A Review of Recent FDA-Approved Biologic-Device Combination Products.

With the remarkably strong growth of the biopharmaceutical market, an increasing demand for self-administration and rising competitions attract substantial interest to the biologic-device combination products. The ease-of-use of biologic-device combination products can minimize dosing error, improve patient compliance and add value to the life-cycle management of biological products. As listed in the purple book issued by the U.S. Food and Drug Administration (FDA), a total of 98 brand biologic-device combination products have been approved with Biologic License Application from January 2000 to August 2023, where this review mainly focused on 63 products containing neither insulin nor vaccine. Prefilled syringes (PFS) and autoinjectors are the most widely adopted devices, whereas innovative modifications like needle safety guard and dual-chamber design and novel devices like on-body injector also emerged as promising presentations. All 16 insulin products employ pen injectors, while all 19 vaccine products are delivered by a PFS. This review provides a systematic summary of FDA-approved biologic-device combination products regarding their device configurations, routes of administration, formulations, instructions for use, etc. In addition, challenges and opportunities associated with biologic-device compatibility, regulatory complexity, and smart connected devices are also discussed. It is believed that evolving technologies will definitely move the boundaries of biologic-device combination product development even further.

Changes in Expression in BMP2 and Two Closely Related Genes in Guinea Pig Retinal Pigment Epithelium during Induction and Recovery from Myopia.

PURPOSE: We previously reported differential gene expression of the bone morphogenetic protein 2 (Bmp2) in guinea pig retinal pigment epithelium (RPE) after 1 day of hyperopic defocus, imposed with a negative contact lens (CLs). The study reported here sought to obtain insights into the temporal profiles of gene expression changes in Bmp2, as well as those of two closely related genes, the inhibitor of DNA binding 3 (Id3) and Noggin (Nog), both during myopia induction and when the CL treatment was terminated to allow recovery from induced myopia. METHODS: To induce myopia, 2-week-old pigmented guinea pigs (New Zealand strain, n = 8) wore monocular -10 diopter (D) rigid gas-permeable (RGP) CLs for one week, while the other eye served as a control. Ocular measurements were made at baseline, 3 days, and 7 days after the initiation of CL wear, with treatment then being terminated and additional measurements being made after a further 3 days, 1 week, and 2 weeks. Spherical equivalent refractive errors (SERs), axial length (AL), choroidal thickness (ChT), and scleral thickness (ScT) data were collected using retinoscopy, optical biometry (Lenstar), and spectral domain optical coherence tomography (SD-OCT), respectively. RPE samples were collected from both eyes of the guinea pigs after either 1 day or 1 week of CL wear or 1 day or 2 weeks after its termination, and RNA was subsequently isolated and subjected to quantitative real-time PCR (qRT-PCR) analyses, targeting the Bmp2, Id3, and Nog genes. RESULTS: Mean interocular differences (treated-control) in AL and SER were significantly different from baseline after 3 and 7 days of CL wear, consistent with induced myopia (p < 0.001 for all cases). Termination of CL wear resulted in the normalization (i.e., recovery) of the ALs and SERs of the treated eyes within 7 days, and the earlier significant ChT thinning with CL wear (p = 0004, day 7) was replaced by rapid thickening, which remained significant on day 7 (p = 0.009) but had normalized by day 14. The ChT changes were much smaller in magnitude than the AL changes in both phases. Interocular differences in the ScT showed no significant changes. The Bmp2 and Id3 genes were both significantly downregulated with CL wear, after 1 day (p = 0.012 and 0.016) and 7 days (p = 0.002 and 0.005), while Bmp2 gene expression increased and Nog gene expression decreased after the termination of CL wear, albeit transiently, which was significant on 1 day (p = 0.004 and 0.04) but not 2 weeks later. No change in Id3 gene expression was observed over the latter period. Conclusions: The above patterns of myopia induction and recovery validate this negative RGP-CL model as an alternative to traditional spectacle lens models for guinea pigs. The defocus-driven, sign-dependent changes in the expression of the Bmp2 gene in guinea pig RPE are consistent with observations in chicks and demonstrate the important role of BMP2 in eye growth regulation.

