Meta-analysis of risk factors for restenosis after stent implantation in patients with ischemic cerebrovascular disease.

OBJECTIVE: The aim of this study was to investigate the risk factors for restenosis after stent implantation in patients with ischemic cerebrovascular disease (ICVD), and to provide a reference for potential measures to prevent ICVD. MATERIALS AND METHODS: Relevant studies were identified by searching PubMed, ScienceDirect and Web of Science databases. Combined adjusted odds ratios and 95% confidence intervals were calculated. RESULTS: Seven case-control studies were identified in the end. Diabetes mellitus and residual stenosis were the two main risk factors for restenosis (OR = 0.59, 95% CI: 0.39-0.91, p = 0.01; OR = 36.73, 95% CI: 19.72-70.02, p < 0.001). Gender, smoking, hypertension, dyslipidemia, and stent type were not significantly associated with restenosis (OR = 0.85, 95% CI: 0.53-1.38, p = 0.52; OR = 1.30, 95% CI: 0.91-1.86, p = 0.15; OR = 0.86, 95% CI: 0.16-4.66, p = 0.86; OR = 1.30, 95% CI: 0.58-2.91, p = 0.53; OR = 1.34, 95% CI: 0.72-2.48, p = 0.35). CONCLUSIONS: The prevention of restenosis after stenting is particularly important for ICVD patients with diabetes or a high residual stenosis rate.

[A case of fungal conjunctivitis manifested by a conjunctival mass].

A 71-year-old man presented with a history of persistent redness and swelling in the left eye accompanied by an enlarging mass in the conjunctiva. He denied any history of trauma. Local anti-inflammatory treatment was ineffective. Slit lamp examination demonstrated a tough and immobile grayish broad basal mass at the corneal limbus and bulbar conjunctiva and a local bulge of 3 mm × 2 mm at the medial and lateral side of the upper palpebral conjunctiva near the eyelid margin. The excisional biopsy showed granulomatous inflammation with irregular and atypical squamous epithelial hyperplasia. Histopathology and immunohistochemical staining revealed a fungal infection. The secretion smear examination was performed to clarify the pathogen as Candida albicans, and chronic fungal maxillary sinusitis was found through imaging tests. Thus a diagnosis of conjunctival candidiasis was made. The conjunctival mass subsided after systemic and local antifungal therapy.

[Clinical analysis of Langerhans cell histiocytosis originating in the base of nasal skull].

Objective:To summarize the clinical features, diagnosis and treatment of Langerhans histiocytosis（LCH） which first appeared in the nasal skull base. Method:Ten cases of LCH with nasal and skull base symptoms were analyzed retrospectively. The clinical characteristics of LCH with nasal and skull base symptoms were summarized. The correlation of other systems involved in LCH was analyzed. Result:Among the 10 patients, the youngest was 1 year and 5 months, and the oldest was 8 years, the average age was 3 years. The main imaging manifestations were osteolytic changes and soft tissue invasion. Seven patients were monofocal and three patients were multifocal. For localized lesions, radical resection and follow-up chemotherapy were performed, and conservative treatment was performed for patients with multiple system involvement and obvious systemic symptoms. Eight patients survived, 2 died. Conclusion:LCH occurs frequently in children and has certain clinical characteristics. Single system and single lesion surgery have a better therapeutic effect, and can achieve a greater survival rate with follow-up chemotherapy.

CalliSpheres® drug-eluting beads (DEB) transarterial chemoembolization (TACE) is equally efficient and safe in liver cancer patients with different times of previous conventional TACE treatments: a result from CTILC study.

