HTRA1 variant increases risk to neovascular age-related macular degeneration in Chinese population

AbstractAge-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the world. Advanced AMD can be divided into wet AMD (choroidal neovascularization) and dry AMD (geographic atrophy, GA). Drusen is characterized by deposits in the macula without visual loss and is an early AMD sign in the Caucasian population. rs11200638 in the promoter of HTRA1 has recently been shown to increases the risk for wet AMD in both Caucasian and Hong Kong Chinese populations. In order to replicate these results in a different cohort, we genotyped rs11200638 for 164 Chinese patients (90 wet AMD and 74 drusen) and 106 normal controls in a Han Mainland Chinese cohort. The genotypes were compared using chi square analysis for an additive allelic model. rs11200638 was significantly associated with wet AMD (p=5.00×10−12). Unlike in the Caucasian population, the risk allele of rs11200638 was not associated with drusen in our Chinese population. These findings confirm the association of HTRA1 with wet AMD

Associations between Body Mass and the Outcome of Surgery for Scoliosis in Chinese Adults

BACKGROUND: In this study we intended to prove that being overweight has an unfavorable impact on the surgical treatment outcome of adult idiopathic scoliosis (AdIS). METHODS: This is a retrospective study on the surgical treatment of seventy-one more than 30 years old (58 females and 13 males; mean age 42.9±12.2) idiopathic scoliotic patients with a minimum follow up of at least 2 years. The patients were divided into an overweight group (BMI≥23) and a non-overweight group (BMI<23). Preoperative, postoperative first erect and final follow-up radiographic measures, perioperative data, the Oswestry disability index (ODI), and the visual analog scale (VAS) were reviewed and compared. FINDINGS: In the overweight group, no significant differences in radiographic measures, perioperative data, preoperative comorbidities, or postoperative complications, except for the more frequent concomitance of preoperative thoracic kyphosis 37.9±7.7 vs. 26.5±11.8 (P = 0.000) and thoracolumbar kyphosis 14.9±10.1 overweighted group vs. 6.5±9.9 non-overweighted group respectively (P = 0.002) were found. A higher morbidity of hypertension 36.8% vs. 9.6% (P = 0.004) was also observed in the overweight group. Postoperative ODI and VAS improved significantly in both groups compared to pre-operative values. The postoperative ODI of the overweight group (19.6±12.4) was significantly higher than that of the non-overweight group (12.4±7.9) (P = 0.022). CONCLUSIONS: Overweight adult idiopathic scoliotic patients had more frequent concomitance of preoperative thoracic kyphosis and thoracolumbar kyphosis and more serious postoperative pain. However, BMI did not affect the outcomes of surgical correction for coronal and sagittal scoliotic deformity and their postoperative complication rates were not significantly affected

Exome Sequencing Identifies ZNF644 Mutations in High Myopia

Myopia is the most common ocular disorder worldwide, and high myopia in particular is one of the leading causes of blindness. Genetic factors play a critical role in the development of myopia, especially high myopia. Recently, the exome sequencing approach has been successfully used for the disease gene identification of Mendelian disorders. Here we show a successful application of exome sequencing to identify a gene for an autosomal dominant disorder, and we have identified a gene potentially responsible for high myopia in a monogenic form. We captured exomes of two affected individuals from a Han Chinese family with high myopia and performed sequencing analysis by a second-generation sequencer with a mean coverage of 30× and sufficient depth to call variants at ∼97% of each targeted exome. The shared genetic variants of these two affected individuals in the family being studied were filtered against the 1000 Genomes Project and the dbSNP131 database. A mutation A672G in zinc finger protein 644 isoform 1 (ZNF644) was identified as being related to the phenotype of this family. After we performed sequencing analysis of the exons in the ZNF644 gene in 300 sporadic cases of high myopia, we identified an additional five mutations (I587V, R680G, C699Y, 3′UTR+12 C>G, and 3′UTR+592 G>A) in 11 different patients. All these mutations were absent in 600 normal controls. The ZNF644 gene was expressed in human retinal and retinal pigment epithelium (RPE). Given that ZNF644 is predicted to be a transcription factor that may regulate genes involved in eye development, mutation may cause the axial elongation of eyeball found in high myopia patients. Our results suggest that ZNF644 might be a causal gene for high myopia in a monogenic form

Human-centered Design for Green Landscape of Urban Streets

This paper first introduces the development process of urban street green landscape in China and the human-centered thinking of the design of urban street green landscape. On the basis of detailed elaboration of the basic theories of urban street green landscape, it analyzes the existing problems and causes for urban street green landscape. Then, from the perspective of human-centered thought, it comes up with several measures for optimizing the green landscape design of urban streets, to provide much more human-centered experience of urban street green landscape

