Modeling and simulating the multi-generation product sales, production and inventory system within the context of quality upgrades.

The rapid development of science and technology has led to an increasing number of high-tech enterprises offering new products through successive generations of product upgrades. This trend presents a new challenge for the sustainable operations of enterprises. Based on the Norton-Bass model, this study begins by constructing a multi-generation product diffusion model within a single enterprise in the context of a monopoly under the quality upgrade scenario. Subsequently, a supply model is established based on this foundation, and these two models are seamlessly integrated using product sales volume as an interface, culminating in a comprehensive sales-supply system. This study analyzes the effects of new-product pricing, quality levels, initial stock, and production capacity on the performance of this system. The system dynamics (SD) method was used to simulate and solve the system in the decentralized and centralized decision-making modes, and the two decision-making modes were compared and analyzed. The research reveals several key findings. i) Comprehensive decision optimization yields enhanced profitability through joint optimization calculation of the multi-generation product diffusion system and the supply adjustment system. ii) consumer price sensitivity significantly affects product quality upgrades and profits. A negative correlation exists between consumer price sensitivity and both factors. The upgrades of product quality should be carefully traded off with consideration of pricing and quality costs. iii) Maximizing profits by maintaining a certain order level of backlog or stock shortage is beneficial for overall enterprise profitability. Additionally, optimal production capacity has been identified as a crucial element in efficient operational inventory management. This study expands the multi-generation product diffusion operational theory and provides valuable theoretical support and decision-making foundations for the sustainable management of enterprises.

METTL3-mediated m6A RNA modification promotes corneal neovascularization by upregulating the canonical Wnt pathway during HSV-1 infection.

BACKGROUND: Corneal neovascularization (CNV) is a symptom of herpes simplex keratitis (HSK), which can result in blindness. The corneal angiogenesis brought on by herpes simplex virus type 1 (HSV-1) is strongly affected by vascular endothelial growth factor A (VEGFA). The N6-methyladenosine (m6A) modification catalyzed by methyltransferase-like 3 (METTL3) is a crucial epigenetic regulatory process for angiogenic properties. However, the roles of METTL3 and m6A in HSK-induced CNV remain unknown. Here, we investigated these roles in vitro and in vivo. METHODS: A PCR array in HSV-1-infected human umbilical vein endothelial cells (HUVECs) was used to screen for METTL3 among the epitranscriptomic genes. Tube formation and scratch assays were conducted to investigate cell migration capacity. The global mRNA m6A abundance was evaluated using a dot blot assay. Gene expression was assessed by RT-qPCR, western blotting, and fluorescence immunostaining. In addition, bioinformatic analysis was conducted to identify the downstream molecules of METTL3 in HUVECs. METTL3 knockdown and STM2457 treatment clarified the specific underlying molecular mechanisms affecting HSV-1-induced angiogenesis in vitro. An acute HSK mouse model was established to examine the effects of METTL3 knockdown or inhibition using STM2457 on pathological angiogenic development in vivo. RESULTS: METTL3 was highly upregulated in HSV-1-infected HUVECs and led to increased m6A levels. METTL3 knockdown or inhibition by STM2457 further reduced m6A levels and VEGFA expression and impaired migration and tube formation capacity in HUVECs after HSV-1 infection. Mechanistically, METTL3 regulated LRP6 expression through post-transcriptional mRNA modification in an m6A-dependent manner, increasing its stability, upregulating VEGFA expression, and promoting angiogenesis in HSV-1-infected HUVECs. Furthermore, METTL3 knockdown or inhibition by STM2457 reduced CNV in vivo. CONCLUSION: Our findings revealed that METTL3 promotes pathological angiogenesis through canonical Wnt and VEGF signaling in vitro and in vivo, providing potential pharmacological targets for preventing the progression of CNV in HSK.

Identification of immune associated potential molecular targets in proliferative diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and causes of blindness in developed countries. Our study was designed to identify immune-related genes involved in the progression of proliferative diabetic retinopathy (PDR). METHODS: The "GSE102485" dataset of neovascular membrane samples (NVMs) from type 1 and 2 diabetes mellitus patients was downloaded from the Gene Expression Omnibus database. Functional enrichment analyses, protein-protein interaction network (PPI) construction, and module analysis of immune pathways in NVMs and controls were conducted via Gene Set Enrichment Analysis and Metascape. RESULTS: The significantly upregulated hallmark gene sets in DR2 and DR1 groups were involved in five immune pathways. Only CCR4, CXCR6, C3AR1, LPAR1, C5AR1, and P2RY14 were not previously reported in the context of PDR molecular pathophysiology. Except for P2RY14, all of the above were upregulated in retinal samples from experimental diabetes mouse models and human retina microvascular endothelial cells (HRMECs) treated with high glucose (HG) by quantitative Real Time Polymerase Chain Reaction (qRT-PCR). CONCLUSION: The genes identified herein provide insight into immune-related differential gene expression during DR progression.

