Mutations in TSPAN12 gene causing familial exudative vitreoretinopathy.

BACKGROUND: To report newly found TSPAN12 mutations with a unique form of familial exudative vitreoretinopathy (FEVR) and find out the possible mechanism of a repeated novel intronic variant in TSPAN12 led to FEVR. RESULTS: Nine TSPAN12 mutations with a unique form of FEVR were detected by panel-based NGS. MINI-Gene assay showed two splicing modes of mRNA that process two different bands A and B, and mutant-type shows replacement with the splicing mode of Exon11 hopping. Construction of wild-type and mutant TSPAN12 vector showed the appearance of premature termination codons (PTC). In vitro expression detection showed significant down-regulated expression level of TSPAN12 mRNAs and proteins in cells transfected with mutant vectors compared with in wild-type group. On the contrary, translation inhibitor CHX and small interfering RNA of UPF1 (si-UPF1) significantly increased mRNA or protein expression of TSPAN12 in cells transfected with the mutant vectors. CONCLUSIONS: Nine mutations in TSPAN12 gene are reported in 9 FEVR patients with a unique series of ocular abnormalities. The three novel TSPAN12 mutations trigger NMD would cause the decrease of TSPAN12 proteins that participate in biosynthesis and assembly of microfibers, which might lead to FEVR, and suggest that intronic sequence analysis might be a vital tool for genetic counseling and prenatal diagnoses.

Genetic Characteristics and Clinical Manifestations of Foveal Hypoplasia in Familial Exudative Vitreoretinopathy.

PURPOSE: This study aimed to ascertain the occurrence of foveal hypoplasia (FH) in individuals diagnosed with familial exudative vitreoretinopathy (FEVR). DESIGN: Retrospective cohort study. METHODS: In this study, FEVR families and sporadic cases were diagnosed at the Eye and ENT Hospital, Fudan University, between 2017 and 2023. All patients attended routine ophthalmologic examinations and genetic screenings. The classification of FH was determined using optical coherence tomography (OCT) scans. The FH condition was classified into 2 subgroups: group A (FH being limited to the inner layers) and group B (FH affecting the outer layers). A total of 102 eyes from 58 patients were suitable for analysis. RESULTS: Forty-nine mutations in LRP5, FZD4, NDP, TSPAN12, KIF11, CTNNB1, and ZNF408 were examined and detected, with 26 of them being novel. Forty-seven eyes (46.1%) revealed FH. The majority (53.2%) were due to the typical grade 1 FH. Patients with mutations in LRP5 and KIF11 were found to exhibit a higher prevalence of FH (P = .0088). Group B displayed the lowest visual acuity compared with group A (P = .048) and the group without FH (P < .001). The retinal arteriolar angle in group B was significantly smaller than in group A (P = .001) and those without FH (P < .001). CONCLUSIONS: This study offers a new diagnostic approach and expands the spectrum of FEVR mutations. LRP5 and KIF11 were found to be more susceptible to causing FH in patients with FEVR. FEVR eyes with FH exhibited both greater visual impairment and reduced retinal arteriolar angles. The assessment of foveal status in patients with FEVR should be valued.

Lipid-inspired biomimicking morphosynthesis of a series of complex concave silica architectures.

The lipid-inspired biosilicification process enables the creation of a series of concave silica nanoarchitectures in the complex shapes of nanobowls, nanodishes, nanoboats, and nanoloops. The reaction at a pH of 8 initially allows the formation of thin and elastic circular gel nanosheets that can undergo inducible stretching and folding, which subsequently evolves into nanodish and nanobowl through a potential global buckling process. The adjustment of the pH to 9 and 4 enables the production of more complex morphogens of nanoboat and nanoloop, respectively. These unique silica nanoarchitectures may have a wide scope of potential application from nanoreactors in heterogenous catalysis to drug delivery systems and optical materials.

Comparison of Clinical Profiles, Demographics, and Surgical Outcomes of 25-Gauge Vitrectomy for Proliferative Diabetic Retinopathy in Young Adults with Type 1 or Type 2 Diabetes.

