CSF N-acylethanolamine acid amidase level and Parkinson's disease risk: A mendelian randomization study.

BACKGROUND: Neuroinflammation is involved in the progression of Parkinson's disease (PD), and N-acylethanolamine acid amidase (NAAA) is involved in regulating inflammation by hydrolyzing bioactive lipid mediators called N-acylethanolamines (NAEs). However, the causal relationship between cerebrospinal fluid (CSF) NAAA protein levels and the risk of PD remains unclear. This study aimed to explore the causal effect of CSF NAAA levels on PD risk through Mendelian randomization (MR) analysis. METHOD: Genome-wide association study (GWAS) summary statistics for CSF NAAA protein quantitative trait loci (pQTL) and GWAS summary statistics for PD were obtained from publicly available databases. Inverse-variance weighted (IVW) was the main causal estimation method for MR analysis. In addition, the maximum likelihood, MR Egger regression, and weighted median were used to supplement the IVW results. Finally, various sensitivity tests were performed to verify the reliability of the MR findings. RESULTS: In the initial MR analysis, the IVW showed that CSF NAAA protein levels significantly increased PD risk (odds ratio [OR] = 1.17, 95% confidence interval [CI]: 1.01-1.35, P = 0.031). This finding was further validated in a replicate MR analysis (OR = 1.20, 95% CI: 1.02-1.41, P = 0.027). Sensitivity analysis showed that MR results were stable and not affected by heterogeneity and horizontal pleiotropy. CONCLUSION: The present MR study supports a causal relationship between elevated CSF NAAA protein levels and increased PD risk.

Effects of saturated and monounsaturated fatty acids on cognitive impairment: evidence from Mendelian randomization study.

BACKGROUND: Prior observational studies have suggested correlations between saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) with cognitive function. However, causal relationships remains unclear. METHODS: We assessed the causal impact of two SFAs (palmitic acid [PA] and stearic acid [SA]) and two MUFAs (oleic acid [OA] and palmitoleic acid [POA]) on cognitive function-related traits, and dementia-related traits by univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) analyses. RESULTS: UVMR indicated ß of 0.060 (P = 4.05E-06) for cognitive performance score and 0.066 (P = 4.21E-04) for fluid intelligence per standard deviation (SD) increase in OA level. MVMR indicated: (i) ß of -0.608 (P = 8.37E-05) for fluid intelligence score per SD increase in POA; (ii) ß of 0.074 (P = 0.018) for fluid intelligence score per SD increase in OA; (iii) ß of 0.029 (P = 0.033) for number of incorrect matches in round per SD increase in PA; and (iv) ß of 0.039 (P = 0.032) for number of incorrect matches in round per SD increase in SA. In addition, a secondary MVMR analysis after excluding the effect of polyunsaturated fatty acids suggested that: (i) ß of -0.043 (P = 1.97E-02) for cognitive performance score per SD increase in PA and (ii) ß of -0.079 (P = 1.79E-03) for cognitive performance score per SD increase in SA. CONCLUSIONS: Overall, UVMR and MVMR suggest that OA may be beneficial for cognitive function, while POA, PA, and SA may have detrimental effects on cognitive function.

Causal association between 25-Hydroxyvitamin D and risk of abnormal spermatozoa: A bidirectional Mendelian randomization study.

