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 The aim of this study was to investigate the characteristic of regional cerebral glucose metabolism in patients with Wilson's disease (WD) using 18F-fluorodeoxyglucose (FDG) PET.Methods Thirteen WD patients and 12 normal controls were studied by brain 18F-FDG PET, and the data were analyzed by visual analysis, semi-quantification and statistical parametric mapping (SPM). The radioactivity ratios of lenticular nuclei, caudate, thalamus and cerebellum to cerebral cortex and the ratio of lenticular nuclei to caudate were calculated, respectively. SPSS 11.0 software for statistics was also used to analyze the data. Results In WD patients, radioactivity of lenticular nuclei and candate was significantly decreased compared with controls. The radioactivity ratios of lenticular nuclei and caudate to cerebral cortex in WD patients were both significantly lower than that in normal controls (0.95±0.05 vs 1.26±0.05, t =15, P < 0.05 ; 1.02±0.06 vs 1.17±0.05, t = 8, P < 0.05), and the ratio of lenticular nuclei to caudate in WD patients was significantly higher than that in normal controls (0.93±0.06 vs 1.09±0.06, t =9, P< 0.05). Conclusion As compared with normal controls, patients with WD had significantly decreased glucose utilization in the basal ganglia, especially in the lenticullar nuclei.

Objective To investigate the presence of occult brain tissue damage in patients with relapsing neuromyelitis optica(RNMO)and its possible mechanism by using diffusion tensor imaging (DTI).Methods DTI scans were performed in 16 patients with RNMO and 16 sex-and age-matched healthy controls.Histogram analysis of mean diffusivity (MD)and fractional anisotropy (FA)was performed in brain tissue (BT),white matter (WM)and gray matter (GM)to detect the presence of occult brain tissue damage in RNMO patients.Region of interest(ROI )analysis of MD and FA was also performed in 6 dedicated regions with or without direct connection with spinal cord or optic nerve to determine the relationship between occult brain tissue damage and the damage of spinal cord and optic nerve.Results Patients with RNMO had a significantly higher average MD of the BT[RNMO(0.95?0.02)? 10~(-3)mm~2/s,controls (0.91?0.03)?10~(-3)mm~2/s,t = 3.940,P

As one of the major sources of infection, viruses could infect all organisms including bacteria, plants, animals, and humans. Infectious diseases caused by viruses pose a great threat and damage to human health and economic activities all over the world. Adaptor-associated protein kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases and a specific key kinase regulating the phosphorylation of AP-2 protein μ2 subunit T156. In the past, AAK1 has been regarded as a feasible biological target for the treatment of nerve pain. Recently, scientists have found that inhibiting AAK1 can regulate endocytosis and inhibit virus invasion into cells. Therefore, AAK1 could be the potential target of anti-virus therapy. This paper reviews the research progress of small molecule AAK1 inhibitors in the field of antiviral, analyzes the future research directions and challenges, and provides new ideas for the development of antiviral drugs targeting AAK1.

OBJECTIVETo investigate the effect of Deferasirox on the micro-angiogenesis in narrow pedicle flap through Epithelial-Mesenchymal Transition.

METHODS32 male rats were randomly divided into group I and II which were subdivided into Ia and Ib, IIa and IIb, 8 rats in each group. The rats were administrated intragastrically for 7 days with Deferasirox 100 mg/kg in group Ia and IIa, with the same dose of N. S. in group Ib and IIb. After that, narrow pedicle flaps were formed on the rats back. In group I, the subcutaneous vascular network was observed intraoperatively. The flap survival rate was recorded. In group II , specimens were collected at the distal end of flaps 3 days after operation. IHC and Western Blot were done to examine the expression of CD34, E-cadherin, Vimentin. The microvessel density was also calculated.

RESULTSThe subcutaneous micro-angiogenesis in group Ia was more exuberant than that in group Ib. The narrow pedicle flaps in group Ia survived completely, while the survival rate was 62.5% in group Ib (P < 0.05). The percentage of flap survival area for Ia and Ib was (100 +/- 0.00) % and (84.06 +/- 4.42)% (P < 0.05). The expression of E-cadherin in IIa was lower than that in IIb, while the expression of Vimentin and CD34 were higher in IIa, showing statistically difference (P < 0.05).

CONCLUSIONDeferasirox can improve the flap micro-angiogenesis through inducing epithelial-mesenchymal transition, so as to improve the survival rate of narrow pedicle flap.

