Over the past few decades,the curative effect of leukemia has been improved significantly.But the effect of refractory acute lymphoblastic leukemia and about 50％ of acute myeloid leukemia has not been improved.At present,targeted therapy,which is unique to the incidence of leukemia,has become a hotspot,such as the antibody drugs targeted cell surface molecules or kinases.At the same time,many drugs have been applied into clinical treatment because of their better clinical results,such as imatinib,bortezomib.

Objective To investigate the possibility of affecting transgenic rescue for Wilson disease using the human ATP7B transgenic LEC rat.Methods The 7.1kb transgene constructed with human ATP7B cDNA and chicken ?-actin promoter was introduced into the fertilized oocytes of LEC rats, an animal model of Wilson disease, by microinjection. The expressions of human ATP7B protein in the transgenic rats were detected by Western blot. The plasma AST and ALT activities, and the total bilirubin levels in transgenic rats were measured continuously from 6 to 16 weeks using non-transgenic rats and LEA rat as controls. The pathological and histochemistry changes in the liver of the transgenic rats at 13 weeks were analyzed. Results The intact and correct product derived from human ATP7B was confirmed in the liver of transgenic rats. At the age around 12 weeks, the plasma AST and ALT activities, and the total bilirubin levels in transgenic rats were significantly decreased, while the inflammatory reation in the liver of transgenic rats was much mild as compared with that of non-transgenic rats, and the granules of stained copper were less in the hepatocytes of transgenic rats. By the age of 16 weeks, the transgenic rats were phenotypically normal, and the survival rate was 100%. These data showed that the LEC rats were successfully rescued from fulminant hepatitis after introducing of human ATP7B gene. Conclusion The hepatitis in Wilson disease is directly related to the toxicity of excessive accumulated copper, which attributed to the functional deficiency of the ATP7B. Gene transfer probably is the effective method for the therapy of Wilson disease.

Objective To investigate the possibility of affecting transgenic therapy for the hepatic cirrhosis and hepatoma in Wilson disease by human ATP7B cDNA. Methods The 7.1*!kb transgene consisting of human ATP7B cDNA and chiken ?-actin promoter was introduced into the LEC rats which is an animal model of Wilson disease by microinjection.The plasma AST and ALT activities in transgenic rats were measured continuously from weeks 17 to 30 using non-transgenic and LEA rats as controls.The histological and histochemistry changes of liver in the transgenic rats at 30 and 60 weeks of age were examined. Results The plasma AST and ALT activities in transgenic rats were kept at the relatvie lower levels from 17 to 60 weeks of age, as compared to the age-matched non-transgenic rats.By the age of 60 weeks,none of the transgenic males developed cholangiofibrosis or hepatoma,whereas all of the non-transgenic rasts had severe cholangiofibrosis at the age of 30 weeks and one male rat had hepatoma at 60 weeks.The transgenic rats were phenotypically normal,and the survival rate was 95.7%.In addition,the distribution and the numbers of the granules of stained copper in the hepatocytes of the transgenic rats did not show any significant difference between 30 and 60 weeks.Conclusion The human ATP7B successfully delayed the onset of hepatic cirrhosis,and suppressed the development of hepatoma in the LEC rats by gene transfer.The hepatic cirrhosis and hepatoma in Wilson disease may be not directly related to the copper accumulation.

Cardiopulmonary Resuscitation ; adverse effects ; Chylothorax ; etiology ; Heart Arrest ; physiopathology ; Humans ; Infant ; Infant, Newborn ; Male ; Neonatology

Chemokine is a family of small chemotactic cytokines.Chemokine mainly locates in neutrophile granulocyte,monocyte,macrophage,T lymphocyte and B lymphocyte,and some cells and immunoactive cells also secret cytokines.Researches showed that chemokine plays important roles in many patho-physiological activities,such as inflammatory response,infection procedure,wound healing,regulation of immunity,angiogenesis,invasion and metastases of cancer,etc..Some chemokine factors,such as hyperglycemia,hypoxia,oxidative stress,stimulate the ocular histiocytes to up-regulate the expressions of CXC chemokines and CC chemokines,which participate in the development of choroidal neovascularization and ocular neovascular diseases.This article reviews current progress in chemokine and the relationship between chemokines and ocular neovascular diseases,especially in diabetic retinopathy (DR) and age-related macular degeneration (AMD) etc..

By analyzed the problems of clinical medicine key disciplines in professional degree graduate education,such as pay more attention to the research rather than clinical work,pay more attention to using rather than cultivating,the new needs were identified in the focus adjustment of this education.The measurements and methodologies of focus adjustment were discussed to match the needs.

