Healthcare utilization and economic burden of myopia in urban China: A nationwide cost-of-illness study.

Background: China contributes to a significant proportion of the myopia in the world. The study aims to investigate the utilization of various correction methods and health service in urban China, and to estimate the cost of myopia treatment and prevention. In addition, we aimed to estimate the cost of productivity loss due to myopia. Methods: The study was a cross-sectional investigation carried out in urban areas in three provinces located in the east (Shanghai), middle (Anhui) and west part (Yunnan) of China, in 2016. A total of 23819 people aged between 5 to 50 years were included. Health utilization and the cost of myopia were analyzed from patients' perspective. Results: The total number of people with myopia in the urban China was estimated to be 143.6 million. The correction rate was 89.5%, 92.1%, and 92.7% for Anhui, Shanghai, and Yunnan (χ2 = 19.5, P < 0.01). Over the recent year, 20.6%, 16.8%, and 28.8% of myopic subjects visited hospital due to myopia, in Anhui, Shanghai and Yunnan. The annual cost of treatment and prevention of myopia was 10.1 billion US dollar (US$, floating from 9.2 to 11.2 billion US$), and the cost per person was 69US$. The annual cost of loss of productivity was estimated to be 6.7 billion US$ for those with mild to moderate visual impairment (floating from 6.1 to 7.4 billion US$), and 9.4 billion US$ (floating from 8.5 to 10.4 billion US$) for those with severe visual impairment to blindness. Therefore, the total economic burden of myopia was estimated as 173.6 billion CNY (26.3 billion US$). Conclusions: The present study shows that myopia leads to substantial economic burden in China. The loss of productivity caused by myopia is an important part of the disease burden compared to the cost of correction and treatment paid by individuals. Therefore, the focus of myopia prevention and control should be to decrease the myopia prevalence, and prevent the uncorrected refractive errors and the irreversible damage of visual acuity by high myopia.

E2F1/2/4 mRNA is associated with immune infiltration and are potential biomarkers for the prognosis of human gastric carcinoma.

BACKGROUND: E2Fs are genes that regulate DNA synthesis and the cell cycle by encoding a family of transcription factors. Increasing experimental evidence has revealed that E2Fs play key roles in tumor progression in various types of cancer. METHODS: We investigated the survival, expression and transcriptional data of E2F1/2/4 in gastric cancer (GC) patients using the immunohistochemistry assay, Kaplan-Meier Plotter, cBioPortal, String, and GEPIA databases. The plasma of GC patients was analyzed using the real-time reverse transcription polymerase chain reaction (RT-PCR) assay. The correlation between E2F1/2/4 expression and clinical features was analyzed using the quartile method. As well, the correlation between E2F1/2/4 and GC immune infiltration was also investigated using the TIMER database. Database of Immune Cell Expression (DICE) was also used to analyze correlations between SOX4 and immune responses. RESULTS: RT-PCR and tissue immunohistochemistry confirmed that E2F1/2/4 was highly expressed in serum and GC tissue samples of GC patients, the expression of which was not affected by patient age and gender. Also, the survival analysis revealed that low levels of E2F1/2/4 expression were significantly associated with a longer overall survival (OS) in GC patients. E2F1/2/4 was correlated with patient prognosis and immune cell infiltration, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in GC. Our findings indicated that E2F1/2/4 could be used as a prognostic biomarker and indicator of immune infiltration in GC. CONCLUSIONS: This study revealed that E2F1/2/4 could be a promising indicator for tumor-associated immune infiltration and prognosis in GC patients.

The Postoperative Lymphocyte to Monocyte Ratio Change Predicts Poor Clinical Outcome in Patients with Esophageal Squamous Cell Carcinoma Undergoing Curative Resection.

BACKGROUND: Postoperative lymphocyte to monocyte ratio (post-LMR) change (LMRc) reflects the dynamic change of balance between inflammatory reaction and immune reaction after curative operation. An elevated preoperative LMR (pre-LMR) has been shown to be a prognostic factor in patients with esophageal squamous cell carcinoma (ESCC), but the clinical value of the LMRc remains unknown. METHODS: 674 patients in ESCC undergoing curative operation were enrolled in this study. LMRc (LMRc = pre-LMR-post-LMR) was counted on the basis of data within one week before and after operation. The median of LMRc was chosen to be the optimal cut-off value to evaluate the prognostic value of LMRc. RESULTS: Kaplan-Meier curves revealed that LMRc ≤ 1.59 was significantly associated with worse overall survival (OS) (P = 0.003) and disease-free survival (DFS) (P = 0.008). Multivariate analysis suggested that LMRc could serve as an independent prognostic predictor for both OS (P = 0.006, HR = 0.687, 95% CI 0.526-0.898) and DFS (P = 0.003, HR = 0.640, 95% CI 0.476-0.859). CONCLUSIONS: LMRc is a promising prognostic predictor for predicting the worse clinical outcome in patients with ESCC undergoing curative operation.