Comparison of femtosecond laser-assisted descemetic and predescemetic lamellar keratoplasty for keratoconus.

PURPOSE: The purpose of this study is to compare the outcomes following femtosecond laser-assisted deep anterior lamellar keratoplasty (DALK) with 75% of stromal dissection (predescemetic group) and femtosecond laser-assisted DALK using big-bubble technique with total stromal resection (descemetic group) for the treatment of keratoconus. SUBJECTS AND METHODS: Twenty eyes of 17 patients with keratoconus were studied. There were 10 eyes of 9 patients in predescemetic group and 10 eyes of 8 patients in descemetic group. The postoperative best-corrected visual acuity (BCVA), manifest refraction, keratometry, endothelial cell density (ECD), and central corneal thickness (CCT) were analyzed. RESULTS: All surgeries were performed uneventfully. At 1 year after surgery, the BCVA, corneal astigmatism, keratometry, CCT, and ECD between two groups were not statistically significant (all P > 0.05). However, the mean manifest refraction was -9.43 ± 7.44 diopter (D) and -1.03 ± 1.13D in predescemetic and descemetic groups, respectively, which was statistically significant between two groups (P < 0.05). CONCLUSIONS: The results of BCVA and corneal astigmatism, keratometry, ECD, and CCT were comparable between two groups. However, the mean postoperative manifest refraction was lower in descemetic group.

Femtosecond laser-assisted anterior lamellar keratoplasty for the treatment of stromal corneal pathology.

BACKGROUND: To describe the initial outcomes and safety of anterior lamellar keratoplasty (ALK) assisted by a femtosecond laser for stromal corneal pathology. METHODS: A non-comparative case series of 14 eyes (13 patients) with various stromal corneal diseases underwent ALK with a femtosecond laser. Femtosecond laser settings, technique, uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), and endothelial cell density (ECD) were measured. RESULTS: All eyes were successfully treated without intraoperative complications. The UCVA improved in 11 eyes (78.6%) compared with preoperative UCVA. The mean difference between preoperative and postoperative UCVA was a gain of 1.7 lines (range, unchanged to 6 lines). The BCVA improved in all eyes compared with preoperative levels. The mean difference between preoperative and postoperative BCVA was a gain of 2.4 lines (range, 1-8 lines). In 3 eyes, phototherapeutic keratectomy was performed. The mean reduction in endothelial cell density was 3.7% after a mean 7.3 months of follow-up. No graft rejection, infection, or epithelial ingrowth was found. CONCLUSIONS: Femtosecond laser-assisted ALK improved UCVA and BCVA in patients with stromal corneal pathology. Our early results indicated that the femtosecond laser produced an effective and smooth dissection through opaque corneas even deeper corneal tissue.

Femtosecond laser-assisted deep anterior lamellar keratoplasty for keratoconus and keratectasia.

AIM: To describe the initial outcomes and safety of femtosecond laser-assisted deep anterior lamellar keratoplasty (DALK) for keratoconus and post-LASIK keratectasia. METHODS: In this non-comparative case series, 10 eyes of 9 patients underwent DALK procedures with a femtosecond laser (Carl Zeiss Meditec AG, Jena, Germany). Of the 9 patients, 7 had keratoconus and 2 had post-LASIK keratectasia. A 500 kHz VisuMax femtosecond laser was used to perform corneal cuts on both donor and recipient corneas. The outcome measures were the uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), corneal thickness, astigmatism, endothelial density count (EDC), and corneal power. RESULTS: All eyes were successfully treated. Early postoperative evaluation showed a clear graft in all cases. Intraoperative complications included one case of a small Descemet's membrane perforation. Postoperatively, there was one case of stromal rejection, one of loosened sutures, and one of wound dehiscence. A normal corneal pattern topography and transparency were restored, UCVA and BCVA improved significantly, and astigmatism improved slightly. There was no statistically significant decrease in EDC. CONCLUSION: Our early results indicate that femtosecond laser-assisted deep anterior lamellar keratoplasty could improve UCVA and BCVA in patients with anterior corneal pathology. This approach shows promise as a safe and effective surgical choice in the treatment of keratoconus and post-LASIK keratectasia.

[The clinical results of femtosecond laser-assisted deep anterior lamellar keratoplasty in patients with keratoconus].

