Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus.

The hypothalamus plays a crucial role in the progression of obesity and diabetes; however, its structural complexity and cellular heterogeneity impede targeted treatments. Here, we profiled the single-cell and spatial transcriptome of the hypothalamus in obese and sporadic type 2 diabetic macaques, revealing primate-specific distributions of clusters and genes as well as spatial region, cell-type-, and gene-feature-specific changes. The infundibular (INF) and paraventricular nuclei (PVN) are most susceptible to metabolic disruption, with the PVN being more sensitive to diabetes. In the INF, obesity results in reduced synaptic plasticity and energy sensing capability, whereas diabetes involves molecular reprogramming associated with impaired tanycytic barriers, activated microglia, and neuronal inflammatory response. In the PVN, cellular metabolism and neural activity are suppressed in diabetic macaques. Spatial transcriptomic data reveal microglia's preference for the parenchyma over the third ventricle in diabetes. Our findings provide a comprehensive view of molecular changes associated with obesity and diabetes.

Chromosome-level genomes of three key Allium crops and their trait evolution.

Allium crop breeding remains severely hindered due to the lack of high-quality reference genomes. Here we report high-quality chromosome-level genome assemblies for three key Allium crops (Welsh onion, garlic and onion), which are 11.17 Gb, 15.52 Gb and 15.78 Gb in size with the highest recorded contig N50 of 507.27 Mb, 109.82 Mb and 81.66 Mb, respectively. Beyond revealing the genome evolutionary process of Allium species, our pathogen infection experiments and comparative metabolomic and genomic analyses showed that genes encoding enzymes involved in the metabolic pathway of Allium-specific flavor compounds may have evolved from an ancient uncharacterized plant defense system widely existing in many plant lineages but extensively boosted in alliums. Using in situ hybridization and spatial RNA sequencing, we obtained an overview of cell-type categorization and gene expression changes associated with spongy mesophyll cell expansion during onion bulb formation, thus indicating the functional roles of bulb formation genes.

A Wearable Biofeedback Device for Monitoring Tibial Load During Partial Weight-Bearing Walking.

Patients with tibial fractures are usually advised to follow a partial weight-bearing gait rehabilitation program after surgery to promote bone healing and lower limb functional recovery. Currently, the biofeedback devices used for gait rehabilitation training in fracture patients use ground reaction force (GRF) as the indicator of tibial load. However, an increasing body of research has shown that monitoring GRF alone cannot objectively reflect the load on the lower limb bones during human movement. In this study, a novel biofeedback system was developed utilizing inertial measurement units and custom instrumented insoles. Based on the data collected from experiments, a hybrid approach combining a physics-based model and neural network architectures was used to predict tibial force. Compared to the traditional physics-based algorithm, the physical guided neural networks method showed better predictive performance. The study also found that regardless of the type of weight-bearing walking, the peak tibial force was significantly higher than the peak tibial GRF, and the time at which the peak tibial compression force occurs may not be consistent with the time at which the peak vertical GRF occurs. This further supports the idea that during gait rehabilitation training for patients with tibial fractures, monitoring and providing feedback on the actual tibial force rather than just the GRF is necessary. The developed device is a non-invasive and reliable portable device that can provide audio feedback, providing a viable solution for gait rehabilitation training outside laboratory and helping to optimize patients' rehabilitation treatment strategies.

Sulfur, sterol and trehalose metabolism in the deep-sea hydrocarbon seep tubeworm Lamellibrachia luymesi.