Previous studies indicated conflicting findings regarding the association between vitamin D and abnormal spermatozoa. Herein, we assessed the causal association between circulating 25-Hydroxyvitamin D (25OHD) levels and the risk of abnormal spermatozoa by utilizing bidirectional Mendelian randomization (MR) analysis. Genome-wide association study summary statistics for 25OHD and abnormal spermatozoa were obtained from publicly accessible databases. Single nucleotide polymorphisms (SNPs) associated with 25OHD and SNPs associated with abnormal spermatozoa were used as instrumental variables (IVs) for forward MR analysis and reverse MR analysis, respectively. Inverse variance weighted (IVW) was the main MR approach, while weighted median, MR-Egger, and maximum likelihood methods were employed to supplement IVW. In addition, several sensitivity tests assessed the reliability of MR analysis. Forward MR analysis showed that elevated 25OHD levels significantly reduced abnormal spermatozoa risk (odds ratio [OR] = 0.75, 95 % confidence interval [CI]: 0.56-1.00, P = 4.98E-02), and the effect remained statistically significant after excluding SNPs associated with confounders (OR = 0.73, 95 % CI: 0.54-0.98, P = 3.83E-02) or only utilizing SNPs located near 25OHD-associated genes only as IVs (OR = 0.58, 95 % CI: 0.41-0.81, P = 1.67E-03). Reverse MR analysis indicated abnormal spermatozoa not affecting 25OHD level (P > 0.05). Sensitivity tests showed that MR analyses were not affected by heterogeneity and horizontal polytropy. Overall, the present MR study supports that elevated 25OHD levels reduce the risk of abnormal spermatozoa. Therefore, ensuring adequate vitamin D intake and maintaining stable levels of 25OHD may be effective strategies to optimize reproductive outcomes.

Mendelian randomization study supports positive bidirectional causal relationships between genetically predicted insomnia symptom and liability to benign prostatic hyperplasia.

BACKGROUND: Sleep quality may be related to benign prostatic hyperplasia (BPH), however causal associations have not been established. This study aimed to evaluate causal relationships between six sleep traits ([i] day time napping, [ii] daytime sleepiness, [iii] insomnia, [iv] long sleep duration, [v] short sleep duration, and [vi] sleep duration per hour) and BPH through a bidirectional Mendelian randomization (MR) study. METHODS: Genome-wide association summary statistics of sleep traits and BPH were downloaded from public databases. Inverse variance weighting (IVW) was used as the main approach for causal inference. For causal estimates identified by IVW, various sensitivity analyses were performed to assess the reliability of the results: (i) four additional MR methods to complement IVW; (ii) Cochran's Q test to assess heterogeneity; (iii) MR-Egger intercept test and MR-PRESSO global test to assess horizontal pleiotropy; and (iv) leave-one-out method to assess stability. RESULTS: Forward MR analyses indicated that genetically predicted insomnia symptom significantly increased BPH risk (OR = 1.267, 95% CI: 1.003-1.601, P = 0.048), while reverse MR analyses identified that genetically predicted liability to BPH significantly increased the incidence of insomnia (OR = 1.026, 95% CI: 1.000-1.052, P = 0.048). In a replicate MR analysis based on summary statistics including exclusively male participants, the finding of increased risk of BPH due to genetically predicted insomnia symptom was further validated (OR = 1.488, 95% CI: 1.096-2.022, P = 0.011). No further causal links were identified. In addition, sensitivity tests demonstrated the reliability of the MR results. CONCLUSION: This study identified that a higher prevalence of genetically predicted insomnia symptoms may significantly increase the risk of BPH, while genetically predicted liability to BPH may in turn increase the incidence of insomnia symptom. Therefore, improving sleep quality and reducing the risk of insomnia could be a crucial approach for the prevention of BPH.

Oleanolic acid exerts bone anabolic effects via activation of osteoblastic 25-hydroxyvitamin D 1-alpha hydroxylase.

Oleanolic acid (OA) is previously shown to exert bone protective effects in aged animals. However, its role in regulating osteoblastic vitamin D bioactivation, which is one of major causes of age-related bone loss, remains unclear. Our results revealed that treatment of OA significantly increased skeletal CYP27B1 expression and circulating 1,25(OH)2D3 in ovariectomized mice (p <0.01). Moreover, OA upregulated CYP27B1 protein expression and activity, as well as the vitamin D-responsive bone markers alkaline phosphatase (ALP) activity and osteopontin (OPN) protein expression, in human osteoblast-like MG-63 cells (p<0.05). CYP27B1 expression increased along with the osteoblastic differentiation of human bone marrow derived mesenchymal stem cells (hMSCs). CYP27B1 expression and cellular 1,25(OH)2D3 production were further potentiated by OA in cells at mature osteogenic stages. Notably, our study suggested that the osteogenic actions of OA were CYP27B1 dependent. In summary, the bone protective effects of OA were associated with the induction of CYP27B1 activity and expression in bone tissues and osteoblastic lineages. Hence, OA might be a potential approach for management of age-related bone loss.