OBJECTIVE: To evaluate the clinical results and safety of deep anterior lamellar keratoplasty (DALK) in patients with keratoconus assisted by a femtosecond laser. METHODS: Six eyes of 5 patients with keratoconus underwent DALK procedures by using a femtosecond laser. The mean thinnest corneal thickness, evaluated with ultrasound and measurement of visual acuity by using the standard logarithm visual chart. A femtosecond laser was used to perform corneal cuts on both donor and recipient corneas. The data were expressed as mean ± SD. Mean follow-up was (8.9 ± 2.3) month (range, 5-12 months) . RESULTS: Corneal pachymetry was (385 ± 48) µm (range, 380-460 µm) . Mean preoperative uncorrected visual acuity was 0.06 ± 0.06 (range,0.01-0.15) and mean preoperative best spectacle-corrected visual acuity was 0.41 ± 0.35 (range,0.12-1.00) . The donor corneal lamella diameters were 0.20 mm larger and thicker than the recipient to restore a physiologic corneal thickness and shape. Mean donor diameter was (7.8 ± 0.2) mm (range, 7.3-8.0 mm) and mean thickness was (372 ± 40) µm (range, 350-400 µm) .Early postoperative evaluation showed a clear graft in all cases. Mean corneal thickness was (459 ± 36) µm (range, 389-488 µm) . At the last postoperative examination mean uncorrected visual acuity was 0.32 ± 0.19 (range, 0.12-0.60) , and the mean best corrected visual acuity was 0.58 ± 0.29 (range,0.20-1.00) . The UCVA and BCVA improved significantly after surgery (t = -4.433, -3.348, P < 0.05). CONCLUSIONS: Our early results indicate that femtosecond laser-assisted deep anterior lamellar keratoplasty shows promise as a safe and effective surgical choice in the treatment of keratoconus.

Efficacy and tolerability of latanoprost compared with timolol in the treatment of patients with chronic angle-closure glaucoma.

OBJECTIVE: To evaluate the efficacy and tolerability of latanoprost compared with timolol in the treatment of patients with chronic angle-closure glaucoma (CACG). METHODS: Pertinent publications were identified through systematic searches of PubMed, EMBASE, the Cochrane Controlled Trials Register and the Chinese Biomedicine Database. Randomized controlled trials comparing latanoprost with timolol in patients with chronic angle-closure glaucoma (CACG) who had inadequate intraocular pressure (IOP) control after peripheral iridotomy (PI) were selected. The main efficacy measures were the weighted mean difference (WMD) in the reduction from baseline to end of treatment in IOP at peak, trough, and diurnal curve. The main tolerability measures were the odds ratio (OR) for the individual adverse events. The pooled estimates and 95% confidence intervals (CIs) were carried out in RevMan version 5.2 software. RESULTS: Five published randomized controlled trials involving 528 patients were included in the present meta-analysis. The IOP reduction (IOPR) was significantly greater in the latanoprost group than in the timolol group at diurnal curve (WMD: 2.22 mmHg [95% CI, 1.65 to 2.79], P < 0.00001), peak (WMD: 2.44 mmHg [0.85 to 4.03], P = 0.003) and trough (WMD: 2.67 mmHg [1.93 to 3.41], P < 0.00001). Timolol caused conjunctival hyperemia in less patients than latanoprost (pooled OR: 2.74 [95% CI, 1.33 to 5.61], P = 0.006). CONCLUSIONS: Latanoprost provides greater IOP-lowering efficacy than timolol in the treatment of patients with CACG. Latanoprost caused conjunctival hyperemia in more patients than timolol. Further clinical trials are needed because of short duration of included studies.

EphB4 expression in pterygium is associated with microvessel density.

OBJECTIVE: Angiogenesis is a key component of the pathogenesis process of pterygium, which is the growth of fibrovascular tissue on the cornea. It has been reported that EphB4, a receptor tyrosine kinase of the ephrin-Eph system, plays important role in vascular development during embryogenesis and tumor angiogenesis and is potentially involved in ocular angiogenesis. The aim of this study is to investigate the role of EphB4 in pterygia. METHODS: Fifteen pterygium samples and their paired upper bulbar conjunctiva were evaluated for expression of EphB4 and CD31 by using immunohistochemical staining. The expression level of the mRNA of EphB4 gene in 7 pterygia and matched upper bulbar conjunctiva was evaluated by using a quantitative real-time RT-PCR analysis. Microvessel density (MVD) was assessed with antibody that targets CD31. RESULTS: EphB4 protein was high expressed in the epithelium and stroma of pterygia compared to those in upper bulbar conjunctiva. Immunohistochemical staining showed that pterygia presented with statistically significant higher average count of microvessel compared to normal conjunctivae (28.24 ± 6.79 vs 11.09 ± 2.96 per high power field, P < 0.001). MVD values in stroma of the pterygium and normal conjunctiva presented a significant correlation with EphB4 staining (P < 0.001). Compared with autologous upper bulbar conjunctiva grafts, the expression of the EphB4 mRNA was increased in pterygia in 4 paired samples, including those 3 recurrent ones. CONCLUSION: The expression of EphB4 in pterygium was significantly related with the increased MVD and may be involved in angiogenesis. EphB4 protein is a potential target for treatment of pterygium.