BACKGROUND: Lamellibrachia luymesi dominates cold sulfide-hydrocarbon seeps and is known for its ability to consume bacteria for energy. The symbiotic relationship between tubeworms and bacteria with particular adaptations to chemosynthetic environments has received attention. However, metabolic studies have primarily focused on the mechanisms and pathways of the bacterial symbionts, while studies on the animal hosts are limited. RESULTS: Here, we sequenced the transcriptome of L. luymesi and generated a transcriptomic database containing 79,464 transcript sequences. Based on GO and KEGG annotations, we identified transcripts related to sulfur metabolism, sterol biosynthesis, trehalose synthesis, and hydrolysis. Our in-depth analysis identified sulfation pathways in L. luymesi, and sulfate activation might be an important detoxification pathway for promoting sulfur cycling, reducing byproducts of sulfide metabolism, and converting sulfur compounds to sulfur-containing organics, which are essential for symbiotic survival. Moreover, sulfide can serve directly as a sulfur source for cysteine synthesis in L. luymesi. The existence of two pathways for cysteine synthesis might ensure its participation in the formation of proteins, heavy metal detoxification, and the sulfide-binding function of haemoglobin. Furthermore, our data suggested that cold-seep tubeworm is capable of de novo sterol biosynthesis, as well as incorporation and transformation of cycloartenol and lanosterol into unconventional sterols, and the critical enzyme involved in this process might have properties similar to those in the enzymes from plants or fungi. Finally, trehalose synthesis in L. luymesi occurs via the trehalose-6-phosphate synthase (TPS) and trehalose-6-phosphate phosphatase (TPP) pathways. The TPP gene has not been identified, whereas the TPS gene encodes a protein harbouring conserved TPS/OtsA and TPP/OtsB domains. The presence of multiple trehalases that catalyse trehalose hydrolysis could indicate the different roles of trehalase in cold-seep tubeworms. CONCLUSIONS: We elucidated several molecular pathways of sulfate activation, cysteine and cholesterol synthesis, and trehalose metabolism. Contrary to the previous analysis, two pathways for cysteine synthesis and the cycloartenol-C-24-methyltransferase gene were identified in animals for the first time. The present study provides new insights into particular adaptations to chemosynthetic environments in L. luymesi and can serve as the basis for future molecular studies on host-symbiont interactions and biological evolution.

Efficacy of MP-3 microperimeter biofeedback fixation training for low vision rehabilitation in patients with maculopathy.

BACKGROUND: To evaluate the efficacy of MP-3 microperimeter biofeedback fixation training (MBFT) in vision rehabilitation of low-vision patients affected by macular disease with central vision loss. METHODS: Seventeen eyes (7 age-related macular degeneration, 10 myopic maculopathy) of 17 patients were included in this prospective, interventional study. The preferred retinal locus was determined by comprehensive ophthalmoscopic fundus evaluation including fundus photography, autofluorescence, optical coherence tomography, and microperimetry. The rehabilitation consisted of three 10-min sessions per eye to be performed twice per week for 20 consecutive weeks using the MP-3 microperimeter. Best corrected visual acuity (BCVA), reading speed, mean central sensitivity, the percentages of fixation points within specified regions, bivariate contour ellipse area (BCEA) and the 25-item National Eye Institute visual function questionnaire (NEI-VFQ-25) were recorded pre- and post-training. RESULTS: The final BCVA, reading speed and mean central sensitivity all showed significant improvements after rehabilitation (P <  0.0001, P = 0.0013, and P = 0.0002, respectively). The percentages of fixation points located within 2° and 4° diameter circles both significantly increased after training (P = 0.0008 and P = 0.0007, respectively). The BCEA encompassing 68.2, 95.4, 99.6% of fixation points were all significantly decreased after training (P = 0.0038, P = 0.0022, and P = 0.0021, respectively). The NEI-VFQ-25 scores were significantly increased at the end of the rehabilitation training (P <  0.0001). CONCLUSION: Rehabilitation with MP-3 MBFT is a user-friendly therapeutic option for improving visual function, fixation stability, and quality of life in advanced macular disease. TRIAL REGISTRATION: The prospective study was registered with the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ). TRIAL REGISTRATION NUMBER: ChiCTR2000029586 . Date of registration: 05/02/2020.

Application of low level red light in myopia and amblyopia in children and adolescents / 中国学校卫生

Abstract@#Low level light therapy utilizes the photochemical effect of red light to induce reactions in the irradiated body tissue to achieve the therapeutic effect. Myopia and amblyopia are diseases which threaten the eye health of children and adolescents. Red light has been used to treat amblyopia for decades. Recently, its application in myopia prevention and control has become a new hotspot. This review summarizes the application of low level red light in children and adolescents with myopia and amblyopia from the aspects of intervention mode, effect, factors, mechanism and safety to provide reference for future researches.

