Alternative splicing of pre-messenger RNA (pre-mRNA) is a crucial mechanism for the diversity of the human transcriptome and proteome. Alternative splicing is a complex gene regulation process. Whole-transcriptome analysis shows that 95% of human exonic genes are alternatively spliced, involving various cis-acting elements and trans-acting factors. Any changes in any component or step may cause erroneous splicing events and lead to the occurrence of various related diseases. In addition to gene replacement therapy that directly changes the splicing results, RNA splicing modification is expected to become a new therapeutic strategy to alleviate or treat diseases by targeting and correcting abnormal pre-mRNA splicing. Splicing modification tools currently developed including RNA trans-splicing, antisense oligonucleotides, small interfering RNA, and small molecule drugs can correct abnormal splicing through different ways. This article reviews the resent progress of epigenetic regulation of pre-mRNA alternative splicing in recent years, and discusses the occurrence and regulation of alternative splicing, the types of diseases caused by related splicing defects, and the current-used tools for targeting and altering splicing. The importance of splicing modification strategies in the future treatment of human diseases is envisioned.

To sum up the experience of microneurosurgical treatment of cavernous sinus tumor, an retrospective analysis was made for 26 cases of cavernous sinus tumor admitted to our hospital from January, 1990 to June, 2001. All the patients received the modified microneurosurgical operation, and the operation was performed in 6 of them by the help of nerve guidance.The tumors were totally removed in 19 patients, and partially removed in the other 7 patients. No patient died, and cranial nerve injury was ameliorated in 14 cases, and some new cranial nerve injuries were found in 6 patients after operation. No recurrence or regrowth of tumor was found during the following up from 8 months to 12 years. It is crucial to master the microneurosurgical techniques for the reduction of operative complications.

Background Perineural invasion is an important biological character for adenoid cystic carcinoma (ACC) of lacrimal gland,which is different from those of other lacrimal gland tumors.As the important part of neurotrophic factors,glial-derived neurotrophic factor (GDNF) plays an important role in perineural invasion for ACC of salivary gland.GDNF regulation in the ACC cell biology function needs to be further explored.Objective This study was to investigate the effect of GDNF on proliferation and migration of ACC cells,and to explore the mechanism of neural invasion in ACC of lacrimal gland.Methods ACC-2 cell line was cultured and passaged in RPMI 1640 medium with 10％ fetal bovine serum,100 U/ml penicillin and 0.1 g/L streptomycin.Single-cell suspension was prepared with the density of 2×104/ml using logarithmic phase of cells and then incubated to 96-well plate.GDNF with the final concentration of 20,60,80,100 and 120 μg/L was added into the medium respectively in the experimental groups,and the cells were cultured in the medium without GDNF as the control group.The expression of GDNF in ACC-2 cells was detected by immunohistochemistry.MTT assay was employed to assay the absorbance value at the wavelength of 570 nm (A570) for the evaluation of proliferation of ACC-2 cells after cultured by different concentrations of GDNF for different time points.Meanwhile,transwell chamber was used to examine the cell migrated number.Results Immunochemistry assay exhibited that ACC-2 cells showed the positive response for GDNF with the brown staining in the cytoplasm.In 48 hours after culture,the A570 value was elevated with the increase of GDNF concentration,showing a significant difference among various groups (F =3.336,P =0.026),and the A570 value in various concentrations of GDNF groups was higher than that of 0 μg/L GDNF group (all P＜0.05).After action of 80 μg/L GDNF,the A570 value of the cells was gradually increased with the prolong of culture time (Ftime =39.979,P=0.000).In 30 minutes after GDNF cultured,the number of migrated cells increased with the increase of GDNF concentration (F=144.886,P=0.000).ACC-2 cells were cultured by 100 μg/L GDNF for 24,30 and 40 hours,the number of migrated cells were more as the time lapse,and more migrated cells were seen in GDNF group at various time points (Ftime =46.747,P =0.000 ; Fgroup =63.786,P =0.000).Conclusions GDNF can stimulate the proliferation and migration of ACC-2 cells in a dose-and time-dependent manner.

0.05). The scores of sub items of MMSE including place orientation,time orientation,short time memory,account ability,language expression,language repetition,figure portrayal in patients with VCI were lower than those in normal subjects (all P

A retrospective study was made on the diagnosis and microsurgical management of 38 cases of cranial orbital tumors treated in our hospital in order to improve its clinical outcome. 29 males and 9 females with an age between 5 ～45 years (mean 32 2 years) were included in this series. 33 cases had their tumor located in anterior fossa, and 5 in middle fossa. 35(92 1%) cases showed malfunction of optic organs. 23(60 5%) cases had symptoms of intracranial hypertension. DSA and preoperative embolization of supplying arteries of tumors were performed in some cases. Microsurgical techniques and different approaches were used to remove tumors. 28 cases received total removal and others subtotal resection. No postoperative morbidity was found. 7 months～9 years follow up study showed that 24 cases resumed normal life, 6 had a dependent life and 5 had a certain recovery. One of the most frequent clinical manifestations of cranial orbital tumor was disorders in optic organs. The preoperative embolization of supplying arteries of tumors makes it possible to decrease bleeding during operation and increase the possibility to remove the total tumor. Microsurgical and piecemeal techniques as well as combined approaches may improve its clinical results.

