Gastroesophageal Reflux Disease and Rhinosinusitis: A Bidirectional Mendelian Randomization Study.

INTRODUCTION: Comorbidities, such as gastroesophageal reflux disease (GERD), are common in patients with rhinosinusitis (RS). However, the link between RS and GERD has not been fully understood. This study aimed to investigate the causal relationship between GERD and acute (ARS) or chronic RS (CRS), providing references for the pathogenesis and management of RS. METHODS: The data were obtained from the Integrative Epidemiology Unit Open GWAS project and FinnGen. A total of 972,838 individuals were included. The inverse variance-weighted (IVW) method was applied to obtain the primary results of the study. Weighted median, MR-Egger, and mode-based methods were used to determine the robustness of the results. Cochran's Q statistic and MR-Egger method were applied to detect heterogeneity and pleiotrophy in instrumental variables (IVs). Other sensitivity analyses included MR-PRESSO and leave-one-out analysis. RESULTS: The MR study showed that GERD was associated with an increased risk of CRS (OR: 1.36, 95% CI: 1.18-1.57, p < 0.001). The results of other analysis methods were broadly consistent with the IVW estimate. No heterogeneity was detected by Cochran's Q test (p = 0.061) and MR-PRESSO (p = 0.074). No horizontal pleiotropy was shown in IVs (p = 0.700). GERD was also associated with an increased risk of ARS (OR: 1.31, 95% CI: 1.17-1.48, p < 0.001). Some analytical results were inconsistent with the IVW estimate. No heterogeneity and pleiotropy were observed. There was no sufficient evidence for a reverse causal effect of RS on GERD. CONCLUSION: Our study supported that GERD promoted the risk of CRS and may be a potential risk factor for ARS. This provides additional support for further investigation into the mechanisms of GERD on RS.

Associations between trans fatty acids and systemic immune-inflammation index: a cross-sectional study.

BACKGROUND: Previous studies have demonstrated that trans fatty acids (TFAs) intake was linked to an increased risk of chronic diseases. As a novel systemic inflammatory biomarker, the clinical value and efficacy of the systemic immune-inflammation index (SII) have been widely explored. However, the association between TFAs and SII is still unclear. Therefore, the study aims to investigate the connection between TFAs and SII in US adults. METHODS: The study retrieved data from the National Health and Nutrition Examination Survey (NHANES) for the years 1999-2000 and 2009-2010. Following the exclusion of ineligible participants, the study encompassed a total of 3047 individuals. The research employed a multivariate linear regression model to investigate the connection between circulating TFAs and SII. Furthermore, the restricted cubic spline (RCS) model was utilized to evaluate the potential nonlinear association. Subgroup analysis was also conducted to investigate the latent interactive factors. RESULTS: In this investigation, participants exhibited a mean age of 47.40 years, with 53.91% of them being female. Utilizing a multivariate linear regression model, the independent positive associations between the log2-transformed palmitelaidic acid, the log2 transformed-vaccenic acid, the log2-transformed elaidic acid, the log2-transformed linolelaidic acid, and the log2-transformed-total sum of TFAs with the SII (all P < 0.05) were noted. In the RCS analysis, no nonlinear relationship was observed between the log2-transformed palmitelaidic acid, the log2 transformed-vaccenic acid, the log2-transformed elaidic acid, the log2-transformed linolelaidic acid, the log2-transformed-total sum of TFAs and the SII (all P for nonlinear > 0.05). For the stratified analysis, the relationship between the circulating TFAs and the SII differed by the obesity status and the smoking status. CONCLUSIONS: A positive association was investigated between three types of TFA, the sum of TFAs, and the SII in the US population. Additional rigorously designed studies are needed to verify the results and explore the potential mechanism.

Neuritin attenuates oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury by promoting autophagic flux.

