SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2) prevents cardiac remodeling after myocardial infarction through ERK/SMAD signaling pathway.

In this study, we aimed to investigate the role of SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2) in cardiac remodeling after myocardial infarction (MI) and explore the underlying molecular mechanism. MI model was established by ligation of the left anterior descending coronary artery. C57/BL6J mice were randomly administered with 3.0 mg/kg/day PHPS1 (PHPS1-treated group) or normal saline (model group) by intraperitoneal injection. After 4 weeks of infusion, the effects of PHPS1 on cardiac remodeling were evaluated. Echocardiography results showed that PHPS1 treatment aggravated the MI-induced deterioration of cardiac function, with worse cardiac function parameters. PHPS1 treatment significantly increased the infarcted area, as well as the fibrotic area and the expression of collagen I and collagen III. Western blots and immunofluorescence staining showed that PHPS1 treatment up-regulated the expression of p-GRK2, p-SMAD2/3 and p-ERK1/2, while U0126 reversed the effect of PHPS1. The present study indicated that PHPS1 treatment contributed to myocardial fibrosis and infarction by activating ERK/SMAD signaling pathway, suggesting that SHP-2 may be a promising treatment target for cardiac remodeling after MI.

Effect of toll-like receptor 3 agonist poly I:C on intestinal mucosa and epithelial barrier function in mouse models of acute colitis.

AIM: To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis. METHODS: Thirty C57BL/6 mice were given either regular drinking water (control group) or 2% (w/v) DSS drinking water (model and poly I:C groups) ad libitum for 7 d. Poly I:C was administrated subcutaneously (20 µg/mouse) 2 h prior to DSS induction in mice of the poly I:C group. Severity of colitis was evaluated by disease activity index, body weight, colon length, histology and myeloperoxidase (MPO) activity, as well as the production of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin 17 (IL-17) and interferon-γ (IFN-γ). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeled-dextran (FITC-D) method. Ultrastructural features of the colon tissue were observed under electron microscopy. Expressions of tight junction (TJ) proteins, including zo-1, occludin and claudin-1, were measured by immunohistochemistry/immunofluorescence, Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: DSS caused significant damage to the colon tissue in the model group. Administration of poly I:C dramatically protected against DSS-induced colitis, as demonstrated by less body weight loss, lower disease activity index score, longer colon length, colonic MPO activity, and improved macroscopic and histological scores. It also ameliorated DSS-induced ultrastructural changes of the colon epithelium, as observed under scanning electron microscopy, as well as FITC-D permeability. The mRNA and protein expressions of TJ protein, zo-1, occludin and claudin-1 were also found to be significantly enhanced in the poly I:C group, as determined by immunohistochemistry/immunofluorescence, Western blot and RT-qPCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-α, IL-17 and IFN-γ. CONCLUSION: Our study suggested that poly I:C may protect against DSS-induced colitis through maintaining integrity of the epithelial barrier and regulating innate immune responses, which may shed light on the therapeutic potential of poly I:C in human colitis.

[Necessity of defunctioning stoma in low anterior resection for rectal cancer: a meta-analysis].

OBJECTIVE: To evaluate the necessity of defunctioning stoma in low anterior resection for rectal cancer below peritoneal reflection. METHODS: The databases of Medline, Embase, Cochrane Library, Wanfang and CNKI were searched. The eligible studies were identified for pooled analyses. RESULTS: Six randomized controlled trials with 648 cases(332 patients with defunctioning stoma and 316 without stoma) and 25 retrospective controlled trials with 10,722 cases(4,470 patients with defunctioning stoma and 6,252 without stoma) were included. Combined analyses showed that defunctioning stoma was effective for decreasing risk of postoperative anastomotic leakage (RR=0.33 and 95% CI:0.21-0.53 for RCTs, OR=0.60 and 95% CI:0.42-0.85 for retrospective studies), reoperation (RR=0.30, 95% CI:0.16-0.53 for RCTs, OR=0.26 and 95% CI:0.21-0.32 for retrospective studies) and mortality(OR=0.41, 95% CI:0.27-0.62 for retrospective studies). CONCLUSION: Defunctioning stoma should be routinely performed in low anterior resection for high-risk patients.

