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.

Adult ; Femur Head Necrosis ; chemically induced ; drug therapy ; Glucocorticoids ; therapeutic use ; Humans ; Male ; Paraquat ; poisoning

AIM: To evaluate the efficacy of vitrectomy and pan-retinal photocoagulation followed with Ahmed implantation in management of neovascular glaucoma ( NVG) retrospectively.
METHODS: Vitrectomy combined with pan retinal photocoagulation and Ahmed implantation was performed on 15 cases ( 15 eyes ) with NVG. All patients were followed up for 12 ~ 36mo. The change of intraocular pressure (IOP), visual acuity, neovascularization of iris, complications were observed.
RESULTS: The visual acuity of 10 eyes was improved postoperative. IOP of postoperative 1, 6 and 12mo were decreased significantly compared with preoperative ( P<0.01 ) . Neovascularization of iris was reduced dramatically. No serious complications occurred.
CONCLUSION: Vitrectomy combined with pan retinal photocoagulation followed Ahmed implantation can manage NVG effectively.

AIM: To explore the effect of lacrimal duct laser with lacrimal drainage tubes and stents implantation for complexity dacryagogatresia.
METHODS: There were 65 patients ( 82 eyes ) with compound tears nasolacrimal duct obstruction who received lacrimal drainage tubes and stents implantation after laser. The lacrimal duct stents were removed through nasal cavity after 1mo. Lacrimal drainage tubes were removed after 3-6mo. Follow-up periods were 6mo to 1a.
RESULTS: In the 65 patients (82 eyes), 71 eyes were cured, 5 eyes improved, the efficient rate was 93%; there were 6 eyes (7%) with epiphora.
CONCLUSION: Lacrimal duct laser with lacrimal drainage tubes and stents implantation was efficient for complexity dacryagogatresia.

Objective To study the causes, clinical feature,diagnoses and prognosis of pseudoprecocious puberty. Methods Thirty-eight cases with pseudoprecocious puberty were diagnosed by the serum LH and FSH of GnRHa stimulation test, pelvic ultrasonography and bone age assessment; they were treated and followed up. Results Peaks of LH were(0.49?0.48) IU/L, peaks of FSH were(0.54?0.78) IU/L, the level of E2 in 26 cases increased (36.11?15.70) ng/L,17-hydroxyprogesterone of 1 case was beyond 266 nmol/L. All cases showed hysterauxesis (3.98?1.18) mL. Cases of wrong contraceptive intake were 29,5 cases of McCune-Albright syndrome,2 cases of ovarian cyst, 1 case of ovarian granular cell tumor,1 case of congenital adrenal hyperplasia. Conclusions The causes of pseudoprecocious puberty are multifactors. Early diagnosis,therapy,follow-up are very important for prognosis.

Objective To explore the role of somatosensory evoked potentials elicited by paraspinal stimulation in the detection of spinal cord lesions.Methods Patients with clinically suspected spinal cord lesions underwent somatosensory evoked potentials(SEPs)and spinal cord conduction velocity(SCCV)test using paraspinal stimulating method.96 patients aged 15 to 75 years old with suspected spinal cord lesions of various aetiologies were tested.36 patients had demyelinating disease of the spinal cord,26 had sub-acute combined degeneration of the spinal cord,19 had myelopathy,10 had acute myelitis,5 had spinal cord corhpression.Results Paraspinal stimulation elicited somatosensory evoked potentials were Performed on all 96 patients,68 of whom underwent spinal MRI as well.SEPs and SCCV were found abnormal in a high ratio in all kinds of spinal cord lesions ; in general,78 among the 96 patients had abnormal SEPs with a sensitivity of 81.25%.27 out of 36 with demyelinating disease of the spine had abnormal SEPs with a sensitivity of 75.00%,23 out of 26 with subacute combined degeneration of the spinal cord had abnormal SEPs with a sensitivity of 88.46%,8 out of 10 with acute myelitis had abnormal SEPs,15 patients with myelopathy having abnormal findings,all 5 patients with spinal cord compression had abnormal SEPs.42 of 68 patients undergoing MRI revealed to be abnormal,in which 35 patients also had abnormal SEPs.The other 26 patients had normal spinal MRI,in which 21 patients had abnormal SEPs.Conclusions Paraspinal stimulation somatosensory evoked potentials and spinal cord conduction velocity may objectively document the abnormalities of electrophysiology,which occurs earlier than those of anatomy and radiological finds, therefore it may detect the dysfunction of spinal cord at an early stage.It is even more useful in the detecting of the metabolic myelopathy,which can hardly be detected by MRI.This technique is simple,inexpensive, and maybe useful in the diagnosis for patients with suspected spinal cord lesions.

