OBJECTIVETo explore the clinical efficacy and toxicity of CLAT protocol (cladribine, cytarabine and topotecan) for treating patients with refractory acute myeloid leukemia (R-AML).

METHODSA total of 18 patients with R-AML (median age 37 years, range 18 to 58 years; male n = 16, female n = 2) were treated with CLAT protocol, which consisted of cladribine 5 mg/m(2)/d, i.v. on days 1-5, cytarabine 1.5 g/m(2)/d, i.v. on days 1-5, topotecan 1.25 mg/m(2)/d, i.v. on days 1-5 and G-CSF 300 µg/d subcutaneous injection on day 6 until neutrophile granulocyte recovery.

RESULTSOut of 18 patients 2 died of severe infection before the assessment. Among 16 evaluated patients, 10 (55.6%) achieved complete remission (CR), and 2 (11.1%) achieved partial remission (PR), the overall response rate was 66.7%, the rest 4 patients did not respond (NR). The median overall survival time and DFS for the CR patients was 9.5 months (95%CI: 6.7-16.64) and 9.5 months (95%CI: 6.1-16.7) respectively. The 1 year OS and DFS rates were 45% and 46.9%, respectively. All patients developed grade 4 of granulocytopenia and thrombocytopenia, the median duration was 13 (range 2 to 21) days and 12 days (range 2 to 21), respectively, all patients developed infection, 2 patients died of severe infection. The most common non-hematological side effects included nausea, vomiting, diarrhoea, rash, aminotransferase or bilirubin elevation and were grade 1 to 2.

CONCLUSIONThe CLAT protocol seems to have promising for the treatment of refractory AML patients, and patients well tolerated. This CLAT protocol offers an alternative treatment for R-AML patients who received severe intensive treatment, especially with anthracycline-containing chemotherapy.

Adolescent ; Adult ; Agranulocytosis ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cladribine ; therapeutic use ; Cytarabine ; therapeutic use ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Remission Induction ; Thrombocytopenia ; Topotecan ; therapeutic use ; Young Adult

OBJECTIVETo investigate the protective effect and mechanism of Shenqi Compound on diabetic angiopathy modeled rats.

METHODSTotally 18 SD rats were randomized into 3 groups, i.e., the normal control group, the diabetic mellitus (DM) group, and Shenqi Compound group, 6 in each group. The DM rat model was established by feeding high-fat diet (to induce hyperlipidemia) +intraperitoneal injection of small dose streptozotocin (STZ). Shenqi Compound was given to rats in the Shenqi Compound group at the daily dose of 2 g/kg. Equal volume of normal saline was given to rats in the model group and the normal control group by gastrogavage. All treatment was lasted for 12 weeks. Then 2-D and ultrasonic integrated backscatter technique were used to evaluate structural and functional changes of abdominal aorta in the progression of diabetic macroangiopathy. The fibrosis degree of the aorta vessel and myocardium capillaries were observed by using HE and Masson trichrome staining. The tension of the aortic vascular ring was determined. The transforming growth factor beta (TGF-beta) mRNA expression was detected by real time PCR (RT-PCR). The protein expression of TGF-beta, collagen I, collagen III, connective tissue growth factor (CTGF), and phosphorylation P38 MAPK were detected by Western blot.

RESULTSCompared with the normal control group, abdominal aortic systolic inner diameter, diastolic inner diameter, Peterson elastic modulus, stiffness index, and backscatter integral significantly increased; the rangeability of integral backscatter and the extension coefficient of cross section significantly decreased in the DM group (all P < 0.05). After 12 weeks aforesaid indices were obviously improved in the Shenqi Compound group (P < 0.05). Results of HE and Masson staining showed that the fibrosis degree of the aorta vessel and myocardium capillaries was obviously alleviated in rats of the Shenqi Compound group (P < 0.05). Results of the aortic vascular ring tension showed that acetylcholine induced vasodilatation and maximum diastolic percent were obviously elevated in the Shenqi Compound group (P < 0.05). Compared with the normal control group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all significantly increased in the DM group (P < 0.05). Compared with the DM group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all decreased (P < 0.05).