Purpose: Proliferative diabetic retinopathy (PDR) is a leading cause of poor vision in young adults. This study sought to evaluate the clinical characteristics and outcomes of primary vitrectomy for PDR in young adults. Patients and Methods: Medical data were retrospectively collected at a large ophthalmology hospital in China. We analyzed data for 99 patients (140 eyes) aged <45 years with T1D or T2D who underwent primary vitrectomy for PDR-related complications. Results: There were 18 patients with T1D and 81 patients with T2D. The proportion of males was significantly greater than that of females in both groups. The T1D group had a longer duration of diabetes (P = 0.008), younger age at primary vitrectomy (P = 0.049), and lower body mass index (P < 0.001) than the T2D group. The proportion of eyes with rhegmatogenous retinal detachment (RRD) was greater but the proportion of eyes with traction retinal detachment (TRD) was lower in the T1D group than in the T2D group. The final best-corrected visual acuity (BCVA) improved or remained stable in 100% and 85.3% of eyes and decreased in 0% and 14.7% of eyes in the T1D and T2D groups, respectively. After surgery, the incidence of postoperative complications was significant greater in the T2D group than in the T1D group (P = 0.045). Factors influencing the final visual acuity included preoperative BCVA in both groups, the duration of diabetes (P = 0.031) and preoperative FVP (P = 0.004) in the T1D group, and preoperative RRD (P < 0.001) and postoperative NVG (P < 0.001) in the T2D group. Conclusion: In this retrospective study, young adults with T2D who underwent vitrectomy had worse final visual acuity and more complications than young adults with T1D.

Clinical Characteristics and Surgical Outcomes of Complications of Proliferative Diabetic Retinopathy in Young versus Older Patients with Type 2 Diabetes.

Purpose: Proliferative diabetic retinopathy (PDR) is a leading vision-threatening disease. In this study, we investigated the clinical features of PDR and the surgical outcomes of its complications in patients with type 2 diabetes (T2D). Patients and Methods: We retrospectively reviewed the medical data of patients with T2D who underwent vitrectomy for PDR between January 2016 and June 2021. The patients were divided into two groups by age (young patients, < 45 years; older patients, ≥ 45 years). Results: There were 149 eyes (100 patients) in the young patient group and 315 eyes (256 patients) in the older patient group. The proportion of males and the proportion of patients requiring binocular surgery were much higher in the young patient group than in the older patient group (P = 0.005 and P < 0.001, respectively). In the young patient group, 26.2% of eyes had active fibrovascular proliferation compared with only 11.4% in the older patient group (P < 0.001). The final best-corrected visual acuity (BCVA) was significantly improved relative to the preoperative BCVA in both groups (P < 0.001). After surgery, there were no significant differences in the incidence of postoperative neovascular glaucoma (NVG) or recurrent vitreous hemorrhage (VH) between the two groups. The incidence of postoperative recurrent retinal detachment was higher in the young patient group (P = 0.033). The risk factors associated with the visual outcomes in the young patient group included preoperative BCVA (P < 0.001), renal diseases (P = 0.001), postoperative NVG (P < 0.001), and recurrent VH (P = 0.028). Conclusion: In this retrospective study, young patients who underwent vitrectomy for PDR had more severe clinical characteristics before vitrectomy. However, vitrectomy (combined with cataract surgery when necessary) achieved better final visual outcomes in young patients than in older patients with T2D.

Use of bentonite-coated activated carbon for improving the sensitivity of RT-qPCR detection of norovirus from vegetables and fruits: The ISO 15216-1:2017 standard method extension.