MiR-596 down regulates SOX4 expression and is a potential novel biomarker for gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most commonly diagnosed malignancies of the human digestive tract, and currently there is a dearth of effective biomarkers for this disease. METHODS: MiR-598 expression levels were analyzed by the cancer genome atlas (TCGA database) mining and verified in GC patient plasma using real-time reverse transcription polymerase chain reaction (RT-PCR) assay. We used the GEPIA and UALCAN databases and immunohistochemistry (IHC) to analyze SOX4 expression. The MTT assay assessed MNK28 and SGC7901 cell proliferation after transfection with miR-596 plasmids. The analytical tools, Functional Enrichment Analysis Tool (FunRich), Database of Immune Cell Expression (DICE) and Tumor IMmune Estimation Resource (TIMER) were used to analyze correlations between SOX4 and immune responses. Furthermore, a Kaplan Meier plotter database explored correlations between miR-596, SOX4 and overall patient survival. RESULTS: Data from TCGA and RT-PCR indicated that miR-598 was lowly expressed in GC patients. The miRWalk database showed that SOX4 was the target genes of miR-596 and also revealed that miR-596 bound directly to SOX4. MiR-596 over-expression further depressed GC cell proliferation. In addition, the FunRich database showed that SOX4 was involved in immune responses, and was further shown to be differentially expressed in CD4+ T cells by DICE. Specifically, TIMER indicated that high expression of SOX4 was negatively correlated with infiltrating CD4+ T cells in stomach adenocarcinoma (STAD). Moreover, high expression of miR-596 and low expression of SOX4 prolonged the overall survival (OS) of GC patients. CONCLUSIONS: Our study reveals a crucial role for miR-596 in tumor-associated immune infiltration and predicting prognoses in GC patients.

Metformin up-regulated miR-107 expression and enhanced the inhibitory effect of miR-107 on gastric cancer growth.

Gastric cancer (GC) is one of the most common malignant neoplasms and is the third leading cause of cancer-related death around the world. Metformin has been well reported to have an inhibitory effect on the growth of various cancers by regulating the expression of microRNAs (miRNAs). However, the specific miRNA(s) regulated by metformin in GC have not been identified. In this study, real-time reverse transcription polymerase chain reaction (RT-PCR) analysis in vitro indicated that miR-107 expression was up-regulated in metformin-treated SGC-7901 cells compared with untreated SGC-7901 and MGC803 cells. Amplification of miR-107 expression further reduced cell proliferation in metformin-treated GC cells. A bioinformatics analysis showed that mitogen-activated protein kinase 8 (MAPK8) was the common target of metformin and miR-107. MAPK8 expression is associated with immune cell infiltration in GC as well as overall GC patient survival. Our study demonstrates that miR-107 enhances the anti-cancer effects of metformin in GC tissues, which offers a novel strategy for the treatment of GC.

Erratum to metformin up-regulated miR-107 expression and enhanced the inhibitory effect of miR-107 on gastric cancer growth.

[This corrects the article DOI: 10.21037/tcr.2020.03.25.].

Impact of the Morphologic Characteristics of Optic Disc on Choroidal Thickness in Young Myopic Patients.

Purpose: To explore the characteristics of tilted optic disc and peripapillary atrophy (PPA), and their associations with choroidal thickness (ChT) in young myopic patients. Methods: A total of 821 patients were enrolled in this cross-sectional study. Optic disc tilt ratio, PPA area, macular ChT (mChT), and peripapillary ChT (pChT) were measured. Subjects were divided into four groups purely on the basis of the axial length (AL). Relationships between ChT and the morphologic characteristics of optic disc were analyzed using logistic regression. Results: The prevalence of tilted optic disc and PPA increased as myopia severity increased. Every 0.1-mm2 increase in PPA area was associated with a 14.93-µm decrease in mChT and a 9.54-µm decrease in pChT; and every 0.1 increase in tilt ratio was correlated with a 5.38-µm increase in mChT and a 6.21 decrease in pChT. After stratifying by myopia severity, these trends were still observed in the high myopia group. A larger PPA area (odds ratio [OR] = 2.33; P < 0.01), a longer AL (OR = 1.34; P < 0.01), an increased pChT (OR = 1.11; P < 0.01), and a decreased mChT (OR = 0.93; P < 0.01) were associated with higher odds of having tilted optic disc. Conclusions: In young myopic patients, mChT was negatively associated with PPA area and positively associated with tilt ratio, while pChT was negatively associated with PPA area and tilt ratio. In this population, larger PPA area, longer AL, and thinner mChT were associated with higher odds of tilted optic disc.