The systemic immune-inflammation index is significantly associated with the severity of silicosis: a 9-year retrospective study in Beijing.

Background: Silicosis shows an increasing trend with the development of new industries. However, the potential biomarkers for predicting the disease severity are lacking. A novel inflammatory marker, the systemic immune-inflammation Index (SII), has not been studied in silicosis. Methods: In this retrospective study, we used data from a big database platform of a tertiary general hospital in Beijing, which was established based on the electronic medical records of the hospital. The clinical data of adult patients diagnosed with silicosis at the Department of Occupational Medicine and Toxicology from 2013 to 2022 were collected. The data extracted from the database were in de-identified form. Only patients with a first diagnosis of silicosis and without conditions that might affect the parameters of routine blood tests were included in the analysis. Analyses were performed to assess the relationship between SII and the advanced stage of silicosis. Results: A total of 246 participants were included in the study. Most of the patients were exposed to silica particles during excavation and digging (n = 149, 60.6%). SII level was significantly higher in patients with advanced stages of silicosis. A multivariate logistic regression analysis revealed that a higher SII level was associated with the advanced stage of silicosis [odds ratio (OR) = 1.002; 95% confidence interval (CI): 1.000-1.003, p < 0.001] after adjusting for all covariates. The best cutoff value of SII was 444.1. The results of the subgroup analysis also showed a significant correlation between SII level over 444.1 and the advanced stage of silicosis in groups stratified by gender, history of smoking, and duration of silica exposure. Moreover, our results showed a significant but weak negative correlation between the level of SII and some lung function parameters in silicosis. Conclusion: Higher SII is associated with the advanced stage of silicosis and impaired lung function. More long-term, large-scale studies are needed to confirm these findings.

Causal relationship between particulate matter 2.5 and infectious diseases: A two-sample Mendelian randomization study.

Background: Previous observational studies suggested a correlation between particulate matter 2.5 (PM2.5) and infectious diseases, but causality remained uncertain. This study utilized Mendelian randomization (MR) analysis to investigate causal relationships between PM2.5 concentrations and various infectious diseases (COVID-19 infection, hospitalized COVID-19, very severe COVID-19, urinary tract infection, bacterial pneumonia, and intestinal infection). Methods: Inverse variance weighted (IVW) was the primary method for evaluating causal associations. For significant causal estimates, multiple sensitivity tests were further performed: (i) three additional MR methods (MR-Egger, weighted median, and maximum likelihood method) for supplementing IVW; (ii) Cochrane's Q test for assessing heterogeneity; (iii) MR-Egger intercept test and MR-PRESSO global test for evaluating horizontal pleiotropy; (iv) leave-one-out sensitivity test for determining the stability. Results: PM2.5 concentration significantly increased the risk of hospitalized COVID-19 (OR = 1.91, 95 % CI: 1.06-3.45, P = 0.032) and very severe COVID-19 (OR = 3.29, 95 % CI: 1.48-7.35, P = 3.62E-03). However, no causal effect was identified for PM2.5 concentration on other infectious diseases (P > 0.05). Furthermore, various sensitivity tests demonstrated the reliability of significant causal relationships. Conclusions: Overall, lifetime elevated PM2.5 concentration increases the risk of hospitalized COVID-19 and very severe COVID-19. Therefore, controlling air pollution may help mitigate COVID-19 progression.

Causal Association Between Sepsis and Neurodegenerative Diseases: A Bidirectional Two-Sample Mendelian Randomization Study.

