Does Postgraduate Education Deepen Temporomandibular Disorders Insights for Dental Professionals?

Objective: This study aims to investigate the impact of postgraduate education on the comprehension of Temporomandibular Disorders (TMDs) among dental professionals. Methods: A cross-sectional observational study was conducted, involving 348 dental professionals, including students and practicing dentists, categorized based on their educational background into two groups: bachelor's degree or lower (Group B) and master's degree or higher (Group M). Questionnaires were utilized to assess attitudes and knowledge across four TMDs-related domains. Statistical analysis was performed to compare responses between groups and identify differences in TMDs comprehension. Results: Among the 348 respondents, who participated in the study, 183 were students and 165 were practicing dentists, yielding a response rate of 79% (348/440). In the dentist group, 11 statements across every TMDs-related domain exhibited statistically significant differences in responses between Group B and Group M (p < 0.05). Only 2 responses from Group M conflicted with the standard answers, whereas Group B had 9 conflicting responses. In the student group, 11 statements also showed statistically significant differences between Group B and Group M (p < 0.05). Group M had no conflicting responses with the standard answers, while Group B had 7 conflicting responses. Conclusions: Postgraduate education deepened dental professionals' understanding of TMDs. Students improved more in the domains of "diagnosis" and "treatment and prognosis," whereas practicing dentists enhanced more in the "etiology" domain. To further advance postgraduate education, there is a need for more systematic course designs for TMDs, emphasizing the enhancement of knowledge related to examination methods and treatment options.

Mapping the evolving trend of research on Class III malocclusion: a bibliometric analysis.

OBJECTIVES: This study aimed to provide visualized knowledge maps to show the evolving trends and key focal points of Class III malocclusion research through a comprehensive bibliometric analysis. MATERIALS AND METHODS: Class III malocclusion research published between 2000 and 2023 was retrieved from the Web of Science Core Collection. VOSviewer was utilized to count the citation and publication number of authors, institutions, countries and journals. Co-occurrence, co-citation, and cluster analyses and burst detection were conducted using CiteSpace. RESULTS: A total of 3,682 publications on Class III malocclusion were included in the bibliometric analysis. During 2000-2023, both the annual publication count and citation frequency exhibited a gradual upward trajectory, with a noticeable surge in recent years. In terms of production and citation counts of Class III malocclusion research, the core journal is the American Journal of Orthodontics and Dentofacial Orthopedics. Furthermore, apart from the primary keyword 'Class III malocclusion', 'orthognathic surgery' was identified as keyword with the most frequency. The cluster analysis of cited references reveals that the research focal points have shifted to 'skeletal anchorage' and 'surgery-first approach'. Furthermore, the burst detection identified 'quality of life' as a potential research hotspot since it has recently gained increasing scholarly attention. CONCLUSIONS: The current study provides scholars with the knowledge maps of evolving trends and prominent topics of Class III malocclusion research and a summary of research progress on various priorities during different periods. These findings are expected to provide a valuable guidance to facilitate the future research on Class III malocclusion.

Deficiency of purinergic P2X4 receptor alleviates experimental autoimmune hepatitis in mice.

Purinergic P2X4 receptor (P2X4R) has been shown to have immunomodulatory properties in infection, inflammation, and organ damage including liver regeneration and fibrosis. However, the mechanisms and pathophysiology associated with P2X4R during acute liver injury remain unknown. We used P2X4R-/- mice to explore the role of P2X4R in three different models of acute liver injury caused by concanavalin A (ConA), carbon tetrachloride, and acetaminophen. ConA treatment results in an increased expression of P2X4R in the liver of mice, which was positively correlated with higher levels of aspartate aminotransferase and alanine aminotransferase in the serum. However, P2X4R gene ablation significantly reduced the severity of acute hepatitis in mice caused by ConA, but not by carbon tetrachloride or acetaminophen. The protective benefits against immune-mediated acute hepatitis were achieved via modulating inflammation (Interleukin (IL)-1ß, IL-6, IL-17A, interferon-γ, tumor necrosis factor-α), oxidative stress (malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase), apoptosis markers (Bax, Bcl-2, and Caspase-3), autophagy biomarkers (LC3, Beclin-1, and p62), and nucleotide oligomerization domain-likereceptorprotein 3(NLRP3) inflammasome-activated pyroptosis markers (NLRP3, Gasdermin D, Caspase-1, ASC, IL-1ß). Additionally, administration of P2X4R antagonist (5-BDBD) or agonist (cytidine 5'-triphosphate) either improved or worsened ConA-induced autoimmune hepatitis, respectively. This study is the first to reveal that the absence of the P2X4 receptor may mitigate immune-mediated liver damage, potentially by restraining inflammation, oxidation, and programmed cell death mechanisms. And highlight P2X4 receptor is essential for ConA-induced acute hepatitis.

