The Remarkable Anti-Breast Cancer Efficacy and Anti-Metastasis by Multifunctional Nanoparticles Co-Loading Squamocin, R848 and IR 780.

Background: Breast cancer is a heterogeneous disease globally accounting for approximately 1 million new cases annually. Chemotherapy remains the main therapeutic option, but the antitumor efficacy needs to be improved. Methods: Two multifunctional nanoparticles were developed in this paper using oleic acid and mPEG2k-PCL2k as the drug carriers. Squamocin (Squ) was employed as a chemotherapeutic agent. Resiquimod (R848) or ginsenoside Rh2 was co-encapsulated in the nanoparticles to remold the immunosuppressive tumor microenvironment, and IR780 was coloaded as a photosensitizer to realize photothermal therapy. Results: The obtained Squ-R848-IR780 nanoparticles and Squ-Rh2-IR780 nanoparticles were uniformly spherical and approximately (162.200 ± 2.800) nm and (157.300 ± 1.1590) nm, respectively, in average diameter, with good encapsulation efficiency (above 85% for each drug), excellent stability in various physiological media and high photothermal conversion efficiency (24.10% and 22.58%, respectively). After intravenous administration, both nanoparticles quickly accumulated in the tumor and effectively enhanced the local temperature of the tumor to over 45 °C when irradiated by an 808 nm laser. At a low dose of 0.1 mg/kg, Squ nanoparticles treatment alone displayed a tumor inhibition rate of 55.28%, pulmonary metastasis inhibition rate of 59.47% and a mean survival time of 38 days, which were all higher than those of PTX injection (8 mg/kg) (43.64%, 25 days and 37.25%), indicating that Squ was a potent and effective antitumor agent. Both multifunctional nanoparticles, Squ-Rh2-IR780 nanoparticles and Squ-R848-IR780 nanoparticles, demonstrated even better therapeutic efficacy, with tumor inhibition rates of 90.02% and 97.28%, pulmonary metastasis inhibition rates of 95.42% and 98.09, and mean survival times of 46 days and 52 days, respectively. Conclusion: The multifunctional nanoparticles coloaded with squamocin, R848 and IR 780 achieved extraordinary therapeutic efficacy and excellent antimetastasis activity and are thus promising in the future treatment of breast tumors and probably other tumors.

Circular RNA circRest regulates manganese induced cell apoptosis by targeting the mmu-miR-6914-5p/Ephb3 axis.

Overexposure to manganese (Mn) can lead to neurotoxicity, the underlying mechanisms remain incompletely understood. Circular RNAs (circRNAs) have emerged as important regulators in various biological processes. It is plausible that circRNAs may be involved in the biological mechanisms underlying Mn caused neurotoxicity. Here, circRest was downregulated in Mn-exposed mouse neuroblastoma cells (N2a cells) by RNA sequencing and quantitative real-time PCR. When circRest was overexpressed, it led to an increase in cell viability and a decrease in apoptosis following Mn exposure. Conversely, silencing circRest resulted in opposite effects in N2a cells. Further investigation revealed that circRest acts as a mmu-miR-6914-5p sponge, and mmu-miR-6914-5p could bind and inhibit Ephb3, thereby promoting apoptosis in N2a cells. This was confirmed through RNA antisense purification and dual luciferase reporter assays. Additionally, the circRest/mmu-miR-6914-5p/Ephb3 axis may influence memory and learning in mice following Mn exposure. In conclusion, our study uncovers a novel mechanism by which circRest may attenuate Mn caused neurotoxicity via the mmu-miR-6914-5p/Ephb3 axis.

Our experience with propranolol for infantile hemangioma.

