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.

Objective:To analyze the clinical characteristics of interstitial pulmonary fibrosis (IPF) in patients with Rheumatoid arthritis (RA). Methods: We retrospectively analyzed 198 RA patients with or without IPF. Characteristics of RA-IPF in clinical and lab data were analyzed. Age, duration of disease,clinical and laboratory parameters, history of smoking and medicine were compared between the patients with and without IPF. Results: (1) Among the 198 RA patients, 15.2% (30/198) were found with IPF. 100% RA-IPF patients had HRCT findings. However, 63.3% (19/30) had positive findings in chest X-ray, and only 46. 7% ( 14/30) had the complaints of cough and short breath. Velcro rales were found in 50.0% (15/30) patients with IPF and no acropachy occurred. Only one patient suffered from hypoxemia. IPF presented after the joint symptoms in most patients. (2 ) RA-IPF patients were older than those without IPF [(65.50±9.71) vs (55.22±12.98) years, P＜0.01]; Higher positivity of anti-keratin antibodies ( AKA) were found in RA-IPF compared to patients without IPF (61. 5% vs 35.9% , P =0.014). Furthermore, the levels of anti-cyclic citrullinated peptide (CCP) antibody were significantly higher in RA-IPF [(4.38±2.08) vs (3.20±2. 12) , P =0.01]. No differentiation of duration of disease, history of smoking and medicine, IgM rheumatoid factor, IgG rheumatoid factor, anti-nuclear antibody, anti-SSA antibody and levels of immunoglobins and complements were found between the two groups of RA patients with and without IPF. Conclusion: The clinical symptoms of IPF in RA patients are mild and more common in older patients. AKA and anti-CCP antibody might be important antibodies associated with RA-IPF.

Background Bulbar conjunctiva tissue appears to be thinning,elasticity declined,tension reduced and fascia atrophied in conjunctivochalasis.Histopathological examination of conjunctivochalasis shows decrease of elastic fibers and melt of collagen fibers.But there are fewer studies on the ultrastructure of conjunctiva of conjunctivochalasis up to now.Objective This study was to investigate the ultrastructure change of conjunctiva tissue in conjunctivochalasis.Methods Five loose conjunctiva samples of conjunctivochalasis and 5 normal conjunctival tissue samples were collected and ultra-microstructure changes of these samples were observed under the transmission electron microscope.Results The number of fibroblasts in conjunctivochalasis lamina was progressively decreased.The shape of fibroblasts was long and fusiform.Somatic synapse was slim.Nucleus-cytoplasm ratio was increased.Disorder,scattered and broken of the collagen fibril were seen,and some areas were dissolved or lacunae.Normal conjunctival fibroblasts were oval or polygonal,with wieners and long somatic synapse,and intercellular matrix was full of collagen fibril and dense arranged fibers.Fibroblasts in fascia of eonjunctivochalasis were linear,and collagen fibril was seriously defected.Fascia fibroblasts of normal bulbar conjunctiva were spindleshaped and bigger than conjunctivochalasis fibroblasts.There were full of collagen fibrils in intercellular matrix.Conclusions The collagen fibril is decreased and fibroblast cells are degenerated in lamina and fascia of conjunctivochalasis.

Objective To evaluate tear ferning changes of conjunctivochalasis.Design Prospective case study series.Partici- pants 30 patients(60 eyes)of conjunctivochalasis and normal subjects were selected.Methods The subjects were observed with gen- eral ophthalmic examination and tear fern test(TFT).Tear ferning was classified into 4 types.TypeⅠand TypeⅡare normal.TypeⅢand TypeⅣare abnormal.Main Outcome Measures The type of tear feming.Results TFT showed that tear ferning was de- creased in conjunctivochalasis group(TypeⅢand TypeⅣoccupied 61.7%).The difference between conjunctivoehalasis and normal control group was significant(P

Objective To discuss the clinical value of 99Tcm-sestamibi(99Tcm-MIBI) myocardial perfusion imaging on detecting myocardial ischemia in children with Kawasaki disease(KD) at convalescence period.Methods Twenty-one children wih KD at convalescence period were divided into 2 groups according to results of echocardiography.Four cases with coronary artery dilation,17 cases without coronary artery dilation.All cases accepted dipyridamole stress myocardial perfusion imaging.These patients who had positive results were given rest myocardial perfusion imaging again next day.Results Among 21 cases,9 cases(42.8%) were positive in perfusion imaging.Four cases with coronary artery dilation showed myocardial ischemia in different degree detected by myocardial perfusion imaging.Among 17 cases without coronary artery dilation,5 cases(29.4%) were positive.Conclusions Compared to echocardiography,99Tcm-MIBI myocardial perfusion imaging can objectively evaluate the location,extent and degree of myocardial ischemia of children with KD.It will be a routine test in observing its phase development.

