Mendelian randomization to evaluate the effect of folic acid supplement on the risk of Alzheimer disease.

We conducted a study to evaluate the impact of folic acid supplementation on the risk of Alzheimer disease (AD). A Mendelian randomization (MR) analysis model assessed the causal effects of folic acid supplementation on AD, utilizing data from recent genome-wide association studies. Effect estimates were scrutinized using various methods: inverse-variance weighted (IVW), simple mode, weighted mode, simple median, weighted median, penalized weighted median, and the MR-Egger method. The sensitivity analysis assessed heterogeneity and pleiotropy of individual single nucleotide polymorphisms (SNPs) using the IVW method with Cochran Q statistics and MR Egger intercept, respectively. Additionally, a leave-one-out sensitivity analysis determined potential SNP-driven associations. Both fixed-effect and random-effect IVW models in the MR analysis revealed a reduced risk of AD associated with folic acid supplementation (odds ratio, 0.930; 95% CI, 0.903-0.958, P < .001; odds ratio, 0.930; 95% CI, 0.910-0.950, P < .001) based on 7 SNPs as instrumental variables. The reverse MR analysis indicated no causal association between AD and folic acid supplementation. This study, utilizing genetic data, suggests that folic acid supplementation may potentially reduce the risk of AD and provides novel insights into its etiology and preventive measures.

Reproductive outcomes of single frozen-thawed embryo transfer in patients with endometriosis after preimplantation genetic testing.

PURPOSE: The reproductive outcomes of patients with endometriosis who are infertile have attracted recent attention. We aimed to explore whether endometriosis affects endometrial receptivity by observing pregnancy outcomes following a euploid blastocyst frozen embryo transfer. METHODS: This retrospective cohort study analyzed the data of patients with endometriosis from the reproductive hospital affiliated to Shandong University between January 2015 and December 2021. Control groups were matched using the 1:3 propensity score. The live birth, clinical pregnancy, biochemical pregnancy, clinical abortion, premature birth, and aneuploid rates were compared between the control group and endometriosis group. RESULTS: A total of 625 patients who underwent preimplantation genetic testing (PGT) prior to embryo implantation were included in the analysis. There were no significant differences in the live birth, clinical pregnancy, biochemical pregnancy, clinical abortion, and premature birth rates between the two groups. The aneuploidy rate of blastocysts obtained from the endometriosis group was higher than that of the control group (P = 0.012). CONCLUSION: Pregnancy outcomes using frozen embryos after PGT in patients with endometriosis did not differ from those in other women experiencing infertility. However, endometriosis may affect the quality of oocytes, resulting in a higher rate of aneuploidy.

Central pontine myelinolysis: a rare finding in hyperosmolar hyperglycemia.

Central pontine myelinolysis (CPM) is a heterogeneous nervous system disease of pontine demyelination, usually caused by rapid correction of hyponatremia. In the present study, we report a unique case of a 46-year-old man with a hyperglycemic state complicated with CPM. MRI demonstrated a high signal on T2 and symmetric restricted diffusion in the pontine. In conclusion, the clinical case described confirmed that the hyperosmolar state inherent in hyperglycemia was a likely cause of CPM.

Bibliometric review on sleep and Alzheimer disease between 1986 and 2023.

OBJECTIVE: Alzheimer disease (AD) is a major disease that affects the elderly worldwide. Therefore, this study aimed to examine the relationship between AD and sleep disorders, identify journal publications and collaborators, and analyze keywords and research trends using a bibliometric method. METHODS: Data retrieval is based on the Web of Science Core Collection database. CiteSpace V.6.1.R6 was used to analyze bibliometric analysis, calculate centrality, and draw co-occurrence maps of countries/regions, institutions, authors, published journals, cited literature, keyword co-occurrence maps, cluster maps, time graphs, and emergent maps from January 1986 to April 2023. RESULTS: There were 4677 publications relevant to AD and sleep disorders. From 1986 to 2023, the number of publications per year showed an increasing trend. The United States not only has the largest output of publications, the first in the centrality ranking, but also owns the 3 highest frequencies of publication institutions. The journal NEUROLOGY has the highest citation frequency, reaching 2671, with a median centrality value of 0.64. A comprehensive analysis of centrality showed that AD, circadian rhythm, dementia, Parkinson disease, sleep, and older adults are both high-frequency words and high centrality words, becoming core keywords in this field. CONCLUSIONS: This was the first study to provide an overview, about the current main status of development, hot spots of the study, and the future trends in sleep disorders and AD, which provides a comprehensive review of the trends and gaps in field of sleep and AD, and thus lays the groundwork for future research.