Objective To investigate the regulation of blood-testis barrier by Rab13-PKA pathway in rats.Meth-od First, shRNA vector targeting at Rab13 was constructed and then the Rab13 shRNA was transfected into the rat testis by injection.Western blot was used to detect the knock-down effect of Rab13 and the expression of blood-testis barrier ( BTB) constituent proteins.PKA activity was detected by autoradiography and scintillation counting.Further, immunoflu-orescence analysis and phalloidin staining were applied to observe the distribution of occludin and F-actin, respectively. Results The expression level of Rab13 in the testis was reduced by approximately 70%after transfection of Rab13 shRNA as compared with the non-targeted control group ( P<0.01 ) , while the expression of BTB constituent proteins remained unchanged.PKA activity was significantly increased after Rab13 RNAi transfection (P<0.01).The distribution of occlu-din at BTB was remarkably increased after Rab13 RNAi silencing around stage VIII but not at other stages of the seminifer-ous epithelial cycle.The assembly of F-actin at BTB was also intensified in Rab13-silenced testis.Both the changes of dis-tribution of occludin and F-actin induced by Rab13 shRNA were found to be antagonized by the PKA specific inhibitor H89.Conclusions Rab13 can modulate the distribution of occludin and F-actin at the blood-testis barrier in rats by regu-lating PKA activity, which may participate in the regulation of BTB function.

Radix Glycyrrhizae is a commonly used herbal drug for traditional Chinese medicine in China, and it is also an important material for drug, food, chemical industry, and dye industry. Furthermore, in Northwest China, Radix Glycyrrhizae acts as a key plant for preventing desertification, which currently is the most serious environmental problem in China. This report concentrated on discussing the great potential value of Glycyrrhiza on ecosystem, introducing the principles of protection and sustainable utilization of Glycyrrhiza resource, offering the suitable methods of utilization, and suggesting how to carry out the research on the substitute drugs. To protect the ecosystem and herbal resource of Radix Glycyrrhizae, we should use this herb in a more reasonable way.

Objective To analyze the immune state and discuss the effects of immunoregulation therapy of combined use of ulinastatin and thymosin ?1 in the treatment of posttraumatic sepsis. Methods Forty-eight patients with posttraumatic sepsis admitted to ICU during Oct. 2005 to Oct. 2007 were included and randomly divided into treatment group and control group (24 each). Patients in control group received conventional SSC treatment, while those in treatment group received conventional SSC treatment plus immunoregulation therapy with a combination of ulinastatin and thymosin ?1. Peripheral blood CD14+ monocyte HLA-DR expression was detected by flow cytometry to determine the innate immunity of posttraumatic septic patients on day 1, 5, 7 and 28 (or death), and serum levels of IL-6 and IL-10 were assessed by ELISA to evaluate the nonspecific immunity at day 1 and 28 (or death). APACHE Ⅱ scores were recorded on day 1, 5, 7 and 28 (or dearth). Ten healthy volunteers were enrolled as healthy controls. Results At admission the expression of CD14+ monocyte HLA-DR was lower than 30% in 9 posttraumatic septic patients. The expression levels of CD14+ monocyte HLA-DR in the patients in treatment group were much higher than those in control group (P0.05). Before treatment, no significant difference existed in APACHE Ⅱ scores between treatment group and control group, while this score in the patients in treatment group was much lower than that in control group on day 5, 7 and 28 (P0.05). Conclusions There is immunosuppression in some posttraumatic patients with somplication of sepsis. All these patients manifest exaggerated nonspecific immunity at the early stage, and then manifest immunodepression as sepsis progresses. The immunoregulation effects of a combination of ulinastatin and thymosin may facilitate the balance of pro-inflammatory and anti-inflammatory media, thus ameliorating septic symptoms. No improvement in 28 day mortality has been seen, probably due to limited number of patients in present study.

Objective To offer the theoretical evidence for clinical application,we observed the changes of angiographic appearances and local pathological changes before and after embolizing the left gastric artery with mitomycin C gelatin microspheres (MMC-MS).Methods Catheter was delivered into the left gastric arteries via femoral artery and then infused MMC-MS.The angiographic appearances and local pathological changes were observed immediately,and then with follow up of 6～8h,24h,72h,1w,2w and 4w. Results The minute arterioles of tunia mucosa and tela submucosa were mainly embolized inducing edema and focal necrosis.With the degradation of MMC-MS,the damage of gastric tissue was alleviated but turned normal after 4 weeks.The results of DSA showed that no recanalization of the embolized vessels occurred after one week of emboliatdion but revealed one recanalization after two weeks and two in four weeks.Conclusions The damage of tissue induced by embolizing the left gastric artery with MMC-MS can be recovered.The application of the MMC-MS is feasible.