Bioinformatics-led design of single-chain antibody molecules targeting DNA sequences for retinoblastoma.

AIM: To analyze the relationship between the structure and function of single-chain Fv antibody (scFv) with bioinformatics methods, so as to provide theoretical basis for retinoblastoma targeted therapy. METHODS: Single-chain antibodies are reconstructed for cancer-targeted therapy to provide good penetration into tumor tissue and to improve their pharmacokinetics in vivo, offering a clinically valuable application. The relationship needs to be analyzed that there may be some variations between the structure and function of the fusion proteins, and the relationship between the structure and function of protein molecules was obtained through analyzing relevant literature at home and abroad as well as modeling analysis. RESULTS: Through our analysis of the interaction region between the antibody and the antigen, and of the binding sites for molecular conformation, it is clear that existing antibodies need to be modified at the DNA sequence level, enhancing the biological activity of the antibodies. Based on the view that bio-molecular computer models are closely integrated with biological experiments, a bio-molecular structure-activity relationship model can be established in terms of molecular conformation, physical and chemical properties and the biological activity of single-chain antibodies. Two enlightenments are obtained from our analysis. On the one hand, the structure-activity relationship is clear for new immune molecules at the gene expression level. On the other hand, a single-chain antibody molecule can be designed and optimized for the cancer-oriented treatment. CONCLUSION: In this article, we provide the theoretical and experimental basis for the development of single-chain antibodies appropriate for retinoblastoma therapy.

Development of biomedical publications on ametropia research in PubMed from 1845 to 2010: a bibliometric analysis.

AIM: We have carried out a bibliometric analysis on the development of ametropia literature to determine its growth rule and tendency, and to provide the basis for the problems related to ametropia research. METHODS: Literatures that contained the descriptors of ametropia in title or paper published before Nov. 10, 2010 in PubMed databases (www.ncbi.nlm.nih.gov/Pubmed) were selected. As bibliometric indicators of ametropia, biomedical journals referring to ophthalmology by ISSN were calculated. The principal bibliometric indicators: Price's and Bradford's laws were applied on the increase or dispersion of scientific literature, the participation index of languages and the journals. By means of manual coding, literatures were classified according to documents study and statistical analysis. RESULTS: The literatures cited in ametropia, astigmatism, myopia and hypermetropia had accumulated to 26475, which consists of Review (n=1560), Randomized Controlled Trial (n=776), Practice Guideline (n=10), Meta-Analysis (n=23), Letter (n=1222), Editorial (n=328), Clinical Trial (n=1726) and Others (n=20830), and Humans (n=23073), Animals(n=1434) and others (n=1968). 1136 literatures were included in PubMed Central, 22384 in MEDLINE and 2955 in others. The ametropia literatures rose every 5 years which of the ametropia-year cumulated amount of the literatures had three periods: before 1900, slowly increasing from 1901 to 1950, rapidly rising from 1951 to 2010 (increased approximate exponentiation exponent). Sixty kinds of languages listed in PubMed databases, of which English is dominant for aborting to ametropia research documents before 2010 (77.32%, 20471/26475). The document languages of top eight account for 95.58% (English, German, French, Japanese, Russian, Italian, Spanish, Chinese), and others for 4.42% (1171/26475). The SCI database includes 48 ophthalmologic journals and the impact factor of 39 journals is ≥1 on Thomson-Reuters in 2010. Of 48 ophthalmologic journals, there were 14785 documents (55.85%) of ametropia, astigmatism, myopia, and hypermetropia. Others were without exception. CONCLUSION: The bibliometric analysis results show that ametropia literature are increased progressively, approximate exponentiation exponent during 1951-2010. In addition, ametropia research has become more popular since nearly half century.

[Association of peripheral and central blood pressure with the alpha-adducin Gly460Trp polymorphism in a Chinese population].

