Culling protein is a member of Cullin-Ring-based E3-ligases ( CRLs family) , which belong to E3 ubiquitin ligases. Cullin plays diverse and essential roles in many biological processes through mediating the ubiquitination of target proteins. This article summarizes the potential functions of Culling proteins in gamete genesis and maturation, embryo development, and reproductive related disorders.
Cullin Proteins ; Humans ; Urogenital System

Objective To analyze the epidemiologic characteristics of epidemic hemorrhagic fever syndrome (EHF) from 2004 to 2010 and provide scientific basis for formulating control measures.Methods Epidemiological data of EHF between 2004 to 2010 were obtained from the“National Disease Surveillance Report on Management Information System”,and the population data were from the“National Disease Surveillance Information Management System for Basic Information Report System”.Descriptive epidemiological methods was used for statistical analysis.ResultsA total of 173 cases were reported in Qian'an from 2004 to 2010.From 2004 to 2010,the cases were 86,67,12,1,0,1,and 7 cases,respectively,and the rate were 13.12/10 million ( 86/640 249 ),10.42/10 million (67/642 688 ),1.86/10 million ( 12/645 124),0.15/10 million (1/647 983 ),0(0/650 720),0.15/10 million( 1/653 839),and 0.11/10 million(7/657 380),respectively.The overall rate was 3.86/10 million(25/648 283) of population.From 2004 to 2008 the incidence reported declined rapidly,then increased slowly after 2009.The cases were found intensively in winter(November - next January) and spring season (february - may).The incidence in the age group of 10 - 45 was higher than that of other age groups,and the total number of cases was 82.08％(142/173).The incidence in males( 114 cases) was higher than that of females(59 cases).Occupational distribution mainly to peasants and students,which accounted for 87.86％ (152/173).Conclusions Epidemic in the city declines rapidly follows by a slow recovery,suggesting that in the future surveillance,mice-killing and protection of vulnerable population should be strengthened.

In the treatment of hypertensive crisis, the novel Rho kinase inhibitor DL0805-2 can rapidly lower systematic blood pressure, reduce pulmonary artery pressure, and has a significant protective effect on lung injury. This experiment intends to evaluate the efficacy of DL0805-2 against pulmonary arterial hypertension (PAH) and preliminarily reveals its underlying mechanism. Animal welfare and experimental procedures are in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Sprague Dawley (SD) rats were randomly divided into DL0805-2 low, medium, and high dose groups (1, 3, and 10 mg·kg^-1), bosentan positive control group, model group, and blank control group. The drug was administered daily on the 7th day after model establishment by monocrotaline injection. On the 25th day of the experiment, relevant indicators were examined to observe the therapeutic effect of DL0805-2 on pulmonary hypertension. DL0805-2 significantly relieved the abnormal changes in the physiological parameters related to PAH induced by monocrotaline, including reducing right ventricular systolic pressure, alleviating cardiac damage caused by pressure overload, and reducing the levels of endothelin-1 and inflammatory factors in lung tissues. DL0805-2 also attenuated pulmonary arteries remodeling. It was preliminarily discovered that DL0805-2 exerts preventive and therapeutic effect on PAH through Rho-kinase pathway. Our results suggested that DL0805-2 had good therapeutic effects on monocrotaline-induced PAH rat model. It intervened early in the disease process, effectively prevented the development of the disease, and reduced the mortality of the diseased animals. The mechanism is related to Rho-kinase pathway.

OBJECTIVETo describe the pitfalls in positron emission tomography/computed tomography (PET/CT) imaging and classify them according to the principles of their generation.

METHODSWe summarized retrospectively the 18F-fluorodeoxyglucose (FDP) PET/CT imaging pitfalls through reviewing the PET/CT images of 872 patients. The pitfalls were divided into artifacts and infrequent physiological uptake, and the artifacts were further classified according to their causes. Meanwhile, we calculated the incidences of various pitfalls. Whether the PET/CT pitfalls influenced the diagnostic decision was analyzed. The appearances of pitfalls in PET were also described.