PURPOSE: To assess the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) in liver cancer patients with different times of previous conventional transarterial chemoembolization (cTACE) treatments. METHODS: 367 liver cancer patients about to receive DEB-TACE treatment were enrolled in this prospective cohort study. All patients were divided into no previous cTACE group (NPC group), 1-2 times previous cTACE group (PC group) and triple or above previous cTACE group (TPC group) according to the times of previous cTACE treatments. RESULTS: There was no difference in complete response (CR) (P = 0.671) and objective response rate (ORR) (P = 0.062) among three groups. Additionally, no difference in overall survival (OS) among groups (P = 0.899) was found. As to liver function, most liver function indexes were deteriorative at 1 week after DEB-TACE operation, but returned to baseline at 1-3 months after DEB-TACE operation in all three groups, while percentage of abnormal total bile acid (TBA) patients was higher in TPC group than NPC and PC groups at 1-3 month post-DEB-TACE (P = 0.018). As for safety profiles, the incidence of pain during DEB-TACE operation was lower in TPC group compared to NPC and PC groups (P = 0.005), while no difference of other adverse events was found during and 1 month post-DEB-TACE treatment among three groups. CONCLUSION: DEB-TACE treatment was equally efficient and tolerated in liver cancer patients with different times of previous cTACE treatments.

Predictive value of cell cycle arrest biomarkers for cardiac surgery-associated acute kidney injury: a meta-analysis.

BACKGROUND: A biomarker test based on a combination of urine tissue inhibitor of metalloproteinases 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) has been used as a potential biomarker of acute kidney injury (AKI). This meta-analysis aimed to evaluate the predictive value of this biomarker for cardiac surgery-associated acute kidney injury (CSA-AKI). METHODS: We searched MEDLINE, PubMed, Cochrane, and EMBASE for studies. We evaluated the methodological quality of each included study using the Quality Assessment of Diagnostic Accuracy Studies 2 criteria. Meta-DiSc and STATA were used for statistical analyses. RESULTS: A total of 10 studies (747 patients) were included in this meta-analysis. Pooled sensitivity and specificity with corresponding 95% confidence intervals (CI) were 0.77 (95% CI: 0.70-0.83, I2=40.7%) and 0.76 (95% CI: 0.72-0.79, I2=69.1%), respectively. Pooled positive likelihood ratio (LR), negative LR, and diagnostic odds ratio were 3.26 (95% CI: 2.51-4.23, I2=50.7%), 0.32 (95% CI: 0.24-0.41, I2=6.7%), and 10.08 (95% CI: 6.85-14.84, I2=6.7%), respectively. The area under the curve estimated by summary receiver operating characteristics was 0.83 [standard error (SE) 0.023] with a Q* value of 0.759 (se 0.021). There was no heterogeneity amongst the 10 studies from both threshold and non-threshold effects. Subgroup analysis showed that the diagnostic value was related to the severity of AKI and time measurement. CONCLUSIONS: Urinary [TIMP-2]·[IGFBP7] is an effective predictive test for cardiac surgery associated acute kidney injury with good diagnostic accuracy within 24 h. Studies examining use of biomarker-guided care bundles are indicated.

[Clinical practice of transnasal endoscopic operation for retrobulbar lesions].

Objective: To summarize the skill and experience of transnasal endoscopic operation for retrobulbar lesions. Methods: Seven patients aged from 25 to 67 years old diagnosed as retrobulbar lesions who underwent transnasal endoscopic operation in Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital between January 2013 and October 2016 were retrospectively analyzed. Two males and five females were included in this study. Five patients underwent transnasal endoscopic operation via media rectus-inferior rectus space, with the other 2 cases via media rectus-superior rectus space. Results: Total lesion removal was achieved in 6 of 7 patients, while 1 patient underwent subtotal removal of the lesion. The visual acuity and visual field improved in 3 cases. The pathological examination showed hemangioma(5 cases), bone cyst(1 case) and fibroma(1 case). All patients were followed up for 9 months to 4 years without complications such as eye movement disorder or blindness, except for 1 case with preoperatively proptosis occurred postoperatively transient diplopia. There was no recurrence in 6 patients with total lesion removal, and the patient underwent subtotal removal of fibroma did not undertake operation again. Conclusion: Transnasal endoscopic operation for retrobulbar lesions is a minimally invasive, safe and effective operatiiv method, which could be taken via different surgical approaches according to the size and location of the lesion.

Clinical application of three-dimensional reconstruction and rapid prototyping technology of multislice spiral computed tomography angiography for the repair of ventricular septal defect of tetralogy of Fallot.