CONCLUSIONSShenqi Compound could effectively improve the arterial function in diabetic marcoangiopathy and microvascular dysfunction. The mechanism might be due to the down-regulating the expression of TGF-beta, and further suppressing the phosphorylation of P38 MAPK, reducing the synthesis of collagen I and collagen III, therefore, ameliorating arterial and myocardial interstitial fibrosis.

Animals ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetic Angiopathies ; prevention & control ; Drugs, Chinese Herbal ; pharmacology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo identify potential mutation in a Chinese family featuring X-linked alpha thalassemia/mental retardation syndrome (ATR-X).

METHODSBased on clinical symptoms and inheritance pattern, linkage analysis of X chromosome short tandem repeats (X-STR) loci was carried out to locate the candidate gene. Subsequently, sequences of exons and exon-intron boundaries of the candidate gene were amplified with polymerase chain reaction (PCR). Potential mutations were detected by direct DNA sequencing. All patients were also analyzed for the trait of thalassemia.

RESULTSLinkage analysis indicated the candidate gene to be ATRX. Subsequently, a homozygous missense mutation c.736C>T (p.R246C) was found in exon 9 of ATRX in all of the 3 patients. And a heterozygous mutation c.736C>T (p.R246C) was also identified in the patient's mother and grandmother. Similar mutations were not detected in other members of the family. Alpha thalassemia was detected in the proband and another patient, whose genotypes were determined as -α(3.7)/αα and --(sea)/αα, respectively.

CONCLUSIONMissense mutation of c.736C>T in ATRX gene is a mutation hotspot, and p.R246C may disturb the function of ATRX-DNMT3-DNMT3L domain (ADD), which may be responsible for the disease in this family.

Asian Continental Ancestry Group ; genetics ; Child, Preschool ; DNA Helicases ; genetics ; DNA Mutational Analysis ; methods ; Female ; Humans ; Male ; Mental Retardation, X-Linked ; genetics ; Mutation, Missense ; Nuclear Proteins ; genetics ; Pedigree ; X-linked Nuclear Protein ; alpha-Thalassemia ; genetics

OBJECTIVETo sum up the experience in administering oral tadalafil on alternate days for the treatment of erectile dysfunction (ED) that fails to respond to on-demand medication.

METHODSWe retrospectively analyzed the clinical data of 15 cases of ED treated with oral tadalafil on alternate days from September 2010 to March 2012. All the patients had failed to respond to on-demand medication of sildenafil previously.

RESULTSAfter 4 weeks of tadalafil treatment, 11 (73.3%) of the cases were remarkably improved, with significant difference in IIEF-5 scores before and after treatment (P < 0.05). Transient adverse reactions were observed in the other 4 cases, including mild headache in 2, slight backache in 1, and facial flush in 1.

CONCLUSIONOral tadalafil on alternate days is safe and effective in the treatment of ED that fails to respond to on-demand medication of sildenafil.

Administration, Oral ; Adult ; Carbolines ; administration & dosage ; therapeutic use ; Erectile Dysfunction ; drug therapy ; Humans ; Male ; Phosphodiesterase Inhibitors ; administration & dosage ; therapeutic use ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Retrospective Studies ; Sildenafil Citrate ; Sulfones ; therapeutic use ; Tadalafil ; Treatment Failure ; Treatment Outcome

Antimicrobial Cationic Peptides ; biosynthesis ; genetics ; DNA-Binding Proteins ; biosynthesis ; genetics ; Humans ; Microbial Sensitivity Tests ; Muramidase ; biosynthesis ; genetics ; Peptides, Cyclic ; biosynthesis ; genetics ; Pichia ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; isolation & purification

BACKGROUNDThe mortality of stroke patients is strongly affected by medical complications. However, there are limited data investigating the effect of in-hospital medical complications on the dependency of stroke patients worldwide. We prospectively and systematically investigated the effect of medical complications on dependency of patients at 3, 6 and 12 months after stroke using the China National Stroke Registry (CNSR).