Produce-related foodborne outbreaks are becoming increasingly prevalent worldwide. In plant tissues, various compounds, including polysaccharides, phenolic compounds, and chlorophyll, can inhibit RT-PCR detection of viruses. In this study, we developed a highly sensitive RT-qPCR in combination with the bentonite-coated activated carbon (BCAC) assay for detection of norovirus from fruits and vegetables, which could be completed within 7 h and was about 10-100 fold more sensitive than the standard procedures (ISO 15216-1:2017). The extraction efficiencies of three surrogate viruses (MS2, MNV-1, and TV) from five fresh produce (lettuce, cherry tomato, blueberry, strawberry, and spinach) were higher with BCAC treatment than those of control groups, ranging from 17.82% to 98.60%. The average detection limit of these viruses using the BCAC-RT-qPCR method was stable at an average of 102 PFU/g or GC/g. Finally, this BCAC-RT-qPCR method was applied for detection of human norovirus GII.4 spiked onto lettuce and cherry tomato. The viral extraction efficiencies were up to 53.43% and 95.56%, respectively, which is almost four and seven times better than those without BCAC. Therefore, the BCAC-RT-qPCR method can be used to detect low levels of foodborne viruses from produce.

Excess Heme Promotes the Migration and Infiltration of Macrophages in Endometrial Hyperplasia Complicated with Abnormal Uterine Bleeding.

In patients, endometrial hyperplasia (EH) is often accompanied by abnormal uterine bleeding (AUB), which is prone to release large amounts of heme. However, the role of excess heme in the migration and infiltration of immune cells in EH complicated by AUB remains unknown. In this study, 45 patients with AUB were divided into three groups: a proliferative phase group (n = 15), a secretory phase group (n = 15) and EH (n = 15). We observed that immune cell subpopulations were significantly different among the three groups, as demonstrated by flow cytometry analysis. Of note, there was a higher infiltration of total immune cells and macrophages in the endometrium of patients with EH. Heme up-regulated the expression of heme oxygenase-1 (HO-1) and nuclear factor erythroid-2-related factor 2 (Nrf2) in endometrial epithelial cells (EECs) in vitro, as well as chemokine (e.g., CCL2, CCL3, CCL5, CXCL8) levels. Additionally, stimulation with heme led to the increased recruitment of THP-1 cells in an indirect EEC-THP-1 co-culture unit. These data suggest that sustained and excessive heme in patients with AUB may recruit macrophages by increasing the levels of several chemokines, contributing to the accumulation and infiltration of macrophages in the endometrium of EH patients, and the key molecules of heme metabolism, HO-1 and Nrf2, are also involved in this regulatory process.

Updating Understanding of Macular Microvascular Abnormalities and Their Correlations With the Characteristics and Progression of Macular Edema or Exudation in Coats' Disease.

Objective: To investigate the associations of macular microvascular abnormalities with the characteristics and progression of macular edema or exudation in Coats' disease, toward an updated understanding of possible risk factors for macular edema or exudation. Methods: Twenty-six eyes (26 patients) with Coats' disease and macular edema or exudation underwent multimodal imaging and were followed for 18 months. The eyes were classified according to their outcomes (refractory or improved). Macular capillary affections were assessed by optical coherence tomography angiography (OCTA) and fluorescein angiography (FA). Histopathological analysis of the macular region of an additional enucleated eye was performed. Results: OCTA revealed telangiectasia in the deep capillary plexus (DCP) in 76.9% and the superficial capillary plexus (SCP) in 34.6% of 26 eyes with macular edema or exudation of Coats' disease, exceeding the rate detected by FA (21.4%). Eyes with intraretinal cystoid spaces/exudates of the macula presented higher presence of telangiectasia in the SCP (57.1% with vs. 8.3% without, X2 = 6.801, P = 0.009) and DCP (92.9 with vs. 58.3% without, X2 = 4.338, P = 0.037). The parafoveal vessel densities (VDs) and fractal dimension in the SCP and DCP were lower in affected eyes than in contralateral eyes (all P < 0.001). The VD in SCP (P = 0.009) and DCP (P = 0.010) were lower in refractory group than in improved group. Dilated capillaries with incomplete vessel walls and adjacent inflammatory cells were detected in the neuroretina of the macula in histopathological specimen. Conclusions: Macular capillary abnormalities, including telangiectasia and VD loss, were positively detected in eyes with macular edema or exudation of Coats' disease. Intraretinal cystoid spaces/exudates of the macula, rather than subretinal exudates, may be related to macular telangiectasia. VD losses in the SCP and DCP may be risk factors for refractory macular edema or exudation.