RESULTSPitfalls could be found in PET/CT images of 684 (78.4%) patients. Artifacts were found in 664 (76.15%) patients, and could be classified into self-factor artifacts and equipment- or technology-related artifacts. Among self-factor artifacts, respiratory motion (57.5%), postprandial or hyperglycemia artifacts (2.41%), and metal or high density matter artifacts (1.38%) were frequent. As for equipment- or technology-related factors, injection point outleakage or radiotracer contamination (13.88%) and truncation artifacts (1.83%) were most common ones. Infrequent physiological FDG uptakes, including fatty uptake, endometrial uptake, and bilateral breast feeding period uptake, were found in 20 (2.29%) patients. Among all pitfalls, the artifacts in 92 (13.4%) patients and infrequent physiological uptakes in 6 (0.88%) patients affected the diagnostic results. Artifact images in PET could be described as hot or cold area and the images of infrequent physiological uptake were always shown as hot area.

CONCLUSIONSThe incidence of pitfall in PET/CT imaging was high and the causes of pitfalls are various. Among all causes that artifacts generated, respiratory motion is the most common. Some pitfalls may disturb clinical physicians' decision, so it is important to recognize artifacts and physiological uptake, and distinguish them from pathological uptakes.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Artifacts ; Breast Feeding ; Child ; Child, Preschool ; Diagnostic Errors ; statistics & numerical data ; Drug Contamination ; Endometrium ; metabolism ; Fatty Acids ; metabolism ; Female ; Fluorodeoxyglucose F18 ; Humans ; Hyperglycemia ; Image Interpretation, Computer-Assisted ; Infant ; Injections, Intravenous ; Male ; Middle Aged ; Movement ; Positron-Emission Tomography ; Respiration ; Young Adult

OBJECTIVETo study the application of multi-slice spiral CT angiography (MSCTA) after endoluminal exclusion of aortic diseases.

METHODS16-slice CT angiography was performed in 15 patients with aortic dissection and 4 patients with aortic aneurysm after endovascular exclusion. Two observers analysed the images and interpreted the outcomes and complications after endovascular exclusions of aortic dissection and aortic aneurysm.

RESULTSIn 19 patients, thrombus was found in all the false lumens of aortic dissection and the outer-stent cavity of aortic aneurysm. However, one patient with aortic aneurysm graft thrombosis; 4 patients had endo-leak (3 with type I endo-leak, 1 with type III endo-leak complicating graft deformation); one achieved perfusion recovery, and one experienced thrombolysis of superior mesenteric artery.

CONCLUSIONMSCTA can be an objective tool for the post-operative evaluation of endovascular exclusion of aortic diseases.

Adult ; Aged ; Aneurysm, Dissecting ; diagnostic imaging ; surgery ; Angiography ; Aortic Aneurysm, Abdominal ; diagnostic imaging ; surgery ; Female ; Humans ; Male ; Middle Aged ; Postoperative Period ; Tomography, Spiral Computed ; methods