METHODSThis prospective cohort study collected data of patients age > 18 years with acute ischemic stroke in 132 clinical centers distributed across 32 provinces and four municipalities (including Hong Kong region) of China, from September 2007 to August 2008. Data on medical complications, dependency and other information were obtained from paper-based registry forms. Medical complications associated with stroke outcomes were assessed using multivariable Logistic regression.

RESULTSOf 11 560 patients with acute ischemic stroke, 1826 (15.80%) presented with in-hospital medical complications. In-hospital medical complications were independent risk factors for dependency of patients at 3 months (adjusted odds ratio (OR) 2.367, 95% confidence interval (CI) 2.021 - 2.771), 6 months (adjusted OR 2.257, 95%CI 1.922 - 2.650), and 12 months (adjusted OR 1.820, 95%CI 1.538 - 2.154) after acute ischemic stroke.

CONCLUSIONThe results demonstrated that the short-term and long-term dependency of acute ischemic stroke patients is significantly associated with in-hospital medical complications in China.

Aged ; Brain Ischemia ; complications ; epidemiology ; China ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Registries ; statistics & numerical data ; Stroke ; complications ; epidemiology

BACKGROUNDIt is generally accepted that gliomas are the most common primary brain tumors with poor prognosis. We aimed to explore the relationship of the immunity of the central nervous system and the genesis and development of glioma.

METHODSG422 glioma was implanted in the brain of BALB/c mice (immuno-competent mice), nude mice (T cell related immuno-deficient) and complement C3 knock-out mice (complement C3 related immunodeficient). The survival time of the host, growth and histopathology of the tumor, and concentrations of tumor necrosis factor-α (TNF-α) and interferon-γ (INF-γ) in tumor tissues were assessed.

RESULTSTumor spheres were formed in all mice after injection, and glial fibrillary acidic protein (GFAP) positive staining of the cells declared their glioma origin. The longest median survival time of (44.3 ± 6.0) days was found in BALB/c mice, followed by (24.8 ± 5.2) days in nude mice and the shortest (18.6 ± 5.8) days in complement C3 knock-out mice. Accordingly, the growth of the tumor was fastest in complement C3 knock-out mice, followed by the nude mice and slowest in the BALB/c mice. Although the proportions of infiltrating CD68(+) lymphocytes in tumor tissues showed no significant difference (P > 0.05), TNF-α level in the nude and C3 knock-out mice, (28.11 ± 4.86) µmol/L and (22.87 ± 6.36) µmol/L respectively, were significantly lower (P < 0.01) than that in the BALB/c mice, which was (230.21 ± 39.17) µmol/L. The INF-γ level was highest in the BALB/c mice ((180.76 ± 29.19) µmol/L), followed by the nude mice ((113.46 ± 23.76) µmol/L) and then the C3 knock-out mice ((16.84 ± 4.45) µmol/L).

CONCLUSIONSThe G422 glioma implanted in the brains of mice with different immune ability would be a useful model for studying the relationship of the immune system and tumor in the central nervous system. Furthermore, the T cells and complement C3 compartments of the immune response may affect the growth of implanted tumors and inflammatory factors such as TNF-α and INF-γ.

Animals ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Brain Neoplasms ; genetics ; metabolism ; Cell Line, Tumor ; Complement C3 ; genetics ; metabolism ; Glioma ; metabolism ; pathology ; Interferon-gamma ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Mice, Nude ; Tumor Necrosis Factor-alpha ; metabolism

Adult ; Anterior Cruciate Ligament ; pathology ; Bone Diseases, Developmental ; diagnosis ; Female ; Hip Dislocation, Congenital ; diagnosis ; Humans ; Scoliosis ; diagnosis

OBJECTIVETo assess the effect of a liquid embolic agent 2-poly-hydroxyethyl -methacrylate (2-P-HEMA) for renal artery embolization in rabbits.