BACKGROUND: Previous observational studies suggested an association between sepsis and neurodegenerative diseases, but causality remains unclear. OBJECTIVE: Determining the causal association between sepsis and four neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Lewy body dementia) through bidirectional two-sample Mendelian randomization (MR) analysis. METHODS: Genome-wide association study summary statistics for all traits were obtained from publicly available databases. Inverse variance weighted (IVW) was the primary method for evaluating causal associations. In addition, three additional MR methods (MR-Egger, weighted median, and maximum likelihood method) were employed to supplement IVW. Furthermore, various sensitivity tests were conducted to assess the reliability: 1) Cochrane's Q test for assessing heterogeneity; 2) MR-Egger intercept test and MR-PRESSO global test for evaluating horizontal pleiotropy; 3) leave-one-out sensitivity test for determining the stability. RESULTS: The results of IVW indicated that sepsis significantly increased the risk of Alzheimer's disease (OR = 1.11, 95% CI: 1.01-1.21, p = 0.025). In addition, three additional MR methods suggested parallel results. However, no causal effect of sepsis on the three other neurodegenerative diseases was identified. Subsequently, reverse MR analysis indicated that the four neurodegenerative diseases do not causally affect sepsis. Furthermore, sensitivity tests demonstrated the reliability of the MR analyses, suggesting no heterogeneity or horizontal pleiotropy. CONCLUSIONS: The present study contributes to a deeper comprehension of the intricate interplay between sepsis and neurodegenerative disorders, thereby offering potential avenues for the development of therapeutic agents that can effectively mitigate the multifarious complications associated with sepsis.

No causal relationship between thyroid function and Parkinson's disease: A bidirectional Mendelian randomization study.

BACKGROUND: Parkinson's disease (PD) is the second most prevalent degenerative disease globally. While observational studies have demonstrated a correlation between thyroid function and PD, the causal relationship between these two factors remains uncertain. METHODS: A bidirectional Mendelian randomization (MR) analysis was performed to explore the causal relationship between thyroid function (free thyroxine [FT4], thyroid-stimulating hormone [TSH], hyperthyroidism, and hypothyroidism) and PD. GWAS summary-level statistics of thyroid function and PD were obtained from publicly available GWAS databases. The inverse variance weighted method was the main MR approach to assess causal associations. In addition, two additional MR methods (MR-Egger regression and weighted median) were performed to supplement the IVW. Furthermore, various sensitivity tests were performed to verify the reliability of the MR findings: (i) Heterogeneity was examined by Cochrane's Q test. (ii) Horizontal pleiotropy was assessed by the MR-Egger intercept test and MR-PRESSO global test. (iii) The robustness of MR results was estimated using the leave-one-out method. RESULTS: Various MR results showed that FT4, TSH, hyperthyroidism, and hypothyroidism did not causally affect PD (P > 0.05). Likewise, PD did not causally affect FT4, TSH, hyperthyroidism, and hypothyroidism (P > 0.05). Cochrane's Q test indicated that MR analysis was not affected by significant heterogeneity (P > 0.05). MR-Egger intercept test and MR-PRESSO global test indicated that MR analysis was not affected by a remarkable horizontal pleiotropy (P > 0.05). The leave-one-out method demonstrated the stability of MR results. CONCLUSION: MR analysis did not support a causal relationship between thyroid function and PD.

GLP-1RAs inhibit the activation of the NLRP3 inflammasome signaling pathway to regulate mouse renal podocyte pyroptosis.

OBJECTIVE: Podocytes are closely related to renal function as an important part of the glomerulus. The reduction and damage of podocytes lead to further decline of renal function and aggravate the progression of DKD. Glucagon-like peptide-1 receptor agonists (GLP-1RAS) have recently attracted great attention in improving podocyte dysfunction, but the specific mechanism remains uncertain. METHODS: We used mouse kidney podocyte MPC5 to construct a high-glucose injury model. Cell viability was detected by the MTT method; RT-qPCR and western blotting were used to detect the expressions of NF-κB p65, NLRP3, GSDMD, N-GSDMD, caspase-1 and cleaved-caspase-1, and we used ELISA to detect the expressions of inflammatory factors IL-1ß and IL-18. RESULTS: Our results showed that high glucose decreased podocyte survival, while liraglutide and semaglutide increased podocyte survival under high glucose. Liraglutide and semaglutide can inhibit the expression of pyroptosis-related genes and proteins and also inhibit the expression of inflammatory factors IL-1ß, IL-18 increase. CONCLUSION: The protective effect of liraglutide and semaglutide on podocytes may be achieved by regulating the NLRP3 inflammasome pathway and inhibiting pyroptosis, and there were no significant differences between the two GLP-1RAs (liraglutide and semaglutide) in inhibiting podocyte pyroptosis.