The autophagy/apoptosis interaction has always been a focus of study in pathogenicity models. Neuritin is a neurotrophic factor that is highly expressed primarily in the central nervous system. Our previous study revealed that it protects against apoptosis in cortical neurons subjected to oxygen-glucose deprivation (OGD)/reoxygenation (OGD/R), and later animal experiments revealed that it can increase the expression of the autophagy-related protein LC3. Whether this neuroprotective effect is closely related to autophagy is still unclear. In this study, we hypothesized that neuritin can promote autophagic flux to protect nerve cells after OGD/R. To verify this hypothesis, we induced OGD/R in primary cortical neurons and assessed cell viability by the CCK8 and LDH assays. Cell apoptosis was assessed by Annexin V-FITC/PI, staining, and the contents and mRNA abundances of the autophagy-related proteins LC3 and p62, the apoptotic protein Caspase3 were quantified by Western blotting and RT-PCR. Autophagic flux was assessed by immunofluorescence after RFP-GFP-LC3 virus transfection, and ultrastructural changes in autophagosomes were observed by transmission electron microscopy (TEM). The results showed that cell viability was decreased, apoptosis was increased and autophagy was enhanced after OGD/R. Neuritin significantly increased cell viability, decreased apoptosis, further increased the expression of the autophagic flux-related protein LC3, further decreased p62 expression, and significantly increased the autophagosome number and autophagosome to lysosome ratio. Bafilomycin A1 (BafA1) is a late autophagy inhibitor, aggravated cell damage and apoptosis and counteracted the enhancement of autophagy activation and protective effects of neuritin. In conclusion, neuritin may promote the completion of autophagic flux by ameliorating neuronal damage after OGD/R.

Fitness of F1 hybrids between 10 maternal wild soybean populations and transgenic soybean.

The releasing of transgenic soybeans (Glycine max (L.) Merr.) into farming systems raises concerns that transgenes might escape from the soybeans via pollen into their endemic wild relatives, the wild soybean (Glycine soja Sieb. et Zucc.). The fitness of F1 hybrids obtained from 10 wild soybean populations collected from China and transgenic glyphosate-resistant soybean was measured without weed competition, as well as one JLBC-1 F1 hybrid under weed competition. All crossed seeds emerged at a lower rate from 13.33-63.33%. Compared with those of their wild progenitors, most F1 hybrids were shorter, smaller, and with decreased aboveground dry biomass, pod number, and 100-seed weight. All F1 hybrids had lower pollen viability and filled seeds per plant. Finally, the composite fitness of nine F1 hybrids was significantly lower. One exceptional F1 hybrid was IMBT F1, in which the composite fitness was 1.28, which was similar to that of its wild progenitor due to the similarities in pod number, increased aboveground dry biomass, and 100-seed weight. Under weed competition, plant height, aboveground dry biomass, pod number per plant, filled seed number per plant, and 100-seed weight of JLBC-1 F1 were lower than those of the wild progenitor JLBC-1. JLBC-1 F1 hybrids produced 60 filled seeds per plant. Therefore, F1 hybrids could emerge and produce offspring. Thus, effective measures should be taken to prevent gene flow from transgenic soybean to wild soybean to avoid the production F1 hybrids when releasing transgenic soybean in fields in the future.

Balancing Industry and Drug Policy Objectives in the Pharmaceutical Sector: The Case of China.

Objectives This article assessed the balance between industry and drug policy objectives in the pharmaceutical sector in China. Methods The articles were mainly identified through databases such as Elsevier, Google Scholar, and SpringerLink, among others. Related articles were mainly separated into three categories: studies on drug policies, studies related to China's new health-care reform policy, and studies concerning patent policies. Results A relatively healthy environment for continuous innovation and drug patent protection in the pharmaceutical industry has been created in China, and the public's drug benefits have also significantly improved. However, the balance between industrial and drug policy objectives in the pharmaceutical sector in China requires additional attention. Discussion and conclusions The results suggest that the government should pay more attention to incentivizing enterprises' innovation, but the current Essential Medicines System in China has limited innovation. Hence, the mechanism for selecting essential medicines should be reformed, and certain appropriate and reasonably innovative medicines should be included. Additionally, medicine coverage, especially the coverage of essential drugs for primary care should be expanded to improve public health benefits. Furthermore, the pharmaceutical industry should be incorporated into the prospective National Drug Policy to achieve a balance between public benefits and pharmaceutical industry development in the future.

Expression and clinical significance of DOK3 in renal clear cell carcinoma.