Long-lived autoreactive memory CD4+ T cells mediate the sustained retinopathy in chronic autoimmune uveitis.

Chronic uveitis comprises heterogeneous clinical entities characterized by sustained and recurrent intraocular inflammation that is believed to be driven by autoimmune responses. The management of chronic uveitis is challenging with the limited availability of efficacious treatments, and the underlying mechanisms mediating disease chronicity remain poorly understood as the majority of experimental data are derived from the acute phase of the disease (the first 2-3 weeks post-induction). Herein, we investigated the key cellular mechanisms underlying chronic intraocular inflammation using our recently established murine model of chronic autoimmune uveitis. We demonstrate unique long-lived CD44hi IL-7R+ IL-15R+ CD4+ memory T cells in both retina and secondary lymphoid organs after 3 months postinduction of autoimmune uveitis. These memory T cells functionally exhibit antigen-specific proliferation and activation in response to retinal peptide stimulation in vitro. Critically, these effector-memory T cells are capable of effectively trafficking to the retina and accumulating in the local tissues secreting both IL-17 and IFN-γ upon adoptively transferred, leading to retinal structural and functional damage. Thus, our data reveal the critical uveitogenic functions of memory CD4+ T cells in sustaining chronic intraocular inflammation, suggesting that memory T cells can be a novel and promising therapeutic target for treating chronic uveitis in future translational studies.

Efficient photocatalysis of tetracycline hydrochloride (TC-HCl) from pharmaceutical wastewater using AgCl/ZnO/g-C3N4 composite under visible light: Process and mechanisms.

AgCl/ZnO/g-C3N4, a visible light activated ternary composite catalyst, was prepared by combining calcination, hydrothermal reaction and in-situ deposition processes to treat/photocatalyse tetracycline hydrochloride (TC-HCl) from pharmaceutical wastewater under visible light. The morphological, structural, electrical, and optical features of the novel photocatalyst were characterized using scanning electron microscopy (SEM), UV-visible light absorption spectrum (UV-Vis DRS), X-ray diffractometer (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and transient photocurrent techniques. All analyses confirmed that the formation of heterojunctions between AgCl/ZnO and g-C3N4 significantly increase electron-hole transfer and separation compared to pure ZnO and g-C3N4. Thus, AgCl/ZnO/g-C3N4 could exhibit superior photocatalytic activity during TC-HCl assays (over 90% removal) under visible light irradiation. The composite could maintain its photocatalytic stability even after four consecutive reaction cycles. Hydrogen peroxide (H2O2) and superoxide radical (·O2) contributed more than holes (h+) and hydroxyl radicals (·OH) to the degradation process as showed by trapping experiments. Liquid chromatograph-mass spectrometer (LC-MS) was used for the representation of the TC-HCl potential degradation pathway. The applicability and the treatment potential of AgCl/ZnO/g-C3N4 against actual pharmaceutical wastewater showed that the composite can achieve removal efficiencies of 81.7%, 71.4% and 69.0% for TC-HCl, chemical oxygen demand (COD) and total organic carbon (TOC) respectively. AgCl/ZnO/g-C3N4 can be a prospective key photocatalyst in the field of degradation of persistent, hardly-degradable pollutants, from industrial wastewater and not only.

Gene Expression Signatures of Contact Lens-Induced Myopia in Guinea Pig Retinal Pigment Epithelium.