Objective To investigate the teaching modes of the course of guide to learn in undergraduate nursing students in order to improve their quality of leaning.Methods Questionnaire survey and interview were conducted to collect the students'general appraisal on learning Science and teaching content and teaching modes as well as ingathering and suggestions of the course.Results Totally 79.5%among 117 students thought it necessary to open the course of Learning Science.96.6%students considered ten subjects of the course reasonable.83.8%students were satisfied with the alternate five-teachers'teaching modes.The most digestible teaching approach Was illustration,and the most valuable experience wag how to regulate the psyehology of learning.Conclusions The course of guide to learn in nursing undergraduate education has positive significance.Nursing educators should always explore and improve the teaching mode of this course so as to help students develop SOundly.

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.

ObjectiveTo evaluate the effect of low dose of dexamethasone on the blood glucose concentration in patients undergoing craniotomy. Methods20 consecutive patients undergoing craniotomy without a preexisting metabolic disorder were prospectively randomized into 1 of 2 groups: Dexamethasone (group D, n=10) and Normal Saline (group S, n=10), who were given dexamethasone 10 mg intravenous bolus or a saline placebo preoperatively. Arterial glucose concentrations were measured immediately before and after treatment and hourly for 5 hours intraoperatively. ResultsThe arterial glucose concentration in group D increased significantly(F=3.133,P<0.05), while those in group S keep stable. Compared with group S, arterial glucose concentration in group D increased significantly 180 min after dosing(P<0.01). ConclusionIf dexamethasone is used during craniotomy, perioperative blood glucose level should be carefully monitored and controled.

Objective To investigate the effect of mild hypothermia on brain edema after severe head injury (SHI) and its clinical significance. Methods Thirty-six patients with SHI were randomly divided into conventional therapy group (control group) and mild hypothermia therapeutic group (therapeutic group), with 18 patients in each group. The patients in the therapeutic group were treated with ice-cap, ice-blanket and ice-bag and lytic cocktail Ⅰas adjuvants, and a rectal temperature of 33 ℃ was maintained for 3~5 d. Intracranial pressure (ICP) of all the patients after operation were monitored postoperatively. The size of brain edema was measured with CT on day 0, 1, 3, 7, 14, 21 respectively after SHI. The size of brain edema at the trauma cite and ICP as well as the clinical outcome were compared and analysed. Results ICP of the control and therapeutic groups were（2.87±0.26）kPa and (1.67±0.23) kPa respectively on day 3 (P<0.01), and were (3.15±0.24)kPa and (1.78±0.24) kPa respectively on day 7 after brain injury (P<0.01). The area of brain edema was the largest on day 14 in the control group (140.90±22.95 cm3)and on day 3 in the therapeutic group (95.83±14.97 cm3). At day 14 posttrauma, the edema area in therapeutic group was 42% smaller than that in the control group (P<0.05). The rates of consciousness recovery within a week were 22.2% (4/18) in the control group and 55.6% (10/18) in the therapeutic group (P<0.05). The rates of unfavorable prognosis was 61.1% (11/18) in the control group and 33.3% (6/18) in the therapeutic group. Conclusion Mild hypothermia treatment can improve the prognosis through alleviating brain edema and stabilizing ICP after SHI.