Naringenin confers protection against experimental autoimmune encephalomyelitis through modulating the gut-brain axis: A multiomics analysis.

Multiple sclerosis (MS) is a disease of the central nervous system that involves the immune system attacking the protective covering of nerve fibers. This disease can be influenced by both environmental and genetic factors. Evidence has highlighted the critical role of the intestinal microbiota in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). The composition of gut microflora is mainly determined by dietary components, which, in turn, modulate host homeostasis. A diet rich in naringenin at 0.5% can effectively mitigate the severity of EAE in mice. However, there is little direct data on the impact of naringenin at optimal doses on EAE development, as well as its intestinal microbiota and metabolites. Our study revealed that 2.0% naringenin resulted in the lowest clinical score and pathological changes in EAE mice, and altered the gene expression profiles associated with inflammation and immunity in spinal cord tissue. We then used untargeted metabolomics and 16S rRNA gene sequences to identify metabolites and intestinal microbiota, respectively. Naringenin supplementation enriched gut microbiota in EAE mice, including increasing the abundance of Paraprevotellaceae and Comamonadaceae, while decreasing the abundance of Deltaproteobacteria, RF39, and Desulfovibrionaceae. Furthermore, the changes in gut microbiota affected the production of metabolites in the feces and brain, suggesting a role in regulating the gut-brain axis. Finally, we conducted a fecal transplantation experiment to validate that gut microbiota partly mediates the effect of naringenin on EAE alleviation. In conclusion, naringenin has potential immunomodulatory effects that are influenced to some extent by the gut microbiome.

Green tea EGCG inhibits naïve CD4+ T cell division and progression in mice: An integration of network pharmacology, molecular docking and experimental validation.

Dietary green tea epigallocatechin-3-gallate (EGCG) could attenuate experimental autoimmune encephalomyelitis via the modification of the balance of CD4+ T helper (Th) cells. Moreover, EGCG administration in vitro has a direct impact on the regulatory cytokines and differentiation of CD4+ T cells. Here, we aim to determine whether EGCG directly affects the cell division and progression in naive CD4+ T cells. We first investigate the effect of EGCG on naïve CD4+ T cell division and progression in vitro. An integrated analysis of network pharmacology and molecular docking was utilized to further identify the targets of EGCG for T cell-mediated autoimmune diseases and multiple sclerosis (MS). EGCG treatment prevented naïve CD4+ T cells from progressing through the cell cycle when stimulated with anti-CD3/CD28 antibodies. This was achieved by increasing the proportion of cells arrested in the G0/G1 phase by 8.6% and reducing DNA synthesis activity by 51% in the S phase. Furthermore, EGCG treatment inhibited the expression of cyclins (cyclin D1, cyclin D3, cyclin A, and cyclin B1) and CDKs (CDK2 and CDK6) during naïve CD4+ T cell activation in response to anti-CD3/CD28 stimulation. However, EGCG inhibited the decrease of P27Kip1 (CDKN1B) during naïve CD4+ T cell activation, whereas it inhibited the increase of P21Cip1 (CDKN1A) expression 48 h after mitogenic stimulation. The molecular docking analysis confirmed that these proteins (CD4, CCND1, and CDKN1A) are the primary targets for EGCG, T cell-mediated autoimmune diseases, and MS. Finally, target enrichment analysis indicated that EGCG may affect the cell cycle, T cell receptor signaling pathway, Th cell differentiation, and NF-κB signaling pathway. These findings reveal a crucial role of EGCG in the division and progression of CD4+ T cells, and underscore other potential targets of EGCG in T cell-mediated autoimmune diseases such as MS.