Purpose: To identify key retinal pigment epithelium (RPE) genes linked to the induction of myopia in guinea pigs. Methods: To induce myopia, two-week-old pigmented guinea pigs (New Zealand strain, n = 5) wore -10 diopter (D) rigid gas-permeable contact lenses (CLs), for one day; fellow eyes were left without CLs and served as controls. Spherical equivalent refractive errors (SE) and axial length (AL) were measured at baseline and one day after initiation of CL wear. RNA sequencing was applied to RPE collected from both treated and fellow (control) eyes after one day of CL-wear to identify related gene expression changes. Additional RPE-RNA samples from treated and fellow eyes were subjected to quantitative real-time PCR (qRT-PCR) analysis for validation purposes. Results: The CLs induced myopia. The change from baseline values in SE was significantly different (P = 0.016), whereas there was no significant difference in the change in AL (P = 0.10). RNA sequencing revealed significant interocular differences in the expression in RPE of 13 genes: eight genes were significantly upregulated in treated eyes relative to their fellows, and five genes, including bone morphogenetic protein 2 (Bmp2), were significantly downregulated. The latter result was also confirmed by qRT-PCR. Additional analysis of differentially expressed genes revealed significant enrichment for bone morphogenetic protein (BMP) and TGF-ß signaling pathways. Conclusions: The results of this RPE gene expression study provide further supporting evidence for an important role of BMP2 in eye growth regulation, here from a guinea pig myopia model.

Daily or Less Frequent Topical 1% Atropine Slows Defocus-Induced Myopia Progression in Contact Lens-Wearing Guinea Pigs.

Purpose: This study compared the efficacy of topical 1% atropine applied daily versus every 3 days for controlling myopia progression in guinea pigs. Methods: To induce myopia, pigmented guinea pigs (New Zealand strain, n = 38) wore monocular -10 D rigid gas-permeable (RGP) contact lenses, which were replaced after 3 weeks with -15 diopter (D) contact lenses. Animals were treated with 1% atropine either daily (Atr-QD; n = 12), or every 3 days (Atr-Q3D; n = 11), or with artificial tears (control group; n = 15). Spherical equivalent refractive error (SER) and axial length (AL) data, as well as retinal and choroidal thickness data were collected weekly. Results: Whereas mean (±SEM) interocular differences (treated - fellow) in both SER and AL at week 0 (baseline) were similar for all groups, significant differences between the atropine-treated and control groups were evident by week 6 (SER and AL, P < 0.001). The treated eyes of the control group showed relatively more axial elongation and myopia progression than both the Atr-QD and Atr-Q3D groups. Choroidal blood vessel area also decreased over time in the treated eyes of the control group, coupled with choroidal thinning overall, with these changes being attenuated by atropine. Retinal thickness showed a developmental decrease over the treatment period but was unaffected by atropine. Conclusions: For this defocus-induced guinea pig model of myopia, application of 1% topical atropine slows myopia progression, even when applied every 3 days. Translational Relevance: The results from this study suggest that the frequency of dosing for topical atropine may be reduced from the widely used daily dosing regimen without loss of myopia control efficacy.

[Relationship between Myopia and Light Exposure].

Epidemiological studies found that the incidence of myopia was increasing year by year and the age of onset of myopia was showing a trend of affecting increasingly younger children. Reducing the occurrence of myopia and controlling the increase of myopia diopter have always been the focus of research on the prevention and control of myopia. Large randomized controlled clinical trials have found that outdoor activities can effectively reduce the incidence of myopia and delay the progression of myopia. Basic experiments also revealed that there were certain connections between light exposure and myopia. We herein review the research progress, limitations and future directions of research on light exposure and myopia. From the perspective of light properties, increasing the intensity of light can slow the progression of myopia and reduce the occurrence of experimentally induced myopia. However, the actual mechanism of action is still unclear. The rhythmic changes of light exposure caused by the light/dark cycle may cause abnormalities in the secretion of melatonin and dopamine, and changes in the circadian rhythm of intraocular pressure and choroidal thickness, thus affecting myopia. The red light, with relatively longer wavelength and forming images behind the retina, tends to induce myopia more easily, while the blue light, with medium and short wavelength and forming images before the retina, tends to delay myopia progression. However, different species respond differently to lights of different wavelengths, and the relationship between light wavelength and myopia needs further investigation. Future research can be done to further explore the mechanism of action of how light exposure changes the progression of myopia, including the following aspects: how light changes dopamine levels, causing changes in downstream signal pathways, and thus controlling the growth of the axial length of the eye; how retinal photoreceptor cells receive light signals of different wavelengths in order to adjust the refractive power of the eyes; and how to design artificial lighting of reasonable intensity, composition and properties, and apply the design in myopia prevention and control.