BACKGROUND/OBJECTIVES: The most frequent benign vascular tumor in children is infantile hemangioma (IH). For severe IHs, propranolol has become the first-line Treatment. Despite the fact that several studies have comprehensive therapy regimens, including the best time to start Treatment, dosage, visit frequency, and treatment duration, there is still controversy about the best time to start and stop propranolol medication. METHODS: Between January 2016 and February 2019, dermatologists experienced hemangioma treatment and recommended propranolol treatment for 232 IHs. A total of 90 patients completed the treatment process after undergoing a color Doppler ultrasound test. RESULTS: Propranolol uniquely affects each IH. Ninety patients were divided into two groups in this study: entire regression (n = 40) and partial regression (n = 50). The entire regression group's initial treatment period (4.3 ± 2.97 months) was substantially shorter than the partial regression group's (5.2 ± 4.57 months) (p < 0.05). Between the entire regression group (23.4 ± 12.8 months) and the partial regression group (24.5 ± 16.6 months), there was no significant difference in time to reduce propranolol. The partial regression group (32.9 ± 25.3month) had a lengthier treatment course than the entire regression group (23.4 ± 13.7 months) (p < 0.05). The partial regression group (22%), like the entire regression group, had a higher recurrence rate (5%). The overall proportion of hemangiomas on the face (particularly periocular hemangioma) in the regression group was greater than in the control group. CONCLUSION: The entire regression group's initial treatment time was significantly shorter than the partial regression group's. As a result, as soon as a hemangioma is discovered, it should be treated. To determine the appropriate time to reduce propranolol, we must evaluate the patient's age and the percentage of tumor regression. Periocular hemangioma may have a better prognosis than other types. Given the small number of patients in our study, we will need to do more research in the future to confirm our findings.

Achieving Net Zero-An Illustration of Carbon Emissions Reduction with A New Meta-Inverse DEA Approach.

To achieve the goal of limiting global warming to 1.5 °C above preindustrial levels, net-zero emissions targets were proposed to assist countries in planning their long-term reduction. Inverse Data Envelopment Analysis (DEA) can be used to determine optimal input and output levels without sacrificing the set environmental efficiency target. However, treating countries as having the same capability to mitigate carbon emissions without considering their different developmental stages is not only unrealistic but also inappropriate. Therefore, this study incorporates a meta-concept into inverse DEA. This study adopts a three-stage approach. In the first stage, a meta-frontier DEA method is adopted to assess and compare the eco-efficiency of developed and developing countries. In the second stage, the specific super-efficiency method is adopted to rank the efficient countries specifically focused on carbon performance. In the third stage, carbon dioxide emissions reduction targets are proposed for the developed and developing countries separately. Then, a new meta-inverse DEA method is used to allocate the emissions reduction target to the inefficient countries in each of the specific groups. In this way, we can find the optimal CO2 reduction amount for the inefficient countries with unchanged eco-efficiency levels. The implications of the new meta-inverse DEA method proposed in this study are twofold. The method can identify how a DMU can reduce undesirable outputs without sacrificing the set eco-efficiency target, which is especially useful in achieving net-zero emissions since this method provides a roadmap for decision-makers to understand how to allocate the emissions reduction targets to different units. In addition, this method can be applied to heterogeneous groups where they are assigned to different emissions reduction targets.

Long noncoding RNA Sh2d3c promotes manganese-induced neuronal apoptosis through the mmu-miR-675-5p/Chmp4b/Bax axis.

Environmental excessive manganese (Mn) exposure can cause neurotoxicity and neurodegenerative diseases. Long noncoding RNAs (lncRNAs) have been shown to affect the development of neurodegenerative diseases. However, whether lncRNAs are also linked to Mn-induced neurotoxicity has not been reported. In this study, we explored the role of lncRNAs in Mn-induced neurotoxicity and its mechanisms. LncSh2d3c was identified to be the significantly increased lncRNA in Mn-exposed N2a cells. Knockdown of lncSh2d3c increased the cell viability and inhibited cell apoptosis. Mechanistically, lncSh2d3c acted as a sponge for mmu-miR-675-5p, thereby preventing the inhibitory effect of mmu-miR-675-5p on Chmp4b. The binding potency of lncSh2d3c/mmu-miR-675-5p and mmu-miR-675-5p/Chmp4b was verified by RNA antisense purification (RAP) and luciferase reporter assays. Furthermore, we also found that the lncSh2d3c/mmu-miR-675-5p/Chmp4b/Bax axis might be associated with the learning ability and memory of mice after Mn exposure. These results revealed a novel mechanism of Mn-induced neuronal apoptosis through the lncSh2d3c/mmu-miR-675-5p/Chmp4b/Bax axis and suggested that lncSh2d3c may act as a key regulatory factor in Mn-induced neurotoxicity.