Effects of natural antioxidants on the oxidative stability of Eucommia ulmoides seed oil: Experimental and molecular simulation investigations.

Eucommia ulmoides seed oil with high health potential is prone to oxidative rancidity due to its rich unsaturated fatty acids. In this work, three natural antioxidants were selected for exploring the oxidation resistance of the oil compared with the common synthetic antioxidant BHT. Antioxidant activity and its dispersion and migration as well as oxygen barrier performance were predicted via the bond dissociation enthalpy (BDE), mean square displacement (MSD), binding energy (Ebinding) and permeability coefficient (S). The predicted comprehensive performance is as follows: myricetin > epicatechin > caffeic acid > BHT. Free radical scavenging assay and Rancimat assay confirmed the antioxidant activity and protective effect on oil. That is the protective effect of three natural antioxidants on Eucommia ulmoides seed oil is better than BHT and myricetin shows the optimal comprehensive performance. The induction period of myricetin/lipid system increased 164.5% compared with the control. The experimental results are in good consistent with the simulation predictions.

Antioxidant Behavior Affected by Polarity in the Olive Oil: Experimental and Molecular Simulation Investigations.

Natural antioxidants are essential potential sources for protecting the oxidation of food oils. However, until now, the mechanisms are still not very clear, especially from the quantitatively theoretical level to analyze the antioxidant behavior. In this work, the micromechanisms of the antioxidant behavior affected by polarity in the olive oil were systematically investigated by experimental and computational methods. The results showed that the polarity of antioxidants decreased with the growth of the alkyl chains, which had multiple impacts on the effectiveness of antioxidants. The excessive polarity gap between the antioxidant and oil molecules would cause the antioxidant to be dispersed at the oil-air interface, which could enhance their antioxidant ability. Meanwhile, the antioxidants with longer alkyl chains had lower polarity and better dispersibility but decreased mobility. Hence, compared with other antioxidants, medium polarity antioxidants presented both good dispersion and relatively suitable migration, indicating that they would have an optimal antioxidant effect.

Protective effects of rapamycin on the retinal vascular bed during the vaso-obliteration phase in mouse oxygen-induced retinopathy model.

Retinopathy of prematurity (ROP) is a vision-threatening disorder characterized with retinal vaso-obliteration in phase 1 and pathological neovascularization (NV) in phase 2. However, there has been no effective and safe treatment for ROP. Current management is mainly focused on the reduction of abnormal NV in phase 2, and anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment, yet, with great risks of late recurrence and systemic side effects. It has been reported that the severity of vaso-obliteration in phase 1 largely influences subsequent NV, suggesting that it may be a promising target to develop novel treatments for ROP. Here, we investigated the therapeutic potential and safety of early rapamycin intervention in treating phase 1 ROP and possible underlying mechanisms using the mouse model of oxygen-induced retinopathy (OIR). We found that intravitreal injection of rapamycin at postnatal day 7 (P7) significantly reduced retinal avascular area, increased vascular density, and reversed the suppression of deep capillaries development in phase 1 of OIR mice. Rapamycin treatment not only reduced vascular apoptosis, but also promoted proliferation and tip cell functions. Additionally, rapamycin did not interfere with normal retinal vascular development. Further investigation showed that Ang1/Tie2 pathway might be involved in rapamycin's vascular protection in phase 1 OIR retinas. Moreover, early rapamycin treatment at P7 had long-term protective effects of reducing retinal NV and avascular area, as well as enhancing vascular maturity in phase 2 of OIR mice. Together, our data suggest that rapamycin may be a safe and promising strategy for early intervention of ROP.

Changes in subsets of immunocytes in endometrial hyperplasia.