Transcriptome sequencing and differential expression analysis of seed starch accumulation in Chinese chestnut Metaxenia.

BACKGROUND: Chestnut seeds are important kinds of edible nuts rich in starch and protein. The characteristics and nutrient contents of chestnut have been found to show obvious metaxenia effects in previous studies. To improve the understanding of the effect of metaxenia on chestnut starch and sucrose metabolism, this study used three varieties of chestnut, 'Yongfeng 1', 'YongRen Zao' and 'Yimen 1', as male parents to pollinate the female parent, 'Yongfeng 1', and investigated the mechanisms of starch and sucrose metabolism in three starch accumulation stages (70 (S1), 82 (S2), and 94 (S3) days after pollination, DAP) in chestnut seed kernels. RESULT: Most carbohydrate metabolism genes were highly expressed in YFF (self-pollinated 'Yongfeng 1') in stage S2 and in YFR ('Yongfeng 1' × 'Yongren Zao') and YFM ('Yongfeng 1' × 'Yimen 1') in stage S3. In stage S3, hub genes encoding HSF_DNA-binding, ACT, Pkinase, and LIM proteins and four transcription factors were highly expressed, with YFF showing the highest expression, followed by YFR and YFM. In addition, transcriptome analysis of the kernels at 70, 82 and 94 DAP showed that the starch granule-bound starch synthase (EC 2.4.1.242) and ADP-glucose pyrophosphorylase (EC 2.7 .7.27) genes were actively expressed at 94 DAF. Chestnut seeds regulate the accumulation of soluble sugars, reducing sugars and starch by controlling glycosyl transferase and hydrolysis activity during development. CONCLUSION: These results and resources have important guiding significance for further research on starch and sucrose metabolism and other types of metabolism related to chestnut metaxenia.

Regulating Glucose Metabolism with Prodrug Nanoparticles for Promoting Photoimmunotherapy of Pancreatic Cancer.

The low immunogenicity, insufficient infiltration of T lymphocytes, and dismal response to immune checkpoint blockade therapy pose major difficulties in immunotherapy of pancreatic cancer. Photoimmunotherapy by photodynamic therapy (PDT) can induce an antitumor immune response by triggering immunogenic cell death in the tumor cells. Notwithstanding, PDT-driven oxygen consumption and microvascular damage can further aggravate hypoxia to exaggerates glycolysis, leading to lactate accumulation and immunosuppressive tumor microenvironment. Herein, a supramolecular prodrug nanoplatform codelivering a photosensitizer and a prodrug of bromodomain-containing protein 4 inhibitor (BRD4i) JQ1 for combinatory photoimmunotherapy of pancreatic cancer are demonstrated. The nanoparticles are fabricated by host-guest complexation between cyclodextrin-grafted hyaluronic acid (HA-CD) and adamantine-conjugated heterodimers of pyropheophorbide a (PPa) and JQ1, respectively. HA can achieve active tumor targeting by recognizing highly expressed CD44 on the surface of pancreatic tumors. PPa-mediated PDT can enhance the immunogenicity of the tumor cells and promote intratumoral infiltration of the cytotoxic T lymphocytes. Meanwhile, JQ1 combats PDT-mediated immune evasion through inhibiting expression of c-Myc and PD-L1, which are key regulators of tumor glycolysis and immune evasion. Collectively, this study presents a novel strategy to enhance photoimmunotherapy of the pancreatic cancer by provoking T cells activation and overcoming adaptive immune resistance.