Household cooking oil type and risk of oral micronucleus frequency in Chinese nonsmokers.

Household animal fat has been linked to increased incidence of cancers compared with vegetable fat. However, few epidemiological studies have associated these two cooking oil types with precancerous genotoxic effects, such as occurrence of micronuclei (MN). This study aimed to explore the association between oral MN frequency and household cooking oil type and whether the association can be attributed to polycyclic aromatic hydrocarbons (PAHs). We collected information about individual cooking oil use, measured genotoxic effects by MN tests and urinary PAHs metabolites (OHPAHs) in 245 nonsmokers. The associations between household cooking oil type and MN frequency and OHPAHs were analyzed using generalized linear models (GLMs) and logistic regression models, evaluating odds ratios and coefficient (95% confidence intervals) (ORs, 95% Cls; ß, 95% Cls). The odds of animal fat consumers, rather than vegetable fat consumers, was positively associated with higher MN frequency (OR = 1.94, P < 0.05). The associations were discovered in participants only using kitchen ventilation (OR = 2.04, P < 0.05). Animal fat consumers had higher total OHPAHs than vegetable fat consumers (1.58 ± 0.22 mg/mol, Cr vs 1.20 ± 0.12 mg/mol, Cr; P = 0.028). Significant correlations were observed between total OHPAHs quartiles and increased MN frequency (ß = 0.38, P-trend = 0.026). After stratifying by household cooking oil type, sensitivity analyses showed that the positive association between total OHPAHs quartiles and increased MN frequency was only observed in animal fat consumers (ß = 0.61, P-trend = 0.030). In conclusion, usage of household animal fat was associated with an increased odds of oral MN frequency in Chinese nonsmokers and the odds correlated with increased PAHs exposure. This finding supplemented evidence associating cooking oil type with genotoxic effects and explained its association with PAHs exposure.

An Innovation Perspective to Explore the Ecology and Social Welfare Efficiencies of Countries.

This study aims to measure the ability of 29 countries in producing competitive products and services that fulfill individual needs and improve the level of welfare with less utilization of natural resources. We build a two-stage network production process model to investigate the ecology efficiency and social welfare efficiency of the countries and then further discriminate the efficient countries in post-analysis. The two-stage network directional distance function is applied to assess the efficiencies of countries, and the network-based ranking approach is used to further discriminate the efficient countries following the panel data between the years 2013 and 2016. Results show that Poland and Spain are strongly referenced by other countries in the ecology stage, whereas Bulgaria, the United States, and Sweden are leaders in the social welfare stage. A remarkable observation is an absence of countries' efficiency in both ecology and social welfare efficiencies. Most of the 29 countries have lower efficiency in the social welfare stage than in the ecology stage. This study suggests the strengths and highlights the weaknesses of the countries to help the governments efficiently improve and operate their countries.

Circular RNA circGLIS3 promotes bladder cancer proliferation via the miR-1273f/SKP1/Cyclin D1 axis.

Extensive research confirmed that circRNA can play a regulatory role in various stages of tumors by interacting with various molecules. Identifying the differentially expressed circRNA in bladder cancer and exploring its regulatory mechanism on bladder cancer progression are urgent. In this study, we screened out a circRNA-circGLIS3 with a significant upregulation trend in both bladder cancer tissues and cells. Bioinformatics prediction results showed that circGLIS3 may be involved in multiple tumor-related pathways. Function gain and loss experiments verified circGLIS3 can affect the proliferation, migration, and invasion of bladder cancer cells in vitro. Moreover, silencing circGLIS3 inhibited bladder cancer cell growth in vivo. Subsequent research results indicated circGLIS3 regulated the expression of cyclin D1, a cell cycle-related protein, and cell cycle progression. Mechanically, circGLIS3 upregulates the expression of SKP1 by adsorbing miR-1273f and then promotes cyclin D1 expression, ultimately promoting the proliferation of bladder cancer cells. In summary, our study indicates that circGLIS3 plays an oncogene role in the development of bladder cancer and has potential to be a candidate for bladder cancer.