Naringenin as a natural immunomodulator against T cell-mediated autoimmune diseases: literature review and network-based pharmacology study.

T cells, especially CD4+ T helper (Th) cells, play a vital role in the pathogenesis of specific autoimmune diseases. Naringenin, a citrus flavonoid, exhibits anti-inflammatory, anti-oxidant, and antitumor properties, which have been verified in animal autoimmune disease models. However, naringenin's possible effects and molecular mechanisms in T cell-mediated autoimmune diseases are unclear. This review summarizes the findings of previous studies and predicts the target of naringenin in T cell-mediated autoimmune disorders such as multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis through network pharmacology analysis. We performed DAVID enrichment analysis, protein-protein interaction analysis, and molecular docking to predict the positive effect of naringenin on T cell-mediated autoimmune disorders. Sixteen common genes were screened, among which the core genes were PTGS2, ESR1, CAT, CASP3, MAPK1, and AKT1. The possible molecular mechanism relates to HIF-1, estrogen, TNF, and NF-κB signaling pathways. Our findings have significance for future naringenin treatment of T cell-mediated autoimmune diseases.

Future climate imposes pressure on vulnerable ecological regions in China.

Ecological regions of medium fragility account for 55 % of China's land. Large-scale afforestation and land reclamation have been carried out in these areas over the past few decades. However, how future climate change poses risks and challenges to them remains unclear. By establishing a multi-algorithm framework combining machine learning algorithms with multi-source dataset, our work predicts Normalized Difference Vegetation Index (NDVI, a proxy for vegetation greenness) and its variations in the 21st century under different climate scenarios. We find that vegetation greening (i.e., NDVI increase) in northern and southwestern China is unstable over four 20-year periods from 2020 to 2100. However, a strikingly prominent greening is expected to occur on the Qinghai-Tibet Plateau until the end of this century. Future warming can not only exacerbate the difficulties of vegetation conservation and restoration in vulnerable ecological regions, also threaten these new croplands, stymieing ambitions to increase crop production in China. Our results underscore the crucible that a warming climate presents to current restoration projects. We highlight the urgency of adapting to climate change to achieve ambitious goals of carbon sequestration and food security in China.

Saturation response of enhanced vegetation productivity attributes to intricate interactions.

Evidence for the multifaceted responses of terrestrial ecosystems has been shown by the weakening of CO2 fertilization-induced and warming-controlled productivity gains. The intricate relationship between vegetation productivity and various environmental controls still remains elusive spatially. Here several inherent preponderances make China a natural experimental setting to investigate the interaction and relative contributions of five drivers to gross primary productivity for the period from 1982 to 2018 (i.e., elevated atmospheric CO2 concentrations, climate change, nutrient availability, anthropogenic land use change, and soil moisture) by coupling multiple long-term datasets. Despite a strikingly prominent enhancement of vegetation productivity in China, it exhibits similar saturation responses to the aforementioned environmental drivers (elevated CO2 , climatic factors, and soil moisture). The CO2 fertilization-dominated network explains the long-term variations in vegetation productivity in humid regions, but its effect is clearly attenuated or even absent in arid and alpine environments controlled by climate and soil moisture. Divergence in interactions also provides distinct evidence that water availability plays an essential role in limiting the potential effects of climate change and elevated CO2 concentrations on vegetation productivity. Unprecedented industrialization and dramatic surface changes may have breached critical thresholds of terrestrial ecosystems under the diverse natural environment and thus forced a shift from a period dominated by CO2 fertilization to a period with nonlinear interactions. These findings suggest that future benefits in terrestrial ecosystems are likely to be counteracted by uncertainties in the complicated network, implying an increasing reliance on human societies to combat potential risks. Our results therefore highlight the need to account for the intricate interactions globally and thus incorporate them into mitigation and adaptation policies.

