Cost-effectiveness and cost-utility of traditional and telemedicine combined population-based age-related macular degeneration and diabetic retinopathy screening in rural and urban China.

Background: To assess the cost-effectiveness and cost-utility of a population-level traditional and telemedicine combined age-related macular degeneration (AMD) and diabetic retinopathy (DR) screening program in rural and urban China. Methods: Decision-analytic Markov models were conducted to evaluate the costs and benefits of traditional and telemedicine combined AMD and DR screening from a societal perspective. A cohort of all participants aged 50 years old and above was followed through a total of 30 1-year Markov cycles. Separate analyses were performed for rural and urban settings. Relevant parameters such as the prevalence of AMD and DR, transition probability, compliance with screening and treatment, screening sensitivity, specificity, utility, and mortality were collected from published studies specific to China, other Asian counties' studies, or unpublished data sources such as the National Committee for the Prevention of Blindness. Costs of screening, full examination, and treatment come from the real medical environments and unified pricing of Beijing Municipal Medical Insurance Bureau. Primary outcomes were incremental cost-utility ratios (ICURs) using quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) using years of blindness avoided. One-way deterministic and simulated probabilistic sensitivity analyses were conducted to reflect uncertainty. Findings: Under the status quo, the total expected medical costs for a 50-year-old patient with AMD or DR were $869·59 and $1,514·18 in rural and urban settings, respectively. Both traditional and telemedicine screening were highly cost-effective. In rural settings, ICURs were $191 (95% confidence interval [CI]: $66 to $239) and $199 (95% CI: $-12 to $217), and ICERs were $2,436 (95% CI: $1,089 to $3,254) and $2,441 (95% CI: $1,452 to $3,900) for traditional and telemedicine screening separately. Even more surprising, both screening strategies dominated no screening in urban settings. Our results were insensitive and robust to extensive sensitivity analyses. Among all acceptable screening intervals (from 1 to 5 years), annual screening could not only produce biggest benefits but also keep ICERs less than three times and one time the per capita gross domestic product (GDP) in rural and urban settings separately. When compared with traditional screening, ICERs of telescreening were less than three times the per capita GDP in rural settings ($2,559 to $8,809) and less than one time the per capita GDP in urban settings (less than $5,564), annual telescreening produced the biggest benefits, it could avert 119 and 270 years of blindness in rural and urban areas separately when 100,000 people were screened. Interpretation: We performed decision-analytic Markov models for combined AMD and DR screening in rural and urban China, and the results showed that population-level combined screening for AMD and DR is likely to be highly cost-effective in both rural and urban China for people over 50 years old. Optimal screening may have an interval of every year based on teleophthalmology platforms. In the future, China should pay more attention to chronic eye diseases and the government should establish a sound chronic disease management system and make every patient enjoy equal medical services. Funding: National Natural Science Foundation of China, NSFC (82171051); the Major Innovation Platform of Public Health & Disease Control and Prevention, Renmin University of China and Beijing Nova program (Z191100001119072).

Prevalence of cataract and cataract surgery in urban and rural Chinese populations over 50 years old: a systematic review and Meta-analysis.

AIM: To summarize the data of epidemiological studies on cataract prevalence over 50 years old in urban and rural areas of China from 2000 to 2020, and to analyze the prevalence of cataract and operation rate in China. METHODS: By searching PubMed, EMBASE, Web of Science, Wanfang Data and CNKI, Chinese and English literatures on the prevalence of cataract in China were retrieved, and the relevant characteristic data were extracted. Then, Stata v15SE software was used for Meta-analysis and heterogeneity test. According to the results of heterogeneity, the corresponding effect models were selected to combine the extracted data. RESULTS: A total of 20 studies were included in this study, with a total of 111 434 cases. Meta-analysis showed heterogeneity. According to the random effect model, the overall prevalence of cataract in Chinese people over 50 years old was 27.45%, that in rural was 28.79%, and that in urban was 26.66%. The overall coverage rate of cataract surgery was 9.19%. CONCLUSION: The prevalence of cataract is high in China, and there is still room for improvement in surgical coverage, so it is very important to promote cataract screening and prevention.