Identification of key lipid metabolism-related genes in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) represents profound degenerative conditions of the brain that cause significant deterioration in memory and cognitive function. Despite extensive research on the significant contribution of lipid metabolism to AD progression, the precise mechanisms remain incompletely understood. Hence, this study aimed to identify key differentially expressed lipid metabolism-related genes (DELMRGs) in AD progression. METHODS: Comprehensive analyses were performed to determine key DELMRGs in AD compared to controls in GSE122063 dataset from Gene Expression Omnibus. Additionally, the ssGSEA algorithm was utilized for estimating immune cell levels. Subsequently, correlations between key DELMRGs and each immune cell were calculated specifically in AD samples. The key DELMRGs expression levels were validated via two external datasets. Furthermore, gene set enrichment analysis (GSEA) was utilized for deriving associated pathways of key DELMRGs. Additionally, miRNA-TF regulatory networks of the key DELMRGs were constructed using the miRDB, NetworkAnalyst 3.0, and Cytoscape software. Finally, based on key DELMRGs, AD samples were further segmented into two subclusters via consensus clustering, and immune cell patterns and pathway differences between the two subclusters were examined. RESULTS: Seventy up-regulated and 100 down-regulated DELMRGs were identified. Subsequently, three key DELMRGs (DLD, PLPP2, and PLAAT4) were determined utilizing three algorithms [(i) LASSO, (ii) SVM-RFE, and (iii) random forest]. Specifically, PLPP2 and PLAAT4 were up-regulated, while DLD exhibited downregulation in AD cerebral cortex tissue. This was validated in two separate external datasets (GSE132903 and GSE33000). The AD group exhibited significantly altered immune cell composition compared to controls. In addition, GSEA identified various pathways commonly associated with three key DELMRGs. Moreover, the regulatory network of miRNA-TF for key DELMRGs was established. Finally, significant differences in immune cell levels and several pathways were identified between the two subclusters. CONCLUSION: This study identified DLD, PLPP2, and PLAAT4 as key DELMRGs in AD progression, providing novel insights for AD prevention/treatment.

Circulating sex hormone-binding globulin levels and ischemic stroke risk: a Mendelian randomization study.

PURPOSE: Previous studies have presented conflicting findings regarding the protective effects of circulating sex hormone-binding globulin (SHBG) on ischemic stroke (IS). This study aimed to assess the causal effect of SHBG on IS using Mendelian randomization (MR) analysis and to identify potential mediators. METHODS: First, the causal effect of SHBG on any IS (AIS), cardioembolic stroke (CES), large artery stroke (LAS), and small vessel stroke (SVS) was assessed by inverse variance weighed (IVW) method. Two additional MR methods (weighted median and MR-Egger) were used to supplement the IVW results. Subsequently, a two-step MR was further performed to assess whether three glycemic profiles [fasting glucose, fasting insulin, and glycated hemoglobin (HbA1c)] and five lipid profiles (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non-HDL cholesterol, total cholesterol, and triglycerides) mediated the causal effect. Furthermore, Cochrane's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis were performed for sensitivity analyses. RESULTS: The IVW results showed that SHBG significantly reduced SVS risk (odds ratio= 0.60, 95% confidence interval: 0.47-0.77, P = 4.60E-05). The weighted median and MR-Egger results were parallel to IVW. However, no significant associations were found between SHBG and AIS, CES, and LAS. Mediation analysis indicated that HbA1c may be involved in SHBG reducing SVS risk. Sensitivity tests demonstrated the reliability of causal estimates. CONCLUSIONS: Circulating SHBG levels may decrease SVS risk by lowering HbA1c levels. Therefore, individuals with low circulating SHBG levels should focus on glycemic control to reduce future SVS risk.