Investigating the association of breast cancer and stroke: A two-sample Mendelian randomization study.

We conducted a two-sample Mendelian randomization (MR) design to evaluate the causal relation between breast cancer and stroke. Genetic variants associated with breast cancer and stroke were both obtained from genome-wide association study summary data. The single nucleotide polymorphisms were selected as instrumental variables. Effect estimates were primarily evaluated using standard inverse variance weighted. Finally, sensitivity analyses were performed for the detection of potential pleiotropy and heterogeneity in the cause-effect evaluation. There was a causal association of ER-positive breast cancer (odds ratio = 0.11, 95% confidence interval: 0.08-0.16, P < .001), and ER-negative breast cancer (odds ratio = 1.04, 95% confidence interval: 1.00-1.07, P = .045) with stroke. MR-egger regression revealed that the cause-effect of ER-positive breast cancer (P < .001) is drove by the directional horizontal pleiotropy, while there was no directional pleiotropy in the cause-effect of ER-negative breast cancer (P = .82). Cochran Q-derived P-value from inverse variance weighted (P = .27) shown that the cause-effect of ER-negative breast cancer on stroke do not need to consider the effect of heterogeneity. In addition, the leave-one-out analysis showed no influential instruments driving the associations, suggesting robust results for all outcomes. The present MR study reveals that ER negative breast cancer increase the risk of stroke.

Bibliometric review on biomarkers for Alzheimer's disease between 2000 and 2023.

BACKGROUND: Alzheimer's disease (AD) is a common cause of dementia and frailty. Therefore, it is important to develop biomarkers that can diagnose these changes to improve the likelihood of monitoring and treating potential causes. Therefore, this study aimed to examine the relationship between biomarkers and AD, identify journal publications and collaborators, and analyze keywords and research trends using a bibliometric method. METHODS: We systematically searched for papers published in the Web of Science Core Collection database on biomarkers and AD. The search strategy was as follows: (TS) = (Alzheimer's OR Alzheimer's OR Alzheimer OR "Alzheimer's disease" OR "Alzheimer disease") AND TS = (biomarker OR biomarkers). Only articles and reviews were included as document types, with English as the primary language. The CiteSpace software was used to analyze the retrieved data on countries/regions, institutions, authors, published journals, and keywords. Simultaneously, the co-occurrence of the keywords was constructed. RESULTS: There were 2625 articles on biomarkers and AD research published by 51 institutions located in 41 countries in 75 journals; the number of articles has shown an increasing trend over the past 20 years. Keywords analysis showed that Alzheimer's disease, cerebrospinal fluid, mild cognitive impairment, amyloid beta, and tau were also highly influential. CONCLUSION: This was the first study to provide an overview of the current status of development, hot spots of study, and future trends in biomarkers for AD. These findings will provide useful information for researchers to explore trends and gaps in the field of biomarkers and AD.

A bibliometric review on vitamins and Alzheimer's disease between 1996 and 2023.

