular free calcium showed a significant increase. Blocking the activity of cyclooxygenase did not abolish the effects of indomethacin on K562 cell apoptosis.

CONCLUSIONSActivation and upregulation of caspase-3 or caspase-8 protein were responsible for Indomethacin-induced K562 cell apoptosis. Variation of intracellular free calcium might switch on the apoptotic pathway and the proapoptotic effect of indomethacin might be cyclooxygenase-independent.

Apoptosis ; drug effects ; Calcium ; metabolism ; Caspase 3 ; Caspase 8 ; Caspases ; genetics ; metabolism ; Cyclooxygenase Inhibitors ; pharmacology ; Enzyme Activation ; Gene Expression Regulation, Enzymologic ; drug effects ; Humans ; Indomethacin ; pharmacology ; K562 Cells

OBJECTIVETo seek a rapid, simple, but effective inquiry method for screening high risk population challenged by schistosomiasis.

METHODSTwo embankment collapsed villages were selected in schistosomiasis epidemic area in Dongting Lake. Information on water exposure was collected through a retrospective study. Data was analyzed by stepwise discriminant analysis.

RESULTSA Fisher's function was established by stepwise discriminant analysis which including 5 variables out of 18. Two hundred and forty-six individuals were discriminated by the function with accuracy, sensitivity and specificity of predicting their current infection status with the results of 87.4%, 84.1% and 89.0% respectively.

CONCLUSIONThe inquiry method might serve as simple, rapid, economic and effective tool for diagnosis in screening high risk population challenged by schistosomiasis in lake communities.

Adult ; China ; epidemiology ; Disasters ; Discriminant Analysis ; Female ; Humans ; Male ; Mass Screening ; methods ; Multivariate Analysis ; Retrospective Studies ; Risk Assessment ; Rural Health ; Sampling Studies ; Schistosomiasis japonica ; epidemiology ; prevention & control ; Sensitivity and Specificity ; Surveys and Questionnaires

OBJECTIVETo summarize the curative effect of surgically treated large or giant cavernous sinus hemangiomas (CSH) via epidural approach.

METHODSFrom June 1999 to June 2011, 19 cases of CSH including 15 female and 4 male patients, ranging from 26 to 70 years (mean 45.3 years) were retrospectively reviewed. Ptosis/ocular motility disorders (10 cases), headache/ophthalmalgia (7 cases), decreased visual acuity (7 cases) and facial hyperesthesia (4 cases) were the most common presenting complaints. The epidural approach was taken and the tumor dissection was performed at the interval between trochlear nerve and ophthalmic nerve and the interval between ophthalmic nerve and maxillary nerve. The curative effect was followed up regularly.

RESULTSGross total resection was attained in 13 cases, near-total resection in 4 cases, subtotal resection in 1 case and partial resection in 1 case. The follow-up period was between 6-144 months (mean 41.5 months). The results of last follow-up were as follows: among the 10 patients with ptosis/ocular motility disorders, complete remission was achieved in 5, improvement in 2, no change in 2 and lost follow-up in 1. Facial hypoesthesia symptom got complete remission in 2 patients and partial remission in the other 2 patients. The other symptoms mentioned above were all relieved. One patient got complication with impairment of vision and ocular motility disorders.

CONCLUSIONSCombined with skilled skull base techniques, surgical treatment of large or giant CSH via epidural approach is an effective method and the preservation of cranial nerves could be attained to an acceptable level.

Adult ; Aged ; Cavernous Sinus ; pathology ; Female ; Follow-Up Studies ; Hemangioma ; surgery ; Humans ; Male ; Middle Aged ; Neurosurgical Procedures ; methods ; Retrospective Studies ; Treatment Outcome

OBJECTIVESTo analyze the clinical characteristics of the atlantoaxial dislocation (AAD) in craniovertebral junction (CVJ) abnormalities and to study the setup of its surgery strategy.

METHODSFrom April 2009 to November 2011, 56 patients of AAD and CVJ abnormalities including 22 male and 34 female patients who had received surgery were analyzed. There were 2 cases of reducible AAD and 54 cases of irreducible AAD. The age of the patients ranged from 9 to 56 years (mean 34 years). Among them, 14 cases achieved reduction/partial reduction via direct posterior fixation, 41 cases had transoral anterior deconpression and occipito-cervical/C₁-C₂ fusion and 1 case had the posterior odontoidectomy and spinal fusion.

RESULTSFifty-three cases had a follow-up between 6 months and 36 months (mean 20 months) and 3 cases lost follow-up (had improvement at discharge). Seven cases had complications as follows: 1 case had irreversible spinal cord injury and muscle weakness of extremities, 2 cases had cerebrospinal leak, 2 cases had pulmonary infection, 1 case had local granuloma hyperplasia and 1 case had delayed healing of the incision. The later 6 cases all got recovery after reasonable treatments. The grades of Nurick at last follow-up were as follows: 6 cases (11.3%) improved by 3 grades, 30 cases (56.6%) improved by 2 grades, 13 cases (24.5%) improved by 1 grade, 3 cases (5.7%) without change, 1 case (1.9%) get worse.

CONCLUSIONSReducible AAD could achieve direct reduction and fixation via posterior pathways. Irreducible AAD needs individualized treatment. To choose the direct reduction and fixation or transoral odontoidectomy and posterior fixation and fusion should consider the pathogenetic condition, the image data and personal clinical experience.

Adolescent ; Adult ; Atlanto-Axial Joint ; surgery ; Child ; Decompression, Surgical ; Female ; Humans ; Joint Dislocations ; surgery ; Male ; Middle Aged ; Postoperative Complications ; epidemiology ; Spinal Fusion ; methods ; Young Adult