NOVA1 promotes SMN2 exon 7 splicing by binding the UCAC motif and increases SMN protein expression.

Spinal muscular atrophy (SMA) is a rare hereditary neuromuscular disease with a high lethality rate in infants. Variants in the homologous genes survival of motor neuron (SMN)1 and SMN2 have been reported to be SMA pathogenic factors. Previous studies showed that a high inclusion rate of SMN2 exon 7 increased SMN expression, which in turn reduced the severity of SMA. The inclusion rate of SMN2 exon 7 was higher in neural tissues than in non-neural tissues. Neuro-oncological ventral antigen (NOVA) is a splicing factor that is specifically and highly expressed in neurons. It plays a key role in nervous system development and in the induction of nervous system diseases. However, it remains unclear whether this splicing factor affects SMA. In this study, we analyzed the inclusion of SMN2 exon 7 in different tissues in a mouse model of SMA (genotype smn-/-SMN22tg/0) and littermate controls (genotype smn+/-SMN22tg/0). We found that inclusion level of SMN2 exon 7 was high in the brain and spinal cord tissue, and that NOVA1 was also highly expressed in nervous system tissues. In addition, SMN2 exon 7 and NOVA1 were expressed synchronously in the central nervous system. We further investigated the effects of NOVA1 on disease and found that the number of neurons in the anterior horn of spinal cord decreased in the mouse model of SMA during postnatal days 1-7, and that NOVA1 expression levels in motor neurons decreased simultaneously as spinal muscular atrophy developed. We also found that in vitro expression of NOVA1 increased the inclusion of SMN2 exon 7 and expression of the SMN2 protein in the U87MG cell line, whereas the opposite was observed when NOVA1 was knocked down. Finally, point mutation and RNA pull-down showed that the UCAC motif in SMN2 exon 7 plays a critical role in NOVA1 binding and promoting the inclusion of exon 7. Moreover, CA was more essential for the inclusion of exon 7 than the order of Y residues in the motif. Collectively, these findings indicate that NOVA1 interacts with the UCAC motif in exon 7 of SMN2, thereby enhancing inclusion of exon 7 in SMN2, which in turn increases expression of the SMN protein.

Sentinel lymph node biopsy compared with axillary lymph node dissection in early breast cancer: a meta-analysis.

Sentinel lymph node biopsy (SLNB) has been recommended as the standard performance for negative sentinel lymph node (SLN) patients without axillary lymph node dissection (ALND) in the surgical management of early breast cancer; however, the efficiency of SLNB for patients with positive SLNs is still unclear. We performed this meta-analysis to compare the effectiveness and safety of SLNB with ALND. Randomized controlled trials (RCTs) comparing SLNB with ALND in early breast cancer were identified in Pubmed, Embase, and The Cochrane Library. Overall survival (OS), disease-free survival (DFS), regional lymph node recurrence, postoperative morbidity, and quality of life (QOL) between the two groups were assessed by using the methods provided by the Cochrane Handbook for Systematic Reviews of Interventions. Eight well-designed RCTs (total 8,560 patients; 4,301 for SLNB and 4,259 for ALND) were included. Meta-analysis showed that there was no statistical difference in OS (HR = 1.07, 95% CI: 0.90-1.27), DFS (HR = 1.00, 95% CI: 0.88-1.14), and regional lymph node recurrence (OR = 1.65, 95% CI: 0.77-3.56) between SLNB and ALND group, whether for SLN (+) subgroup or for SLN (-) subgroup. However, SLNB results in a significant reduction of postoperative morbidity and improved QOL. In conclusion, SLNB can be recommended as preferred care for SLN-negative patients and selected patients with SLN-micrometastasis. Despite this, ALND remains the standard management in breast cancer patients with SLN-macrometastasis.

