LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Objective: To detect norovirus (NoV) GⅠ.1- and GⅡ.4-specific IgG, IgA and histo-blood group antigen (HBGA)-blocking antibodies in healthy populations of all age groups in China for better understanding the epidemiological features of norovirus in China from a serological point of view and providing basic data for vaccine development and clinical trial design. Methods: Indirect ELISA and HBGA-blocking assay were used to detect NoV-specific IgG, IgA and HBGA-blocking antibodies in serum samples collected from healthy natural populations (n=839, aged from six months to 88 years old) in Guangzhou, Fuyang and Yantai. The results were statistically analyzed. Results: The total positive rates of NoV GⅠ.1- and GⅡ.4-specific IgG antibodies were 91.9% and 93.0%. The positive rates of GⅠ.1- and GⅡ.4-specific IgA antibodies were 48.6% and 75.6%, and the titers of HBGA-blocking antibodies to GⅠ.1 and GⅡ.4 norovirus were 5.04 (95%CI: 4.63-5.49) and 18.15 (95%CI: 16.11-20.44). The positive rates of IgG and IgA antibodies generally showed an increasing trend with age. The positive rates of GⅠ.1- and GⅡ.4-specific IgG antibodies ranged from 79.2% to 100.0% and 76.7% to 100.0% in different age groups. They were 81.7% and 85.0% in the age group of 0.5-<1 year, 79.2% and 76.7% in the age group of 1-<2 years, and 98.1% and 96.3% in the age group of 12-<18 years, and maintained at 96% and 98% in the older age groups. The positive rates of GⅠ.1-specific IgA antibody ranged from 11.7% to 93.8% in different age groups and rapidly increased with age. It was 11.7% in the age group of 0.5-<1 year, and reached 93.3% in people aged 45-<60 years and 93.8% in people aged ≥60 years. The positive rates of GⅡ.4-specific IgA antibody ranged from 50.8% to 88.8% in different age groups with 50.8% in people aged 0.5-<1 year, and 86.7%-90.7% in people aged 12-<18 years and older. The titer of GⅠ.1 HBGA-blocking antibody generally increased with age. The antibody titer in populations aged 0.5-<12 years old was lower than that in those aged 18 years and above (GMT: 2.98-4.07 vs 8.21-11.62, P<0.001), and the titer in people of 12-<18 years old was lower than that in those of 45 years old and above (GMT: 5.21 vs 11.03-11.62, P<0.05). No obvious change with age was observed in the titer of GⅡ.4 HBGA-blocking antibody excepting the significant difference between populations of 2-<5 and 22-<45 years old (GMT: 26.73 vs 11.87, P<0.01). Conclusions This study revealed the characteristics of serum NoV GⅠ.1- and GⅡ.4-specific IgG, IgA and HBGA blocking antibodies in populations of different age groups in central and eastern China through analyzing their positive rates and titers and provided preliminary seroepidemiological data for the development of NoV vaccines in China.

Objective To investigate the hemodynamic changes in a tortuous coronary to elucidate the effects of tortuosity on coronary perfusion and wall shear stress (WSS). Methods A single tortuous and non-tortuous patient-specific left anterior descending (LAD) coronary artery cases were selected. Two LAD models with and without coronary tortuosity were reconstructed in Mimics software and then transferred to the ANSYS Fluent software for performing computational fluid dynamics (CFD) simulation. The hemodynamic characteristics of both the LAD models were compared. Results The vessel WSS of the tortuous coronary artery clearly decreased in the bend section where the maximum curvature was larger than 1 mm-1.Such a scenario could led to an inadequate blood supply in the downstream vessels. A low WSS (0-26 Pa) acted on the outer wall of the bend, whereas the inner wall of the bend had a high WSS (>100 Pa). The mean WSS of the non-tortuous and tortuous models was 10.79 Pa and 36.12 Pa, respectively. The overall WSS of the tortuous model was larger compared with that of the non-tortuous model. Conclusions Coronary tortuosity increased the overall WSS, which could delay the progress of coronary atherosclerosis.

Objective: To conduct a preliminary evaluation for the usability of Carelink remote monitoring system by clinical physician. Methods: A total of 215 patients received cardiovascular implantable electronic devices (CIED) with Carelink remote monitoring function from 12 hospitals in China between 2012-01 and 2013-10 were prospectively enrolled. The patient's mean age was (62.3±14.3) years including 108 male and 107 female. There were 54 physicians completed questionnaire survey. Based on the type of CIED, the patients were divided into3 groups: PM (pace maker) group,n=110, ICD (implantable cardioverter defibrillator) group,n=54 and CRT (cardiac resynchronization therapy) group,n=51. The patients received routine hospital visit at 3 months of CIED implantation and meanwhile, they performed device data transmission at 3 and 6 months of Carelink remote monitoring. The time physician spent to evaluate data was collected at 3 months and the questionnaire survey was completed by physician at 6 months after CIED implantation. Results: All 54 physicians felt that Carelink remote monitoring system was simple to operate and easy to use. There were 147 patients ifnished hospital visit at 3 months after CIED implantation, the mean time for physician to evaluate data was (14.8±8.4) min; 150 patients ifnished Carelink remote monitor at 3 months after CIED implantation, the mean time for physician to evaluate data was (8.2 ±4.6) min,P<0.0001.Conclusion: Carelink remote monitoring system was easy to use, it may save time in follow-up study which with high satisfaction in clinical practice.