Application of low level red light in myopia and amblyopia in children and adolescents / 中国学校卫生

Abstract@#Low level light therapy utilizes the photochemical effect of red light to induce reactions in the irradiated body tissue to achieve the therapeutic effect. Myopia and amblyopia are diseases which threaten the eye health of children and adolescents. Red light has been used to treat amblyopia for decades. Recently, its application in myopia prevention and control has become a new hotspot. This review summarizes the application of low level red light in children and adolescents with myopia and amblyopia from the aspects of intervention mode, effect, factors, mechanism and safety to provide reference for future researches.

Towards practical and robust DNA-based data archiving using the yin-yang codec system.

DNA is a promising data storage medium due to its remarkable durability and space-efficient storage. Early bit-to-base transcoding schemes have primarily pursued information density, at the expense of introducing biocompatibility challenges or decoding failure. Here we propose a robust transcoding algorithm named the yin-yang codec, using two rules to encode two binary bits into one nucleotide, to generate DNA sequences that are highly compatible with synthesis and sequencing technologies. We encoded two representative file formats and stored them in vitro as 200 nt oligo pools and in vivo as a ~54 kbps DNA fragment in yeast cells. Sequencing results show that the yin-yang codec exhibits high robustness and reliability for a wide variety of data types, with an average recovery rate of 99.9% above 104 molecule copies and an achieved recovery rate of 87.53% at ≤102 copies. Additionally, the in vivo storage demonstration achieved an experimentally measured physical density close to the theoretical maximum.

Adipose Tissue-derived Microvascular Fragments as Vascularization Units for Dental Pulp Regeneration.

INTRODUCTION: The transplantation of dental pulp stem cells (DPSCs) has emerged as a novel strategy for the regeneration of lost dental pulp after pulpitis and trauma. Dental pulp regeneration of the young permanent tooth with a wide tooth apical foramen has achieved significant progress in the clinical trials. However, because of the narrow apical foramen, dental pulp regeneration in adult teeth using stem cells remains difficult in the clinic. Finding out how to promote vascular reconstitution is essential for the survival of stem cells and the regeneration of dental pulp after transplantation into the adult tooth. METHODS: Adipose tissue-derived microvascular fragments (ad-MVFs) were isolated from human adipose tissues. The apoptosis and senescence of DPSCs cultured in conditioned media were evaluated to explore the effects of ad-MVFs on DPSCs. DPSCs combined with ad-MVFs were inserted into the human tooth root segments and implanted subcutaneously into immunodeficient mice. Regenerated pulplike tissues were analyzed by hematoxylin and eosin and immunohistochemistry. The vessels in regenerated tissues were analyzed by Micro-CT and immunofluorescence. RESULTS: The isolated ad-MVFs contained endothelial cells and pericytes. ad-MVFs effectively prevented the apoptosis and senescence of the transplanted DPSCs both in vivo and in vitro. Combined with DPSCs, ad-MVFs obviously facilitated the formation of vascular networks in the transplants. DPSCs combined with ad-MVFs formed dental pulp-like tissues with abundant cells and matrix after 4 weeks of implantation. The supplementation of ad-MVFs led to more odontoblastlike cells and increased the formation of mineralized substance around the root canal. CONCLUSIONS: Cotransplantation with ad-MVFs promotes the angiogenesis and revascularization of transplanted DPSC aggregates, leading to robust regeneration of dental pulp.

Long-Term Tea Consumption Is Associated with Reduced Risk of Diabetic Retinopathy: A Cross-Sectional Survey among Elderly Chinese from Rural Communities.

AIM: To investigate the association between variables related to tea consumption (duration, frequency, and type) and the risk of diabetic retinopathy. METHODS: A rural community-based, cross-sectional survey was conducted in Weitang Town, Suzhou, China. People aged 60 years or above were invited to complete the survey. All eligible patients underwent detailed eye examination. Diabetic retinopathy (DR) was diagnosed and graded based on the retinal fundus imaging. Diabetes was defined as fasting glucose concentrations of ≥7.0 mmol/L or self-reported diagnosis of diabetes. Information about tea consumption such as duration, type, and frequency, together with demographics and lifestyle characteristics, were collected using a face-to-face questionnaire interview. The association between tea consumption and the risk of DR was determined by univariate and multivariate logistic regression analyses. RESULTS: Among the 5,281 participants, 614 had diabetes mellitus (prevalence of 11.63%). The prevalence rate of DR was 10.38% in the diabetic population and 1.04% in the general population. Compared with non-tea consumers, the crude OR values for DR in subjects with long-term and short-term tea consumption were 0.34 (95%CI = 0.14-0.82, p = 0.016) and 1.64 (95%CI = 0.74-3.64, p = 0.221), respectively. When adjusted for age, gender, and other confounders, consumption of tea for ≥20 years was associated with reduced odds of DR (OR = 0.29, 95%CI = 0.09-0.97, p = 0.044). Thus, long-term tea consumption was significantly associated with a lower risk of DR. There was no statistical significance between frequency or type of tea consumption with DR (p > 0.05). CONCLUSION: Elderly diabetic Chinese residents who consumed tea for more than twenty years had a lower risk of DR compared to non-tea consumers. The long-term tea consumption may be an independent protective factor for DR. However, further studies are warranted to examine the association.