Propranolol inhibits the angiogenic capacity of hemangioma endothelia via blocking ß-adrenoceptor in mast cell.

BACKGROUND: Propranolol, a non-selective blocker of the ß-adrenoceptor (AR), is a first-line treatment for infantile hemangioma (IH). Mast cells have been implicated in the pathophysiology of propranolol-treated hemangioma. However, the function of mast cells remains unclear. METHODS: HMC-1s (Human mast cell line) having been treated with propranolol for 24 h were centrifuged, washed with PBS twice, and maintained in cell culture medium for another 24 h. The supernatants with propranolol which were named as propranolol-treated HMC-1s supernatants were obtained. The expression of cytokines and mediators was examined among HMC-1s dealt with propranolol. HemECs (hemangioma endothelial cells) were co-cultured with propranolol-treated HMC-1s supernatants, and their proliferation and apoptosis were investigated. The autophagic-related protein was examined in HemECs using immunoblot. RESULTS: In propranolol-treated HMC-1s, the expressions of ADRB1 (ß1-AR) and ADRB2 (ß2-AR) were reduced by 70% and 60%, respectively, and that of cytokines and mediators were reduced. The proliferation was decreased, but apoptosis and autophagy were induced in HemECs treated with propranolol-treated HMC-1s supernatants. However, propranolol can work well in shRNA-ADRB1 or shRNA-ADRB2 transfected HMC-1s. CONCLUSIONS: Propranolol inhibit the proliferation of HemECs and promote their apoptosis and autophagy through acting on both ß1 and ß2 adrenoceptor in mast cell. IMPACT: Treated with propranolol, ß1, and ß2 adrenoceptor on human mast cell expression was reduced significantly. After hemangioma endothelial cell treated with the supernatants from propranolol-treated human mast cell, its proliferation was decreased, but apoptosis and autophagy were significantly induced. Propranolol can work well in shRNA-ADRB1 or shRNA-ADRB2 transfected HMC-1s. Mast cells may have a role in the action of propranolol in infantile hemangioma through both ß1 and ß2 adrenoceptors to inhibit the angiogenic capacity of hemangioma endothelial cells.

Polymorphisms in MicroRNA Target Sites of TGF-ß Signaling Pathway Genes and Susceptibility to Allergic Rhinitis.

BACKGROUND: The polymorphisms inside microRNA target sites locating in the 3'-UTR region may introduce the micro-RNA-binding changes, which may regulate the gene expression and correlate with the potential diseases. OBJECTIVES: We aimed to investigate whether the polymorphisms in microRNA target sites of transforming growth factor beta (TGF-ß) signaling pathway genes are associated with the susceptibility of mite-sensitized allergic rhinitis (AR) in a Han Chinese population. METHODS: In this case-control study, 454 AR patients and 448 healthy controls were recruited. Three HapMap single-nucleotide polymorphisms (SNPs) were mapped to putative microRNA recognition sites and genotyped by TaqMan allelic discrimination assay. RESULTS: The genotype and allele frequencies of 3 SNPs (rs1590 in TGFBR1; rs1434536 and rs17023107 in BMPR1B) showed lack of significant association with AR. However, in the subgroup analysis, the TG, GG, and TG/GG genotypes of rs1590 exhibited significantly increased risk of AR in the male subgroup (TG: adjusted OR = 1.57, 95% CI = 1.08-2.31; GG: adjusted OR = 1.76, 95% CI = 1.09-2.86; TG/GG: adjusted OR = 1.62, 95% CI = 1.13-2.33). The CT genotypes of rs17023107 might have potential to protect against AR in the patients age of <15 years (adjusted OR = 0.37, 95% CI = 0.14-0.95) and the males (adjusted OR = 0.48, 95% CI = 0.25-0.95). No significant association was found between SNPs and the total serum IgE level. CONCLUSIONS: In a Han Chinese population, stratified by age and gender, susceptibility to mite-sensitized AR may be associated with 2 SNPs (rs1590 and rs17023107) in microRNA target sites of TGF-ß signaling pathway genes.

Super-Enhancer LncRNA LINC00162 Promotes Progression of Bladder Cancer.

