International Journal of Medical Sciences最新文献

Background: A multitude of studies have presented inconsistent outcomes regarding the association between maternal folic acid (FA) and/or multivitamin (MV) supplementation and congenital heart disease (CHD) in offspring. This study aimed to estimate supplementation time and CHD based on a prospective China birth cohort study (CBCS). Methods: In the CBCS, 114,670 singleton pregnant women who had pregnancy outcomes until August 2021 and responded to the early pregnancy questionnaire were recruited. The participants were divided into three groups: no FA or MV supplementation, supplementation commencing before pregnancy, and supplementation commencing from early pregnancy. Unadjusted and adjusted logistic regression analyses were employed to calculate the odds ratio (OR) to estimate the relative risk (RR) value of CHD exposure to FA and/or MV. Additionally, the results of this study were combined with previous studies to calculate the pooled RR. Finally, stratification and sensitivity analyses, including the propensity score matching method, were conducted to identify the robustness of the association. Results: Compared with the non-supplemented group, the RRs of CHD in groups with FA and/or MV supplementation, with supplementation before pregnancy, and with supplementation from early pregnancy were 1.23 (95% confidence interval [CI]: 0.76-2.00), 1.30 (95% CI: 0.80-2.13) and 1.19 (95% CI: 0.73-1.93), all demonstrating no statistically significant difference. The pooled RR from the forest plot was 0.98 (95% CI: 0.95-1.01), which is consistent with the findings of this study. Furthermore, the results remained approximately the same in the stratification or sensitivity analyses in different datasets, including performing 1:1 or 1:2 propensity score matching. Conclusions: The present study suggests that FA or MV supplementation before or during early pregnancy may not influence the risk of offspring developing CHD.

Purpose: To evaluate the association between coronary heart disease (CHD) severity and the risk of developing keratopathy. Method: A retrospective cohort study was conducted with data from the Taiwan National Health Insurance Research Database (NHIRD). A total of 593100, 593100 and 296500 patients were included in the control, mild CHD and severe CHD groups, respectively. The primary outcomes were the development of superficial keratopathy and infectious keratitis with antibiotic usage. Cox proportional hazard regression was used to calculate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the primary outcomes among the groups. Results: A total of 30697, 32134, and 15977 superficial keratopathy episodes and 6021, 6010, and 2982 infectious keratitis episodes were recorded in the control, mild CHD, and severe CHD groups, respectively. The incidence of superficial keratopathy was significantly greater in the severe CHD group (P = 0.037), and both groups presented a greater risk of developing superficial keratopathy than did the control group (both P < 0.05). The cumulative incidence of superficial keratopathy was also significantly greater in the severe CHD group than in the mild CHD group (P < 0.001). In the subgroup analyses, the incidence of superficial keratopathy was significantly greater in severe CHD patients than in mild CHD patients older than 70 years, and the correlation between CHD severity and superficial keratopathy incidence was significantly greater in those older than 70 years of age (P = 0.002). Conclusions: Severe CHD is related to a greater risk of developing superficial keratopathy, especially in those older than 70 years of age.

Persistent methamphetamine use causes many toxic effects in various organs, including the brain, heart, liver, kidney and eyes. The extent of its toxicity depends on numerous pharmacological factors, including route of administration, dose, genetic polymorphism related to drug metabolism and polysubstance abuse. Several molecular pathways have been proposed to activate oxidative stress, inflammation and apoptosis: B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax)/Bcl2/caspase-3, nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1), protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/p70S6K, trace amine-associated receptor 1 (TAAR1)/cAMP/lysyl oxidase, Sigmar1/ cAMP response element-binding protein (CREB)/mitochondrial fission-1 protein (Fis1), NADPH-Oxidase-2 (NOX-2), renal autophagy pathway, vascular endothelial growth factor (VEGF)/phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS), Nupr1/Chop/P53/PUMA/Beclin1 and Toll-like receptor (TLR)4/MyD88/TRAF6 pathways. The activation promotes pathological changes, including the disruption of the blood-brain barrier, myocardial infarction, cardiomyopathy, acute liver failure, acute kidney injury, chronic kidney disease, keratitis, retinopathy and vision loss. This review revisits the pharmacological profiles of methamphetamine and its effects on the brain, heart, liver, eyes, kidneys and endothelium. Understanding the mechanisms of methamphetamine toxicity is essential in developing treatment strategies to reverse or attenuate the progress of methamphetamine-associated organ damage.