Objective: Alzheimer's disease (AD) is a major disease that affects the elderly worldwide. Several studies have revealed that vitamins may influence the risk of developing AD. However, information in this field remains ambiguous. Therefore, this study aimed to examine the relationship between AD and vitamins, identify journal publications and collaborators, and analyze keywords and research trends using a bibliometric method. Methods: We systematically searched the Web of Science (WOS) Core Collection for papers published on AD and vitamins. Retrieved data regarding institutions, journals, countries, authors, journal distribution, keywords, and so on. SPSS 25 software was used for the statistical analysis, and CiteSpace V.6.1.R6 was used to visualize the information through collaborative networks. Results: A total of 2,838 publications were ultimately included in accordance with the specified inclusion criteria. The number of publications gradually increased from 1996 to 2023, with papers published in 87 countries/regions and 329 institutions. China (centrality: 0.02) and the University of Kentucky (centrality: 0.09) were the major research countries and institutions, respectively. NEUROLOGY was cited most frequently, reaching 1,573, and had the greatest impact. The cited keywords show that "Alzheimer's disease," "oxidative stress," "vitamin E," and "dementia" have been research hotspots in recent years. Beta-carotene emerged in 2023 and was identified as a developmental trend in this field. Conclusion: This is the first bibliometric analysis of vitamins associated with AD. We identified 2,838 articles in the field of vitamins and AD, analyzed the information of major countries/regions, institutions, and core journals in this field, and summarized the research hotspots and frontiers. These findings provide useful information for researchers to explore the role of vitamins in AD further.

Efficacy of remote ischemic conditioning does not differ between men and women: A secondary analysis of the RICAMIS study.

BACKGROUND AND PURPOSE: The present study aimed to determine sex difference in clinical outcomes after Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke (RICAMIS). METHODS: In this secondary analysis of the RICAMIS study, eligible patients aged 18 years or older with acute moderate ischemic stroke who received remote ischemic conditioning (RIC) within 48 h of stroke onset were divided into two groups: men and women. The primary endpoint was an excellent functional outcome, defined as a modified Rankin Scale score of 0-1 at 90 days. Binary logistic regression analyses and generalized linear models were used. RESULTS: Of 1707 eligible patients, 34% (579) were women. Women had a higher burden of hypertension and diabetes, and less alcohol and smoking consumption than men. The mean systolic blood pressure and blood glucose level at randomization were higher in women than in men. Compared with the control group, RIC was associated with an increased rate of primary endpoint in men (unadjusted odds ratio [OR] = 1.277; 95% confidence interval [CI] 0.933-1.644; p = 0.057) and women (unadjusted OR = 1.454; 95% CI 1.040-2.032; p = 0.028). Furthermore, a higher absolute risk difference in primary endpoint between control and RIC groups was found in women (9.2%) than in men (5.7%), but there was no significant interaction effect between sex and intervention on primary outcome (p interaction = 0.545). CONCLUSION: Compared with men, women may have a higher probability of excellent functional outcomes at 90 days in the RIC group than in the control group; however, no interaction effect between sex and intervention was found.

Prevalent characteristics of human papillomavirus infection in 29,508 women in Jinshan District, Shanghai.

OBJECTIVE: This study aimed to investigate the prevalence characteristics of human papillomavirus (HPV) infections in 29,508 female cases in Jinshan District, Shanghai. MATERIALS AND METHODS: The current research represents a retrospective study that included 29,508 women who received cervical screening in the Jinshan Branch of Shanghai Sixth People's Hospital from 2010 to 2020. The overall prevalence, distribution types, age-specific prevalence and annual trends were analysed. RESULTS: The overall HPV infection rate among the patients was 21.97%. They were primarily high-risk HPV (HR-HPV) infections (20.30%) and single HPV infections (15.91%). A general decline in HPV and HR-HPV prevalence was observed with time from 33.52% to 25.45% in 2011 to 21.47% and 20.18% in 2020. The most common HPV genotypes were HPV52, HPV16, HPV58, HPV51, HPV53 and HPV68. The infection rates of HPV genotypes, including HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV42, HPV43, HPV66 and HPV68, showed overall declines across different years. The age-specific prevalence of total HPV and HR-HPV infections formed an approximate U-shaped curve with two peaks, one in the ≥55 age group (29.75%, 28.43%) and the other in the <25 age group (22.93%, 20.85%). Both total HPV and HR-HPV infection rates decreased to their lowest in the 25-34-year age groups. CONCLUSIONS: The prevalence of HPV infections showed a downward tendency with time. Single HPV genotype infections and HR-HPV infections were predominantly detected. The after prevalent characteristics of HPV can help to guide HPV vaccinations and cervical cancer screenings: 1) non-HPV16/HPV18 H R-HPV genotypes were prevalent; 2) non-vaccine-covered HPV53, HPV51 and HPV68 were also prevalent; 3) women above the age of 55 years had the highest HPV and HR-HPV infection rates.