Animals ; Benzoates ; pharmacology ; Epithelial-Mesenchymal Transition ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Surgical Flaps ; blood supply ; Triazoles ; pharmacology

OBJECTIVETo study the long-term follow-up result of partial laryngectomy and reservation of laryngeal function.

METHODSFive hundred and fifty-nine patients who underwent partial laryngectomy from 1996 to 2002 were summarized (male 435 cases, female 124 cases). Among them, 200 cases were supraglottic carcinomas (classified accordingly by UICC standard of years 2002 into: 15 cases of I, 81 cases of II, 72 cases of III, and 32 cases of IV), 354 cases were glottic carcinomas (141 cases of I, 124 cases of II, 88 cases of III, and 1 cases of IV), 5 cases were transglottic carcinomas (2 cases of II and 3 cases of III). In common 7 kinds of operations were performed: 66 cases underwent cordectomy, 119 vertical laryngectomy, 62 horizontal supraglottic laryngectomy, 113 horizontovertical (3/4) laryngectomy, 88 subtotal laryngectomy with cricoglossoepiglottic anastomosis, 26 near total laryngectomy with cricoglossal anastomosis (with reservation of unilateral arytenoid cartilage), 85 laser laryngectomy. Two hundred and sixty-one cases underwent concurrent neck dissection (174 unilateral, 87 bilateral). Safety margin of less than or equal to 5 mm was suspected of having residual lymph node metastasis, the postoperative radiation therapy to treatment.

RESULTSAll cases restored their phonation and overcame aspiration with removing nasal feeding from 7 to 24 days after operations. Four hundred and sixty-six cases were decannulated from 9 days to 3 months after operations. Decannulation rate was 98.3%. Through periodic review of out-patient clinics or telephone follow-up, family members follow-up a variety of ways, three, five or ten years follow-up rate: 99.6% (557/559), 98.2% (549/559), 95.8% (183/191), dollars lost to death. The three years survival rates were 89.6% (501/559). Among them, the survival rates for supraglottic carcinoma patients of stage I and II was 90.6%, stage III and IV 81.7%, for glottic carcinoma patient of stage I and II was 95.2%, stage III and IV 82.4%. The five years survival rates were 75.0% (419/559). Among them, the survival rates for supraglottic carcinoma patients of stage I and II was 75.0%, stage III and IV 62.5%, for glottic carcinoma patient of stage I and II was 81.8%, stage III and IV 70.6%. The ten year survival rates were 71.2% (136/191). Among them, the survival rates for supraglottic carcinoma patients of stage I and II was 69.7%, stage III and IV 65.2%, for glottic carcinoma patient of stage I and II was 77.6%, stage III and IV 72.1%.

CONCLUSIONSPartial laryngectomy is a kind of radical operation with reservation of laryngeal function. Qualities of life and curative effect, were greatly improved.

Adult ; Aged ; Carcinoma, Squamous Cell ; mortality ; surgery ; Female ; Follow-Up Studies ; Humans ; Laryngeal Neoplasms ; mortality ; pathology ; surgery ; Laryngectomy ; Male ; Middle Aged ; Neoplasm Staging ; Survival Rate ; Treatment Outcome

BACKGROUNDReliable early prediction response to therapy and time-to-progression (TTP) remain an important goal of high-grade gliomas (HGGs) research. Proton magnetic resonance spectroscopy ((1)H-MRS) has been applied with variable success in clinical application, and we hypothesize that (1)H-MRS in predictive value should perform well as a marker of TTP in patients treated with radiotherapy (RT) after surgery.

METHODS(1)H-MRS was performed before surgery on 25 patients who had undergone resection of HGGs; then the ratios of lipid/creatine (Lip/Cr) and myo-inositol/creatine (mI/Cr) were determined in the solid tumor. RT response was classified as follows: complete resolution (CR), partial response (PR), stable disease (SD), and progressive disease (PD) by comparison of pre-treatment and post-radiotherapy scans. TTP was defined at the time to radiographic progression by MacDonald criteria. Correlation was evaluated between the ratios of Lip/Cr, mI/Cr and treatment response, TTP. The chi-square test and Pearson correlation test were used for data analyses.

RESULTSMultivariate analysis revealed that the prognostic value of spectroscopic variables was independent of age, sex, WHO histologic grade, extent of surgery, and Karnofsky score (KPS). The correlation between the ratios of lipid/Cr and TTP was significant (r = 0.894, P = 0.000), and between the ratios of mI/Cr and TTP was also significant (r = 0.891, P = 0.000). As predicted, RT response correlated significantly with TTP (r = 0.59, P = 0.002): median TTP was 49.9 days for patients with PD compared with 202.7 days for SD, 208.0 days for PR, and 234.5 days for CR.