Due to the lack of effective early diagnostic measures and treatment methods, bladder cancer has become a malignant tumor that seriously threatens people's lives and health. Here, we reported that LINC00162, a super-enhancer long noncoding RNA, was highly expressed in bladder cancer cells and tissues. And LINC00162 was negatively correlated with neighboring PTTG1IP expression. Knocking down LINC00162 expression can inhibit the proliferative activity of bladder cancer cells and the growth of transplanted tumors in vivo, while knocking down the expression of PTTG1IP could restore the proliferative activity of bladder cancer cells. In addition, both LINC00162 and PTTG1IP were found to be able to bind to THRAP3, a transcription-related protein. And THRAP3 can regulate PTTG1IP expression. Finally, we demonstrated a mechanism that LINC00162 could regulate PTTG1IP expression through binding THRAP3. This study provided a potential target molecule for clinical treatment of bladder cancer.

2,5-Hexanedione influences primordial follicular development in cultured neonatal mouse ovaries by interfering with the PI3K signaling pathway via miR-214-3p.

The mechanisms by which 2,5-hexanedione (2,5-HD) exposure adversely affects reproduction are unclear. In the present study, whole neonatal mouse ovaries were exposed to 2,5-HD in vitro and then assessed for progesterone levels to determine the effects of this compound on ovary function. Ovarian histomorphological analyses were performed to assess the effects of 2,5-HD on follicular development, and PI3K signaling pathway was evaluated to elucidate the molecular mechanisms of 2,5-HD-mediated toxicity on follicular development. The results showed that after ovarian exposure to 2,5-HD in vitro, the percentage of secondary follicles decreased, while the progesterone levels and the percentage of unhealthy follicles increased, with oocytes identified as the target of damage. The 2,5-HD treatment significantly decreased the of the gene encoding the apoptosis-related protein caspase-8, and PI3K/AKT/FOXO3 pathway signaling was also altered. Furthermore, the effects of 2,5-HD on the gene expression of the PI3K/AKT/FOXO3 and follicular development were blocked by 740Y-P (a PI3K activator), miR-214-3p was abnormally expressed, and luciferase reporter assay results demonstrated that the 3' untranslated region of PI3K was a direct target of miR-214-3p. Overall, the results of the present study indicate that 2,5-HD exposure inhibits follicular development, and the underlying mechanism may involve interference with miR-214-3p-mediated regulation of the PI3K signaling pathway.

[The Local Alternative Ti-6Al-4V Alloy Coating of Surgery Steel Instruments for Laser Deposition Forming].

Aiming at the medical practice problems of the surgical steel medical instruments, such as the crevice corrosion, the poor mechanical compatibility and the Ni, Cr plasma exudation, the laser deposition of Ti-6Al-4V alloy cladding layer at the local functional area as alternative coating was proposed and realized as a new process method. The accurate element content and good formability Ti-6Al-4V cladding powder was chosen, the low power and high duty cycle optimized laser process was adopt, the alternative coating of good fusion and low dilution was prepared. Through the elemental line scanning, the interface microstructure analysis and the experiments of basic mechanical properties, the basic properties of the cladding were characterized and verified. The experiments results showed that, the Ti, Al and V contents of the top coating were respectively about 88%, 4.9% and 3.9%, no sensitizing ions such as Cr and Ni were detected. Initial equiaxed α phase, flake ß phase dist were distributed in the coating and interface, the α' martensite was precipitated at the boundary of the flake ß phase, some refined granular ß phase dispersion pinned to the grain boundary of basket structure. The microhardness of cladding layer was 352.08~312.76 HV0.1. The friction coefficient of the cladding layer was about 0.22~0.65. A new technology and method reference for improving and upgrading the performance of surgical medical devices is provided by this research.

Nanomedicine-mediated prevention of inflammatory monocytes infiltration ameliorate ovalbumin-induced allergic rhinitis in mouse model.