Background: Antiepileptics and antidepressants are frequently prescribed for chronic pain, but their efficacy and potential adverse effects raise concerns, including dependency issues. Increased prescriptions, sometimes fraudulent, prompted reclassification of antiepileptics in some countries. Our aim is to comprehend opinions, perceptions, beliefs, and attitudes towards co-analgesics from online discussions on X (formerly known as Twitter), offering insights closer to reality than conventional surveys. Methods: In this cross-sectional study, we collected 77,183 public posts about co-analgesics in English or Spanish from January 1^st 2019 to December 31st, 2020. A total of 51,167 post were included, and 2,000 were manually analyzed using a researcher-created codebook. Machine learning classifiers were then applied to the remaining datasets to determine the number of publications for each user type and identify categories through content analysis. Results: Of the 51,167 posts analyzed, 78% discussed anticonvulsants and 24% discussed analgesic antidepressants (Percentages add up to more than 100% because there were 1,300 posts containing references to both types of medications). Only 13% were authored by healthcare professionals, while 67% were from patients. Medical content predominated, with 70% noting low medication efficacy and almost 50% referencing side effects. Non-medical content included challenges in dispensing (25%), complaints about high costs (15%), and trivialization of medication use (10%). Conclusions: This study offers valuable insights into public perceptions of co-analgesics. Findings aid in designing public health communications to raise awareness of associated risks, urging both healthcare providers and the public to optimize drug use.

Background: The progression and metastasis of colorectal cancer (CRC) remain major clinical challenges due to a lack of effective therapeutic targets. Our preliminary study identified the upregulation of the propionyl-CoA carboxylase alpha chain (PCCA) gene in CRC, prompting further investigation into its functional roles. Methods: Bioinformatics analysis, colorectal tumor tissues, and CRC cell lines were used to determine PCCA expression. Wound healing, Transwell, and cell counting kit-8 (CCK-8) assays were conducted to evaluate the impacts of PCCA expression on CRC cell migration, invasion, and proliferation. Western blotting was used to assess epithelial-mesenchymal transition (EMT) markers and associated signaling pathways. Mouse models, flow cytometry, and quantitative polymerase chain reaction (PCR) were performed to investigate the influences of PCCA on CRC tumor growth, lung metastasis, and macrophage polarization. Results: PCCA is highly expressed in CRC tumor tissues compared to normal tissues and is associated with a poor prognosis. Knocking down PCCA reduced CRC cell migration, invasion, and proliferation, which were associated with the upregulation of E-cadherin, the downregulation of N-cadherin, Vimentin, and Fibronectin, as well as the inactivation of the extracellular signal-regulated kinase (ERK)/glycogen synthase kinase 3 beta (GSK3β) signaling pathway. Moreover, PCCA knockdown suppressed CRC tumor growth and lung metastasis, accompanied by an increase in M1-macrophage polarization. Conclusion: Knockdown PCCA inhibits the progression and metastasis of CRC, which is associated with EMT reversion, ERK/GSK3β signaling inactivation, and M1-macrophage polarization. These findings suggest that PCCA is a potential target for controlling CRC.

Aims: Investigate the role of the apelin/APLNR axis in metabolic dysfunction-associated steatotic liver disease (MASLD), focusing on the progression from metabolic dysfunction-associated simple steatotic liver (MASS) to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis, with emphasis on liver B cells. Methods: Serum samples from MASLD patients and liver tissues from hepatocellular carcinoma patients were collected to measure apelin and APLNR protein expression. C57BL/6J mouse models of varying MASLD stages were developed using a high-fat diet and CCl₄. RNA sequencing was used to study the apelin/APLNR axis's regulatory functions in the Raji B cell line. Results: Bioinformatic and clinical analyses show that apelin and APLNR are up-regulated in MASLD, correlating with disease severity. Animal models demonstrate that apelin and ML221 injections affect liver steatosis, inflammation, and fibrosis. Sequencing and RT-PCR in Raji cells indicate that the apelin/APLNR axis promotes the expression of inflammatory cytokines and extracellular matrix molecules. Conclusion: The apelin/APLNR axis is crucial in MASLD progression. Targeting this axis may offer therapeutic potential to modulate B cell function and mitigate MASLD advancement.

Introduction and Importance: Some experimental studies on brain injury associated with traumatic brain injury (TBI) and hypoxic-ischaemic encephalopathy (HIE) reveal a positive effect of hyperbaric oxygen therapy (HBOT). However, in clinical medicine, most of the scientific evidence available in the current literature relates only to TBI. Methods: The primary objective is to empirically assess the efficacy of HBOT in mitigating the symptoms of disability associated with brain injury in children, with a view to elucidating its therapeutic potential and clinical benefits. Outcomes: A total of 21 patients have been treated with HBOT. The mean age was 6±4.6 years. There were 12 cases (57%) of TBI, 8 cases (38%) of HIE and 1 case (5%) of ischaemic stroke. The mean initial Glasgow Coma Scale (GCS) at hospital admission immediately after accident was 3.3±0.9. The mean time from injury to HBOT was 5.2 ± 3.8 weeks. The mean number of HBOT exposures was 10±4.3. The mean GCS pre-HBOT was 10.7±3.7 and 12.3±3.4 (p=0.004) after post-HBOT, respectively. The mean Glasgow Outcome Scale (GOS) was 3.3±0.8 pre-HBOT, and 3.9±1.1 (p<0.001) after post-HBOT, respectively. Eighteen cases were included in response to HBOT assessment. Six cases (33%) were evaluated as large clinically significant response (CSR), 7 cases (39%) were evaluated as partial response with minimally important difference (MID). Five cases (28%) were evaluated as non-response. The results showed better response to HBOT in cases of starting HBOT up to 4 weeks (p=0.02) after the injury. There was no serious HBOT-related complication or injury. Conclusion: Results of our study demonstrate both clinical and statistically significant patient response to HBOT. Our data also suggest that the earlier HBOT started after diagnosis up to 4 weeks, the more pronounced patients' response to HBOT was achieved. The provision of HBOT to pediatric patients is feasible in large regional hyperbaric centers.