To study the effect of endotoxin on liver apoptosis, LO2 liver ceils were cultured and passaged in vitro, and then stimulated by endotoxin at 10 mg/mL for 4, 8, 16 and 24 h respectively. Liver apoptosis was flow cytometrically and fluorescently detected. Immunohistochemistry was used to detect the delivery of smac and caspase9. The delivery of liver cell smac and the activity of caspase3 were measured by caspase3 assay kit. The hepatic failure models of rats were established by using D-galactosamine. The blood serum and liver tissues were collected for the detection of the liver function, the level of endotoxin and the activity of caspase3 by using chromogenic substrate limulus amebocyte lysate method (LAL) and caspase3 active assay kit. The expression of smac and caspase9 in liver ceils was detected by Western blotting. With in vitro study, the LO2 cells stimulated by LPS condensed into conglobation and formed apoptotic bodies. After those cells were stained.by hoechst,the apoptotic cells displayed blue color under the fluorescent microscope. The apoptosis rate was increased over time and the apoptosis was mainly of advanced stage. Meanwhile, the rate of smac delivery and activity of caspase9 and caspase3 were increased on LO2 cell membrane. In vivo, hepatic failure and obvious endotoxemia were induced by injection of more than 200 mg/kg D-GaIN. Hepatic mitochondria smac was reduced with dosage of D-GaIN and, on the contrary, the activity of caspase3 was increased. D-GaIN at 200 mg/kg increased Caspase9 while D-GaIN at 300 mg/kg decreased caspase9. Mitochondria signal channel plays an important role in the endotoxin-induced apoptosis of hepatic cells by promoting the release of smac from mitochondria to cytoplasm and activating caspase9 and caspase3 in its low-level channel.

Microdialysis coupled with RP-HPLC was used to study the blood pharmacokinetics of pingyangmycin hydrochloride in rabbits. Supelco RP-amide C16 column was adopted for the analysis of pingyangmycin hydrochloride. The data was analyzed with 3P87 program. The calibration curve was linear in the concentration range from 1.04 to 66.56 microg x mL(-1) (r2 = 0.999 4). The in vivo recovery of microdialysis probe was (42.8 +/- 3.4)% (n = 4). The concentration-time curve of pingyangmycin hydrochloride was fitted to two-compartment model. T1/2 alpha and T1/2 beta were 14.9 and 60.3 min, respectively. The method is proved to be accurate, simple and suitable for the pharmacokinetics study of pingyangmycin hydrochloride in rabbits.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Bleomycin ; analogs & derivatives ; blood ; chemistry ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Female ; Injections, Intravenous ; Male ; Microdialysis ; methods ; Molecular Structure ; Rabbits

OBJECTIVETo investigate effects of low-dose cyclophosphamide and prednisone (CP) metronomic chemotherapy on microvessel density of bone marrow, serum vascular endothelial growth factor (VEGF) and platelet derived growth factor BB (PDGF-BB)in multiple myeloma (MM) patients.

METHODS54 refractory or relapsed MM patients were treated with CP metronomic chemotherapy consisted of oral cyclophosphamide (CTX, 50 mg/d) and prednisone (Pred, 15 mg/d). Bone marrow and peripheral blood of each patient were collected before and 2, 4, 6 months after treatment. Among the 37 assessable patients, 30 cases were responsive with the response rate of 81.08%. Another 17 cases were follow-uped less than 6 months or failure to obtain serum samples or lost to follow-up. Microvessel density of bone marrow was measured by immunohistochemistry and serum VEGF/PDGF-BB expression was analyzed by ELISA in the 37 assessable patients.

RESULTS2, 4, 6 months following CP metronomic chemotherapy, microvessel densities of bone marrow in the responders were 33.1 ± 4.8/HP, 24.8 ± 3.7/HP, 19.7 ± 2.1/HP respectively; the expressions of VEGF were (394 ± 57) ng/L, (268 ± 32) ng/L and (217 ± 20) ng/L respectively; the expressions of PDGF-BB were (304 ± 31) ng/L, (274 ± 31) ng/L and (196 ± 22) ng/L respectively. After CP metronomic chemotherapy, there were significantly lower of microvessel density, VEGF and PDGF-BB levels than pretreatment \[MVD 48.5 ± 5.9/HP, VEGF (517 ± 60) ng/L, PDGF-BB (484 ± 60) ng/L\]in the responders (P < 0.01). While in the non-responders, after treated by CP metronomic chemotherapy for 2 months, microvessel density, the expression of VEGF and the expression of PDGF-BB were 32.5 ± 4.7/HP, 512 ± 39 ng/L and (452 ± 39) ng/L respectively. There were no significant changes of MVD, VEGF and PDGF-BB levels compared with pretreatment \[MVD 33.2 ± 5.6/HP,VEGF (498 ± 55) ng/L, PDGF-BB (488 ± 44) ng/L\] (P > 0.05).