BACKGROUND:The treatment difficulties of thoracolumbar angular kyphosis surgery are:low correction rate, hard to rebuild sagittal plane, easily induce neurological complications, postoperative loss of balance, high incidence of pseudarthrosis and postoperative loss of correction degree.
OBJECTIVE:To explore the safety and efficacy of modified posterior vertebral column resection osteotomy and bilateral pedicle screw combined with echelon tight closure spinal cord technique and implant fixation for severe spinal angular kyphosis.
METHODS:A total of 87 severe spinal angular kyphosis patients, 36 males and 51 females, who were treated in the Department of Orthopedics, the 306 Hospital of Chinese PLA from January 2006 to December 2013, were enrol ed in this study. They underwent posterior vertebral column resection, bilateral pedicle screw combined with echelon tight closure spinal cord, and implant fixation. Kyphosis, spinal sagittal imbalance, offset rate towards trunk side, operation time and intraoperative blood loss were observed before and after treatment.
RESULTS AND CONCLUSION:The preoperative average kyphosis was 90.1° (31°-138°). The postoperative average kyphosis was 27.9° (15°-57°). The improvement rate was 76%. The improvement rate of trunk sagittal offset was 76%. Intraoperative blood loss was 800-3 000 mL, and average blood loss was 2 300 mL. The operation time was 5-7 hours, averagely 5.9 hours. Before treatment, two patients affected neurologic symptoms in double lower extremity, and their Frankel classification was grade C and became grade E after treatment. Al patients were fol owed up for 9-57 months. Bony fusion was achieved in al patients. No complications of spinal cord injury appeared, and no orthopedic angle missing occurred. These results indicate that during posterior vertebral column resection for treating severe angular stiffness of the thoracic kyphosis, blood vessels could be maintained greatly. Blood vessel injury-induced ischemic changes in spinal cord and ischemic reperfusion injury could be avoided. To reduce hemorrhage and to keep effective blood volume in patients with low body mass are effective for early recovery after treatment. Bilateral pedicle screw combined with echelon tight closure spinal cord technique greatly protected spinal cord cells against injury. We should pay attention to the protection and loose of nerve root to avoid postoperative nerve root irritation. Sufficient bone fusion ensures kyphosis correction, avoids spine lateral offset, and plays a key role in spinal function and postoperative orthopedic effect.

Objective To observe the therapeutic effect of Dioscorea opposita polysaccharide on gastric ulcer in rats,and to investigate the effects of Dioscorea opposita polysaccharide on level of epidermal growth factor ( EGF) in stomach tissues .Methods 50 rats were randomly divided into five groups [ A group ( normal control group ) , B group(model group),C group(Dioscorea opposita polysaccharide group ),D group(teprenone group)].The healing condition of gastric ulcer and EGF level were observed and compared .Results (1)The ulcer index of C group was obviously reduced compared with B group (P<0.01).(2)Between C group and A group,the significant difference existed in the level of EGF(P<0.05),while the difference was not statistically significant between C group and D group(P>0.05).Conclusion Dioscorea opposita polysaccharide has protective effects for gastric mucosa .The mechanism of protection may be related to promote synthesis of EGF .

BACKGROUNDMicroRNAs (miRNAs) contribute to tumorigenesis by acting as either oncogenes or tumor suppressor genes. In this study, we investigated the role of miR-145 in the pathogenesis of uveal melanoma.

METHODSExpression profiles of miRNAs in uveal melanoma were performed using Agilent miRNA array. Quantitative real-time polymerase chain reaction was used to screen the expression levels of miR-145 in normal uveal tissue, uveal melanoma tissue, and uveal melanoma cell lines. Lenti-virus expression system was used to construct MUM-2B and OCM-1 cell lines with stable overexpression of miR-145. Cell proliferation, cell cycle, and cell apoptosis of these miR-145 overexpression cell lines were examined by MTT assay and flow cytometry respectively. The target genes of miR-145 were predicted by bioinformatics and confirmed using a luciferase reporter assay. The expression of insulin-like growth factor-1 receptor (IGF-1R), insulin receptor substrate-1 (IRS-1) proteins was determined by Western blotting analysis. IRS-1 was knocked down in OCM-1 cells. TUNEL, BrdU, and flow cytometry assay were performed in IRS-1 knocked down OCM-1 cell lines to analyze its function.

RESULTSForty-seven miRNAs were up regulated in uveal melanoma and 61 were down regulated. miR-145 expression was significantly lower in uveal melanoma sample and the cell lines were compared with normal uveal sample. Overexpression of miR-145 suppressed cell proliferation by blocking the G1 phase entering S phase in uveal melanoma cells, and promoted uveal melanoma cell apoptosis. IRS-1 was identified as a potential target of miR-145 by dual luciferase reporter assay. Knocking down of IRS-1 had similar effect as overexpression of miR-145.