Causal associations between blood lipids and brain structures: a Mendelian randomization study.

The potential causal association between dyslipidemia and brain structures remains unclear. Therefore, this study aimed to investigate whether circulating lipids are causally associated with brain structure alterations using Mendelian randomization analysis. Genome-wide association study summary statistics of blood lipids and brain structures were obtained from publicly available databases. Inverse-variance weighted method was used as the primary method to assess causality. In addition, four additional Mendelian randomization methods (MR-Egger, weighted median, simple mode, and weighted mode) were applied to supplement inverse-variance weighted. Furthermore, Cochrane's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis were performed for sensitivity analyses. After Bonferroni corrections, two causal associations were finally identified: elevated non-high-density lipoprotein cholesterol level leads to higher average cortical thickness (ß = 0.0066 mm, 95% confidence interval: 0.0045-0.0087 mm, P = 0.001); and elevated high-density lipoprotein cholesterol level leads to higher inferior temporal surface area (ß = 18.6077 mm2, 95% confidence interval: 11.9835-25.2320 mm2, P = 0.005). Four additional Mendelian randomization methods indicated parallel results. Sensitivity tests demonstrated the stability. Overall, the present study showed causal relationships between several lipid profiles and specific brain structures, providing new insights into the link between dyslipidemia and neurological disorders.

Impact of blood pressure and antihypertensive drug classes on intracranial aneurysm: a Mendelian randomization study.

BACKGROUND: Blood pressure is a risk factor for intracranial aneurysms (IA). Nevertheless, whether various antihypertensive drug classes discriminate in reducing IA risk is unclear. METHODS: Genome-wide association study summary statistics for systolic blood pressure (SBP), diastolic blood pressure (DBP), IA (non-ruptured), and IA [subarachnoid hemorrhage (SAH)] were downloaded. To proxy the effects of antihypertensive drugs, genetic variants associated with SBP adjacent to the coding regions of different antihypertensive drugs were selected. The inverse-variance-weighted (IVW) method was employed as the primary method for causal estimation. In addition, three additional MR methods and sensitivity tests were utilized to assess the reliability. RESULTS: Elevated blood pressure significantly increases the risk of IA: (i) SBP-IA (non-ruptured): odds ratio (OR) = 1.046, 95 % confidence interval (CI): 1.032-1.061, P = 1.05E-10; (ii) SBP-IA (SAH): OR = 1.040, 95 % CI: 1.030-1.050, P = 2.56E-15; (iii) DBP-IA (non-ruptured): OR = 1.082, 95 % CI: 1.056-1.110, P = 3.15E-10; (iv) DBP-IA (SAH): OR = 1.066, 95 % CI: 1.047-1.085, P = 1.25E-12. In addition, among calcium channel blockers (CCBs), beta-blockers (BBs), and thiazide diuretics (TDs), only SBP mediated by TDs target genes significantly increased the risk of IA (non-rupture) (OR = 1.164, 95 % CI: 1.060-1.279, P = 0.001) and IA (SAH) (OR = 1.136, 95 % CI: 1.063-1.214, P = 1.58E-04), while SBP mediated by target genes of BBs or CCBs did not causally associate with IA. CONCLUSION: Elevated blood pressure significantly increases IA risk, while TDs may be a promising antihypertensive medication for reducing IA risk. Further research with larger cohorts is essential for validation.

Access to Polysulfides through Photocatalyzed Dithiosulfonylation.

In this study, we outline a general method for photocatalyzed difunctionalization of alkenes, a diene, alkynes, 1,3-enynes, and [1.1.1]propellane using dithiosulfonate reagents (ArSO2 -SSR) with improved atom economy. Both "ArSO2 -" and "-SSR" on the dithiosulfonate are transferred under mild conditions with broad substrate scope, high stereoselectivity, and complete regioselectivity. Significantly, the resulting dithiosulfonylated styrene is a general and practical nucleophilic disulfuration reagent, reacting with a variety of electrophiles efficiently. Both reactions can be conducted on gram scale, rendering the approach highly valuable.