The effect of endometriosis on IVF/ICSI and perinatal outcome: A systematic review and meta-analysis.

PURPOSE: The purpose of the study was whether endometriosis influences IVF/ICSI and subsequent pregnancy and obstetric outcomes. METHODS: Searches were performed on PubMed, EMBASE, Medline, and Web of Science. Most of the included studies were retrospective case control study and retrospective cohort study. The risk ratio with 95% confidence intervals were calculated using the random and fixed effects model. Random effects models were applied in the case of significant heterogeneity (I2>50%), and fixed effects models were used if the heterogeneity was not significant. The main outcome measure was the live birth rate. RESULTS: Seventy studies were included in our analysis. Compared with the control group, the implantation rate (p = 0.04) and the number of oocyte retrieved (p<0.00001) were significantly lower in women with endometriosis. About late pregnancy complications, there were significant statistical differences in multiple pregnancies rate, placenta previa rate, ectopic pregnancy rate, and postpartum hemorrhage rate between the two groups (p<0.05). All other major reproductive and obstetric outcomes were similar in women with and without endometriosis. CONCLUSIONS: Our results demonstrate women with or without endometriosis have similar reproductive outcomes, but women with endometriosis who conceived after assisted reproductive technology are in high risk pregnancy.

The newly non-uniform endometrial echogenicity on transvaginal ultrasound do not impact in vitro fertilization and embryo transfer success: A retrospective cohort study.

OBJECTIVE: To evaluate the effect of newly non-uniform endometrial echogenicity diagnosed by transvaginal ultrasound on the outcome of pregnancy in vitro fertilization-embryo transfer (IVF-ET) during controlled ovarian hyperstimulation (COH) by retrospective cohort analysis. METHODS: A retrospective cohort study of a total of 604 patients with newly non-uniform endometrial echogenicity from January 2013 to June 2017, each woman was matched with three control subjects of similar age (±1 year), type of infertility (primary or secondary), the protocol used for COH, and the number of ET cycles in our unit. The patients in the study group and control group were matched according to the strict 1:3 matching principle. Baseline characteristics and pregnancy outcomes were compared. RESULTS: There were no statistically significant difference in baseline characteristics, live birth rate, biochemical pregnancy rate, clinical pregnancy rate, clinical pregnancy miscarriage rate and ectopic pregnancy rate between the two groups. But there were significant statistical differences in past history of uterine cavity surgery between the two groups (35.26% VS 21.19%), especially in history of endometrial polyp surgery (94.84% VS 90.10%). CONCLUSIONS: Our results demonstrate the newly diagnosed non-uniform endometrial echogenicity during controlled ovarian hyperstimulation does not affect the pregnancy outcome of in vitro fertilization-embryo transfer, and fresh embryo transfer can be continued.

Association of Headache Disorders and the Risk of Dementia: Meta-Analysis of Cohort Studies.