Three-dimensional (3D) reconstruction and rapid prototyping technology (RPT) of multislice spiral computed tomography angiography (CTA) was applied to prepare physical models of the heart and ventricular septal defects of tetralogy of Fallot (ToF) patients in order to explore their applications in the diagnosis and treatment of this complex heart disease. CTA data of 35 ToF patients were collected to prepare l:l 3D solid models using digital 3D reconstruction and RPT, and the resultant models were used intraoperatively as reference. The operations of all 35 patients were completed under the guidance of the 3D solid model, without difficulty. Intraoperative findings of the patients were consistent with the morphological and size changes of the 3D solid model, and no significant differences were found between the patches obtained from the 3D solid model and the actual intraoperative measurements (t = 0.83, P = 0.412). 3D reconstruction and RPT of multislice spiral CTA can accurately and intuitively reflect the anatomy of ventricular septal defects in ToF patients, providing the foundation for a solid model of the complex congenital heart.

Flavonoids health benefits and their molecular mechanism.

Flavonoids are a group of polyphenolic compounds, diverse in chemical structure and characteristics, found ubiquitously in plants. Until now, more than 9000 different flavonoid compounds were described in plants, where they play important biological roles by affecting several developmental processes. There has been increasing interest in the research of flavonoids from dietary sources, due to growing evidence of the versatile health benefits of flavonoids including anti-inflammatory, antioxidant, antiproliferative and anticancer activity, freeradical scavenging capacity, antihypertensive effects, coronary heart disease prevention and anti-human immunodeficiency virus functions. This paper reviews the current advances in flavonoids in food with emphasis on mechanism aspects on the basis of the published literature, which may provide some guidance for researchers in further investigations and for industries in developing practical health agents.

A minimum folding unit in the ankyrin repeat protein p16(INK4).

The ankyrin repeat is an abundant, 33 residue sequence motif that forms a consecutive beta-hairpin-helix-loop-helix (beta(2)alpha(2)) fold. Most ankyrin repeat proteins consist of four or more complete repeats, which provide stabilizing interactions between adjacent modules. The cyclin-dependent kinase inhibitor and tumor suppressor p16(INK4) (p16) is one of the smallest ankyrin repeat proteins with a known structure. It consists of four complete repeats plus short N and C-terminal flanking regions that are unstructured in solution. On the basis of preliminary proteolysis studies and predictions using a computer algorithm for identifying autonomous folding units, we have identified a fragment consisting of the third and fourth ankyrin repeats of p16, called p16C, that can fold independently, without the rest of the protein. Far-UV circular dichroism studies showed that p16C has a significant level of alpha-helical secondary structure, and two proline substitutions that disrupt the alpha-helical secondary structure in wild-type p16 disrupt the secondary structure in p16C. The thermal denaturation of p16C is cooperative and reversible, with a midpoint of transition at 30. 5(+/-1) degrees C. From urea-induced denaturation studies, the free energy of unfolding for p16C was estimated to be 1.7(+/-0.3) kcal/mol at 20 degrees C. (1)H-(15)N 2D NMR studies suggest that the ankyrin repeats in p16C are likely to fold into a structure similar to that of full-length p16. In order to define the minimum autonomous folding unit in p16, we have further dissected p16C into two complementary peptides, each containing a single ankyrin repeat. These peptides are unstructured in solution. Thus, p16C is the smallest ankyrin repeat module that is known to fold independently and, in general, we believe that the two-ankyrin repeat fold could be the minimum structural unit for all ankyrin repeat proteins. We further discuss the significance of p16C in protein folding and engineering.

The Shp-2 tyrosine phosphatase activates the Src tyrosine kinase by a non-enzymatic mechanism.

Previously, we demonstrated that the Src tyrosine kinase interacts with the Shp-2 tyrosine phosphatase. To determine whether Shp-2 regulates Src kinase activity, we measured Src activity in cells overexpressing wild-type or catalytically-inactive C463S Shp-2. We observed a 2-3-fold increase in the specific activity of Src in both cell types and the increase did not appear to be due to dephosphorylation of Tyr 527 or phosphorylation of Tyr 416 on Src. Conversely, we observed a 2-3-fold decrease in the specific activity of Src when Shp-2 expression was inhibited. Using glutathione S-transferase-fusion proteins, we demonstrated that Shp-2 binds to the SH3 domain of Src. Our findings reveal that the Shp-2 tyrosine phosphatase can regulate the Src tyrosine kinase by a non-enzymatic mechanism. We also found that the phosphatase activity of Shp-2 immunoprecipitates is downregulated in cells transformed by Src or other proteins, and that Shp-2 preferentially associates with the membrane fraction of transformed cells. We suggest that membrane-association of Shp-2 is important for regulating Shp-2 activity.