Pink Lotus Essential Oil and Alleviates on Free Fatty Acid Induced Steatosis in HepG2 Cells via PI3K/Akt and NF-κB Pathways.

Pink lotus essential oil (PLEO) is the volatile components extracted from lotus flowers and there are few relevant research. The purpose of this study was to observe the effect of PLEO on NAFLD in vitro model and its possible mechanism. The ingredients of PLEO were determined by gas chromatography-mass spectrometry (GS-MS) and its lipid-lowering and hepatoprotective activities were investigated. HepG2 cells were treated with free fatty acid (FFA) to establish a cell model of NAFLD. Cell viability was evaluated by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Total cholesterol (TC), triglyceride (TG), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were determined by Enzyme-Linked Immune Sorbent Assay (ELISA). Oil red O staining was performed to observe the lipid accumulation in the HepG2 cells. Lipid metabolism enzymes including fatty acid synthase (FAS), acetyl-coA carboxylase (ACC), stearoyl-CoA desaturase 1 (SCD-1), and carnitine palmitoyltransferase-1 (CPT-1), insulin signaling pathways including phosphatidylinositol 3 kinase (PI3K) and protein kinase B Akt, inflammatory signaling pathways such as nuclear factor kappa-B (NF-κB), were determined by Western blotting. There were 46 components determined in PLEO with many terpenoids compounds. PLEO decreased TC and TG contents in the FFA-treated HepG2 cells. Furthermore, PLEO inhibited TNF-α, IL-6 and IL-1ß excretion, decreased NF-κB, FAS, ACC and SCD-1 while increased phosphorylation of NF-κB, PI3K, Akt, and CPT-1 expression. It is the first time to reveal that PLEO alleviates FFA-induced steatosis in HepG2 cells by regulating lipid metabolism, inhibiting inflammatory response, and improving insulin sensitivity.

The Association between Myopia and Primary Open-Angle Glaucoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous studies identified myopia as a risk factor for primary open-angle glaucoma (POAG). However, recent studies have shown different results, and the definitive relationship between myopia and POAG remains controversial. OBJECTIVES: The aim of this study was to investigate the relationship between myopia and POAG. METHODS: Published articles were searched from PubMed, Embase, and Scopus databases between 1970 and 2020. A pooled analysis of the odds ratios (ORs) was performed using a random-effects model. RESULTS: Data on the association between myopia and POAG were obtained from 16 cross-sectional studies, and the pooled OR was 2.26 (95% confidence interval [CI], 1.77-2.89, p < 0.001) in random-effects model (I2 = 86%; p < 0.01). For the relationship of myopia and POAG progression, data from 7 longitudinal cohort studies were included, and the pooled OR was 0.85 (95% CI, 0.73-0.99, p = 0.042) in the random-effects model (I2 = 88%; p < 0.01). CONCLUSION: Our findings demonstrated that myopia may be a risk factor associated with POAG and a possible protective factor for POAG progression. It may be due to myopia with the presence of a lamina cribrosa defect, slowing down the visual field loss and also POAG progression. Further research for underlying mechanisms is still needed.

Cost-Utility Analysis of Screening for Diabetic Retinopathy in China.

Background. Diabetic retinopathy (DR) has been primarily indicated to cause vision impairment and blindness, while no studies have focused on the cost-utility of telemedicine-based and community screening programs for DR in China, especially in rural and urban areas, respectively.Methods. We developed a Markov model to calculate the cost-utility of screening programs for DR in DM patients in rural and urban settings from the societal perspective. The incremental cost-utility ratio (ICUR) was calculated for the assessment.Results. In the rural setting, the community screening program obtained 1 QALY with a cost of $4179 (95% CI 3859 to 5343), and the telemedicine screening program had an ICUR of $2323 (95% CI 1023 to 3903) compared with no screening, both of which satisfied the criterion of a significantly cost-effective health intervention. Likewise, community screening programs in urban areas generated an ICUR of $3812 (95% CI 2906 to 4167) per QALY gained, with telemedicine screening at an ICUR of $2437 (95% CI 1242 to 3520) compared with no screening, and both were also cost-effective. By further comparison, compared to community screening programs, telemedicine screening yielded an ICUR of 1212 (95% CI 896 to 1590) per incremental QALY gained in rural setting and 1141 (95% CI 859 to 1403) in urban setting, which both meet the criterion for a significantly cost-effective health intervention.Conclusions. Both telemedicine and community screening for DR in rural and urban settings were cost-effective in China, and telemedicine screening programs were more cost-effective.