Lamivudine with or without adefovir dipivoxil for postoperative hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a significant cause of death, especially in Asia and sub-Saharan Africa. Removal of the cancer through surgery or other techniques is considered the first-line therapy in early HCC, but relapse of HCC is the main postoperative problem. The main risk factor for HCC is hepatitis B virus (HBV) infection. Lamivudine and adefovir dipivoxil are effective and tolerable for chronic hepatitis B by suppressing the viral load and to reduce fibrosis in the liver.   OBJECTIVES: To assess the benefits and harms of postoperative administration of lamivudine with or without adefovir dipivoxil in participants with surgically treated HCC and chronic HBV infection or HBV carrier state. SEARCH METHODS: A systematic search was performed in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded (SCI Exp) in October 2011. Further trials have been sought through scanning reference lists of relevant articles. SELECTION CRITERIA: Randomised clinical trials comparing the administration of lamivudine with and without adefovir dipivoxil for participants with ablation treated HCC (surgical or through other techniques) and chronic HBV infection or HBV carrier state, regardless of publication status, language, blinding, and publication status, were to be included in this review. We planned to extract data on harms from quasi-randomised studies or cohort studies when retrieved with the search results. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion, and extracted and analysed the data. The type and number of adverse events were reported descriptively. MAIN RESULTS: No randomised trials could be included into this systematic review. Thus, we were unable to follow our pre-published protocol and perform meta-analyses.Through our searches for randomised clinical trials, four cohort trials with 230 participants were retrieved. We read them in order to find data on harm, ie, adverse events. Breakthrough hepatitis was a serious adverse event attributable to lamivudine. No other adverse events seemed to be caused by the administration of lamivudine or adefovir dipivoxil were reported in the four cohort studies. AUTHORS' CONCLUSIONS: No evidence from randomised trials on the beneficial or harmful effects of lamivudine with or without adefovir dipivoxil for postoperative HCC was found. Randomised clinical trials with large number of participants and long follow-up period should be carried out to direct clinical practice.

[Fine mapping of mutant gene related corneal opacity mouse with SNPs].

To further investigate the genetic mechanism of the mutant mice(B6-Co) with hereditary corneal opacity phenotype obtained by ENU-induced mutagenesis from B6 in previous study, SNP markers were used to map the mutant gene of B6-Co mice. F2 generation mice were bred by backcrossing (B6-CoPxD2 )F1 with D2 and the DNA samples of F2 mutant mice were extracted from the tails. Five SNP sites that showed differences between B6 and D2 strains nearby the located region on chromosome 13 were screened from MGI database. Five SNPs, PCR-RFLP and linkage analyses were carried out to map the mutant gene. The result showed that the mutant gene was located between 112 546 283~113 397 654 bp on chromosome 13. There are five identified genes including Map3k1 that is associated with eye morphogenesis and eyelid closure of mouse in this region. This suggests that Map3k1 is the most probable candidate mutant gene of B6-Co mice.

Comparison of efficacy of simo decoction and acupuncture or chewing gum alone on postoperative ileus in colorectal cancer resection: a randomized trial.

To compared the ability of chewing gum or simo decoction (SMD) and acupuncture to reduce incidence of postoperative ileus (POI) after colorectal cancer resection, patients with colorectal cancer undergoing open or laparoscopic resection were randomized to receive SMD and acupuncture (n = 196), chewing gum alone (n = 197) or no intervention (n = 197) starting on postoperative day 1 and continuing for 5 consecutive days. Patients treated with SMD and acupuncture experienced significantly shorter hospital stay, shorter time to first flatus and shorter time to defecation than patients in the other groups (all P < 0.05). Incidence of grade I and II complications was also significantly lower in patients treated with SMD and acupuncture. Patients who chewed gum were similar to those who received no intervention in terms of hospital stay, incidence of complications, and time to first bowel motion, flatus, and defecation (all P > 0.05). The combination of SMD and acupuncture may reduce the incidence of POI and shorten hospital stay for patients with colorectal cancer after resection. In contrast, chewing gum does not appear to affect recovery of bowel function or hospital stay, though it may benefit patients who undergo open resection. (Clinicaltrials.gov registration number: NCT02813278).

Pathological and ultrastructural observations and liver function analysis of Eimeria stiedai-infected rabbits.

To study the pathogenicity of Eimeria stiedai, sporulated oocysts were given orally to coccidian-free two-month-old New Zealand rabbits(1000±20g). After 30days, blood samples from the rabbit hearts were collected for routine blood tests, liver functions and four characteristics of blood coagulation. Additionally, specimens of the liver, bile duct and duodenum were collected to observe the changes in pathology and ultrastructure. E. stiedai severely restricted the growth and development of rabbits. Blood tests showed that glutamine transferase (GGT) and serum cholinesterase (ChE) were significantly different from the non-infected controls. Other extremely significant differences were observed in the biochemical indices of routine blood tests, liver function and four blood coagulation characteristics, indicating that the liver functions were significantly affected. Staining showed that, compared with the negative control group, the liver, bile duct and duodenum contained significant numbers of lesions, and organs and cell structures suffered severe damage in ultrastructure, which greatly affecting bodily functions. E. stiedai-infected rabbits model was successfully established, which might provide a theoretical basis for research on the pathogenesis of rabbit coccidia, and the diagnosis and prevention of coccidiosis in rabbits.