OBJECTIVES: The purpose of this meta-analysis is to assess whether there is an association between headache disorders and all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). METHODS: PubMed, Cochrane Library, Embase, and Web of Science were searched for cohort studies published from database inception to October 8, 2021, using medical subject headings (MeSH) and keywords. All statistical analyses were performed using Stata statistical software version 14.0. If P > 0.1 and I 2 ≤ 50%, a fixed-effects model was adopted. If I 2 > 50% (which indicated great heterogeneity), a random-effects model was adopted. The funnel plot and Egger's test were used to evaluate publication bias. RESULTS: This meta-analysis included 12 cohort studies covering 465,358 individuals, which were published between 2001 and 2020. The pooling analysis shows that a history of any headache disorder is associated with an increased risk of all-cause dementia (OR = 1.35; 95% CI: 1.21-1.50; I 2 = 81.6%, P < 0.001). The history of any headache was associated with an increased risk of AD (OR = 1.49; 95% CI: 1.08-2.05; I 2 = 70.0%, P = 0.003) and VaD (OR = 1.72; 95% CI: 1.32-2.25; I 2 = 0%, P < 0.001). In the subgroup analysis, females with a history of headache have a slightly higher risk of dementia than males (OR = 1.32; 95% CI: 1.16-1.51; I 2 = 88.3%, P < 0.001) and the risk of dementia in the retrospective cohort was slightly higher than in the prospective cohort (OR = 1.38; 95% CI: 1.22-1.56; I 2 = 83.4%, P < 0.001). CONCLUSIONS: Our meta-analysis shows that any headache disorder increases the risk of all-cause dementia, AD, or VaD. These findings provide evidence that headache should be recognized as an independent risk factor for dementia, AD, or VaD.

Serum Uric Acid and the Risk of Dementia: A Systematic Review and Meta-Analysis.

Background: This meta-analysis aimed to evaluate the relationship between serum uric acid (UA) and the risk of dementia and its subtypes. Methods: Embase, PubMed, and Web of Science were searched from inception to July 2020. Random-effect models were employed to analyze the standard mean difference (SMD) with the corresponding 95% confidence intervals (CI). Results: Twenty-three eligible studies involving 5,575 participants were identified. The overall results showed lower levels of UA in dementia relative to non-dementia controls [SMD = -0.32 (-0.64; -0.01) p = 0.04]. The subgroup analysis of the type of dementia demonstrated a significant association of UA with Alzheimer's disease (AD) [SMD = -0.58 (-1.02; -0.15) p = 0.009] and Parkinson's disease with dementia (PDD) [SMD = -0.33 (-0.52; -0.14) p = 0.001] but not with vascular dementia (VaD). The stratification analysis of the concentrations of UA revealed that the UA quartile 1-2 was negatively correlated with dementia and neurodegenerative subtypes (p < 0.05), whereas a positive correlation of UA quartile 4 with dementia was noted (p = 0.028). Additionally, the meta-regression analysis on confounders showed that not age, body mass index, diabetes mellitus, hypertension, or smoking but education (p = 0.003) exerted an influence of the UA in the risk estimate of dementia. Conclusions: Low concentrations of UA (< 292 µmol/L or 4.91 mg/dL) is a potential risk factor for AD and PDD but not for VaD. The mechanism of different concentrations of the UA in dementia needs to be confirmed through further investigation.

Berberine reduces temozolomide resistance by inducing autophagy via the ERK1/2 signaling pathway in glioblastoma.

BACKGROUND: The ability to treat glioblastoma (GBM) using the chemotherapeutic agent temozolomide (TMZ) has been hampered by the development of therapeutic resistance. In this study, we assessed the ability of the isoquinoline alkaloid berberine to alter GBM TMZ resistance using two different TMZ-resistant cell lines to mimic a physiologically relevant GBM experimental system. METHODS: By treating these resistant cell lines with berberine followed by TMZ, we were able to assess the chemosensitivity of these cells and their parental strains, based on their performance in the MTT and colony formation assays, as well as on the degree of detectable apoptosis that was detected in the strains. Furthermore, we used Western blotting to assess autophagic responses in these cell lines, and we extended this work into a xenograft mouse model to assess the in vivo efficacy of berberine. RESULTS: Through these experiments, our findings indicated that berberine enhanced autophagy and apoptosis in TMZ-resistant cells upon TMZ treatment in a manner that was linked with ERK1/2 signaling. Similarly, when used in vivo, berberine increased GBM sensitivity to TMZ through ERK1/2 signaling pathways. CONCLUSIONS: These findings demonstrate that berberine is an effective method of increasing the sensitization of GBM cells to TMZ treatment in a manner that is dependent upon the ERK1/2-mediated induction of autophagy, thus making berberine a potentially viable therapeutic agent for GBM treatment.