Draft genome sequence of Solanum aethiopicum provides insights into disease resistance, drought tolerance, and the evolution of the genome.

BACKGROUND: The African eggplant (Solanum aethiopicum) is a nutritious traditional vegetable used in many African countries, including Uganda and Nigeria. It is thought to have been domesticated in Africa from its wild relative, Solanum anguivi. S. aethiopicum has been routinely used as a source of disease resistance genes for several Solanaceae crops, including Solanum melongena. A lack of genomic resources has meant that breeding of S. aethiopicum has lagged behind other vegetable crops. RESULTS: We assembled a 1.02-Gb draft genome of S. aethiopicum, which contained predominantly repetitive sequences (78.9%). We annotated 37,681 gene models, including 34,906 protein-coding genes. Expansion of disease resistance genes was observed via 2 rounds of amplification of long terminal repeat retrotransposons, which may have occurred ∼1.25 and 3.5 million years ago, respectively. By resequencing 65 S. aethiopicum and S. anguivi genotypes, 18,614,838 single-nucleotide polymorphisms were identified, of which 34,171 were located within disease resistance genes. Analysis of domestication and demographic history revealed active selection for genes involved in drought tolerance in both "Gilo" and "Shum" groups. A pan-genome of S. aethiopicum was assembled, containing 51,351 protein-coding genes; 7,069 of these genes were missing from the reference genome. CONCLUSIONS: The genome sequence of S. aethiopicum enhances our understanding of its biotic and abiotic resistance. The single-nucleotide polymorphisms identified are immediately available for use by breeders. The information provided here will accelerate selection and breeding of the African eggplant, as well as other crops within the Solanaceae family.

Application of a Cloud Model-Set Pair Analysis in Efficacy Assessment for Diabetic Ulcers.

Because treatment of diabetic ulcers includes various uncertainties, efficacy assessments are needed and significant. In previous studies, set pair analysis (SPA) has been applied to the efficacy assessments of traditional Chinese medicine (TCM) that pick out uncertainties related to the development and prognosis of disease. Optimized clinical protocols of SPA improve clinical efficacy. In the article, cloud model (CM) is employed to improve SPA, and a novel efficacy assessment method for a treatment of diabetic ulcers is proposed based on the cloud model-set pair analysis (CM-SPA). It is recommended to replace connection degree (CD) with cloud connection degree (CCD) that the efficacy assessment results are shown as normal clouds. Then, three diabetic ulcers patients treated with TCM made importance assessment by both CM-SPA and AHP based SPA. The comparison of assessment results shows that the CM-SPA is efficacious for the efficacy assessment of a treatment for diabetic ulcers and the results will be more scientific and accurate via CM-SPA.

Sequencing and comparative analysis of three Chlorella genomes provide insights into strain-specific adaptation to wastewater.