Clinical significance of colonoscopy in patients with upper gastrointestinal polyps and neoplasms: a meta-analysis.

BACKGROUND: Some authors have studied the relationship between the presence of polyps, adenomas and cancers of upper gastrointestinal tract (stomach and duodenum) and risk of colorectal polyps and neoplasms; however, the results are controversial, which may be due to study sample size, populations, design, clinical features, and so on. No meta-analysis, which can be generalized to a larger population and could provide a quantitative pooled risk estimate of the relationship, of this issue existed so far. METHODS: We performed a meta-analysis to evaluate risk of colorectal polyps or neoplasms in patients with polyps, adenomas or cancers in upper gastrointestinal tract comparing with controls. A search was conducted through PubMed, EMBASE, reference lists of potentially relevant papers, and practice guidelines up to 27 November 2013 without languages restriction. Odd ratios (ORs) were pooled using random-effects models. RESULTS: The search yielded 3 prospective and 21 retrospective case-control studies (n = 37152 participants). The principal findings included: (1) OR for colorectal polyps was 1.15 (95% CI, 1.04-1.26) in the gastric polyps group comparing with control groups; (2) Patients with gastric polyps and neoplasms have higher risk (OR, 1.31 [95% CI, 1.06-1.62], and 1.72 [95% CI, 1.42-2.09], respectively) of colorectal neoplasms comparing with their controls; and (3) Positive association was found between the presence of colorectal neoplasms and sporadic duodenal neoplasms (OR, 2.59; 95% CI, 1.64-4.11). CONCLUSIONS: Findings from present meta-analysis of 24 case-control studies suggest that the prevalence of colorectal polyps was higher in patients with gastric polyps than in those without gastric polyps, and the risk of colorectal neoplasms increases significantly in patients with gastric polyps, neoplasms, and duodenal neoplasms. Therefore, screening colonoscopy should be considered for patients with upper gastrointestinal polyps and neoplasms.

Epidermal growth factor gene polymorphism and risk of hepatocellular carcinoma: a meta-analysis.

BACKGROUND: Hepatocarcinogenesis is a complex process that may be influenced by many factors, including polymorphism in the epidermal growth factor (EGF) gene. Previous work suggests an association between the EGF 61*A/G polymorphism (rs4444903) and susceptibility to hepatocellular carcinoma (HCC), but the results have been inconsistent. Therefore, we performed a meta-analysis of several studies covering a large population to address this controversy. METHODS: PubMed, EMBASE, Google Scholar and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to examine the association between EGF 61*A/G polymorphism and susceptibility to HCC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: Eight studies were chosen in this meta-analysis, involving 1,304 HCC cases (1135 Chinese, 44 Caucasian and 125 mixed) and 2,613 controls (1638 Chinese, 77 Caucasian and 898 mixed). The EGF 61*G allele was significantly associated with increased risk of HCC based on allelic contrast (OR = 1.29, 95% CI = 1.16-1.44, p<0.001), homozygote comparison (OR = 1.79, 95% CI = 1.39-2.29, p<0.001) and a recessive genetic model (OR = 1.34, 95% CI = 1.16-1.54, p<0.001), while patients carrying the EGF 61*A/A genotype had significantly lower risk of HCC than those with the G/A or G/G genotype (A/A vs. G/A+G/G, OR = 0.66, 95% CI = 0.53-0.83, p<0.001). CONCLUSION: The 61*G polymorphism in EGF is a risk factor for hepatocarcinogenesis while the EGF 61*A allele is a protective factor. Further large and well-designed studies are needed to confirm this conclusion.

High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding: a meta-analysis.

AIM: To evaluate the efficacy of high-dose proton pump inhibitors (PPIs) vs low-dose PPIs for patients with upper gastrointestinal bleeding. METHODS: PubMed, Embase, the Cochrane Library, and Web of Science were searched to identify relevant randomized controlled trials (RCTs). Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis. The primary endpoint was rebleeding; secondary endpoints were patient numbers that needed surgery, and mortality. The meta-analysis was performed with a fixed effects model or random effects model. RESULTS: Nine eligible RCTs including 1342 patients were retrieved. The results showed that high-dose intravenous PPI was not superior to low-dose intravenous PPI in reducing rebleeding [odds ratio (OR) = 1.091, 95% confidential interval (CI): 0.777-1.532], need for surgery (OR = 1.522, 95% CI: 0.643-3.605) and mortality (OR = 1.022, 95% CI: 0.476-2.196). Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients (OR = 0.831, 95% CI, 0.467-1.480) and European patients (OR = 1.263, 95% CI: 0.827-1.929). CONCLUSION: Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.