CONCLUSIONSOur findings suggested that continuous low-dose CP metronomic chemotherapy could decrease microvessel density of bone marrow in MM patients. Furthermore, it down-regulated expression of serum VEGF and PDGF-BB to exert its anti-angiogenesis in MM.

Aged ; Aged, 80 and over ; Angiogenesis Inhibitors ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; administration & dosage ; Female ; Humans ; Male ; Microvessels ; drug effects ; Middle Aged ; Multiple Myeloma ; blood ; blood supply ; drug therapy ; Prednisone ; administration & dosage ; Proto-Oncogene Proteins c-sis ; blood ; Vascular Endothelial Growth Factor A ; blood

This study was purposed to investigate the expression of the growth-factor independence 1 (GFI1) in patients with leukemia and its clinical significance. Bone marrow mononuclear cells were obtained from 65 newly diagnosed leukemia patients including 24 acute myeloid leukemia (AML), 18 chronic myelogenous leukemia (CML), 6 acute lymphoblastic leukemia (ALL), 17 blast crisis of chronic myelogenous leukemia and 13 patients with iron deficiency anemia (IDA) were used as controls. The relative expression of gene gfi1 was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and taqman quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR). The results showed that gene expression of gene gfi1 in leukemia patients was obviously higher than that in controls and the difference was statistically significant (p < 0.01), in which the expression of gene gfi1 in newly diagnosed CML patients was higher than that in newly diagnosed AML, newly diagnosed ALL, CML-BCP patients and the difference was significant (p < 0.01). Expression of gene gfi1 in lymphocytic blast crisis of CML was higher than that in nonlymphocytic blast crisis of CML, and the difference was significant. It is concluded that gene gfi1 may play an important role in leukemia, especially in CML incidence and progression. The high level expression of gene gfi1 may be participate in the development of lymphoma.
DNA-Binding Proteins ; genetics ; Gene Expression ; Humans ; Leukemia ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors ; genetics ; Transcription, Genetic ; genetics

Purpose To explore the mutation characteristics of common driver genes in non-small cell lung cancer (NSCLC) and its relationship with clinicopathological features.Methods Next generation sequencing (NGS) was used to detect the mutations of common driving genes such as EGFR, KRAS, ALK, ROS1, BRAF, MET, RET and HER-2 in 300 paraffin-embedded NSCLC tissues. Results In 300 patients with NSCLC, the mutation rates of EGFR, KRAS, ALK, ROS1, BRAF, MET, RET, HER-2 were 52.00％, 10.33％, 6.67％, 1.67％, 3.67％, 3.33％, 1.00％, and 2.33％, respectively. A case of EGFR 21 exon L858 R mutation was combined with LINCO1446-EGFR gene fusion. EGFR 20 th exon C797 S and T790 M existed in cis or trans form and merged with EGFR sensitive mutations in 1 case each. 3 cases of EGFR gene point mutation was associated with MET gene copy number amplification. EGFR mutations were more commonly detected in non-smoking women with lung adenocarcinoma (P<0.05).KRAS mutations were more commonly found in smoking men (P<0.05). ALK mutations were associated with age (P<0.05), and more commonly noted in patients younger than 60 years.ROS1 fusion mutations were associated with gender (P<0.05), more commonly detected in women. BRAF, MET, RET, and HER-2 gene mutations were not associated with gender, age, smoking, histological type, and c TNM stage. Conclusion EGFR can coexist with other driver gene mutations. Gene mutations and clinicopathological features like gender, age, smoking, and histological types have corresponding links. The incidence of BRAF, MET, RET, and HER-2 mutations is low, and its clinical significance remains to be explored. Coexisting gene mutations and rare mutations discovered by NGS should be taken seriously.