Contribution of individual residues to formation of the native-like tertiary topology in the alpha-lactalbumin molten globule.

Molten globules are partially folded forms of proteins that have native-like secondary structure and a compact geometry, but often without rigid, specific side-chain packing. Recently, the molten globule of alpha-lactalbumin (alpha-LA) has been shown to adopt a native-like tertiary topology, mainly localized in the alpha-helical domain. This native-like topology is reflected by the high effective concentration (Ceff) for formation of the 28-111 disulfide bond, which is approximately 10 to 40 times higher than the Ceff for formation of any non-native disulfide bond in the alpha-helical domain. In order to understand the mechanism for formation of the native-like tertiary topology, we substituted alanine for each of the 23 buried residues in the alpha-helical domain of alpha-LA and determined the effect of these substitutions on the Ceff for formation of the 28-111 disulfide bond. Our results indicate that a subset of hydrophobic residues is most important for formation of the native-like topology. These residues form a densely packed core in the three-dimensional structure of alpha-LA. In contrast, the less important residues consist of both hydrophobic and hydrophilic amino acids located at peripheral positions. These results suggest that a relatively small number of hydrophobic residues may be sufficient for specifying the overall structure of a protein during early stages of protein folding.

Regulation of the Src tyrosine kinase and Syp tyrosine phosphatase by their cellular association.

The specific activity of the Src tyrosine kinase is elevated in human colon carcinoma cells. To identify Src-binding proteins that might upregulate Src activity in these cells, a human colon carcinoma lambda gt11 expression library was screened with purified, 32P-labeled Src. The SH-PTP2 (Syp) tyrosine phosphatase was isolated and shown to associate with Src. In vitro studies demonstrated that: (1) transforming F527 Src phosphorylates Syp, and (2) Syp dephosphorylates Src at Tyr 527. Both events are known to upregulate enzyme activity. Others have shown that overexpression of the receptor tyrosine phosphatase alpha in rat embryo fibroblasts results in Src activation by dephosphorylation of Tyr 527, cell transformation and tumorigenesis. Thus, transmembrane tyrosine phosphatases may be involved in cell transformation exerting at least some of their effects through activation of Src. To the best of our knowledge, this is the first identification of an intracellular tyrosine, phosphatase which may activate Src by a similar mechanism.

Bipartite structure of the alpha-lactalbumin molten globule.

Molten globules are thought to be general intermediates in protein folding. Apparently conflicting studies have failed to clarify whether one of the best characterized molten globules, that of alpha-lactalbumin, resembles an expanded native-like protein or a nonspecific collapsed polypeptide. Here we show that the molten globule properties of alpha-lactalbumin are largely confined to one of its two domains. The alpha-helical domain forms a helical structure with a native-like tertiary fold, while the beta-sheet domain is largely unstructured. Molten globules thus possess a native-like backbone topology, but this topology does not necessarily encompass the entire polypeptide chain. Our studies indicate that molten globules provide an approximate solution to, and considerable simplification of the protein folding problem.

Some phosphonic acid analogs as inhibitors of pyrophosphate-dependent phosphofructokinase, a novel target in Toxoplasma gondii.