Ivermectin contributes to attenuating the severity of acute lung injury in mice.

Ivermectin has been proposed as a potential anti-inflammatory drug in addition to its antiparasitic activity. Here we investigated the potential role of ivermectin in the pathogenesis of acute lung injury (ALI) using the lipopolysaccharide (LPS)- or bleomycin (BLM)-induced mice models. Male C57BL/6 mice were given ivermectin orally every day for the remainder of the experiment at doses of 1 or 2 mg/kg after 24 h of LPS or BLM treatment. Ivermectin reversed severe lung injury caused by LPS or BLM challenge, including mortality, changes in diffuse ground-glass and consolidation shadows on lung CT imaging, lung histopathological scores, lung wet/dry ratio, and protein content in the bronchoalveolar lavage fluid (BALF). Furthermore, ivermectin also reduced total lung BALF inflammatory cells, infiltrating neutrophils, myeloperoxidase activity, and plasma TNF-α and IL-6 levels in mice treated with LPS or BLM. Finally, the mechanism study showed that LPS or BLM administration increased JNK, Erk1/2, and p38 MAPK phosphorylation while decreasing IκBα expression, an inhibitor of NF-κB. However, ivermectin increased IκBα expression but blocked elevated phosphorylated JNK and p38 MAPK, not Erk1/2, in both ALI mice. These findings suggested that ivermectin may alleviate ALI caused by LPS or BLM in mice, partly via lowering the inflammatory response, which is mediated at least by the inhibition of MAPK and NF-κB signaling. Collectively, ivermectin might be used to treat acute lung injury/acute respiratory distress syndrome.

Fructose Induces Pulmonary Fibrotic Phenotype Through Promoting Epithelial-Mesenchymal Transition Mediated by ROS-Activated Latent TGF-ß1.

Fructose is a commonly used food additive and has many adverse effects on human health, but it is unclear whether fructose impacts pulmonary fibrosis. TGF-ß1, a potent fibrotic inducer, is produced as latent complexes by various cells, including alveolar epithelial cells, macrophages, and fibroblasts, and must be activated by many factors such as reactive oxygen species (ROS). This study explored the impact of fructose on pulmonary fibrotic phenotype and epithelial-mesenchymal transition (EMT) using lung epithelial cells (A549 or BEAS-2B) and the underlying mechanisms. Fructose promoted the cell viability of lung epithelial cells, while N-Acetyl-l-cysteine (NAC) inhibited such. Co-treatment of fructose and latent TGF-ß1 could induce the fibrosis phenotype and the epithelial-mesenchymal transition (EMT)-related protein expression, increasing lung epithelial cell migration and invasion. Mechanism analysis shows that fructose dose-dependently promoted the production of total and mitochondrial ROS in A549 cells, while NAC eliminated this promotion. Notably, post-administration with NAC or SB431542 (a potent TGF-ß type I receptor inhibitor) inhibited fibrosis phenotype and EMT process of lung epithelial cells co-treated with fructose and latent TGF-ß1. Finally, the fibrosis phenotype and EMT-related protein expression of lung epithelial cells were mediated by the ROS-activated latent TGF-ß1/Smad3 signal. This study revealed that high fructose promoted the fibrotic phenotype of human lung epithelial cells by up-regulating oxidative stress, which enabled the latent form of TGF-ß1 into activated TGF-ß1, which provides help and reference for the diet adjustment of healthy people and patients with fibrosis.

Artificial light pollution inhibits plant phenology advance induced by climate warming.