Engineering Oxaliplatin Prodrug Nanoparticles for Second Near-Infrared Fluorescence Imaging-Guided Immunotherapy of Colorectal Cancer.

Colorectal cancer (CRC) ranks as the third common and the fourth lethal cancer type worldwide. Immune checkpoint blockade therapy demonstrates great efficacy in a subset of metastatic CRC patients, but precise activation of the antitumor immune response at the tumor site is still challenging. Here a versatile prodrug nanoparticle for second near-infrared (NIR-II) fluorescence imaging-guided combinatory immunotherapy of CRC is reported. The prodrug nanoparticles are constructed with a polymeric oxaliplatin prodrug (PBOXA) and a donor-spacer-acceptor-spacer-donor type small molecular fluorophore TQTCD. The later displays large Stokes shift (>300 nm), fluorescence emission over 1000 nm, and excellent photothermal conversion performance for NIR-II fluorescence imaging-guided photothermal therapy (PTT). The prodrug nanoparticles show seven times higher intratumoral OXA accumulation than free oxaliplatin. TQTCD-based PTT and PBOXA-induced chemotherapy trigger immunogenic cell death of the tumor cells and elicit antitumor immune response in a spatiotemporally controllable manner. Further combination of the prodrug nanoparticle-based PTT/chemotherapy with programmed death ligand 1 blockade significantly promotes intratumoral infiltration of the cytotoxic T lymphocytes and eradicates the CRC tumors. The NIR-II fluorescence imaging-guided immunotherapy may provide a promising approach for CRC treatment.

Efficacy of bilateral lateral rectus recession versus unilateral recession and resection for basic-type intermittent exotropia: a meta-analysis.

PURPOSE: To investigate the efficacy of bilateral lateral rectus recession (BLR) versus unilateral recession and resection (RR) for the treatment of patients with basic-type intermittent exotropia (IXT). METHODS: We systematically searched the EMBASE, PubMed, Web of Science and Cochrane Library databases for relevant studies published before April 2020 with no language restrictions. Related studies meeting the eligibility criteria were included. The primary outcomes were success rate and mean postoperative deviation. Odds ratios (ORs) and weighted mean differences (MDs) with 95% confidence intervals (CIs) were calculated. RESULTS: From 1243 screened articles, a total of 10 studies involving 967 patients were included in the analysis. No differences were observed in success rates between the BLR and RR groups at 1-day to 1-week postoperatively (OR: 0.9, 95% CI: 0.53 to 1.53, p = 0.69), or at 6-month postoperatively (OR: 1.11, 95% CI: 0.59 to 2.11, p = 0.74), or at the last follow-up visit (OR: 0.76, 95% CI: 0.44 to 1.34, p = 0.34). The unsatisfactory effects (the overcorrection and undercorrection rates) between the two groups were comparable. In addition, there were no significant differences between the two groups in postoperative deviation at 1-day to 1-week postoperatively (MD: 0.03, 95% CI: -1.32 to 1.27, p = 0.97), or at 6-month postoperatively (MD: 1.42, 95% CI: -0.43 to 3.27, p = 0.13) or at the last follow-up visit (MD: 0.29, 95% CI: -1.39 to 1.97, p = 0.74). CONCLUSION: This meta-analysis provides evidence that both the BLR and RR procedures have similar efficacy for the treatment of basic-type IXT.

Altered Expression of GJD2 Messenger RNA and the Coded Protein Connexin 36 in Negative Lens-induced Myopia of Guinea Pigs.