[Effect of extensively hydrolyzed formula on growth and development of infants with very/extremely low birth weight].

OBJECTIVE: To study the effect of extensively hydrolyzed formula on the growth and development in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants. METHODS: A total of 375 VLBW or ELBW infants were enrolled and divided into an observation group (187 infants) and a control group (188 infants) using a random number table. The infants in the observation group were given extensively hydrolyzed formula, and when the amount of extensively hydrolyzed formula reached 10 mL/time, it was changed to the standard formula for preterm infants. The infants in the control group were given standard formula for preterm infants. Both groups were fed for 4 consecutive weeks and were compared in terms of incidence rate of feeding intolerance, time to establish full enteral feeding, time to complete meconium excretion, number of spontaneous bowel movements, growth and development, motilin level at 4 and 10 days after feeding, and incidence rate of infection. RESULTS: Compared with the control group, the observation group had a lower rate of feeding intolerance (P<0.05), a shorter duration to full enteral feeding and time to complete meconium excretion (P<0.05), a higher mean number of daily spontaneous bowel movements (P<0.05), higher body weight (1 793±317 g vs 1 621±138 g; P<0.05), head circumference (30.5±1.1 cm vs 30.0±1.6 cm; P<0.05), and body length (43.9±1.2 cm vs 42.1±2.0 cm; P<0.05), a higher motilin level at 4 and 10 days after feeding (P<0.05), and a significantly lower infection rate (P<0.05). CONCLUSIONS: Extensively hydrolyzed formula can increase motilin level, improve gastrointestinal feeding tolerance, promote early growth and development, and reduce the incidence of infection in VLBW and ELBW infants.

miR-125b inhibited epithelial-mesenchymal transition of triple-negative breast cancer by targeting MAP2K7.

MicroRNAs (miRNAs) play important roles in diverse biological processes and are emerging as key regulators of tumorigenesis and tumor progression. Among the differentially expressed miRNAs in breast cancer, miR-125b was revealed to be deregulated and associated with poor prognosis and chemoresistance in triple-negative breast cancer (TNBC), but the mechanism is still unknown. In our study, we showed downregulated expression of miR-125b in TNBC tissues and decreased migration and invasion in miR-125b-expressing Hs578T cells. MAP2K7 was then detected to be a novel target of miR-125b, and downregulation of MAP2K7 by miR-125b was similar to transient knockdown of MAP2K7 which hindered epithelial-mesenchymal transition (EMT) of Hs578T cells. Upregulation of MAP2K7 in miR-125b-overexpressing Hs578T cells partly rescued the migration and invasion suppression of miR-125b. Furthermore, MAP2K7 was overexpressed in TNBC samples compared with normal tissues and negatively correlated with miR-125b expression. In light of these findings, miR-125b emerged as a tumor suppressor in TNBC by targeting MAP2K7 to inhibit EMT.

[Effect of hypothermia therapy on serum GFAP and UCH-L1 levels in neonates with hypoxic-ischemic encephalopathy].

OBJECTIVE: To evaluate the effect of hypothermia therapy on serum glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) levels in neonates with hypoxic-ischemic encephalopathy (HIE). METHODS: Sixty-four HIE neonates were enrolled in this study. Thirty-three neonates with mild HIE were given conventional treatment and 31 neonates with moderate or severe HIE received conventional treatment and hypothermia therapy. Serum levels of GFAP and UCH-L1 were measured using ELISA before treatment and 6-12 hours after treatment. RESULTS: Serum levels of IL-6, IL-8, GFAP and UCH-L1 in the moderate/severe HIE group were significantly higher than in the mild HIE group (P<0.05) before treatment. Serum GFAP level was positively correlated with serum IL-6 (r=0.54; P<0.05) and IL-8 levels (r=0.63; P<0.05), while negatively correlated with Apgar score (r=-0.47, P<0.05). After treatment, serum levels of IL-6, IL-8 and UCH-L1 in the moderate/severe HIE group were significantly reduced (P<0.05), while serum GFAP levels increased significantly (P<0.05). The patients with abnormal neurological development showed higher serum GFAP levels than those with favourable prognosis (P<0.05). Receiver operating characteristic (ROC) curves analysis demonstrated that the area under curve (AUC) of GFAP and UCH-L1 were 0.714 and 0.703 respectively. At a cut-off value of 0.07 ng/mL, the sensitivity and specificity of GFAP for the diagnosis of HIE were 77% and 78% respectively. CONCLUSIONS: Hypothermia therapy can decrease serum UCH-L1 levels and increase serum GFAP levels in neonates with HIE. Based on their diagnostic value of brain injury, GFAP and UCH-L1 are promising to be novel biomarkers for HIE.