In Vivo Delivery of siRNAs Targeting EGFR and BRD4 Expression by Peptide-Modified Redox Responsive PEG-PEI Nanoparticles for the Treatment of Triple-Negative Breast Cancer.

The study aims to investigate the in vivo distribution, antitumor effect, and safety of cell membrane-penetrating peptide-modified disulfide bond copolymer nanoparticles loaded with small-interfering RNA (siRNA) targeting epidermal growth factor receptor (EGFR) and bromodomain-containing protein 4 (BRD4) in triple-negative breast cancer (TNBC). Polyethylene glycol disulfide bond-linked polyethylenimine (PEG-SS-PEI) was modified with peptides GALA and CREKA and used as vectors to prepare siRNA nanoparticles. The GALA- and CREKA-modified PEG-SS-PEI nanoparticles (GC-NPs) were prepared by mixing siEGFR and siBRD4 (1:1) with GALA-PEG-SS-PEI and CREKA-PEG-SS-PEI (1:1) in an aqueous solution at an N/P ratio of 30:1. Nanoparticles loaded with scrambled siRNA were prepared with the same method. The gene silencing effect on EGFR and BRD4 in vitro was evaluated by Western blotting analysis. TNBC xenograft models were established by subcutaneous injection of MDA-MB-231 cells into female nude mice. At 1, 3, 6, 12, and 24 h after administration of five formulations of Cy5-siRNA (133 µg/10 g) via the tail vein, the mice were observed and imaged for a biodistribution study using an in vivo imaging system. In the pharmacodynamics experiment, tumor-bearing mice were treated with respective siRNA preparations at a dose of 133 µg/10 g for 18 days, and the body weight and tumor size were recorded every other day. The protein expression levels of EGFR, p-EGFR, PI3K, p-PI3K, Akt, p-Akt, BRD4, and c-Myc were determined using Western blotting analysis. Hematological and serum biochemical parameters, organ indices, and HE staining results for the heart, liver, spleen, lung, and kidney were analyzed to evaluate the safety of the nanoparticles. GC-NPs loaded with siEGFR and siBRD4 significantly inhibited the expression of EGFR and BRD4 in vitro. The strongest fluorescence signals were observed in the GC-NP group, especially in tumors, indicating the excellent tumor-targeted delivery of GC-NPs we constructed. Tumor growth was significantly inhibited in the GC-NP-treated group, and the expression of EGFR, p-EGFR, PI3K, p-PI3K, Akt, p-Akt, BRD4, and c-Myc in the tumors decreased by 71%, 68%, 61%, 68%, 48%, 58%, 59%, and 74% compared to the control group, respectively. There was no significant change in hematological parameters, biochemical indices, or tissue morphology in GC-NP-treated mice. SiRNA cotargeting EGFR and BRD4 delivered by GALA- and CREKA-modified PEG-SS-PEI had favorable antitumor effects in vivo toward TNBC with tumor-targeting efficacy and good biocompatibility.

Luteolin alleviates non-alcoholic fatty liver disease in rats via restoration of intestinal mucosal barrier damage and microbiota imbalance involving in gut-liver axis.