OBJECTIVES: Docking Protein 3 (DOK3) is an adapter protein that has been implicated in various cellular processes relevant to diseases, such as cancer. In this study, we aimed to evaluate the role of DOK3 in kidney renal clear cell carcinoma (KIRC) by examining how its expression levels are correlated with patient characteristics and prognosis. METHODS: We analyzed KIRC-related data from The Cancer Genome Atlas and used several bioinformatics tools, such as LinkedOmics and Oncomine, to evaluate DOK3 mRNA expression in KIRC. DOK3 protein expression was examined in 150 clinical KIRC samples and 100 non-cancerous renal tissues with immunohistochemistry assays. The prognostic value of DOK3 mRNA expression on patient overall survival was analyzed retrospectively using Kaplan-Meier survival and Cox regression analyses. RESULTS: DOK3 mRNA expression was notably higher in KIRC samples compared with normal tissues. Significant correlations were found between DOK3 mRNA expression levels and tumor size, lymph node metastasis, distant metastasis, and pathological grade using the bioinformatics data. This was confirmed at the protein level with immunohistochemistry data. Survival analyses indicated that elevated DOK3 expression is linked to a lower overall survival rate in KIRC patients. CONCLUSIONS: DOK3 is a potential biomarker for determining KIRC patient clinical prognosis.

Serum folate associated with nonalcoholic fatty liver disease and advanced hepatic fibrosis.

The role played by serum folate in the progression of nonalcoholic fatty liver disease (NAFLD) remains controversial. The purpose of this study was to investigate the association of serum folate with NAFLD and advanced liver fibrosis (AHF). We conducted a cross-sectional study with 5417 participants using 2011-2018 NHANES data. Multiple logistic regression analysis and propensity score matching analysis were used to investigate the association of serum folate with NAFLD and AHF. In the completely adjusted model, participants in the high serum folate group had a 27% (OR 0.73, 95% CI 0.62, 0.87, p = 0.0003) and 53% (OR 0.47, 95% CI 0.35, 0.63, p < 0.0001) lower odds of suffering from NAFLD and AHF, respectively, compared to the low serum folate group. The similar results in propensity score matching further validated the above association. Stratified analysis showed that the negative correlation of serum folate with NAFLD and AHF demonstrated a broad consistency across populations. The results of this study indicate that higher serum folate level was associated with lower odds of NAFLD and AHF among US adults. Further prospective studies are necessary due to the limitations of cross-sectional studies.

Pulmonary sarcoidosis: A novel sequelae of drug reaction with eosinophilia and systemic symptoms: A case report.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon yet serious adverse drug hypersensitivity reaction with the presentations including rash, fever, lymphadenopathy, and internal organ involvement. Sarcoidosis is a systematic granulomatous disease with unknown etiology. We herein report a case of pulmonary sarcoidosis secondary to allopurinol-induced DRESS. CASE SUMMARY: A 37-year-old man with a history of hyperuricemia was treated with allopurinol for three weeks at a total dose of 7000 milligrams before developing symptoms including anorexia, fever, erythematous rash, and elevated transaminase. The patient was diagnosed with DRESS and was treated with prednisone for 6 mo until all the symptoms completely resolved. Three months later, the patient presented again because of a progressively worsening dry cough. His chest computed tomography images showed bilateral lung parenchyma involvement with lymph node enlargement, which was confirmed to be nonnecrotizing granuloma by pathological examination. Based on radiologic and pathological findings, he was diagnosed with sarcoidosis and was restarted on treatment with prednisone, which was continued for another 6 mo. Reexamination of chest imaging revealed complete resolution of parenchymal lung lesions and a significant reduction in the size of the mediastinal and hilar lymph nodes. Following a 6-month follow-up of completion of treatment, the patient's clinical condition remained stable with no clinical evidence of relapse. CONCLUSION: This is the first case in which pulmonary sarcoidosis developed as a late complication of allopurinol-induced DRESS. The case indicated that the autoimmune reaction of DRESS may play an important role in the pathogenesis of sarcoidosis.

Reverse relationship between autophagy and apoptosis in an in vitro model of cortical neuronal injury.