Interleukin (IL)-21 promoter polymorphism increases the risk of thyroid cancer in Chinese population.

Polymorphisms in Interleukin (IL)-21 have been researched in several cancers, but the association between IL-21 polymorphisms and thyroid cancer remains unclarified. This case-control study explored the role of five tagSNPs (rs12508721C>T, rs907715G>A, rs13143866G>A, rs2221903A>G and rs4833837A>G) in IL-21 gene in thyroid cancer development. IL-21 genotypes were examined in 615 thyroid cancer patients and 600 controls in Chinese population, and the associations with the risk of thyroid cancer were estimated by logistic regression. Moreover, the potential role of rs12508721C>T in thyroid cancer was further explored by biochemical assays. Compared with the rs12508721CC genotype, CT genotype presented a significantly decreased risk of thyroid cancer (adjusted odds ratios [OR]=0.72; 95%CI=0.57-0.94), the TT carriers had a further decreased risk of thyroid cancer (OR=0.56; 95%CI=0.41-0.87). Furthermore, our quantitative real-time PCR and Enzyme-linked immunosorbent assay (ELISA) results demonstrated that the presence of rs12508721T allele led to more IL-21 expression. However, no significant difference was found in genotype frequencies for other four sites between cases and controls. These findings suggested that rs12508721 polymorphism in IL-21 might be a genetic modifier for the development of thyroid cancer.

Polymorphisms of CD44 gene and nasopharyngeal carcinoma susceptibility in a Chinese population.

As members of adhesion molecule families, CD44 transmembrane glycoproteins have been originally thought to be essential for the formation of multicellular organisms and soon recognised to be able to initiate metastatic spread of tumour cells. To investigate the association between CD44 polymorphisms and nasopharyngeal carcinoma (NPC), we carried out a two-stage case-control study in 906 patients and 943 healthy controls in Eastern populations. Five single nucleotide polymorphisms of CD44 (rs10836347C>T, rs13347C>T, rs1425802A>G, rs11821102G>A and rs713330T>C) with proper frequency were selected from the HapMap database and genotyped with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Compared with the most common rs13347CC genotype, CT+TT genotypes significantly increased individuals' susceptibility to NPC (odds ratio = 2.58, 95% confidence interval = 2.13-3.13). Furthermore, our transient transfection focusing on reporter gene expression modulated by CD44 3'UTR demonstrated that the presence of an rs13347T allele led to greater transcriptional activity than the C allele. Similarly, more CD44 expression was shown in rs13347T carriers than C carriers in our western blotting results. All these findings suggest that CD44 rs13347C>T polymorphism may affect NPC development by improving CD44 expression.

The effects of functional polymorphisms in the TGFß1 gene on nasopharyngeal carcinoma susceptibility.

OBJECTIVE: Transforming growth factor ß1 (TGFß1) promotes tumor growth and metastasis in the later stage of cancer development. In this study, we explored whether TGFß1 polymorphisms were associated with increased risk of nasopharyngeal carcinoma (NPC) in a Chinese population. DESIGN: Case-control study. SETTING: Hospitals of the Department of Otorhinolaryngology-Head and Neck Surgery. SUBJECTS AND METHODS: Two single nucleotide polymorphisms of TGFß1 gene promoter -509C/T (rs1800469) and 869T/C (Leu 10 Pro, rs1800470) at exon 1 were analyzed in 522 NPC patients and 712 age- and sex-matched controls in a Chinese population, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Functional relevance of the polymorphism was determined by biochemical assays. RESULTS: The -509T allele carriers were associated with a significantly reduced risk of NPC as compared with the noncarriers (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.53-0.89 and OR, 0.50; 95% CI, 0.31-0.67, respectively). Moreover, -509C-containing TGFß1 promoter drove an ~1.7-fold increase in reporter expression, compared with the -509T-containing counterpart in both CNE-1 and CNE-2 cell lines. The TGFß1 -509 CC genotype carriers had a higher TGFß1 mRNA level than the TGFß1 -509TT genotype carriers did (P < .01). However, no significant association was observed between the 869T/C polymorphism and risk of NPC. CONCLUSION: These findings indicate that the -509C/T polymorphism in TGFß1 may play a vital role in mediating individual susceptibility to NPC.