CONCLUSIONThe ratios of Lip/Cr and mI/Cr of the solid tumor region before surgery could provide important information in predicting RT response and TTP in patients with HGGs treated by radiation alone after surgery.

Glioma ; radiotherapy ; surgery ; Humans ; Magnetic Resonance Spectroscopy ; methods ; Multivariate Analysis

OBJECTIVEThis review focuses on the state-of-the-art of CXCL12/CXCR4 signaling axis in pancreatic cancer and its role in tumor progression.

DATA SOURCESRelevant articles published in English were identified by searching in Pubmed from 1997 to 2013, with keywords "CXCL12", "CXCR4" and "pancreatic cancer". Important references from selected articles were also retrieved.

STUDY SELECTIONArticles about CXCL12/CXCR4 signaling axis in pancreatic cancer and relevant mechanisms were selected.

RESULTSPancreatic cancer has been one of the most lethal human malignancies, with median survival less than one year and overall 5-year survival only 6%. Tumor cells from pancreatic cancer express high level of CXCR4. CXCL12, the ligand for CXCR4, is extensively secreted by neighboring stromal cells and other distant organs. CXCL12 primarily binds to CXCR4, induces intracellular signaling through several divergent pathways, which are involved in progression and metastasis of pancreatic cancer.

CONCLUSIONSCXCL12/CXCR4 signaling axis may play an important role in the communication between pancreatic cancer cells and their microenvironment, which may have effect on tumor proliferation, invasion, angiogenesis, metastasis and chemoresistance. CXCL12/CXCR4 signaling axis may serves as a novel therapeutic target for pancreatic cancer.

Chemokine CXCL12 ; genetics ; metabolism ; Humans ; Pancreatic Neoplasms ; genetics ; metabolism ; Receptors, CXCR4 ; genetics ; metabolism ; Signal Transduction ; genetics ; physiology

OBJECTIVETo explore correlation of seven apoptosis-related proteins (Hsp90a, p53, MDM2, Bcl-2, Bax, Cytochrome C, and Cleaved caspase3) with clinical outcomes of ALK+ anaplastic large-cell lymphoma (ALCL).

METHODSUsing immunohistochemistry and immunofluorescence double staining methods, the expressions of these seven apoptosis-associated proteins were studied to clarify their relationship with clinical outcomes of 36 ALK+ and 25 ALK-systemic ALCL patients enrolled between 1996 and 2006. The relationship of these apoptosis-regulating proteins with NPM-ALK status was also evaluated with the tyrosine inhibitor herbimycin A (HA) in vitro by immunocytochemistry, Western blotting and flow cytometric assays.

RESULTSThe presence of Hsp90α-, MDM2-, Bax-, Cytochrome C, and Cleaved caspase3-positive tumor cells was found significantly different in ALK+ and ALK-ALCLs, which was correlated with highly favorable clinical outcome. The Bcl-2- and p53-positive tumor cells were found in groups of patients with unfavorable prognosis. Inhibition of NPM-ALK by HA could reactivate the p53 protein and subsequent apoptosis-related proteins and therefore induced apoptosis in ALK+ ALCL cells.

CONCLUSIONOur results suggest that these seven proteins might be involved in apoptosis regulation and associated with clinical outcome of ALK+ systemic ALCLs. We also reveal a dynamic chain relation that NPM-ALK regulates p53 expression and subsequent apoptosis cascade in ALK+ ALCLs.

Adolescent ; Adult ; Aged ; Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; metabolism ; Benzoquinones ; pharmacology ; Biomarkers, Tumor ; metabolism ; Blotting, Western ; Cell Culture Techniques ; Cell Survival ; drug effects ; Child ; Child, Preschool ; Disease-Free Survival ; Enzyme Inhibitors ; pharmacology ; Female ; Flow Cytometry ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lactams, Macrocyclic ; pharmacology ; Lymphoma, Large-Cell, Anaplastic ; enzymology ; metabolism ; pathology ; Male ; Microscopy, Fluorescence ; Middle Aged ; Neoplasm Staging ; Prognosis ; Protein-Tyrosine Kinases ; metabolism ; Receptor Protein-Tyrosine Kinases ; antagonists & inhibitors ; metabolism ; Retrospective Studies ; Rifabutin ; analogs & derivatives ; Young Adult

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.