Background Our previous study determined that expressions of matrix metalloproteinases (MMPs) and tissue matrix metalloproteinase inhibitors (TIMPs)change in the conjuntival fibroblasts of conjunctivochalasis in vitro.To seek a suitable drug is very important in the prevention and treatment of conjunctivochalasis.Objective This study was to explore the effect of qijingmingmu soup on the expressions of MMPs and TIMPs in human conjunctival fibroblasts of conjunctivochalasis.Methods Twenty-four SD rats were randomized into two groups.Qijingmingmu soup was administration gastrically for consecutive 3 days,and normal saline solution was given in the same way in the control group.The blood was collected from aortaventralis and drug serum was prepared.Human conjunctival samples were obtained during the surgery of conjunctivochalasis relaxation and cultured in the DMEM containing 10％ fetal bovine serum,20％,15％,10％,5％ of drug serum and 8 ml/L epidermal growth factor(EGF) was added into the medium respectively.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expressions of MMP1,MMP3,TIMP1 and TIMP3in conjunctival fibroblasts.Results Cultured cells grew well with the fusiform shape and showed the positive response for vimentin.The expression value of MMP1 (A value)in the cells was declined after administration of qijingmingmu soup.A significant difference was found in the expression of MMP1 among the control group,20％,15％,10％,5％ drug serum groups and EGF group(F=466.664,P＜0.05),and that in the 10％ ([9.92±0.14] mg/L) and 20％ ([11.87 ±0.11] mg/L) drug serum groups was significantly lowed in comparison with the control group([16.31±0.10] mg/L)(t=99.974,87.394,P＜0.05).The expression value of the MMP3in the cells in the various drug serum groups,EGF group and the control group was significantly different(F=158.168,P＜0.05),with a lower value in the 20％ drug serum group compared with the control group ([3.50±0.03] mg/L vs.[4.44 ± 0.11] mg/L) (t =21.991,P ＜ 0.05).Also,the significantly different expressing value of TIMP1 was seen among all the groups (F=183.508,P＜0.05),and expressing value of TIMP1 in the 15％ drug serum group was(1.88±0.06)mg/L,which was lower than(3.20±0.32) mg/L of the control group(t=10.353,P＜0.05).Furthermore,the expressing value of the TIMP3 in the cells was significantly different among the various groups(F=54.503,P＜0.05),and that of the 20％ drug serum group was (1.743±0.065)mg/L and it was significantly higher than (1.54 ± 0.05) mg/L of the control group (t =5.046,P =0.004).However,the expressing value of TIMP3of the 15％,10％ and 5％ drug serum groups was lower than that of the control group,respectively all at(P＜0.05).Conclusions Qijingmingmu soup drug serum at the concentration of 20％ can down-regulate the expressions of MMP1,MMP3,TIMP1 and up-regulate the expression of TIMP3 in human conjunctivochalasis bulbar conjunctival fibroblastsin vitro,which probably plays preventive and therapeutic effects on conjunctivochalasis.

Background Researches showed that the incidence rate of cataract is high in the nickel mining area. Nickel sulphate can apparently inhibit the metabolism and proliferation of human lens epithelium cells. But the study on the injury mechanism of nickel on lens is still seldom. Objective Present study was to investigate the effect of nickel sulphate on the lens of SD rats. Methods Forty-five SPF SD rats aged from 7 to 14 days were grouped randomly into subcutaneous injection group, intraperitoneal injection group and blank group. Nickel sulphate of 2 g/L ( 10 mg/kg) was subcutaneously or intraperitonealy injected for 45 days. The opacity of rat lens was examined under the slit lamp at two-week interval and scored based on the criteria of LOCS II and LOCS III. The rats were sacrificed in 45 days after experiment and the lens were obtained for the pathological examination. Result The mean score of the anterior subcapsule opacity of rat lens was obviously higher in subcutaneous injection group compared with blank control group with a significant difference between them (t= 14. 311, P < 0. 05 ) , but no significant difference in the anterior subcapsule opacity between intraperitoneal injection group and blank control group (t = 4. 355 , P>0. 05 ). The score of posterior subcapsule opacity of lens were evidently higher in both subcutaneous injection group and intraperitoneal injection group than the blank control group (t = 9. 316,P = 0. 004;t = 7. 464, P = 0. 009) ,so was the mean score of the anterior +posterior subcapsule opacities(t = 23. 387,P=0. 000;t= 10. 533,P = 0. 002) and the total score of rat lens opacity ( t = 12. 358 , P = 0. 001; t = 10. 188 , P = 0. 003 ) . No significant differences were found in cortex opacity score and nuclear opacity score among three groups ( P > 0.05 ). Histopathology examination revealed that the degeneration of lens collagen protein was more serious in subcutaneous injection group and intraperitoneal injection group than the blank control group,and the injury degree of lens collagen protein was more dominant in subcutaneous injection group. Conclusion System administration of nickel sulphate induced the injury of anterior and posterior subcapsule of lens in SD rat.