Genetic polymorphisms of MDM2 and TP53 genes are associated with risk of nasopharyngeal carcinoma in a Chinese population.

BACKGROUND: The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous case-control studies also revealed TP53 72Arg>Pro and MDM2 309T>G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and nasopharyngeal carcinoma (NPC) susceptibility has not been explored. METHODS: In this study, we performed a case-control study between 522 NPC patients and 722 healthy controls in a Chinese population by using PCR-RFLP. RESULTS: We found an increased NPC risk associated with the MDM2 GG (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 2.08-3.96) and TG (OR = 1.49, 95% CI = 1.16-2.06) genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 2.22, 95% CI = 1.58-3.10) compared to the Arg/Arg genotype. The gene-gene interaction of MDM2 and TP53 polymorphisms increased adult NPC risk in a more than multiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 7.75, 95% CI = 3.53-17.58). CONCLUSION: The findings suggest that polymorphisms of MDM2 and TP53 genes may be genetic modifier for developing NPC.

Geometrical-optics approximation of forward scattering by gradient-index spheres.

By means of geometrical optics we present an approximation method for acceleration of the computation of the scattering intensity distribution within a forward angular range (0-60 degrees ) for gradient-index spheres illuminated by a plane wave. The incident angle of reflected light is determined by the scattering angle, thus improving the approximation accuracy. The scattering angle and the optical path length are numerically integrated by a general-purpose integrator. With some special index models, the scattering angle and the optical path length can be expressed by a unique function and the calculation is faster. This method is proved effective for transparent particles with size parameters greater than 50. It fails to give good approximation results at scattering angles whose refractive rays are in the backward direction. For different index models, the geometrical-optics approximation is effective only for forward angles, typically those less than 60 degrees or when the refractive-index difference of a particle is less than a certain value.

Debye series for Gaussian beam scattering by a multilayered sphere.

The Debye series has been a key tool for the understanding of light scattering features, and it is also a convenient method for understanding and improving the design of optical instruments aimed at optical particle sizing. Gouesbet has derived the Debye series formulation for generalized Lorenz-Mie theory (GLMT). However, the scattering object is a homogeneous sphere, and no numerical result is provided. The Debye series formula for plane-wave scattering by multilayered spheres has been derived before. We have devoted our work to the Debye series of Gaussian beam scattering by multilayered spheres. The integral localized approximation is employed in the calculation of beam-shape coefficients (BSCs) and allows the study of the scattering characteristics of particles illuminated by the strongly focused beams. The formula and code are verified by the comparison with the results produced by GLMT and also by the comparison with the result for the case of plane-wave incidence. The formula is also employed in the simulation of the first rainbow by illuminating the particle with one or several narrow beams.

Debye series of normally incident plane-wave scattering by an infinite multilayered cylinder.

We derive the formula of the Debye-series decomposition for normally incident plane-wave scattering by an infinite multilayered cylinder. A comparison of the scattering diagrams calculated by the Debye series and Mie theory for a graded-index polymer optical fiber is given and the agreement is found to be satisfied. This approach permits us to simulate the rainbow intensity distribution of any single order and the interference of several orders, which is of good use to the study of the scattering characteristics of an inhomogeneous cylinder and to the measurement of the refractive index profile of an inhomogeneous cylinder.

Debye series for light scattering by a multilayered sphere.

We have derived the formula for the Debye-series decomposition for light scattering by a multilayered sphere. This formulism permits the mechanism of light scattering to be studied. An efficient algorithm is introduced that permits stable calculation for a large sphere with many layers. The formation of triple first-order rainbows by a three-layered sphere and single-order rainbows and the interference of different-order rainbows by a sphere with a gradient refractive index, are then studied by use of the Debye model and Mie calculation. The possibility of taking only one single mode or several modes for each layer is shown to be useful in the study of the scattering characteristics of a multilayered sphere and in the measurement of the sizes and refractive indices of particles.