Th2 immune cells infiltration into nasal mucosa is one of the characters of allergic rhinitis (AR). We aimed to explore whether inhibition of Th2 immune cells infiltration would attenuate AR progression. AR mouse model was established by i.p. injection of ovalbumin (OVA). The infiltrated immune cells into nasal lavage fluid were detected by flow cytometry. Cytokine concentration in serum was determined by ELISA. AR mice symptoms were indicated by the number of sneezing and nasal rubbing events. In AR mice, CCL2 expression levels and CD45+CD11b+Ly6Chi inflammatory monocytes cells significantly increased as compared with control mice. CCL2 siRNA encapsulated nanoparticles (NPsiCCL2) prevent CCL2 expression and inflammatory monocytes infiltration in AR mice. NPsiCCL2 treatment dramatically decreased the number of sneezing and nasal rubbing events in AR mice. Moreover, NPsiCCL2 treatment attenuated serum OVA-specific IgE, OVA-specific IgG1 and histamine levels. Mechanically, NPsiCCL2 treatment attenuates AR symptoms via inhibiting Th2 cytokine (IL-4, IL-5 and IL-13) production. Nanomedicine-mediated prevention of inflammatory monocytes infiltration ameliorates ovalbumin-induced allergic rhinitis in mouse model.

A new species of Urothrips (Thysanoptera, Phlaeothripidae) from canopy of monsoon forest in China.

Urothrips is one of a group of 10 genera of fungus-feeding Phlaeothripinae in which species have the tenth abdominal segment greatly elongate and bearing long anal setae (Mound 1972; Okajima 2006). The genus is recorded from Africa, Asia and Australia (ThripsWiki 2019), and currently comprises 11 species. A key to nine of these species was provided by Ulitzka and Mound (2014), to which two further species from China were added subsequently (Tong Zhao 2017; Zhao Tong 2017). The purpose of this paper is to describe a new species of Urothrips. This is the fifth member of the genus recorded from China, the others being U. calvus Tong Zhao, U. lancangensis Zhao Tong, U. gibberosa Kudo and U. tarai Stannard.

Dynamic eco-efficiency evaluation of the semiconductor industry: a sustainable development perspective.

Serious environmental problems have accompanied remarkable global economic growth for decades. To assist managers in the semiconductor industry with economic and environmental management, this study executes DuPont analysis to examine economic impacts from the effective implementation of sustainability initiatives. We propose a two-stage process including economic development efficiency and environmental protection efficiency through the dynamic data envelopment analysis (DDEA) to reflect the characteristics of eco-efficiency. Through DuPont analysis, the main finding shows the potential improvement in firms' return on equity (ROE) by efficiently utilizing assets to generate sales quickly.Relative to economic development efficiency, the firms show lower scores and higher standard deviations in the environmental protection ability, thus denoting a large gap in the level of environmental protection production technology. The findings in this study reveal that the financial foundations and sustainable development of industries should be improved simultaneously even though specific levels of semiconductor industrial eco-efficiency improvement vary among companies in Taiwan.

Impulse response function analysis of the impacts of hospital accreditations on hospital efficiency.

Improving hospital efficiency is an emerging area of interest among policy makers in the new global economy's healthcare system. To ensure accurate efficiency analyses, we consider the nonhomogeneous input/output characteristics of various hospital departments, particularly the Department of Medicine, Department of Surgery, and Department of Other Specialist Medicine. These departments employ co-inputs to produce nonhomogeneous outputs. Specifically, we employ data envelopment analysis to evaluate the efficiency of 15 veterans hospitals in Taiwan. Empirical results show that the performance of the Department of Surgery has higher quality than that of the Department of Medicine and Department of Other Specialist Medicine. In addition, we include another data science technique, namely, impulse response function analysis. The findings indicate that "the New Hospital Accreditation" introduced in 2007 and revised in 2011 improved the efficiency of all departments in their respective first year of introductions. By contrast, the efficiencies of the Department of Surgery and Department of Other Specialist Medicine immediately decreased in the second year after the introductions.

Intramural chondroid hamartoma in the distal esophagus in an adult: A case report and review of the literature.

Hamartoma of the esophagus is a rare lesion and the number of cases reported in the literature to date is limited. The majority of hamartomas are intraluminal tumors located in the upper third of the esophagus. Histopathologically, the majority of these tumors comprise a mixture of adipose tissue, skeletal/smooth muscle tissue, vascular components and fibrous connective tissue. We herein present the case of a 33-year-old man with an intramural chondroid hamartoma located in the lower third of the esophagus. The patient underwent esophagotomy and the histopathological examination revealed that the tumor was mainly composed of chondroid tissue (60%) admixed with adipose tissue (25%) and fibrous connective tissue (15%). The aim of this study was to describe another variant of esophageal hamartoma, which exhibits a versatile phenotype.