Autophagy and apoptosis are intertwined, and their relationship involves complex cross-talk. Whether the activation and inhibition of autophagy protect or damage neurons in the central nervous system has been a matter of longstanding controversy. We investigated the effect of autophagy on the apoptosis of cortical neurons after oxygen- and glucose-deprivation/reoxygenation (OGD/R) injury in vitro and found that protective mechanism activation was the predominant response to enhanced autophagy activation and increased autophagic flux. After successful establishment of an OGD/R model with cortical neurons, the autophagy activator rapamycin (Rap) or the late-autophagy inhibitor bafilomycin A1 (BafA1) was added to cell groups according to the experimental design. Cell viability was determined by Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) assays, and the apoptosis rate was measured by analysing Annexin V-FITC/PI-stained cells. The protein and mRNA expression levels of the apoptosis factors Caspase8 and Caspase3 and autophagy-associated proteins LC3 and p62 were measured by Western blotting and RT-qPCR. The extent of autophagic flux was determined by measuring the intensity of double immunofluorescence labelled protein after cells were transfected with RFP-GFP-LC3-expressing virus, and the ultrastructures of autophagosomes were observed by transmission electron microscopy (TEM). The results showed that cell viability decreased and that cells underwent autophagy and apoptosis after OGD/R. After the addition of Rap, cell viability was increased, and the apoptosis rate was decreased significantly. In addition, the level of the autophagic flux protein LC3II was increased, and the level of p62 was decreased. The number of autophagosomes and the ratio of autophagosomes to lysosomes were increased significantly. After BafA1 intervention, however, these results were reversed, with decreased cell viability, a significantly increased apoptosis rate, and disrupted autophagic flux. In conclusion, enhanced autophagy activation or autophagic flux exerted a significant protective effect on neurons after OGD/R injury in vitro.

Effects of taillight shape on conspicuity of vehicles at night.

Taillight shape in a vehicle provides an essential lighting signal that enables the vehicle to be seen from the rear at night, thereby preventing rear-end crashes. This study aims to investigate the effects of taillight shape on vehicle conspicuity, and proposes ergonomic taillight shape solutions to vehicle designers and manufacturers. Two complementary experiments were conducted to examine three types of taillight shapes at three design levels. The first experiment was designed to investigate the detection speed of a driver and the fixation duration and fixation counts on leading vehicles with different taillight shapes, based on an eye-tracking methodology. The second experiment was designed to investigate the dynamic visual searching performance of a trailing driver for leading vehicles with different taillight shapes, based on a visual search task. The experimental results indicated that a long line-shaped taillight (striplight) was the optimal ergonomic solution for enhancing vehicle conspicuity. Vehicles with an enclosed contour-shaped taillight were more salient than those with an open contour-shaped taillight. Moreover, the experience and gender of the driver and the vehicle-observer distance were found to be closely related to vehicle conspicuity, and therefore, must be considered by vehicle designers when applying a specific taillight shape design. This study provides insights into the taillight shape design that not only aid vehicle designers or manufacturers in enhancing vehicle safety but also enable potential vehicle buyers to choose a safe lighting system.

Detection of autophagic flux in primary cerebral cortical neurons after oxygen glucose deprivation/reperfusion (OGD/R) using various methods.

The current research hot spot in the field of autophagic flux is to explain and alleviate disease from the perspective of autophagy. A highly sophisticated, sensitive, quantifiable and comprehensive method is required to accurately determine the dynamic process of autophagic flux. There are very few methods in neuroscience that specifically examine autophagic flux. Therefore, primary cortical neurons were divided into oxygen glucose deprivation/reperfusion (OGD/R) (group A) and OGD/R plus bafilomycin A1 (BafA1) (group B) groups. ① Transfection of the LC3 gene with the RFP-GFP tandem fluorescent label was performed. ② Direct quantification was performed using transmission electron microscopy (TEM). ③ Autophagy-related tools were used to detect the transformation of LC3I/II. ④ SQSTM1/P62 combined with the LC3 protein flip test was performed to comprehensively evaluate autophagic flux. Using method one, the ratio of autophagolysosomes to autophagosomes in group A was significantly increased based on fluorescence microscopy analysis. Using method two, the autophagy process in group A was more continuous and unobstructed based on TEM analysis, while only some partial processes were observed in group B, and the number of autophagosomes and autophagy lysosomes in group A was significantly greater more than that in group B. The LC3II/I ratio measured in method three was analysed in detail to explain the autophagic flux. The ratio of soluble p62 combined with the ratio of LC3II/I detected using method four reflected the activation of autophagy. In summary, each method has its own advantages, and different methods and indicators can be used to monitor different stages of autophagy. An understanding of these advantages and mastery of these methods, is a very promising strategy to systematically and objectively study central nervous system diseases, facilitate the rational use of drugs, and formulate effective treatment plans from the perspective of autophagy.