Fibrinogen and risk of dementia: A systematic review and meta-analysis.

BACKGROUND: The aim of this meta-analysis is to evaluate the association of fibrinogen with risk of dementia and its subtypes. METHODS: Embase, Pubmed and Web of Science were retrieved systematically up to February 2019. Standard mean difference (SMD) with 95 % confidence intervals was estimated using random-effects models. RESULTS: Sixteen studies involving 3,649 participants were summarized. Patients with all-cause dementia exhibited higher fibrinogen levels than those in non-dementia controls (SMD = 0.90 [0.43;1.36] p < 0.01). Further subgroup analysis revealed a positive association of fibrinogen with vascular dementia (VaD) (SMD = 1.11 [0.45;1.78] p < 0.01) rather than Alzheimer's disease (AD) (SMD = 0.01 [-0.17;0.19]) p = 0.92) and Parkinson's disease dementia (PDD) (SMD = 0.35 [-0.23;0.93] p = 0.24). This correlation was significant in Europeans (SMD = 0.92 [0.34;1.49] p < 0.01), but probably not in Asian based populations (SMD = 1.04 [-0.09;2.17] p = 0.07), and gradually declined with advancing age (60 ≤ age < 70: SMD = 1.22 [0.38;2.06] p < 0.01; 70 ≤ age < 80: SMD = 0.29 [0.04;0.53] p = 0.02; age ≥ 80: SMD = 0.01 [-0.12;0.15] p = 0.84). CONCLUSIONS: Plasma fibrinogen is a potential risk factor for all-cause dementia and VaD under the age of 80, and is more obvious in cohorts with people of European descent.

Cabozantinib induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3ß/NF-κB signaling pathway.

Cabozantinib is a multi-kinase inhibitor targeting MET, AXL, and VEGFR2, and has been approved for use in multiple malignancies. The means by which Cabozantinib acts to target colorectal cancer (CRC) cells remains poorly understood, and we sought to investigate how this drug disrupts cell growth in CRC cells and how it interacts to enhance the efficacy of other chemotherapeutic agents. In this study, we found that Cabozantinib activated a p65-dependent signaling pathway in response to both inhibition of AKT and activation of glycogen synthase kinase 3ß (GSK3ß), leading to upregulation of PUMA in CRC cells regardless of p53 activity. PUMA upregulation facilitates CRC apoptosis in response to Cabozantinib, which also acts synergistically with the chemotherapeutic agents Cetuximab and 5-FU to induce robust apoptosis in a PUMA-dependent manner. Eliminating PUMA expression ablated this apoptosis induced by Cabozantinib in xenograft mouse model. Our findings revealed that Cabozantinib acts to drive CRC cells apoptosis via a PUMA-dependent mechanism, thus identifying PUMA expression as a potential predictor of Cabozantinib efficacy and a potential novel therapeutic target.

Bumetanide: A review of its neuroplasticity and behavioral effects after stroke.

Stroke often leads to neuronal injury and neurological functional deficits. Whilst spontaneous neurogenesis and axon regeneration are induced by ischemic stroke, effective pharmacological treatments are also essential for the improvement of neuroplasticity and functional recovery after stroke. However, no pharmacological therapy has been demonstrated to be able to effectively improve the functional recovery after stroke. Bumetanide is a specific Na+-K+-Cl- co-transporter inhibitor which can maintain chloride homeostasis in neurons. Therefore, many studies have focused on this drug's effect in stroke recovery in recent years. Here, we first review the function of Na+-K+-Cl- co-transporter in neurons, then how bumetanide's role in reducing brain damage, promoting neuroplasticity, leading to functional recovery after stroke, is elucidated. Finally, we discuss current limitations of bumetanide's efficiency and their potential solutions. These results may provide new avenues for further exploring mechanisms of post-stroke functional recovery as well as promising therapeutic targets for functional disability rehabilitation after ischemic stroke.