PROBLEM: Endometrial hyperplasia (EH) is characterized by an endometrial gland-to-stroma ratio >1 and is one of the most common gynecological diseases in the world. The role of immunocyte subsets in the development of EH remains unknown. METHODS: Patients who underwent dilatation and curettage due to abnormal uterine bleeding were recruited in the present study. Alterations in the numbers of different types of immune cell subsets in the endometrium of patients were analyzed by flow cytometry. RESULTS: The present study included 48 patients who were divided into three groups, based on the pathological results: (a) proliferative period (PP, n = 12); (b) simple EH (SEH, n = 30); and (c) complex EH (CEH, n = 6). The results showed that immune cell subpopulations were significantly different between these three groups. Compared with the PP group, the proportion of CD45+ cells and neutrophils and the subtypes of T cells and macrophages were significantly increased in the SEH patients. Compared with the PP and SEH groups, subsets of immunocytes in the CEH group were significantly decreased, including the population of CD45+ cells and the subtypes of T cells and natural killer cells; in contrast, the proportion of macrophages was significantly increased. There were no significant differences between the other cell subsets in each group. CONCLUSION: The changes in immune cell subsets may be closely associated with the progression of EH. Although the specific role of different immune cell subsets in the development of the diseases requires further study, the changes in the proportions of immune cell subsets should not be ignored.

Collagen at the maternal-fetal interface in human pregnancy.

The survival and development of a semi-allogenic fetus during pregnancy require special immune tolerance microenvironment at the maternal fetal interface. During the establishment of a successful pregnancy, the endometrium undergoes a series of changes, and the extracellular matrix (ECM) breaks down and remodels. Collagen is one of the most abundant ECM. Emerging evidence has shown that collagen and its fragment are expressed at the maternal fetal interface. The regulation of expression of collagen is quite complex, and this process involves a multitude of factors. Collagen exerts a critical role during the successful pregnancy. In addition, the abnormal expressions of collagen and its fragments are associated with certain pathological states associated with pregnancy, including recurrent miscarriage, diabetes mellitus with pregnancy, preeclampsia and so on. In this review, the expression and potential roles of collagen under conditions of physiological and pathological pregnancy are systematically discussed.

Excess palmitate induces decidual stromal cell apoptosis via the TLR4/JNK/NF-kB pathways and possibly through glutamine oxidation.

During gestation, excess palmitate (PA) is enriched in decidua. Both excess PA and decidual dysfunctions are associated with numerous adverse pregnancy outcomes such as gestational diabetes, preeclampsia and preterm birth and intrauterine growth restriction. Here, mRNA data about the effects of PA were collected from multiple databases and analyzed. Human decidual tissues were obtained from clinically normal pregnancies, terminated for non-medical reasons, during the first trimester, and decidual stromal cells (DSCs) were isolated and exposed to PA, alone or together with the inhibitors of Toll-like receptor 4 (TLR4), Jun N-terminal kinase (JNK), nuclear factor-kappa-gene binding (NF-kB) or glutamine (GLN) oxidation. Furthermore, DSCs were transfected with lentiviral particles overexpressing human TLR4. We demonstrate that excess PA interacting with its receptor TLR4 disturbs DSC hemostasis during the first trimester. Specifically, high PA signal induced DSC apoptosis and formed an inflammatory program (elevated interleukin-1 beta and decreased interleukin-10) via the activation of TLR4/JNK/NF-kB pathways. A complexed cross-talk was found between TLR4/JNK/NF-kB signals and PA deposition in DSCs. Besides, under an excess PA environment, GLN oxidation was significantly enhanced in DSCs and the suppression of GLN oxidation further augmented PA-mediated DSC apoptosis and inflammatory responses. In conclusion, excess PA induces apoptosis and inflammation in DSCs via the TLR4/JNK/NF-kB pathways, which can be augmented by the suppression of GLN oxidation.

The role of CXC chemokine ligand 16 in physiological and pathological pregnancies.

The survival and development of a semi-allogeneic fetus during pregnancy require the involvement of a series of cytokines and immune cells. Chemokines are a type of special cytokine those were originally described as having a role in leukocyte trafficking. CXC chemokine ligand (CXCL) 16 is a member of the chemokine family, and CXC chemokine receptor (CXCR) 6 is its sole receptor. Emerging evidence has shown that CXCL16/CXCR6 is expressed at the maternal-fetal interface, by cell types that include trophoblast cells, decidual stroma cells, and decidual immune cells (eg, monocytes, γδT cells, and natural killer T (NKT) cells). The regulation of expression of CXCL16 is quite complex, and this process involves a multitude of factors. CXCL16 exerts a critical role in the establishment of a successful pregnancy through a series of molecular interactions at the maternal-fetal interface. However, an abnormal expression of CXCL16 is associated with certain pathological states associated with pregnancy, including recurrent miscarriage, pre-eclampsia, and gestational diabetes mellitus (GDM). In the present review, the expression and pleiotropic roles of CXCL16 under conditions of physiological and pathological pregnancy are systematically discussed.