Elevated lipoprotein(a) [Lp(a)] levels are increasingly recognized as a significant risk factor for cardiovascular diseases and may also contribute to atrial fibrillation (AF). This review investigated the indirect mechanisms through which Lp(a) may influence AF, including proatherogenic, prothrombotic, and proinflammatory pathways. Traditional lipid-lowering therapies, such as lifestyle modifications and statins, have limited effects on Lp(a) levels. Emerging treatments, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lipoprotein apheresis, small interfering RNA, antisense oligonucleotides, cholesterol ester transfer protein inhibitors, and interleukin-6 receptor monoclonal antibodies, are promising alternatives. Notably, only PCSK9 inhibitors and lipoprotein apheresis have been shown to reduce both Lp(a) levels and cardiovascular events. Research indicates varying associations between Lp(a) and AF across different populations, underscoring the need for diverse, large-scale studies to elucidate these differences. Ongoing trials aim to provide clearer insights into these relationships. Addressing these gaps is essential for developing targeted therapies to manage elevated Lp(a) and mitigate the risk of AF and associated cardiovascular events.

Marburg virus (MARV) disease (MVD) is an uncommon yet serious viral hemorrhagic fever that impacts humans and non-human primates. In humans, infection by the MARV is marked by rapid onset, high transmissibility, and elevated mortality rates, presenting considerable obstacles to the development of vaccines and treatments. Bats, particularly Rousettus aegyptiacus, are suspected to be natural hosts of MARV. Previous research reported asymptomatic MARV infection in bats, in stark contrast to the severe responses observed in humans and other primates. Recent MARV outbreaks highlight significant public health concerns, underscoring the need for gene expression studies during MARV progression. To investigate this, we employed two models from the Gene Expression Omnibus, including kidney cells from Rousettus aegyptiacus and primary proximal tubular cells from Homo sapiens. These models were chosen to identify changes in gene expression profiles and to examine co-regulated genes and pathways involved in MARV disease progression. Our analysis of differentially expressed genes (DEGs) revealed that these genes are mainly associated with pathways related to the complement system, innate immune response via interferons (IFNs), Wnt/β-catenin signaling, and Hedgehog signaling, which played crucial roles in MARV infection across both models. Furthermore, we also identified several potential compounds that may be useful against MARV infection. These findings offer valuable insights into the mechanisms underlying MARV's pathophysiology and suggest potential strategies for preventing transmission, managing post-infection effects, and developing future vaccines.

Background: Myocardial injury is prone to occur during myocardial ischemia-reperfusion, which further causes adverse cardiac events. Cardiomyopeptide (CMP) has been found to protect the heart against ischemia-reperfusion injury. The present study will explore the molecular and signaling mechanisms associated with the therapeutic effects of CMP. Methods: In this study, the rat myocardial ischemia-reperfusion model was constructed, the pathological changes of myocardial tissues were observed via hematoxylin-eosin (H&E) and Masson staining, and the levels of myocardial injury markers (AST, Mb, TnT) were detected by ELISA. Myocardial tissues of rats in each group were analyzed using transcriptome sequencing (RNA-seq), and the obtained gene expression profiles were analyzed differentially to determine differentially expressed genes (DEGs). In addition, the signaling pathway related to CMP therapy was found by gene set enrichment analysis (GSEA), and PPARγ was detected by qRT-PCR, WB, and IHC staining. The mitochondrial function of myocardial tissues was detected by mitochondrial respiratory chain activity, JC-1, and reactive oxygen species (ROS). Results: Animal assays showed that CMP could significantly improve myocardial injury and reduce the levels of AST, MB and cTnT. RNA-seq analysis results showed that PPARγ signaling pathway is a potential signaling pathway for CMP treatment of myocardial injury in rats. The experimental results showed that CMP can significantly up-regulate PPARγ expression in myocardial tissues, inhibit ischemia reperfusion-induced myocardial injury, and alleviate mitochondrial respiratory disorders. Conclusion: CMP can improve myocardial injury in rats by alleviating mitochondrial respiratory dysfunction and reducing myocardial tissue damage and inflammatory infiltration via the regulation of PPARγ signaling pathway.