Two polymorphisms (rs699947, rs2010963) in the VEGFA gene and diabetic retinopathy: an updated meta-analysis.

BACKGROUND: The vascular endothelial growth factor (VEGFA) gene has been suggested to play an important role in the pathogenesis of diabetic retinopathy (DR). However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the associations between VEGFA polymorphisms and DR risk. METHODS: Published literature from PubMed, EMBASE, Web of Science and Google Scholar were retrieved. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects model. RESULTS: A total of eight studies (1204 cases and 1198 controls) for rs699947 polymorphism and ten studies (1666 cases and 1782 controls) for rs2010963 polymorphism were included in the meta-analysis. The results suggested that rs699947 polymorphism was marginally associated with DR under a homogeneous co-dominant model (AA vs. CC: OR = 1.69, 95% CI = 1.03-2.77, p = 0.040) and a dominant model (AA + AC vs. CC: OR = 1.38, 95% CI = 1.01-1.90, p = 0.040), whereas the association between rs2010963 polymorphism and DR was not significant under all genetic models (all p > 0.05). In the subgroup analysis, the effect size for rs699947 polymorphism was only marginally significant among European populations under a dominant model (OR = 1.47, 95% CI = 1.07-2.02, p = 0.018), but not among East Asians. After exclusion of outliers which were the source of between-study heterogeneity, there was significant association between rs699947 polymorphism and DR under a homogeneous co-dominant model (OR = 1.64, 95% CI = 1.18-2.28, p = 0.003), even after multiple comparison correction. CONCLUSIONS: Our meta-analysis confirmed the significant association between rs699947 polymorphism and DR after exclusion of outliers, and rs2010963 polymorphism might be not associated with DR.

Occupational cooking and risk of uveal melanoma: a meta-analysis.

BACKGROUND: Many observational studies have assessed the possible association between occupational cooking and uveal melanoma risk, but reported results are controversial. Our goal was to evaluate the association between occupational cooking and uveal melanoma risk by conducting a meta-analysis of observational studies. METHODS: PubMed, EMBASE, and Web of Science were searched through June 2012 to identify all eligible studies. The pooled odds ratio (OR) with its 95% confidence interval (95%CI) was used to evaluate this association. Either a fixed- or a random-effects model were used to calculate pooled ORs. RESULTS: Five case-control studies involving a total of 1,199 cases and 6,927 controls were included in the meta-analysis. Overall, occupational cooking was associated with an increased risk of uveal melanoma (OR: 1.81, 95%CI 1.33-2.46, P < 0.001). Subgroup analysis by gender suggested occupational cooking was associated with increased risk of uveal melanoma in both men (OR: 2.16, 95%CI 1.06-4.40, P = 0.034) and women (OR: 1.92, 95%CI 1.19-3.10, P = 0.008). CONCLUSION: This meta-analysis suggests that occupational cooking is associated with an increased risk of uveal melanoma in both men and women.

Association between angiotensin-converting enzyme gene polymorphism and diabetic retinopathy in the Chinese population.

OBJECTIVE: The angiotensin-converting enzyme (ACE) gene has been implicated in the development of diabetic retinopathy (DR). However, the results have been conflicting. In this study, we performed a meta-analysis to assess the association of insertion/deletion (I/D) polymorphism in the ACE gene with DR in the Chinese population. METHODS: Published literature from PubMed, CNKI, CBM and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. RESULTS: Seventeen studies (1039 cases and 1185 controls) for I/D polymorphism in the ACE gene were identified. The results suggested that I/D polymorphism D allele might increase the risk of DR (DD vs. II: OR = 1.73, 95% CI 1.19-2.51; DD+ID vs. II: OR = 1.41, 95% CI 1.16-1.72; DD vs. ID+II: OR = 1.55, 95% CI 1.13-2.12). Subgroup analyses based on the type of DR showed that the effect size was statistically significant for proliferative DR (PDR) (DD vs. II: OR = 2.67, 95% CI 1.53-4.64; DD+ID vs. II: OR = 1.86, 95% CI 1.18-2.93; DD vs. ID+II: OR = 2.22, 95% CI 1.38-3.55), but not for background DR (BDR) (DD vs. II: OR = 1.38, 95% CI 0.85-2.25; DD+ID vs. II: OR = 1.40, 95% CI 0.98-2.02; DD vs. ID+II: OR = 1.15, 95% CI 0.74-1.79). CONCLUSION: The results indicated that I/D polymorphism in the ACE gene was associated with PDR, but not with BDR in the Chinese population.