MACULAR CAPILLARY DROPOUT IN FAMILIAL EXUDATIVE VITREORETINOPATHY AND ITS RELATIONSHIP WITH VISUAL ACUITY AND DISEASE PROGRESSION.

PURPOSE: To quantitatively detect the macular microvascular alterations of eyes with familial exudative vitreoretinopathy (FEVR) and analyze their associations with the severity and visual acuity of FEVR. METHODS: A case-control study comprising 62 patients (62 eyes) with FEVR and 21 age-matched healthy individuals (21 eyes) with normal vision was conducted. Parafoveal vascular density (VD) was measured using optical coherence tomography angiography. Visual acuity, intraocular pressure, and axial length were recorded. RESULTS: Parafoveal VD of eyes with FEVR was lower than that of the controls (P < 0.05). Parafoveal VD decreased with increasing FEVR stages (P < 0.05), and decreased VD in superficial capillary plexus (SCP) was independently correlated with FEVR severity (odds ratio: 1.558, P < 0.001) after controlling for other confounding variables. Vascular density in eyes with FEVR and decreased visual acuity was lower than eyes with FEVR and normal visual acuity (SCP, P < 0.001; deep capillary plexus, P = 0.001). Moreover, VD loss had independent association with visual loss in FEVR (SCP: odds ratio: 0.817, P = 0.019; deep capillary plexus: odds ratio: 0.763, P = 0.016). CONCLUSION: There may be parafoveal microvascular defects in FEVR and that VD loss in SCP may be correlated with the severity of FEVR. In addition, VD loss in SCP and deep capillary plexus may be associated with the visual loss in FEVR.

THE EVOLUTION OF ISOLATED NEOVASCULAR TUFTS ("POPCORN") IN RETINOPATHY OF PREMATURITY.

PURPOSE: To explore the natural evolution of isolated neovascular tufts ("popcorn") in retinopathy of prematurity (ROP) and its significance in the progression of acute ROP. METHODS: In this retrospective case series, 89 infants (89 eyes) in total having acute ROP were analyzed during serial retinal examinations with a RetCam III wide-angle fundus imaging system, among which 53 eyes were observed to have popcorn and 36 eyes did not. The clinical outcomes of the popcorn (+) group and the popcorn (-) group were compared. RESULTS: Popcorn was located only in Zone II, Stage 2 ROP, primarily in the temporal field (65%). It appeared at a mean postmenstrual age of (37.6 ± 1.3) weeks, disappeared at (41.0 ± 2.2) weeks, and lasted for (2.8 ± 1.1) weeks. The popcorn (+) group had a significantly higher natural regression incidence than the popcorn (-) group (P < 0.05). The laser-treated eyes in the popcorn (+) group had earlier presentations (36.4 ± 0.7 vs. 38.2 ± 1.3 weeks) and shorter existences (1.5 ± 0.5 vs. 3.2 ± 0.9 weeks) of popcorn than the regressed eyes (P < 0.01, respectively). CONCLUSION: Popcorn is generally a "benign" indicator of the regression of ROP. The early presentation (

IL-2 and IL-27 synergistically promote growth and invasion of endometriotic stromal cells by maintaining the balance of IFN-γ and IL-10 in endometriosis.