Global research trends on COVID-19 and stroke: A bibliometric analysis.

Background: The pandemic of COVID-19 has had a profound influence on worldwide healthcare systems. Our study aimed to conduct a bibliometric analysis to explore the impact of COVID-19 on stroke and to highlight the major research trends in this field. Methods: We searched the original articles and review articles regarding COVID-19 and stroke from the Web of Science collection (WOSCC) database between January 1, 2020 and December 30, 2022. Subsequently, we performed bibliometric analyses and visualization using VOSviewer, Citespace, and Scimago Graphica. Results: A total of 608 original articles or review articles were included. JOURNAL OF STROKE and CEREBROVASCULAR DISEASES published the most studies on this subject (n = 76), while STROKE was the source of the most-cited references (n = 2,393). The United States is the most influential country in this field, with the highest number of publications (n = 223) and citations (n = 5,042). Shadi Yaghi from New York University is the most prolific author in the field, while Harvard Medical School is the most prolific institution. In addition, through keyword analysis and reference co-citation analysis, three major research topics were identified: (i) the impact of COVID-19 on stroke outcomes (including risk factors, clinical characteristics, mortality, stress, depression, comorbidities, etc.); (ii) the management and care of stroke patients during the COVID-19 pandemic (including thrombolysis, thrombectomy, telemedicine, anticoagulation, vaccination, etc.); and (iii) the potential relationship and pathological mechanism between COVID-19 and stroke (including renin-angiotensin system activation, SARS-CoV-2 virus-induced inflammation leading to endothelial impairment, coagulopathy, etc.). Conclusion: Our bibliometric analysis provides a comprehensive overview of the current state of research on COVID-19 and stroke and highlights key areas of focus in the field. Optimizing the treatment of COVID-19-infected stroke patients and elucidating the underlying pathogenic mechanisms of COVID-19 and stroke co-morbidity are key areas of future research that will be beneficial in improving the prognosis of stroke patients during the ongoing COVID-19 epidemic.

[Systemic Lupus Erythematosus Combined with Chorea: Report of One Case and Literature Review].

Systemic lupus erythematosus combined with chorea is relatively rare in China,and there are no unified diagnostic criteria or specific ancillary tests.Therefore,it is confirmed by exclusionary clinical diagnosis.To improve the understanding of this disease among rheumatologists,we report the clinical data of a patient with systemic lupus erythematosus combined with chorea admitted to the Department of Rheumatology and Immunology in the First Affiliated Hospital of Jinan University in January 2022.Furthermore,we review the relevant literature in the past 10 years and summarize the clinical features of these cases.

The causal role of gastroesophageal reflux disease in anxiety disorders and depression: A bidirectional Mendelian randomization study.

Background: Observational studies have shown an association between gastroesophageal reflux disease (GERD) and anxiety disorders/depression. However, these evidences may be influenced by confounding factors. Therefore, our study aimed to determine the causal relationship between GERD and anxiety disorders/depression by conducting a bidirectional Mendelian randomization (MR) study. Methods: We performed a bidirectional MR analysis using summary statistics from genome-wide association studies (GWAS) in European individuals. The inverse-variance weighted (IVW) method was used as the primary analytical method to assess causality. In addition, five additional MR methods [maximum likelihood, MR-Egger, weighted median, robust adjusted profile score (MR-RAPS), and mode-based estimate (MR-MBE)] were performed to supplement the IVW results. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability. Finally, a multivariable MR (MVMR) analysis was performed to determine the causal relationship by adjusting for potential confounders. Results: MR results of the IVW method indicated that GERD significantly increases the risk of anxiety disorders [odds ratio (OR) = 1.35, 95% confidence interval (CI) 1.15-1.59, P = 2.25 × 10-4] and depression (OR = 1.32, 95% CI: 1.15-1.52, P = 1.26 × 10-4). In addition, the MR results of maximum likelihood, MR-Egger, weighted median, MR-RAPS, and MR-MBE remained parallel to the IVW results. Furthermore, sensitivity analysis suggested that the results were robust, with no pleiotropy or heterogeneity detected. Nevertheless, reverse MR analysis showed that anxiety or depression did not increase GERD risk. Finally, MVMR analysis showed that the effect of GERD on increasing the risk of anxiety disorders/depression was independent of confounders. Conclusion: This MR study supports a causal association between GERD and an increased risk of anxiety disorders and depression. Therefore, complementing symptomatic treatment of GERD with psychological assessment and necessary psychological support therapy may help reduce the risk of future anxiety disorders and depression.