Nonalcoholic fatty liver disease (NAFLD) is demonstrated to be closely related to the disorder of gut microbiota and the intestinal mucosal barrier. Luteolin is a natural flavonoid with various activities. We aimed to investigate whether Luteolin can alleviate NAFLD and its possible mechanism involving the gut-liver axis. A rat NAFLD model was established by feeding a high-fat diet (HFD), and Luteolin was administered intragastrically. The effects of Luteolin on liver biochemical parameters, intestinal histopathology and integrity, gut microbiota, lipopolysaccharides (LPS), inflammatory cytokines, and the Toll-like receptor 4 (TLR4) signaling pathway were evaluated. We found that Luteolin restored the expression of the tight junction proteins in the intestine and ameliorated the increase permeability of the intestinal mucosa to Fluorescein isothiocyanate-dextran (FD4) caused by a high-fat diet, thus enhancing the function of the intestinal barrier. In addition, Luteolin inhibited the TLR4 signaling pathway in the liver, thereby reducing the secretion of pro-inflammatory factors and alleviating NAFLD. 16S rRNA gene sequencing revealed that Luteolin intervention significantly altered the composition of the gut microbiota in NAFLD rats and increased the richness of gut microbiota. Luteolin alleviates NAFLD in rats via restoration and repair of the damaged intestinal mucosal barrier and microbiota imbalance.

In vivo and in vitro effects of Salsola collina on gastrointestinal motility in rats.

OBJECTIVES: Salsola collina is widely distributed along the Bohai coast and consumed as an edible plant by native residents. We have found surprisingly that S. collina extracts promoted gastrointestinal motility in mice previously. In the present study, effects of S. collina on gastrointestinal motility in rats and its underlying mechanism were explored. MATERIALS AND METHODS: In vivo, different fraction extracts from S. collina were prepared and the effects on gastric emptying and small intestinal propulsion in normal rats were measured. Plasma ghrelin (GRL), motilin (MTL), gastrin (GAS) and vasoactive intestinal peptide (VIP) and expressions of GRL receptor (GHSR), MTL receptor (MTLR), VIP receptor 2 (VIPR2) in the duodenum were also detected. In vitro, gastric antrum strips were prepared and activities of different extracts on gastric smooth muscle contractions were evaluated. RESULTS: Results showed that the ethyl acetate extract (EAE) was the most effective fraction to promote gastric emptying and intestinal propulsion, showing a dose-dependent manner. EAE increased plasma GRL and GAS, elevated GHSR expression and restrained VIPR2 expression in the duodenum. In vitro, EAE promoted contraction of normal gastric antrum strips as well as relaxed strips induced by atropine. CONCLUSION: These data indicate that EAE has a significant prokinetic activity via a mechanism that mainly involves in modulating plasma GRL and GAS, expressions of GSHR and VIPR2 in the duodenum and activating M-cholinergic receptor. Our study provides a pharmacological basis for the use of S. collina extract in treating gastrointestinal motility disorders.

Ghrelin and electrical stimulating the lateral hypothalamus area regulated the discharges of gastric distention neurons via the dorsal vagal complex in cisplatin-treated rats.

OBJECTIVE: Cisplatin is an important antineoplastic drug and has side effects such as nausea, vomiting, and dyspepsia. The detailed mechanisms for its side effects are yet not well be illustrated. Our purpose was to investigate the discharges of gastric distention (GD) sensitive neurons regulated by ghrelin and electrical stimulation of the lateral hypothalamus area (LHA) via the dorsal vagal complex (DVC) in cisplatin-treated rats. MATERIALS AND METHODS: Extracellular discharge recording was performed to observe the effects of ghrelin and electrical stimulation of the LHA on discharges of GD neurons in the DVC. RESULTS: GD neurons were recorded in DVC in saline-treated and cisplatin-treated rats and identified as GD-excitatory (GD-E) neurons, which are excited by gastric distension, and GD-inhibitory (GE-I) neurons, which are inhibited by gastric distension. Microinjection of ghrelin into the DVC increased the firing frequency of most GD neurons, while the ratios of excited GD-E and GD-I neurons in cisplatin-treated rats were significantly lower than those in saline-treated rats. The excitatory effect of ghrelin was eliminated completely by DVC pretreatment with ghrelin receptor antagonist [D-Lys-3]-GHRP-6. After electrical stimulation of the LHA, the firing frequency of these neurons significantly increased. This excitatory effect was weaker in cisplatin-treated rats than in saline-treated rats and could be partly blocked by DVC pretreatment with [D-Lys-3]-GHRP-6. CONCLUSION: GD neurons in the DVC could be excited by microinjecting ghrelin into the DVC and electrical stimulation of the LHA, respectively. The excitatory effect was attenuated by cisplatin injected intraperitoneally.