OBJECTIVE: To investigate the association of peripheral and central blood pressure with the alpha-adducin Gly460Trp polymorphism in Chinese. METHODS: We randomly selected 6 villages from JingNing County, ZheJiang Province. We invited nuclear families to take part in our study. We measured each participant's blood pressure at the non-dominant arm by means of a standard mercury sphygmomanometer at subjects' homes. Five consecutive readings were averaged for analysis. Central blood pressures were obtained by use of SphigmoCor pulse wave analysis system. The observers administered a standardized questionnaire to collect information on smoking habits, alcohol consumption and use of antihypertensive drugs. Venous blood was sampled and the adducin genotype was determined by restrictive fragment length polymorphism (RFLP). RESULTS: Four hundred and forty-two subjects included 230 (52.0%) women, and 116 (26.2%) hypertensive patients, of whom 49 (11.1%) took antihypertensive drugs. The frequencies of alpha -adducin GlyGly, GlyTrp and TrpTrp genotypes were 21.3%, 54.5% and 24.2%, respectively. There was no association between the alpha-adducin Gly460Trp polymorphism and peripheral systolic and diastolic blood pressure and pulse pressure. However, both before and after adjustment for sex, age, age(2), body-mass index, current smoking, alcohol intake, and antihypertensive treatment, the alpha-adducin polymorphism was significantly (P < 0.02) associated with central systolic blood pressure and central pulse pressure. After adjustment, central systolic blood pressure (+/- SE) averaged 122.5 +/- 3.5, 114.1 +/- 1.5 and 109.1 +/- 1.8 mm Hg (P = 0.01) in the GlyGly, GlyTrp and TrpTrp subjects, respectively. The corresponding values for central pulse pressure were 39.4 +/- 1.3, 36.4 +/- 1.0 and 32.9 +/- 0.9 mm Hg (P = 0.002), respectively. CONCLUSIONS: In the JingNing population, the adducin 460Trp allele was associated with lower levels of central systolic pressure and pulse pressure.

Palliative operation procedures for pancreatic head carcinoma.

OBJECTIVE: To investigate the procedure choice of palliative operation for carcinoma of the head of the pancreas (CHP). METHODS: The clinical data from 187 patients with CHP treated in the last 20 years were analyzed retrospectively. RESULTS: The operation mortality rate was 8.6%, the mortality of hepatic duct-jejunostomy (HDJS) was not higher than that of cholecystojejunostomy (CJS) (P>0.05). The postoperative relapse of jaundice and cholangitis was significantly lower than that of CJS (P<0.025), while the survival was apparently higher than that of CJS (P<0.01). The mortality of HJDS or CJS with gastrojejunostomy (GJS) was not significantly higher than that of the simple procedure without GJS (P>0.05), whereas the survival was significantly higher than that of the simple procedure without GJS (P<0.01). The occurrence of duodenal obstruction after HDJS or CJS was 29.3%. CONCLUSION: As a palliative operation, Roux-en-Y choledochojejunostomy especially in combination with preventive gastrojejunostomy is strongly recommended.

Procedures for congenital choledochal cysts and curative effect analysis in adults.

OBJECTIVE: To evaluate the procedures and timing of operation as well as long-term postoperative effect of congenital choledochal cysts (CCC) in adults. METHODS: The procedures and timing of operation, effective rate, re-operation rate and incidence of carcinoma after operation for 70 adult patients with CCC from January 1980 to June 1999 were analyzed retrospectively. RESULTS: The re-operation rate of external drainage was 86% (6/7). The effective rate of internal drainage was significantly lower than that of cyst resection (3/10 vs 45/49, chi2=20.94, P<0.001). The re-operation rate and incidence of carcinoma of internal drainage were higher than those of cyst resection (5/10 vs 3/49, chi2=13.64, P<0.001 and 3/10 vs 3/49, chi2=5.18, P<0.025). The reoperation rate of emergency surgery was higher than that of selective operation (8/10 vs 6/56, chi2=24.37, P<0.001). CONCLUSIONS: External drainage should be the first-aid measure and the therapy of choice on emergency basis. Internal drainage should never be attempted. Cyst resection with Roux-en-Y hepaticojejunostomy is recommended as the treatment of choice in selective operation.