METHODSThe precipitation time of different concentrations (2%, 3.5%, 5%, 6.5%, 8% and 9.5%) of 2-P-HEMA dissolved in different solutions (ethanol, ethanol/iobitridol, and ethanol/Bi2O3) were determined in flowing water. The mixtures of 2-P-HEMA (2%, 5%, and 8%) with ethanol/ Bi2O3 were injected into the renal arteries of the rabbits, and the artery-embolizing effects were assessed using angiography at 2 and 12 weeks after the injection, with also macroscopic and microscopic examination of the embolized kidneys.

RESULTSThe mixtures of 2-P-HEMA and ethanol formed flocculent precipitation a few seconds after injection into flowing water, and the precipitation time showed no significant variations with the concentration of 2-P-HEMA in the mixture. Low and moderate concentrations of 2-P-HEMA could pass through the microcatheter smoothly with little injection resistance, and resulted in complete occlusion of the renal arteries without adhesion to the microcatheter. Angiography at 2 and 12 weeks detected no recanalization of the occluded renal arteries. Macroscopically, the lumen of the renal arteries was found to be occluded by the embolic agents, and deep penetration of the embolic agents into the glomerular arteries was observed microscopically. The mixture containing high-concentration 2-P-HEMA was difficult to deliver through the microcatheter due to high injection resistance.

CONCLUSION2-P-HEMA can be rapidly precipitated after injection into flowing water, and allows complete embolization of the renal arteries of rabbits at proper concentrations, suggesting its great potential as an endovascular liquid embolic agent.

Animals ; Embolization, Therapeutic ; methods ; Female ; Male ; Polyhydroxyethyl Methacrylate ; Rabbits ; Radiography ; Random Allocation ; Renal Artery ; diagnostic imaging ; pathology

OBJECTIVETo study the effect of betaine on the formation of atherosclerotic plaque in apolipoprotein E (ApoE)-deficient mice and explore its anti-inflammatory mechanism.

METHODSSeven-week-old ApoE-deficient mice (C57BL/6J background) were divided into four groups randomly based on body weight: model group and three betaine groups. Wild-type mice with the same age and genetic background were used as control group. The control group and model group were fed AIN-93G diet. Three betaine groups were fed AIN-93G diet supplemented with 1, 2, 4 g betaine/100 g diet, respectively. Serum tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1, lipid levels and methylation status of TNF-alpha promotor in aorta were determined at 0, 7 and 14 weeks. The percentage of aorta sinus plaque to lumen area was measured at 14-week.

RESULTSThe percentage of aorta sinus plaque to lumen area of 1% and 2% betaine groups were (11.43+/-2.65)% and (12.09+/-3.07)%, respectively, which were 41% and 33% smaller than that of the model group (t=3.117, 3.010, respectively, and P<0.01). Serum TNF-alpha level of three betaine groups were (56.33+/-3.86), (63.04+/-4.67) and (65.52+/-3.97) pg/ml, respectively, which were lower than that of the model group (79.40+/-4.68) pg/ml (t=9.270, 6.571 and 5.576, respectively, P<0.001), but there was no significant difference in the methylation status of TNF-alpha promotor among all five groups.

CONCLUSIONBetaine could inhibit the development of atherosclerosis via anti-inflammation.

Animals ; Apolipoproteins E ; deficiency ; genetics ; Atherosclerosis ; blood ; drug therapy ; Betaine ; pharmacology ; therapeutic use ; Chemokine CCL2 ; metabolism ; Dietary Supplements ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Tumor Necrosis Factor-alpha ; metabolism