HMGB1 mediates lipopolysaccharide-induced macrophage autophagy and pyroptosis

Abstract Autophagy and pyroptosis of macrophages play important protective or detrimental roles in sepsis. However, the underlying mechanisms remain unclear. High mobility group box protein 1 (HMGB1) is associated with both pyroptosis and autophagy. lipopolysaccharide (LPS) is an important pathogenic factor involved in sepsis. Lentivirus-mediated HMGB1 shRNA was used to inhibit the expression of HMGB1. Macrophages were treated with acetylation inhibitor (AA) to suppress the translocation of HMGB1 from the nucleus to the cytosol. Autophagy and pyroptosis-related protein expressions were detected by Western blot. The levels of caspase-1 activity were detected and the rate of pyroptotic cells was detected by flow cytometry. LPS induced autophagy and pyroptosis of macrophages at different stages, and HMGB1 downregulation decreased LPS-induced autophagy and pyroptosis. Treatment with acetylation inhibitor (anacardic acid) significantly suppressed LPS-induced autophagy, an effect that was not reversed by exogenous HMGB1, suggesting that cytoplasmic HMGB1 mediates LPS-induced autophagy of macrophages. Anacardic acid or an anti-HMGB1 antibody inhibited LPS-induced pyroptosis of macrophages. HMGB1 alone induced pyroptosis of macrophages and this effect was inhibited by anti-HMGB1 antibody, suggesting that extracellular HMGB1 induces macrophage pyroptosis and mediates LPS-induced pyroptosis. In summary, HMGB1 plays different roles in mediating LPS-induced autophagy and triggering pyroptosis according to subcellular localization

A Sub-Pathway Based Method to Identify Candidate Agents for Ankylosing Spondylitis

The need for new therapeutics for Ankylosing Spondylitis (AS) is highlighted by the general lack of efficacy for most agents currently available for this disease. Many recent studies have detailed molecular pathways in AS, and several molecule-targeting agents are undergoing evaluation. We aimed to explore the mechanism of AS and identify biologically active small molecules capable of targeting the sub-pathways which were disregulated in the development of AS. By using the GSE25101 microarray data accessible from the Gene Expression Omnibus database, we first identified the differentially expressed genes (DEGs) between AS samples and healthy controls, followed by the sub-pathway enrichment analysis of the DEGs. In addition, we propose the use of an approach based on targeting sub-pathways to identify potential agents for AS. A total of 3,280 genes were identified as being significantly different between patients and controls with p-values &lt; 0.1. Our study showed that neurotrophic signaling pathway and some immune-associated pathways may be involved in the development of AS. Besides, our bioinformatics analysis revealed a total of 15 small molecules which may play a role in perturbing the development of AS. Our study proposes the use of an approach based on targeting sub-pathways to identify potential agents for AS. Candidate agents identified by our approach may provide the groundwork for a combination therapy approach for AS

Protective Effect of Foxtail Millet Protein Hydrolysate on Ethanol and Pyloric Ligation-Induced Gastric Ulcers in Mice

Foxtail millet has been traditionally considered to possess gastroprotective effects, but studies evaluating its use as a treatment for gastric ulcers are lacking. Here, we assessed the antiulcer effects of foxtail millet protein hydrolysate (FPH) and explored its mechanism by using blocking agents. In a mouse model of ethanol-induced gastric ulcers, pretreatment with FPH reduced the ulcerative lesion index, downregulated the expression of inflammatory cytokines in the gastric tissue, increased the activity of antioxidant enzymes, and improved the oxidative status. FPH increased constitutive the activity of nitric oxide synthase (cNOS), NO levels, and mucin expression in gastric mucosa, and inhibited the activation of the ET-1/PI3K/Akt pathway. In a mouse model of pyloric ligation-induced gastric ulcers, FPH inhibited gastric acid secretion and decreased the activity of gastric protease. Pretreatment of mice with the sulfhydryl blocker NEM and the NO synthesis inhibitor L-NAME abolished the gastroprotective effect of FPH, but not the KATP channel blocker glibenclamide and the PGE2 synthesis blocker indomethacin. Among the peptides identified in FPH, 10 peptides were predicted to have regulatory effects on the gastric mucosa, and the key sequences were GP and PG. The results confirmed the gastroprotective effect of FPH and revealed that its mechanism was through the regulation of gastric mucosal mucus and NO synthesis. This study supports the health effects of a millet-enriched diet and provides a basis for millet protein as a functional food to improve gastric ulcers and its related oxidative stress

41-year-old female with a BMI of 27.7 diagnosed with thoracolumbar idiopathic scoliosis.

<p>(A) anterior-posterior standing and (B) standing lateral full-length spinal preoperative X-rays showing coronal imbalance and sagittal thoracolumbar kyphosis; (C) anterior-posterior standing and (D) standing lateral full-length spinal X-rays: the first post-surgical erect X-rays showing the correction and fusion; (E) anterior-posterior standing and (F) standing lateral full-length spinal X-rays: the two-year follow-up X-rays showed a good balance.</p

Postoperative Radiographic Measures of Adult Idiopathic Scoliotic Patients.

<p>SD indicates standard deviation; CSVL, center sacral vertical line.</p