OBJECTIVETo study the clinicopathologic features, immunohistochemical findings, diagnosis and differential diagnosis of atypical teratoid/rhabdoid tumors (AT/RT) of central nervous system in childhood.

METHODSThe clinicopathologic data, morphologic features and immunophenotypes were reviewed in 6 cases of AT/RT. EnVision method was applied. Antibodies include cytokeratin (CK), epithelial membrane antigen (EMA), vimentin, smooth muscle actin (SMA), muscle specific actin (MSA), glial fibrinary acid protein (GFAP), desmin, placental alkaline phosphatase (PLAP) and INI1.

RESULTSFive of the six cases of AT/RT occurred in infancy and early childhood. Histologically, the predominant component was rhabdoid cells. Cytoplasmic inclusions were present in all cases. Primitive neuroectodermal tumor (PNET) component was also identified in 5 of the 6 cases studied. Immunohistochemically, the tumor cells were positive for cytokeratin, epithelial membrane antigen and vimentin. The staining for INI1, desmin and PLAP was negative. Smooth muscle actin was expressed in 2 cases and glial fibrillary acidic protein in 5 cases. The proliferative index as demonstrated by Ki-67 staining was high.

CONCLUSIONSAT/RT is not a particularly uncommon malignancy in childhood. The histologic hallmark is the presence of rhabdoid cells with cytoplasmic inclusions. The tumor cells are positive for cytokeratin, epithelial membrane antigen and vimentin, and negative for INI1. Differential diagnosis includes PNET, medulloblastoma and medullomyoblastoma.

Brain Neoplasms ; metabolism ; pathology ; surgery ; Child, Preschool ; Diagnosis, Differential ; Female ; Humans ; Infant ; Keratins ; metabolism ; Male ; Medulloblastoma ; metabolism ; pathology ; Mucin-1 ; metabolism ; Neuroectodermal Tumors, Primitive ; metabolism ; pathology ; Rhabdoid Tumor ; metabolism ; pathology ; surgery ; Teratoma ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

Objective To explore the changes of plasma angiotensinⅡ (AngⅡ) and cardiac function,and the curative effect of children with acute viral myocarditis (VMC) treated with captopril(CAP).Methods Concentrations of plasma AngⅡ were measured with radio-immunity and cardiac function was detected by Doppler echocardiography for the VMC group (n=60) before and after treatment [the CAP group (n=30), the routine group (n=30) and the control group (n=30)].Results 1. The level of plasma AngⅡ significantly increased and the contractive and diastolic function obviously declined in children with acute VMC. There was a significant difference between VMC group and control group, with a significant correlation between the level of AngⅡand the contractive diastolic function.2. Compared with the level before treatment, the level of AngⅡ decreased and the contractive function obviously ameliorated in two groups; the diastolic function obviously ameliorated in the CAP group and did not ameliorate in the routine group after treatment. In CAP group the level of AngⅡ and the cardiac function significantly improved; there were statistical differences between the two groups after treatment.Conclusions 1.The increase of the plasma AngⅡ was an important factor for decrements of the contractive and diastolic function in acute viral myocarditis.2.It could decrease the concentration of plasma AngⅡ and ameliorate cardiac function in children with acute VMC treated with captopril,which was an effective therapy for acute VMC.

Objective To evaluate the efficacy and safety of oxiracetam in the treatment of neurological deficits resulting from brain injury through the comparison of oxiracetam for injection and piracetam for injection in clinical trials. Methods A multiple-center, randomized, double-blind,parallel study was performed on 239 patients; these patients were divided into experimental group (oxiracetam for injection, n=120) and control group (piracetam, n=119). National institutes of health stroke scale (NIHSS), Glasgow coma scale (GCS), myodynamia grading, mini-metal state examination (MMSE) were employed to evaluate the therapeutic effects; electrocardiogram and laboratory examination were performed, and the side effects were also observed. Results The scores of NIHSS,GCS and myodynamia grading after treatment in the 2 groups were all significantly higher than those before treatment (P＜0.05); however, no significant differences on these scores were noted between the experimental group and control group (P＞0.05). No serious adverse events were noted in both groups.Conclusion Oxiracetam, the same as piracetam, is safe and effective in the treatment of neurological deficits secondary to brain injury.