Genomic instability is one of the most pervasive characteristics of cancer cells,and DNA damage response (DDR) pathway plays a crucial role in genomic stability.The DDR pathway is a complex signaling network,which involves cell DNA repair,apoptosis and cell cycle regulation.Deficiencies in these repair pathways can result in several different genetic disorders,including cancer.Targeted therapy based on inhibiting the DDR pathway in cancers offers a novel therapy strategy for patients with tumors lacking specific DDR functions.Many small-mole-cule compounds targeting DDR pathway are typically developed for solid cancer therapy.The poly (ADP-ribose) polymerase (PARP) inhibitor is a kind of DDR inhibitors which exploits the principle of synthetic lethality to selectively kill cancer cells.This review highlights the molecular mechanisms of PARP inhibitor action,the progress of PARP inhibitors in cancer therapy,drug resistance and the challenge of PARP inhibitor in the future.

Objective To explore the relationship between apolipoprotein E gene polymorphism and cerebral infarction in Taishun county.Methods Determination of 112 cases of Taishun Siqian cerebral infarction patients and healthy persons 88 cases of ApoE gene polymorphism,and the cerebral infarction patients were admitted to the hospital for different period of time after the NIHSS score.Results The cerebral infarction group and the control group were ApoE -/3 genotype most were 70.5%(79 /112)and 63.6%(56 /88),both had significant difference(P >0.05);The cerebral infarction group and the control group in terms of ApoE -up to 3,respectively 82.1%(92 /112)and 75.6%(66.5 /88),both had no significant difference (P >0.05).The cerebral infarction group epsilon 4 to 9.8%(11 /112),and was significantly higher than that of the control group 4.0%(3.5 /88);E2 was 6.2% (7 /112), which was significantly lower than that of the control group [19.3% (17 /88)],the differences were significant (χ2 =6.189,7.970,all P <0.05).Carrying ApoE -4 of the cerebral infarction patient each time period at the time of admission,admission 7d and 14d NIHSS scores were not carrying epsilon 4 patients increased significantly (t =7.853,6.185,5.165,allP <0.05);and at each time point carrying epsilon 2 gene in patients with and without carry-ing epsilon 2 patients NIHSS scores had no significant difference (P >0.05 ).Conclusion Cerebral infarction patients ApoE gene polymorphism and disease progression and prognosis are closely related,ApoE -4 Taishun Siqian cerebral infarction patients predisposing factors.At the same time,the detection of apoE genotype and NIHSS score is helpful to the prognosis of the patients.

As pioneer of tumor stem cell research, leukemia stem cell research has not only important theoretical significance, but also clinical application potential. The survival and development of stem cells are directly impacted by their microenvironment. The research on leukemia stem cells and their microenvironment are now becoming a hot topic. The author presumes that stem cells are a population with heterogenecity and hierarchy; any single cell from the population is difficult to form a clone; the interaction between the leukemia stem cell and its microenvironment can be described by the concept of leukemia stem cell niche. In this article, the leukemia cell population with heterogenecity and hierarchy as well as leukemia stem cell niche were summarized and discussed.
Cell Line, Tumor ; Humans ; Leukemia ; genetics ; pathology ; Neoplastic Stem Cells ; metabolism ; pathology ; Stem Cell Niche ; cytology ; Stromal Cells ; cytology ; immunology

Relapse, which puzzled several generations of hematologists, is the bottle-neck of radical treatment for leukemias. The progress of Human Microbiome Project at the beginning of 21st century suggested that human body was a super-organism constituted by the core of human cells and symbiotic microorganisms. The elucidation and characterization of endogenous retrovirus and prion protein suggested the possible effects of co-evolutional microorganisms on human health. Recently, the elucidation of the roles of tunneling nanotubes in intercellular communication and transportation suggested a novel way for cellular communication and transport of oncogenic materials. The role and significance of in vivo cell fusion have been studied in more detail. On the other hand, donor cell leukemia was reported. All of these approaches provide novel insights for studying the mechanism of leukemia relapse. Based on previous work, the authors suggest the hypothesis: there are two possible mechanisms for the relapse of leukemias: the minimal residual disease (MRD) and intercellular transportation of oncogenic materials.
Cell Fusion ; Humans ; Leukemia ; pathology ; Neoplasm, Residual ; pathology ; Recurrence

AIMTo develop an HPLC method for the determination of crocetin in rat plasma and study the pharmacokinetics in rats.

METHODSHypersil C18 column (5 microns, 4.6 mm x 200 mm) was used at column temperature 30 degrees C. The mobile phase consisted of methanol-water-acetic acid (75:24.5:0.5) at the flow rate of 1.0 mL.min-1. The UV detection wave length was 423 nm.

RESULTSThe calibration curve was linear (gamma = 0.9996) in the range from 0.49 microgram.mL-1 to 7.87 micrograms.mL-1 for crocetin. The mean recovery was 105.2%. The lowest detectable concentration of crocetin was 0.14 microgram.mL-1 (S/N = 3). The RSDs of within-day and between-day were all less than 5%. The plasma crocetin was steady. The HPLC method of determination of crocetin in the plasma was established. After single dose of 50 mg.kg-1 ig in 10 rats, the main pharmacokinetic parameters were estimated as follows: T1/2 alpha (30 +/- 6) min, Tmax(65 +/- 16) min, Cmax(5.0 +/- 1.0) microgram.mL-1, AUC0-T(845 +/- 109) microgram.min.mL-1, Vd(5.0 +/- 0.8) L.kg-1. Crocetin was shown to be absorbed into the blood through the gastrointestinal tract.