SIGNIFICANCE: Decreased expression of the retinal GJD2 gene messenger RNA (mRNA) and connexin 36 (Cx36) protein in the guinea pig negative lens-induced myopia (LIM) model suggests their involvement in local retinal circuits regulating eye growth. PURPOSE: Previous studies suggest that the GJD2 gene and Cx36 protein encoded by the GJD2 gene play important roles in retinal signaling pathways and eye development. The aim of this study was to investigate the changes in GJD2 mRNA and Cx36 protein expression in the guinea pig lens-induced myopia model. METHODS: Four-week-old guinea pigs were randomly divided into two groups. Animals in the experimental group were fitted with monocular -10 D lenses; and animals in the control group, with monocular plano lenses. Biometric measurements, including the spherical equivalent refractive error and axial length, were monitored. Animals were killed after 0, 1, 2, and 3 weeks of treatment, and their retinas were isolated. Retinal GJD2 mRNA and Cx36 protein expression levels were assessed by quantitative real-time polymerase chain reaction and Western blot analysis, respectively. RESULTS: Spherical equivalent refractive error values indicated that negative lens-treated eyes became significantly more myopic than plano lens-treated eyes (P = .001), consistent with their longer axial lengths compared with those of control eyes. Both GJD2 mRNA and Cx36 protein expression levels were decreased in the retinas of negative lens-treated eyes compared with levels in the retinas of plano lens-treated eyes, although there were differences in the timing; GJD2 mRNA, levels were significantly decreased after 1 and 2 weeks of treatment (P = .01 and P = .004, respectively), whereas Cx36 protein expression was significantly decreased after only 1 week (P = .01). CONCLUSIONS: That both retinal GJD2 mRNA and Cx36 protein expression levels were decreased after induction of myopia with negative lenses points to retinal circuits involving Cx36 in myopia development in the guinea pig.

[Fabrication of La-MHTC Composites for Phosphate Removal: Adsorption Behavior and Mechanism].

Lanthanum (La)-based materials have shown great potential for phosphate removal owing to the strong affinity between La and phosphate. In this study, magnetic hydrothermal biochar immobilized La(OH)3 (La-MHTC) were prepared and used as phosphate adsorbents. Hydrochar was produced by the hydrothermal carbonization process (220℃, 2 h). Magnetic La-MHTC with different La-to-Fe mass ratios were synthesized by the co-precipitation method. Subsequently, La-MHTC was applied to remove phosphate from wastewater. Results indicate that La-MHTC (with a La-to-Fe mass ratio of 2:1) exhibited excellent magnetic properties for easy recovery and high phosphate adsorption capacity up to 100.25 mg·g-1. Effective phosphate removal was obtained over a wide pH range of 3-10. The absorption isotherm and kinetics were better fitted by the Langmuir model and the pseudo second-order model, respectively, which showed a fast adsorption rate and exhibited superior La utilization efficiency. The La-MHTC has strong selectivity for phosphate in the presence of coexisting ions (Cl-, NO3-, and SO42-). The adsorption-desorption experiment suggested its excellent stability and cyclic utilization. In addition, La-MHTC was applied to treat real domestic wastewater, efficiently reducing the phosphate concentration (from 0.87 mg·L-1 to 0.05 mg·L-1). Electrostatic attraction and inner-sphere complexation between La(OH)3 and P via ligand exchange were the main mechanisms of phosphate adsorption by La-MHTC.

Tetracycline degradation by Klebsiella sp. strain TR5: Proposed degradation pathway and possible genes involved.

Microorganisms with high tetracycline (TC) degradation efficiencies are required for biological processes for TC-containing wastewater treatment. With multiple enrichment cultures, a TC-degrading strain TR5 was isolated from chicken manure mixture in a large broiler farm, which was identified as Klebsiella pneumoniae by 16S rRNA gene sequencing and biochemical properties. Strain TR5 could degrade TC quickly (∼90% within 36 h) with the initial TC concentration of 200 mg/L under optimized conditions via single-factor experiment coupled with RSM. Strain TR5 could detoxify TC and generate much less toxic products as long as cultured more than one day. Three TC-degrading pathways were proposed based on 8 possible products. A transformant containing a plasmid from TR5 acquired TC-degrading ability, indicating that TC-degrading genes were located on this plasmid. Complete sequencing of pYK5 showed that isomerase-, oxidoreductase-, and transferases-encoding genes were found and were inferred to be involved in TC degradation. TR5 may not degrade TC completely and it can utilize some carbon-containing compounds derived from TC via the effect of formylglutathione hydrolase-encoding gene. Our findings showed that strain TR5 could be a promising agent for wastewater treatment, and genes involved in TC degradation are worthy of further investigations for enzyme preparations development.