Natural photic regime has been drastically altered by the artificial night sky luminance. Despite evidence of sufficient light brightness inducing plant physiology and affecting phenology, generalization regarding effects of light pollution on plant phenology across species and locations is less clear. Meanwhile, the relative contributions and joint effects of artificial light pollution and climate change or other anthropic stressors still remain unknown. To fill this knowledge gap, we utilized in situ plant phenological observations of seven tree species during 1991-2015 in Europe, night-time light dataset and gridded temperature dataset to investigate the impacts of the artificial light pollution on spatial-temporal shifts of plant phenological phases under climatic warming. We found 70% of the observation sites were exposed to increased light pollution during 1992-2015. Among them, plant phenological phases substantially delayed at 12-39% observation sites of leaf-out, and 6-53% of flowering. We also found plant species appeared to be more sensitive to artificial light pollution, and phenology advancement was hindered more prominently and even delay phenomenon exhibited when the color level showed stronger sky brightness. Linear mixed models indicate that although temperature plays a dominant role in shifts of plant phenological phases at the spatial scale, the inhibitory effect of artificial light pollution is evident considering the interactions. To our knowledge, this study is the first to quantitatively establish the relationship between artificial light pollution and plant phenology across species and locations. Meanwhile, these findings provide a new insight into the ecological responses of plant phenology to the potential but poorly understood environmental stressors under this warmer world and call for light pollution to be accorded the equal status as other global change phenomena.

Development and multicenter performance evaluation of fully automated SARS-CoV-2 IgM and IgG immunoassays.

Objectives: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread globally. The laboratory diagnosis of SARS-CoV-2 infection has relied on nucleic acid testing; however, it has some limitations, such as low throughput and high rates of false negatives. Tests of higher sensitivity are needed to effectively identify infected patients. Methods: This study has developed fully automated chemiluminescent immunoassays to determine IgM and IgG antibodies to SARS-CoV-2 in human serum. The assay performance has been evaluated at 10 hospitals. Clinical specificity was evaluated by measuring 972 hospitalized patients and 586 donors of a normal population. Clinical sensitivity was assessed on 513 confirmed cases of SARS-CoV-2 by RT-PCR. Results: The assays demonstrated satisfied assay precision with coefficient of variation of less than 4.45%. Inactivation of specimen did not affect assay measurement. SARS-CoV-2 IgM showed clinical specificity of 97.33 and 99.49% for hospitalized patients and the normal population respectively, and SARS-CoV-2 IgG showed clinical specificity of 97.43 and 99.15% respectively. SARS-CoV-2 IgM showed clinical sensitivity of 82.54, 92.93, and 84.62% before 7 days, 7-14 days, and after 14 days respectively, since onset of symptoms, and SARS-CoV-2 IgG showed clinical sensitivity of 80.95, 97.98, and 99.15% respectively at the same time points above. Conclusions: We have developed fully automated immunoassays for detecting SARS-CoV-2 IgM and IgG antibodies in human serum. The assays demonstrated high clinical specificity and sensitivity, and add great value to nucleic acid testing in fighting against the global pandemic of the SARS-CoV-2 infection.

Real-time in-situ distributed fiber core temperature measurement in hundred-watt fiber laser oscillator pumped by 915/976 nm LD sources.

In this manuscript, we studied the thermal properties of hundred-watt fiber laser oscillator by real-time in-situ distributed temperature measurement. Optical frequency domain reflectometry (OFDR) was introduced to measure the temperature distribution of gain fiber core. The fiber laser oscillator operated at 1080 nm and the wavelength of detecting signal from OFDR was ~1550 nm. The maximum output power of this fiber oscillator was 100 W. The fiber core temperature distributions in experiment agree well with our theoretical simulation. The temperature measurement of gain fiber core in oscillator has always been a problem because the backward laser from the oscillator may reduce the signal-to-noise ratio in OFDR. To the best of our knowledge, this is the first temperature distribution measurement of fiber core in hundred-watt oscillator. By the experimental measurement and theoretical model, we also analyzed the thermal properties of laser oscillator respectively pumped by 915 nm and 976 nm LD sources. We found fiber laser oscillator pumped by 976 nm LD sources experienced not only higher maximum thermal load but also higher average thermal load than that pumped by 915 nm LD sources at the same level output power. We also analyzed the fiber core temperature of other components in system, such as combiners and fiber Bragg gratings (FBG). These results are meaningful for us to improve the thermal design and management in fiber lasers.

D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19.