Immune cells and cytokines have important roles in the pathogenesis of endometriosis. However, the production and role of cytokines of T helper type 1 (Th1) and Th2 cells in the progress of endometriosis have remained to be fully elucidated. The present study reported that the interferon (IFN)-γ levels and the percentage of IFN-γ+CD4+ cells were significantly increased in the peritoneal fluid (PF) at the early stage and maintained at a higher level at the advanced stage of endometriosis; furthermore, interleukin (IL)-10 and IL-10+CD4+ cells were elevated in the advanced stage of endometriosis. In addition, IL-2 levels in the PF at the advanced stage of endometriosis were elevated and negatively associated with IFN-γ expression. In a co-culture system of ectopic endometrial stromal cells (ESCs) and macrophages, elevated IL-2 was observed, and treatment with cytokines IL-2 and transforming growth factor-ß led to upregulation of the ratio of IL-2+ macrophages. IL-27-overexpressing ESCs and macrophages were able to induce a higher ratio of IL-10+CD4+ T cells. Blocking of IL-2 with anti-IL-2 neutralizing antibody led to upregulation of the ratio of IFN-γ+CD4+ T cells in the co-culture system in vitro. Recombinant human IL-10 and IFN-γ promoted the viability, invasiveness and transcription levels of matrix metalloproteinase (MMP)2, MMP9, and prostaglandin-endoperoxide synthase 2 of ESCs, particularly combined treatment with IL-10 and IFN-γ. These results suggest that IL-2 and IL-27 synergistically promote the growth and invasion of ESCs by modulating the balance of IFN-γ and IL-10 and contribute to the progress of endometriosis.

Heterogeneous network embedding enabling accurate disease association predictions.

BACKGROUND: It is significant to identificate complex biological mechanisms of various diseases in biomedical research. Recently, the growing generation of tremendous amount of data in genomics, epigenomics, metagenomics, proteomics, metabolomics, nutriomics, etc., has resulted in the rise of systematic biological means of exploring complex diseases. However, the disparity between the production of the multiple data and our capability of analyzing data has been broaden gradually. Furthermore, we observe that networks can represent many of the above-mentioned data, and founded on the vector representations learned by network embedding methods, entities which are in close proximity but at present do not actually possess direct links are very likely to be related, therefore they are promising candidate subjects for biological investigation. RESULTS: We incorporate six public biological databases to construct a heterogeneous biological network containing three categories of entities (i.e., genes, diseases, miRNAs) and multiple types of edges (i.e., the known relationships). To tackle the inherent heterogeneity, we develop a heterogeneous network embedding model for mapping the network into a low dimensional vector space in which the relationships between entities are preserved well. And in order to assess the effectiveness of our method, we conduct gene-disease as well as miRNA-disease associations predictions, results of which show the superiority of our novel method over several state-of-the-arts. Furthermore, many associations predicted by our method are verified in the latest real-world dataset. CONCLUSIONS: We propose a novel heterogeneous network embedding method which can adequately take advantage of the abundant contextual information and structures of heterogeneous network. Moreover, we illustrate the performance of the proposed method on directing studies in biology, which can assist in identifying new hypotheses in biological investigation.

Low-dose adefovir dipivoxil-induced hypophosphatemia osteomalacia in five chronic hepatitis B virus-infected patients. Is low-dose adefovir dipivoxil-induced nephrotoxicity completely reversible?

Adefovir dipivoxil (ADV) is one of the most important nucleostide analogues currently in use for the treatment of chronic hepatitis B virus (HBV) infection. Low-dose ADV-induced nephrotoxicity in most cases was reported to be reversible after the discontinuation of ADV or by decreasing the dose of ADV. In our study, we have 5 documented cases of low-dose ADV-induced hypophosphatemia osteomalacia with or without Fanconi syndrome which were diagnosed in our hospital between 2010 and 2017. Three patients were observed to have a full recovery after the discontinuation of ADV. Two patients had persistently elevated urine ß2-microglobulin levels and out of these two patients, one patient had persistent hypophosphatemia after the cessation of ADV. These cases illustrated that the use of low-dose ADV increased the risk of nephrotoxicity, and in some patients, low-dose ADV-induced nephrotoxicity was not completely reversible. Patients of East Asian origin, especially those with a low body mass index, were prone to a relatively higher risk of developing low-dose ADV-induced nephrotoxicity; therefore, it was worth paying attention to the side effects caused by low-dose ADV.