Decreased expression of gap junction delta-2 (GJD2) messenger RNA and connexin 36 protein in form-deprivation myopia of guinea pigs.

BACKGROUND: More than ten genome-wide association studies have identified the significant association between the gap junction delta-2 (GJD2) gene and myopia. However, no functional studies have been performed to confirm that this gene is correlated with myopia. This study aimed to observe how this gene changed in mRNA and protein level in the form-deprivation myopia (FDM) animal model. METHODS: Four-week-old guinea pigs were randomly divided into two groups: control and FDM groups (n = 12 for each group). The right eyes of the FDM group were covered with opaque hemispherical plastic lenses for 3 weeks. For all the animals, refractive status, axial length (AL), and corneal radius of curvature were measured at baseline and 3 weeks later by streak retinoscope, A-scan ultrasonography, and keratometer, respectively. Retinal GJD2 mRNA expression and connexin 36 (Cx36) levels in FDM and control groups were measured by quantitative real-time PCR and Western blot analyses, respectively. Those results were compared using independent t test, Mann-Whitney U test, or paired t test. A significance level of P < 0.05 was used. RESULTS: Three weeks later, the FDM group (form-deprived eyes) showed about a myopic shift of approximately -6.75 (-7.94 to -6.31) D, while the control group remained hyperopic with only a shift of -0.50 (-0.75 to 0.25) D (Z = -3.38, P < 0.01). The AL increased by 0.74 (0.61-0.76) and 0.10 (0.05-0.21) mm in FDM and control groups, respectively (Z = -3.37, P < 0.01). The relative mRNA expression of GJD2 in the FDM group decreased 31.58% more than the control group (t = 11.44, P < 0.01). The relative protein expression of CX36 on the retina was lowered by 37.72% in form-deprivation eyes as compared to the controls (t = 17.74, P < 0.01). CONCLUSION: Both the mRNA expression of GJD2 and Cx36 protein amount were significantly decreased in the retina of FDM guinea pigs. This indicates that Cx36 is involved in FDM development, providing compensating evidence for the results obtained from genome-wide association studies.

The use of contact lenses among university students in Chengdu: Knowledge and practice of contact lens wearers.

PURPOSE: To assess the prevalence and general knowledge of contact lens wearers among college students in Chengdu, a metroplolitan of Chinaand find out the routine habits of use and hygienic conditions when wearing contact lenses. METHOD: The questionnaire was distributed to 1,600 ametropic participants who were from 8 different universities. Data about demographics, general contact lens handling habits, personal attitudes, hygiene behaviors and eye health conditions were collected. We made the analysis ofthe demographics and wearing of contact lenses. Possible reasons for behaviors related to the care of contact lenses were analyzed. RESULTS: The prevalence of contact lens use was 19.80%. Most users (82.15%) were females. An aesthetic effect was cited as the first reason for using (57.91%). The comfort of eyes was the first consideration (75.76%) when buying. To keep clean and use safe, 86.20% subjects washed hands before handling and 83.50% cleaned the lens carefully after removing. There was significant difference between males and females regarding the replacement of the solution (p=0.014). 32.66% wears knew the removal of protein deposits. A total of 54.88% were not informed of the potential complications of contact lens. The incidence of ocular discomfort was 44.78%. Only 3.03% of the students paid regular visits to ophthalmic clinics. CONCLUSION: The prevalence of contact lenses was relatively low in Chengdu. The wears had limited knowledge about using and careof contact lens. More education on standard lens wear and care should be provided to wearers.