Microalgal Chlorella has been demonstrated to process wastewater efficiently from piggery industry, yet optimization through genetic engineering of such a bio-treatment is currently challenging, largely due to the limited data and knowledge in genomics. In this study, we first investigated the differential growth rates among three wastewater-processing Chlorella strains: Chlorella sorokiniana BD09, Chlorella sorokiniana BD08 and Chlorella sp. Dachan, and the previously published Chlorella sorokiniana UTEX 1602, showing us that BD09 maintains the best tolerance in synthetic wastewater. We then performed genome sequencing and analysis, resulting in a high-quality assembly for each genome with scaffold N50 > 2 Mb and genomic completeness ≥91%, as well as genome annotation with 9,668, 10,240, 9,821 high-confidence gene models predicted for BD09, BD08, and Dachan, respectively. Comparative genomics study unravels that metabolic pathways, which are involved in nitrogen and phosphorus assimilation, were enriched in the faster-growing strains. We found that gene structural variation and genomic rearrangement might contribute to differential capabilities in wastewater tolerance among the strains, as indicated by gene copy number variation, domain reshuffling of orthologs involved, as well as a ~1 Mb-length chromosomal inversion we observed in BD08 and Dachan. In addition, we speculated that an associated bacterium, Microbacterium chocolatum, which was identified within Dachan, play a possible role in synergizing nutrient removal. Our three newly sequenced Chlorella genomes provide a fundamental foundation to understand the molecular basis of abiotic stress tolerance in wastewater treatment, which is essential for future genetic engineering and strain improvement.

Cytotoxic Activities of Total Saponins from Plena Clematis on Human Tumor Cell Lines In Vitro.

OBJECTIVE: To investigate the anti-proliferative effects of saponins prepared from Plena Clematis (PC) cultured in Fujian Province, China on 4 human tumor cell lines and its possible anti-tumor mechanism. METHODS: The growth inhibition assays of saponins on human esophageal squamous carcinoma cell line (EC9706), human hepatoma cell line (HepG-2), human oral cancer cell line (KB) and human gastric cancer cell line (BGC-823) were evaluated in vitro by thiazolyl blue (MTT) method. The inhibitory effects on EC9706 treated with different concentrations of saponins (15.62, 31.25, 62.50, 125, 250 and 500 µg/mL) were performed in vitro by MTT method. The morphology and nuclear staining with acridine orange/ethidium bromide of EC9706 cells treated with saponins were illustrated under an inverted phase fluorescence microscope. The apoptotic effects of saponins were further evaluated by annexin-V/propidium iodide dual staining experiment to examine the occurrence of phosphatidylserine externalization onto the cell surface by a flflow cytometer. RESULTS: MTT assay showed that the saponins could inhibit the proliferation of 4 tumor cell lines. Among them, the maximum inhibition rate of 73.1% was detected in EC9706 cells at the saponins concentration of 250 µg/mL for 24 h. Further investigation indicated that the saponins induced EC9706 cells apoposis. The EC9706 cells presented apoptotic characteristics when treated with saponins, including that the morphologies of EC9706 cells were appeared round-shaped with higher refraction, and the cell nuclear stained orange with EB after 250 µg/mL saponins exposure. The flow cytometry analysis results showed that the induction of cell cycle arrest in apoptotic system may participate in the anti-proliferative activity of saponins on EC9706 cells. CONCLUSION: The saponins from PC exhibited significant cytotoxicity against human EC9706, KB, BGC-823, and HepG-2 cells and might be beneficial to development of ethnic pharmaceutical plant for potential anti-tumor drugs.

Sheng-ji Hua-yu formula promotes diabetic wound healing of re-epithelization via Activin/Follistatin regulation.

BACKGROUND: Sheng-ji Hua-yu(SJHY) formula is one of the most useful Traditional Chinese medicine (TCM) in the treatment of the delayed diabetic wound. However, elucidating the related molecular biological mechanism of how the SJHY Formula affects excessive inflammation in the process of re-epithelialization of diabetic wound healing is a task urgently needed to be fulfilled. The objectives of this study is to evaluate the effect of antagonisic expression of pro-/anti-inflammatory factors on transforming growth factor-ß(TGF-ß) superfamily (activin and follistatin) in the process of re-epithelialization of diabetic wound healing in vivo, and to characterize the involvement of the activin/follistatin protein expression regulation, phospho-Smad (pSmad2), and Nuclear factor kappa B p50 (NF-kB) p50 in the diabetic wound healing effects of SJHY formula. METHODS: SJHY Formula was prepared by pharmaceutical preparation room of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. Diabetic wound healing activity was evaluated by circular excision wound models. Wound healing activity was examined by macroscopic evaluation. Activin/follistatin expression regulation, protein expression of pSmad2 and NF-kB p50 in skin tissue of wounds were analyzed by Real Time PCR, Western blot, immunohistochemistry and hematoxylin and eosin (H&E) staining. RESULTS: Macroscopic evaluation analysis showed that wound healing of diabetic mice was delayed, and SJHY Formula accelerated wound healing time of diabetic mice. Real Time PCR analysis showed higher mRNA expression of activin/follistatin in diabetic delayed wound versus the wound in normal mice. Western Blot immunoassay analysis showed reduction of activin/follistatin proteins levels by SJHY Formula treatment 15 days after injury. Immunohistochemistry investigated the reduction of pSmad2 and NF-kB p50 nuclear staining in the epidermis of diabetic SJHY versus diabetic control mice on day 15 after wounding. H&E staining revealed that SJHY Formula accelerated re-epithelialization of diabetic wound healing. CONCLUSION: The present study found that diabetic delayed wound healing time is closely related to the high expression level of activin/follistatin, which leads to excessive inflammation in the process of re-epithelization. SJHY Formula accelerates re-epithelialization and healing time of diabetic wounds through decreasing the high expression of activin/follistatin.

Analyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment.

Antidiabetic medication may modulate the gut microbiota and thereby alter plasma and faecal bile acid (BA) composition, which may improve metabolic health. Here we show that treatment with Acarbose, but not Glipizide, increases the ratio between primary BAs and secondary BAs and plasma levels of unconjugated BAs in treatment-naive type 2 diabetes (T2D) patients, which may beneficially affect metabolism. Acarbose increases the relative abundances of Lactobacillus and Bifidobacterium in the gut microbiota and depletes Bacteroides, thereby changing the relative abundance of microbial genes involved in BA metabolism. Treatment outcomes of Acarbose are dependent on gut microbiota compositions prior to treatment. Compared to patients with a gut microbiota dominated by Prevotella, those with a high abundance of Bacteroides exhibit more changes in plasma BAs and greater improvement in metabolic parameters after Acarbose treatment. Our work highlights the potential for stratification of T2D patients based on their gut microbiota prior to treatment.

Draft genome sequence of the Tibetan medicinal herb Rhodiola crenulata.

Rhodiola crenulata, a well-known medicinal Tibetan herb, is mainly grown in high-altitude regions of the Tibet, Yunnan, and Sichuan provinces in China. In the past few years, increasing numbers of studies have been published on the potential pharmacological activities of R. crenulata, strengthening our understanding into its putitive active ingredient composition, pharmacological activity, and mechanism of action. These findings also provide strong evidence supporting the important medicinal and economical value of R. crenulata. Consequently, some Rhodiola species are becoming endangered because of overexploitation and environmental destruction. However, little is known about the genetic and genomic information of any Rhodiola species. Here we report the first draft assembly ofthe R. crenulata genome, which was 344.5 Mb (25.7 Mb Ns), accounting for 82% of the estimated genome size, with a scaffold N50 length of 144.7 kb and a contig N50 length of 25.4 kb. The R. crenulata genome is not only highly heterozygous but also highly repetitive, with ratios of 1.12% and 66.15%, respectively, based on the k-mer analysis. Furthermore, 226.6 Mb of transposable elements were detected, of which 77.03% were long terminal repeats. In total, 31 517 protein-coding genes were identified, capturing 86.72% of expected plant genes in BUSCO. Additionally, 79.73% of protein-coding genes were functionally annotated. R. crenulata is an important medicinal plant and also a potentially interesting model species for studying the adaptability of Rhodiola species to extreme environments. The genomic sequences of R. crenulata will be useful for understanding the evolutionary mechanism of the stress resistance gene and the biosynthesis pathways of the different medicinal ingredients, for example, salidroside in R. crenulata.

Therapeutic effects of a novel PIGF-1 derived peptide, ZY-1, on corneal neovascularization in vitro and in vivo.

Corneal neovascularization (NV) is one of the major sight-threatening pathological changes caused by corneal diseases. Current therapeutics generate various adverse effects. Small peptides derived from endogenous protein display certain advantages. This study aims to evaluate the anti-angiogenic effect and molecular mechanism of a novel peptide ZY-1, derived from placental growth factor-1 (PlGF-1), on corneal NV by topical administration, and to investigate its safety profile after long-term treatment. CCK-8 assay and tube formation assay were used to evaluate the effect of ZY-1 on human umbilical vein endothelial cells (HUVECs). The anti-angiogenic effect of topical ZY-1 was estimated in a rat model of alkali burn induced corneal NV. The safety profile of topical ZY-1 was analyzed by CCK-8 assay, tear film break-up time (BUT), and histological examination. Firstly, we found that ZY-1 co-localized with membrane vascular epithelial growth factor receptor-1 (VEGFR-1) and effectively inhibited VEGF/PlGF-1 induced proliferation and tube formation of HUVECs. The topical ZY-1 administration efficiently inhibited alkali-burn induced corneal NV, while it did not show any significant effect on human corneal epithelial cell (HCEC) proliferation, as well as the functionality and morphology of cornea and conjunctiva. Our findings suggested that topical administration of ZY-1 could effectively and safely inhibit corneal NV partially through competing for VEGFR-1 binding, and it would be a promising alternative for ocular topical anti-angiogenic therapy.