[Objective]To establish a method for obtaining well-differentiated goat chondrocytes quickly in large scale by RCSS using microcarriers technique. [Method]Articular chondrocytes were harvested from goat by sequential digestion with trypsin and collagenase , and then grown in RCSS bioreactor culture system which contained the Cytodex-3 microcarriers in the culture medium (DMEM) . Growth of chondrocytes on Cytodex-3 microcarriers was observed dynamically under phase contrast microscope . Immunocytochemical analysis was performed for type Ⅰcollagen and type Ⅱcollagen. [Result]The articular chondrocytes attached rapidly to the surface of Cytodex-3 microcarriers. Quick growth of these cells was observed after they fully spread onto the microcarriers. The density of chondrocytes increased by 15～17 times in later stage of culture as compared with the initial density. The harvested chondrocytes had no detectable staining for collagen type Ⅰ, but stained intensively for collagen type Ⅱ. [Conclusion]Microcarrier culture of chondrocytes can yield a large quantity of goat cells within a short time ,which will be of benefit for banking cartilage cells for reconstruction of impaired cartilage by way of tissue engineering.

0.05).5.The clinical symptoms of hMPV infection could not be discriminated from the infection of other common respiratory viruses.Conclusion The acute respiratory-tract infections among children of Xi'an city are associated with cough and fever are major clinical symptoms.

Glioma is the most common form of brain cancer. Despite recent advances in the treatment of solid tumors, there are few effective treatments for malignant gliomas due to its infiltrative nature. It has important significance to improve the treatment of glioma through in-depth understanding the intracerebral metabolic characteristics and pharmacokinetics of chemotherapeutics. Brain microdialysis (B-MD), an effective method to monitor central nervous system anticancer drug disposition, conditions of drugs through the blood-brain barrier, basic pathophysiologic metabolism, bioactive compounds and the changes of neurotransmitter in brain, provides the unique opportunity to allow the simultaneous determination of unbound concentrations of drugs in several tissues, and directly measure gliomas biochemistry continuously. B-MD has been able to monitor the change of brain drugs, metabolites and neurotransmitters, dynamic analysis of the drug concentration and pharmacological effect after administration, pharmacodynamic interaction between drugs, receptor mechanism of drug transport, as well as feedback information of internal environment. B-MD is expected to provide reference for clinical individual chemotherapy of glioma, but also provide powerful tools for the evaluation of new anticancer drugs in vivo. In this review, a comprehensive overview of B-MD for studies on glioma is elucidated with special emphasis on its application to neurochemistry and pharmacokinetic studies.
Animals ; Antineoplastic Agents ; pharmacokinetics ; Blood-Brain Barrier ; Brain Neoplasms ; metabolism ; Glioma ; metabolism ; Humans ; Magnetic Resonance Spectroscopy ; Metabolomics ; methods ; Microdialysis ; methods ; Neurotransmitter Agents ; pharmacokinetics ; Pharmaceutical Preparations ; metabolism ; Positron-Emission Tomography

To study the Realgar induced T lymphocytic leukemia cell line CEM apoptosis in vitro.

Objective To explore the relationship between CD146(MCAM),microvessel density(MVD)in renal cell carcinoma(RCC) and its clinic-pathology,and to explore their correlation with clinic-pathologic parameter of RCC. Methods Immunohistochemisty was employed to determine the expression of CD146 and MVD in 43 RCC tissues and 20 normal control renal tissues. Results The positive expression of CD146 in RCC(90.7 ％,39/43) was remarkably higher than that in normal renal tissue(30.0 ％,6/20)(x2=27.77,P＜0.05).The expression of CD146 was not correlated with the category of RCC (x2=1.37,all P ＞0.05),but had a significant correlation to(the tumor volume x2=7.57)clinical stage(r=0.62) and metastasis of RCC(x2=19.99,P＜0.05). The MVD of RCC [(78.00±23.10)/200HP]was significantly higher than that of normal renal tissue [(23.05±7.93)/200HP].The MVD of CD146 was not correlated with the tumor volume and category of RCC (t=1.33,t=1.46,au P＞ 0.05),but had a significant correlation to clinical stage and metastasis of RCC (t=2.37,t=2.10,P＜ 0.05). There was a positive correlation between expression of CD146 and MVD in RCC(r=0.74,P＜0.05). Conclusion The overexpression of CD146 in RCC has a significant relation with tumor angiogenesis.The expression of CD146 and angiogenesis might serve as an important indicator of the development, progress and metastasis of RCC.