Gene-Gene Interactions among Pparα/δ/γ Polymorphisms for Apolipoprotein (Apo) A-I/Apob Ratio in Chinese Han Population.

BACKGROUND: The peroxisome proliferator-activated receptors (PPARs) -α, -δ/ß and -γ are the ligand-activated transcription factors involved in the regulation of fatty acid and lipoprotein metabolism, energy balance, cell proliferation and differentiation and atherosclerosis, etc. We investigated the associations of 10 single-nucleotide polymorphisms (SNPs) in PPARs with apolipoprotein (apo) A-I/apoB ratio in Chinese Han population. METHODS: Overall, 630 subjects (212 males, 418 females) were randomly selected from the Prevention of Metabolic Syndrome and Multiple Metabolic Disorders in Jiangsu Province of China Study Cohort. Population analyzed was as the general population which involved healthy people and individuals with disorders of apoA-I or apoB. 10 SNPs (rs1800206, rs135539, rs4253778, rs2016520, rs9794, rs10865710, rs1805192, rs709158, rs3856806 and rs4684847) were genotyped. Mean difference (Difference) and 95% confident interval (95%CI) were calculated. RESULTS: After covariates adjustment, rs1800206-V allele (LV+VV) and rs3856806-T allele (CT+TT) were significantly associated with a decreased apoA-I/apoB ratio than those wild type carriers, Difference (95%CI) were -1.29 (-1.96-0.62) and -0.8 (-1.42~-0.17), respectively. Rs4253778-C allele was significantly associated with an increased apoA-I/apoB ratio compared to the wild type carriers (GG), Difference (95%CI) was 0.76 (0.04-1.48). Generalized multifactor dimensionality reduction analysis showed that three-to-eight-locus models were significant with apoA-I/apoB ratio (P<0.05). We chose the seven-locus model (P=0.0010) as the best GMDR model (cross-validation consistency was 7/10 and testing accuracy was 62.97%). CONCLUSION: Our data provided the evidence that PPARs polymorphisms might be involved in regulation of apoA-I/apoB ratio in independently and/or in an interactive manner.

[Interaction of both hypertriglyceridemic waist and impaired fasting glucose on the incidence of diabetes mellitus].

OBJECTIVE: To study the use of hypertriglyceridemic waist (HTGW) to predict the occurrence of diabetes. Also to independently study whether there was an interaction between HTGW and impaired fasting glucose impaired fasting glucose (IFG) on the cause of diabetes. METHODS: We undertook a cohort study based on data from the "Prevention of Multiple Metabolic Disorders and Metabolic Syndrome (MS) Study in Jiangsu Province, China". We used the logistic regression model to analyze the relations between both HTGW, IFG and diabetes mellitus and to evaluate the multiplied interaction between HTGW and IFG to include product terms method. Counting additive interaction was carried out under the Excel Calculation Sheet, compiled by Anderson and his colleagues. RESULTS: After adjusted for general risk factors and baseline fasting plasma glucose (FPG), results showed that subjects with HTGW had a 2.10 (95% CI: 1.36 - 3.25) adjusted relative risk (HR) of developing a diabetes when compared with those individuals without HTGW at the baseline study. When IFG was stratified, participants with HTGW were significantly associated with diabetes, regardless of IFG. The multi-adjusted HRs of diabetes were 3.09 (1.70 - 5.61) and 2.09 (1.08 - 4.02), respectively. Compared to the participants with non-HTGW and their FPG level below the threshold, those having HTGW and their FPG level was above the threshold, had the highest adjusted HR values [12.05 (95% CI: 6.89 - 21.07)]. Data from the additive interaction analysis showed that RERI as 7.00 (95% CI: 0.49 - 13.51), AP as 0.57 (95% CI: 0.32 - 0.82) and SI as 2.66 (95% CI: 1.36 - 5.21). CONCLUSION: HTGW could predict the occurrence of diabetes, independent from IFG while the presence of HTGW with IFG could have an additive interaction on the cause of diabetes.