Association of VDR and CYP2R1 Polymorphisms with Mite-Sensitized Persistent Allergic Rhinitis in a Chinese Population.

As recent studies have described an association between vitamin D and allergic rhinitis, we hypothesized that vitamin D pathway-related genes may be candidate genes for susceptibility to allergic rhinitis. Thus, we sought to evaluate whether polymorphisms in the vitamin D receptor (VDR) and CYP2R1 genes are associated with mite-sensitized persistent allergic rhinitis (PER) in a Han Chinese population. A hospital-based case-control study consisting of 519 patients with mite-sensitized PER and 447 healthy controls was conducted. Five single nucleotide polymorphisms (SNPs) in VDR and CYP2R1 were selected for genotyping. The genotype and allele frequencies of rs9729, rs2228570, rs1544410, and rs731236 in VDR as well as rs2060793 in CYP2R1 were not significantly associated with susceptibility to mite-sensitized PER. After stratification analyses, however, both the CT and CT/TT genotypes of rs2228570 in VDR exhibited a significantly decreased risk (CT: adjusted odds ratio (OR)=0.58, 95% confidence intervals (CI)=0.37-0.91; CT/TT: adjusted OR=0.61, 95% CI=0.40-0.93) of mite-sensitized PER, while the AA genotype of rs2060793 in CYP2R1 exhibited a significantly increased risk (adjusted OR=1.85, 95% CI=1.03-3.34) of PER in the age subgroup of <16 years old. Both the AG and AG/GG genotypes of rs731236 in VDR exhibited a significantly decreased risk (AG: adjusted OR=0.43, 95% CI=0.21-0.89; AG/GG: adjusted OR=0.46, 95% CI=0.23-0.94) of PER in the female subgroup. Analysis of the locus-locus interactions of VDR and CYP2R1 revealed two models that involved combined SNPs of VDR and CYP2R1 were statistically significant (P<0.05). Our data suggest that age and gender may have an impact on the association of three SNPs (rs2228570, rs731236, and rs2060793) in genes of the vitamin D pathway with the risk of mite-sensitized PER in this Chinese population. The VDR and CYP2R1 variants may be involved in genetic interactions in the pathogenesis of PER.

Association study on ADAM33 polymorphisms in mite-sensitized persistent allergic rhinitis in a Chinese population.

BACKGROUND: The ADAM33 gene has been identified as a potentially important asthma candidate gene and polymorphisms in this gene have been shown to be associated with asthma and seasonal allergic rhinitis. OBJECTIVE: To assess whether the ADAM33 polymorphisms are associated with persistent allergic rhinitis (PER) due to house dust mites in a Chinese population. METHODS: In a hospital-based case-control study of 515 patients with mite-sensitized PER and 495 healthy controls, we genotyped seven single nucleotide polymorphisms (SNPs) in ADAM33. Serum levels of eosinophil cationic protein, total IgE and allergen-specific IgE against Dermatophagoides pteronyssinus and Dermatophagoides farinae were measured by the ImmunoCAP assays. RESULTS: In the single-locus analysis, three polymorphisms, rs3918392 (F1), rs528557 (S2) and rs2787093, were significantly associated with mite-sensitized PER. SNP S2 was associated with significantly increased risk both of asthmatic and nonasthmatic mite-sensitized PER. In the combined genotypes analysis, individuals with 2-4 risk alleles had a significantly higher risk of mite-sensitized PER (adjusted OR = 1.99, 95% CI = 1.50-2.62) than those with 0-1 risk alleles. Haplotype-based association analysis revealed that the ACAGCCT haplotype might have potential to protect against mite-sensitized PER (adjusted OR = 0.67; 95% CI = 0.49-0.90). CONCLUSIONS: Polymorphisms in the ADAM33 gene may contribute to susceptibility of mite-sensitized PER in this Chinese population.