CONCLUSIONThis method is quick, precise and reliable. Crocetin was shown to be quickly absorbed in rats.

Animals ; Antineoplastic Agents, Phytogenic ; blood ; isolation & purification ; pharmacokinetics ; Carotenoids ; blood ; isolation & purification ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Crocus ; chemistry ; Female ; Male ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley

Up to date, eight types of human herpes viruses have been identified, all of which are ubiquitous, and usually establish latent infection in the host after primary infection. Since most of the herpes viruses are maintained in an asymptomatic form, they are often neglected. However, under some circumstances, these herpes viruses can cause fatal or severe diseases. Furthermore, the association of herpes viruses with hematopoietic malignancies is attracting researchers' attention. With the extensive development of hematopoietic stem cell and organ transplantation, reports regarding transplantation failure and complication caused by infection of human herpes virus has been increasing. Cytokine storm was firstly suggested as the mechanism of graft-versus-host diseases. In recent years, which has also been applied in the pathogenesis research of inflammation, and is supposed to play an important role in severe virus infection. In this paper, through discussing the possible role of latent infection of human herpes virus in the failure or complication of bone marrow or hematopoietic stem cell transplantation, and in refractory leukemia, the function and significance of latent infection of human herpes virus and the cytokine storm it caused were investigated.
Cytokines ; immunology ; Hematopoietic System ; immunology ; virology ; Herpesviridae Infections ; Humans ; Virus Latency

Objective To investigate the safety and feasibility of early intervention treatment for aneurysmal subarachnoid hemorrhage in the elderly. Methods Within 6 to 72 hours after hemorrhage,89 aneurysms were detected by overall brain angiogram in 84 elderly patients(aged above 60 years)Who were diagnosed as subarachnoid hemorrhage on CT.HUNT-HESS grade was as following:26 cases of grade Ⅱ,31 cases of grade Ⅲ,25 cases of grade Ⅳ,2 cases of grade Ⅴ.Interventional embolization treatment was performed immediately.Aceording to the structure of the aneurysm,pure coil embolization,balloon assisted technique and combined with stent technique were performed.Anhydration,fluid expansion,vessel dilatation,lumbar puncture and/or lumbar drainage were performed after procedure.At the same time,the complications were treated. Results Eighty-three aneurysms were embolized successfully in 89 patients.The Success rate of the technique was 93.3%.The Glasgow Outcome Seale(GOS)score at 3 months post procedure showed a good result in 68 patients.medium disability in 7 patients,severe disability in 4 patients,death in 5 patients (1 case was related to the technique). Conclusions Interventional embolization iS a safe and effective therapeutic approach in elderly patients with subarachnoid hemorrhage.

on,size and the extent structures of atrial septal defect on line.

Objective To detect the type of gene mutation of thalassemia in Kunming city.Methods Sixty-three cases highly suspec-tive of thalassemia were determined with the methods of ploymerase chain reaction(PCR) and reverse dot blot(RDB) for the type of gene mutation.Results According to gene analysis,35 cases were final diagnosed from 63 cases suspective of thalassemia.Among the total,4 cases were gene deficiency ?-thalassemia,and 30 cases were gene deficiency ?-thalassemia,and there was 1 case both ?-thalassemia and ?-thalassemia.There were 9 types of gene mutation with 15 gene combinations in 35 samples.The main type of ?-thalassemia was--SEA/??,there were 6 types with 11 gene combinations from the types of genes of ?-thalassemia,the highest incidence of gene mutation was 17 site,including 17 site homozygote,heterozygote and double heterozygote.Conclusions The thalassemia invasion of Yunnan has its characters,and it is valuable to launch further research.In the same patient,there are ?-thalassemia and ?-thalassemia,it signifies that those 2 types should be diagnosed in the same time,to prevent missed diagnosis.

Objective To observe the effects of vitamin C (VC) and E (VE) on the uhrastrueture of liver, kidney and brain tissue of fluorosis rats. Methods One hundred and twenty Wistar rats were chosen as the experimental animals and were divided into 9 groups randomly. The control group were given distilled water and the fluoride exposed group were given distilled water containing sodium fluoride 150 mg/L. The throe VC-fluoride exposed groups were given VC orally in a dose of 50,100,150 mg·kg-1.d-1, respectively, and the three VE-fluoride exposed groups were given VE of 25,50,75 mg·kg-1·d-1, respectively. The VC-VE-fluoride exposed group were given VC of 100 mg·kg-1·d-1and VE of 50 mg·kg-1·d-1at the same time of high fluoride water intake. The rats were sacrificed after 9 months and the ultrastructure changes on liver, kidney and brain tissues of each group were observed under transmission electron microscope(TEM). Results The uhrastrueture of liver, kidney and brain showed pathologic changes in the rats that drank water containing high eoneentrations of sodium fluoride. ①Edema of hepatocytes, smeared mitochontria and nuclear matrix, lipid droplet in eytoplasm of hepatocytes, margination of nueleohs as well as obvious swelling of liver sinusoidal endothelial were observed in fluoride exposed group. ② There were marginafion of heterochromatin, expansion of cell space and endoplasmic reticulum in the kidney after the exposure to excess fluoride.③Signifieant changes were found on glial eells on the brain, including cell swelling, increase and marginafion of heterochromatin in the fluoride exposure group. There were no significant uhrastrueture changes in the VC or VE intervention group, while the VC-VE-fluoride exposure group was almost the same as the control group. Conclusions Fluoresis may cause damage on liver, kidney and brain in rats. VC and VE, alone or combined, have protective effects, and the combined supplementation was stronger than single supplementations.