BACKGROUND: The outbreak of the coronavirus disease 2019 (Covid-19) has shown a global spreading trend. Early and effective predictors of clinical outcomes are urgently needed to improve management of Covid-19 patients. OBJECTIVE: The aim of the present study was to evaluate whether elevated D-dimer levels could predict mortality in patients with Covid-19. METHODS: Patients with laboratory confirmed Covid-19 were retrospective enrolled in Wuhan Asia General Hospital from January 12, 2020, to March 15, 2020. D-dimer levels on admission and death events were collected to calculate the optimum cutoff using receiver operating characteristic curves. According to the cutoff, the subjects were divided into two groups. Then the in-hospital mortality between two groups were compared to assess the predictive value of D-dimer level. RESULTS: A total of 343 eligible patients were enrolled in the study. The optimum cutoff value of D-dimer to predict in-hospital mortality was 2.0 µg/mL with a sensitivity of 92.3% and a specificity of 83.3%. There were 67 patients with D-dimer ≥2.0 µg/mL, and 267 patients with D-dimer <2.0 µg/mL on admission. 13 deaths occurred during hospitalization. Patients with D-dimer levels ≥2.0 µg/mL had a higher incidence of mortality when comparing with those who with D-dimer levels <2.0 µg/mL (12/67 vs 1/267, P < .001; hazard ratio, 51.5; 95% confidence interval, 12.9-206.7). CONCLUSIONS: D-dimer on admission greater than 2.0 µg/mL (fourfold increase) could effectively predict in-hospital mortality in patients with Covid-19, which indicated D-dimer could be an early and helpful marker to improve management of Covid-19 patients. (Chinese Clinical Trial Registry: ChiCTR2000031428).

Leukocyte telomere length, mitochondrial DNA copy number, and coronary artery disease risk and severity: A two-stage case-control study of 3064 Chinese subjects.

BACKGROUND AND AIMS: Leukocyte telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN), as hallmarks of cellular aging, may be involved in the development of coronary artery disease (CAD) by modulating oxidative stress. This study aimed to investigate the effects of leukocyte TL and mtDNA-CN alone or in combination on CAD risk and severity in the Chinese population. METHODS: In this two-stage case-control study with 1511 CAD patients and 1553 controls, leukocyte TL and mtDNA-CN were determined by a quantitative PCR assay. Three oxidative parameters, including leukocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG), plasma malondialdehyde, and plasma reactive oxygen species (ROS), were quantified by ELISA or colorimetric kits in a subset of 129 cases and 129 controls. RESULTS: In the combined cohort, each 1-SD decrease in TL and mtDNA-CN was significantly associated with a 1.17-fold and 1.14-fold increased risk of CAD (p < 0.001 for all), respectively, after adjusting for confounders. The aggregated score, which reflected the cumulative dosage of the tertiles of TL and mtDNA-CN, showed inverse dose-response correlations with CAD risk (ptrend < 0.001), and severity, as determined by the severity of clinical presentations (ptrend = 0.037), the presence of multi-vessel CAD (ptrend = 0.004), and modified Gensini scores (ptrend = 0.009). Similar dose-response relations of the aggregated score to leukocyte 8-OHdG and plasma ROS were also identified. CONCLUSIONS: Our data suggested reductions in both TL and mtDNA-CN as independent risk factors for CAD. The combination of TL and mtDNA-CN might jointly contribute to CAD risk, CAD severity, and oxidative stress.

Spatially-distributed orbital angular momentum beam array generation based on greedy algorithms and coherent combining technology.

A novel approach to generate a spatially-distributed orbital angular momentum (OAM) beam array based on coherent combining technology is presented. The arrangement of the multiple fundamental Gaussian beams at the initial plane, as well as the intensity weights and the phase distributions of the array beams, is determined by the reversal of Huygens Fresnel diffraction and the greedy algorithm. This method ensures that a vortex beam array is formed at a specified distance, and the distance can be adjusted by phase modulation. The evolution properties of the synthesized beam array near the receiver plane are studied as well to estimate the robustness of the method. The experimental limitations of this technique are discussed, including the maximum number of beams, the relative separation of each beam and the maximum topological charges. The results illustrate that a spatially-distributed OAM beam array can be effectively generated within a finite distance interval, and the distance is adjustable. This new method enables further applications of a structured optical field, such as optical communication and spatial light structuring.