CONCLUSIONmiR-145 might act as a tumor suppressor in uveal melanoma, and downregulation of the target IRS-1 might be a potential mechanism.

Apoptosis ; genetics ; physiology ; Blotting, Western ; Cell Cycle ; genetics ; physiology ; Cell Line, Tumor ; Cell Proliferation ; genetics ; physiology ; Humans ; In Vitro Techniques ; Insulin Receptor Substrate Proteins ; genetics ; metabolism ; Melanoma ; genetics ; metabolism ; pathology ; MicroRNAs ; genetics ; metabolism ; Polymerase Chain Reaction ; Uveal Neoplasms ; genetics ; metabolism ; pathology

OBJECTIVE: To explore the cause of cardiac perforation and tamponade during cardiac catheterization and intervention and to evaluate the effectiveness of the emergency treatment for tamponade in our hospital. METHODS: The clinical data from 23, 319 patients who received diagnostic catheterization or therapeutic procedures were analyzed retrospectively. RESULTS: Cardiac perforation and cardiac tamponade were observed in 22 of the 23, 319 patients during catheter procedures. It includes 1 in coronary artery angiography, 9 in percutaneous balloon mitral valvuloplasty, 3 in diagnosis, 2 in congenital heart disease intervention, 2 in pacemaker implantation, 2 in atrial fibrillation ablation and the other 3 in coronary revascularization. The occurrence of cardiac perforation in 11 patients was related to puncture of the interatrial septum and/or the procedure in the left atrial procedure and 2 were related to high pressure injection. Seventeen patients were found cardiac tamponade in the process of catheterization, and 5 were found at 2-14 h after operation. Pericardiocentesis and pericardial catheter drainage were performed in 20 patients and 11 of them succeeded. Among the other 11 patients, 7 were successfully saved by thoracotomy and 4 died. CONCLUSION Cardiac tamponade is a severe and fatal complication that may occur in different catheter procedures. Early prevention and diagnosis and performingperi cardiocentesis and drainage timely are critical to reduce the mortality.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Angioplasty, Balloon, Coronary ; adverse effects ; Cardiac Catheterization ; adverse effects ; Cardiac Tamponade ; etiology ; Child ; Child, Preschool ; Female ; Heart Injuries ; epidemiology ; etiology ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Pacemaker, Artificial ; adverse effects ; Retrospective Studies ; Young Adult

Objective To analyze the feasibility of the recombinant cholera toxin B subunit (rCTB) as a carrier protein candidate for the preparing of polysaccharide-protein conjugate, and to discuss the immune effects of tetanus toxoid (TT) as the carrier protein in mucosal delivery vaccine. Methods The refolded pentrumer protein, rCTB was obtained by genetic engineering methods. Then conjugated the refold-ed protein with group A meningococcal polysaccharide (GAMP) using the chemical method(ADH) ,the pol-ysaccharide-protein conjugates(GAMP-rCTB) were prepared. BALB/c mice were immunized either intraper-itoneally ( i. p. ) or intranasally ( i. n. ) with GAMP-rCTB. Moreover, GAMP-TT vaccine that TT as carrier proteins was i.n. immunized to the mice. The evaluation of immunology is performed. Results The conju-gates of polysaccharide-potein with the rCTB and TT as protein carrier both are able to elicit high level of GAMP specific IgG antibody in serum after i.n. immunization, and the conjugates can also elicit specific IgA antibody in lung lavage and intestinal mucosa. Conclusion rCTB and TT can both as the protein carri-er for polysaccharide-protein conjugate as mucosal vaccine. The route of intranasal may be more ways for im-mune function than i.p. immunization when rCTB is used as the carrier of the polysaccharide-protein conju-gates.

Objective To summarize the nursing methods for patients with chronic congestive heart failure treated with local renal nerve block. Methods 10 cases of patients with chronic congestive heart failure were treated with renal nerve block. The blood and urine electrolytes, plasma neuroendocrine hor-mones, the 24-hour urine volume were measured before and after the renal nerve block to calculate the rate of excretion of urinary sodium. The changes of the heart rate and blood pressure and the improvement of the dyspnoea, swelling and other symptoms of heart failure were monitored continuously before and after the re-nal nerve block. Results There was a significant increase in the 24-hour urine volume and the rate of excretion of urinary sodium in the patients with heart failure after the renal nerve block (P<0.05),and there was a significant decrease in the amount of plasma neuroendocrine hormones after the renal nerve block (P<0.01);there was no signifieant changes in the heart rate and the average blood pressure with improvement of dyspnoea, swelling and other symptoms of heart failure. No significant complications were found. Conclusions The nursing measures taken by the nurses in the clinical application of local renal nerve block as a new treatment modality to the treatment of patients with chronic congestive heart failure are safe, effective and feasible.