Pyrophosphate-dependent phosphofructokinase (PPi-PFK) was identified previously in Toxoplasma gondii as the only kinase that phosphorylates fructose-6-P to fructose-1,6-bisP. Since such an enzyme is not present in mammals, it was considered to be a good target for prospective selective inhibitors of the parasite. We have examined the effects of several phosphonic acid derivatives, analogs of pyrophosphate, on PPi-PFK activity, as well as on the replication of T. gondii in human foreskin fibroblast (HFF) cells. The most active compound in inhibiting PPi-PFK was tetrasodium carbonyldiphosphonate. Several bisphosphonates and related arylhydrazones showed inhibition of the enzyme, but with higher IC50 values. Although several phosphonoacetic acid derivatives also inhibited PPi-PFK, as a group they were less potent than the bisphosphonate derivatives. Comparison among the structures of various inhibitors and their effects against PPi-PFK indicates that a carbonyl (C=O) or amino (C=N) group between two phosphoryl moieties is associated with more potent enzyme inhibiton. Tetrasodium carbonyldiphosphonate did not show a significant effect against replication of T. gondii cells, probably because, as a charged molecule, it could not cross the cell membrane to reach the intracellular parasite. Tetraisopropyl carbonyldiphosphonate 2,4-dinitrophenylhydrazone showed some selective inhibitory effect against replication of the parasite in the HFF cells and protected the mammalian cells from damage by T. gondii. The results indicate that carbonyldiphosphonic acid is a good prototype compound that is amenable to chemical manipulation, which, in turn, may optimize selective inhibition of T. gondii PPi-PFK and increase accessibility to the intracellular parasite.

Purification and properties of a pyrophosphate-dependent phosphofructokinase from Toxoplasma gondii.

Inorganic pyrophosphate-dependent phosphofructokinase was identified in toxoplasma gondii and purified to near homogeneity from the crude extracts. The purified enzyme displayed one major protein band which coincided with enzyme activity on nondenaturing polyacrylamide gel electrophoresis. This phosphofructokinase had a molecular weight of 100,000 determined by gel filtration and was composed of one type of subunit with the molecular weight of 45,000 estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting that the enzyme is a homodimer. Some kinetic parameters of the purified enzyme were investigated in the forward and the reverse directions. The substrate saturation curves for fructose 6-phosphate and pyrophosphate were all hyperbolic. The apparent Km values for fructose 6-phosphate and for pyrophosphate were 2.7 x 10(-4) M and 3.3 x 10(-5) M respectively. Kinetics for Fru-1,2-P2 and for Pi in the reverse reaction were also hyperbolic. The activity of this enzyme was magnesium-dependent. Nucleoside triphosphates and polyphosphates did not serve as phosphate donor and the enzyme activity was not altered in the presence of any of these nucleotides. As in the case of pyrophosphate-dependent phosphofructokinases from other anaerobic eukaryotes the Toxoplasma enzyme was not activated by fructose 2,6-biphosphate.

Purification and characterization of glycogen synthase from a glycogen-deficient strain of Saccharomyces cerevisiae.

Chromatography of wild-type yeast extracts on DEAE-cellulose columns resolves two populations of glycogen synthase I (glucose-6-P-independent) and D (glucose-6-P-dependent) (Huang, K. P., Cabib, E. (1974) J. Biol. Chem. 249, 3851-3857). Extracts from a glycogen-deficient mutant strain, 22R1 (glc7), yielded only the D form of glycogen synthase. Glycogen synthase D purified from either wild-type yeast or from this glycogen-deficient mutant displayed two polypeptides with molecular masses of 76 and 83 kDa on sodium dodecyl sulfate-gel electrophoresis in a protein ratio of about 4:1. Phosphate analysis showed that glycogen synthase D from either strain of yeast contained approximately 3 phosphates/subunit. The 76- and 83-kDa bands of the mutant strain copurified through a variety of procedures including nondenaturing gel electrophoresis. These two polypeptides showed immunological cross-reactivity and similar peptide maps indicating that they are structurally related. The relative amounts of these two forms remained constant during purification and storage of the enzyme and after treatment with cAMP-dependent protein kinase or with protein phosphatases. The two polypeptides were phosphorylated to similar extent in vitro by the catalytic subunit of mammalian cyclic AMP-dependent protein kinase. Phosphorylation of the enzyme in the presence of labeled ATP followed by tryptic digestion and reversed phase high performance liquid chromatography yielded two labeled peptides from each of the 76- and 83-kDa subunits. Treatment of wild-type yeast with Li+ increased the glycogen synthase activity, measured in the absence of glucose-6-P, by approximately 2-fold, whereas similar treatment of the glc7 mutant had no effect. The results of this study indicate that the GLC7 gene is involved in a pathway that regulates the phosphorylation state of glycogen synthase.