S-adenosyl-L-methionine supplementation alleviates damaged intestinal epithelium and inflammatory infiltration caused by Mat2a deficiency.

Methionine is important for intestinal development and homeostasis in various organisms. However, the underlying mechanisms are poorly understood. Here, we demonstrate that the methionine adenosyltransferase gene Mat2a is essential for intestinal development and that the metabolite S-adenosyl-L-methionine (SAM) plays an important role in intestinal homeostasis. Intestinal epithelial cell (IEC)-specific knockout of Mat2a exhibits impaired intestinal development and neonatal lethality. Mat2a deletion in the adult intestine reduces cell proliferation and triggers IEC apoptosis, leading to severe intestinal epithelial atrophy and intestinal inflammation. Mechanistically, we reveal that SAM maintains the integrity of differentiated epithelium and protects IECs from apoptosis by suppressing the expression of caspases 3 and 8 and their activation. SAM supplementation improves the defective intestinal epithelium and reduces inflammatory infiltration sequentially. In conclusion, our study demonstrates that methionine metabolism and its intermediate metabolite SAM play essential roles in intestinal development and homeostasis in mice.

Identification and validation of metabolism-related hub genes in idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal and irreversible interstitial lung disease. The specific mechanisms involved in the pathogenesis of IPF are not fully understood, while metabolic dysregulation has recently been demonstrated to contribute to IPF. This study aims to identify key metabolism-related genes involved in the progression of IPF, providing new insights into the pathogenesis of IPF. Methods: We downloaded four datasets (GSE32537, GSE110147, GSE150910, and GSE92592) from the Gene Expression Omnibus (GEO) database and identified differentially expressed metabolism-related genes (DEMRGs) in lung tissues of IPF by comprehensive analysis. Then, we performed GO, KEGG, and Reactome enrichment analyses of the DEMRGs. Subsequently, key DEMRGs were identified by machine-learning algorithms. Next, miRNAs regulating these key DEMRGs were predicted by integrating the GSE32538 (IPF miRNA dataset) and the miRWalk database. The Cytoscape software was used to visualize miRNA-mRNA regulatory networks. In addition, the relative levels of immune cells were assessed by the CIBERSORT algorithm, and the correlation of key DEMRGs with immune cells was calculated. Finally, the mRNA expression of the key DEMRGs was validated in two external independent datasets and an in vivo experiment. Results: A total of 101 DEMRGs (51 upregulated and 50 downregulated) were identified. Six key DEMRGs (ENPP3, ENTPD1, GPX3, PDE7B, PNMT, and POLR3H) were further identified using two machine-learning algorithms (LASSO and SVM-RFE). In the lung tissue of IPF patients, the expression levels of ENPP3, ENTPD1, and PDE7B were upregulated, and the expression levels of GPX3, PNMT, and POLR3H were downregulated. In addition, the miRNA-mRNA regulatory network of key DEMRGs was constructed. Then, the expression levels of key DEMRGs were validated in two independent external datasets (GSE53845 and GSE213001). Finally, we verified the key DEMRGs in the lung tissue of bleomycin-induced pulmonary fibrosis mice by qRT-PCR. Conclusion: Our study identified key metabolism-related genes that are differentially expressed in the lung tissue of IPF patients. Our study emphasizes the critical role of metabolic dysregulation in IPF, offers potential therapeutic targets, and provides new insights for future studies.