Incoherent beam combining of fiber lasers by an all-fiber 7 × 1 signal combiner at a power level of 14 kW.

We demonstrate an all-fiber 7 × 1 signal combiner with an output core diameter of 50 µm for high power incoherent beam combining of seven self-made Yb-doped single-mode fiber lasers around a wavelength of 1080 nm and output power of 2 kW. 14.1 kW combined output power is achieved with a total transmission efficiency of higher than 98.5% and a beam quality of M2 = 5.37, which is close to the theoretical results based on finite-difference beam propagation technique. To the best of our knowledge, this is the highest output power ever reported for all-fiber structure beam combining generation, which indicates the feasibility and potential of >10 kW high brightness incoherent beam combining based on an all-fiber signal combiner.

PARP-1 Variant Rs1136410 Confers Protection against Coronary Artery Disease in a Chinese Han Population: A Two-Stage Case-Control Study Involving 5643 Subjects.

Inhibition of poly(ADP-ribose) polymerase (PARP) may protect against coronary artery disease (CAD) in animal models, and rs1136410, a non-synonymous single nucleotide polymorphism (SNP) in PARP-1, has a potential impact on PARP activities in vitro. This two-stage case-control study, involving 2803 CAD patients and 2840 controls, aimed to investigate the associations of PARP-1 rs1136410 with CAD development, lipid levels, PARP activities, 8-hydroxy-2'-dexyguanosine (8-OHdG), and interleukin (IL)-6 levels in a Chinese Han population. Assuming a recessive model, the variant genotype GG of SNP rs1136410 showed a significantly inverse association with CAD risk (adjusted odds ratio (OR) = 0.73, P < 0.001), left main coronary artery (LMCA) lesions (P = 0.003), vessel scores (P = 0.003), and modified Gensini scores (P < 0.001). There were significant correlations of SNP rs1136410 with higher levels of total cholesterol (TC) and lower levels of high-density lipoprotein cholesterol (HDL-c). In gene-environment interaction analyses, participants with the variant genotype GG, but without smoking habit, type 2 diabetes mellitus, and hyperlipidemia, conferred an 84% (P < 0.001) decreased risk of CAD. The genotype-phenotype correlation analyses further supported the functional roles of SNP rs1136410 in decreasing PARP activities and 8-OHdG levels. Taken together, our data suggest that SNP rs1136410 may confer protection against CAD through modulation of PARP activities and gene-environment interactions in a Chinese Han population.

Polymorphism in ERCC1 confers susceptibility of coronary artery disease and severity of coronary artery atherosclerosis in a Chinese Han population.

Excision repair cross-complementing 1 (ERCC1) gene encodes ERCC1 protein, which is mainly responsible for the repair of DNA damage in different diseases including coronary artery atherosclerosis by acting as a rate-limiting element in nucleotide excision repair (NER). Using a three-stage case-control study with 3037 coronary artery disease (CAD) patients and 3002 controls, we investigated associations of three single nucleotide polymorphisms (SNPs) with CAD risk and severity of coronary artery atherosclerosis in Chinese Han population. In the discovery set, the variant allele T of rs11615 was significantly associated with higher CAD risk (adjusted OR = 1.27, P = 0.006) and severity of coronary artery atherosclerosis (adjusted OR = 1.54, P = 0.003). These associations were more remarkable in the merged set (adjusted OR = 1.23, P = 8 × 10-6 for CAD risk; adjusted OR = 1.36, P = 4.3 × 10-5 for severity of coronary artery atherosclerosis). And the expression level of ERCC1 was significantly higher in CAD cases than controls. Multiplicative interactions among SNP rs11615, alcohol drinking, history of T2DM, and history of hyperlipidemia could increase 5.06-fold risk of CAD (P = 1.59 × 10-9). No significant association of rs2298881 and rs3212986 with CAD risk was identified. Taken together, SNP rs11615 in ERCC1 gene might confer susceptibility to CAD and severity of coronary atherosclerosis in a Chinese Han population.