Single-site Baseline and Short-term Outcomes of Clinical Characteristics and Life Quality Evaluation of Chinese Wet Age-related Macular Degeneration Patients in Routine Clinical Practice.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the older population. In China, treatment of age-related ocular diseases is becoming a priority in eye care services. This study was to investigate the clinical characteristics and quality of life of Chinese patients with wet AMD and current treatment types, to evaluate short-term gains in different treatments, and to investigate associations between visual function and vision-related quality of life (VRQoL). METHODS: A prospective, observational, noninterventional study was conducted. Basic data were collected from patients with clinical diagnoses of wet AMD before clinical assessments at baseline. VRQoL was measured with the Chinese version of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). Correlations of the NEI VFQ-25 subscale scores with best-corrected visual acuity (BCVA) and between-group differences were analyzed. RESULTS: A total of 80 wet AMD patients were enrolled, with the mean age of 68.40 years. About one-quarter of wet AMD patients received intravitreal (IVT) ranibizumab treatment, and 67% of them were treated on a pro re nata basis. The visual acuity of patients treated with IVT ranibizumab at month 3 after treatment was significantly increased, whereas patients treated with traditional Chinese medicine achieved no significant improvement. Cronbach's α for the NEI VFQ-25 subscales ranged from 0.697 to 0.843. Eight subscale and overall composite scores were moderately correlated with the BCVA of the better-seeing eye. Significant differences in the overall NEI VFQ-25 scores and other subscales were observed between patients with BCVA in the better-seeing eye of less than 50 letters and the others. CONCLUSIONS: Patients treated with IVT ranibizumab experienced better vision improvement at short-term follow-up. The Chinese version of the NEI VFQ-25 is a valid and reliable tool for assessing the VRQoL of Chinese wet AMD patients.

A randomised, parallel-group comparison study of diquafosol ophthalmic solution in patients with dry eye in China and Singapore.

AIMS: To compare the efficacy and safety of 3% diquafosol ophthalmic solution with those of 0.1% sodium hyaluronate ophthalmic solution in patients with dry eye in China and Singapore. METHODS: A total of 497 patients with dry eye (Schirmer's test, 5 mm; fluorescein and RB score, 3 points) from China and Singapore were randomised to receive either diquafosol ophthalmic solution (diquafosol) or sodium hyaluronate ophthalmic solution (HA) at 1:1 ratio. The fluorescein staining scores and rose bengal (RB) subjective symptom scores and tear film breakup time were evaluated before treatment and 2 and 4 weeks after start of treatment. RESULTS: In the diquafosol group, changes in fluorescein and RB scores compared with baseline at week 4 or at the time of discontinuation were -2.1±1.5 and -2.5±2.0, respectively. Compared with the HA group, changes in fluorescein score were non-inferior and changes in RB score were superior (p=0.019). In addition, diquafosol and HA improved tear film breakup time by 1.046±1.797 and 0.832±1.775 s, respectively (no significant intergroup difference). Adverse event onset rates were 16.3% (40 of 246 subjects) and 10.0% (25 of 251 subjects) in the diquafosol group and HA group, respectively, with borderline significant intergroup differences (p=0.046), while adverse drug reaction incidence rates were 12.2% (30 of 246 subjects) and 6.0% (15 of 251 subjects), respectively (p=0.019). Only mild adverse drug reactions (>2%) in the form of eye discharge, itching or irritation were observed. CONCLUSIONS: Diquafosol improved fluorescein staining score in a manner similar to HA, and significantly improved RB score compared with HA. TRIAL REGISTRATION NUMBER: NCT01101984.