Autoimmune glial fibrillary acidic protein astrocytopathy with anti-NMDAR and sulfatide-IgG-positive encephalitis overlap syndrome: A case report and literature review.

RATIONALE: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a rare autoimmune disease of the central nervous system that affects the meninges, brain, spinal cord, and optic nerves. GFAP astrocytopathy can coexist with a variety of antibodies, which is known as overlap syndrome. Anti-NMDAR-positive encephalitis overlap syndrome has been reported; however, encephalitis overlap syndrome with both anti-NMDAR and sulfatide-IgG positivity has not been reported. PATIENT CONCERNS: The patient was a 50-year-old male who was drowsy and had chills and weak limbs for 6 months. His symptoms worsened after admission to our hospital with persistent high fever, dysphoria, gibberish, and disturbance of consciousness. Positive cerebrospinal fluid NMDA, GFAP antibodies, and serum sulfatide antibody IgG were positive. DIAGNOSES: Autoimmune GFAP astrocytopathy with anti-NMDAR and sulfatide-IgG-positive encephalitis overlap syndrome. INTERVENTIONS: In addition to ventilator support and symptomatic supportive treatment, step-down therapy with methylprednisolone (1000 mg/d, halved every 3 days) and pulse therapy with human immunoglobulin (0.4 g/(kg d) for 5 days) were used. OUTCOMES: After 6 days of treatment, the patient condition did not improve, and the family signed up to give up the treatment and left the hospital. CONCLUSIONS: Patients with autoimmune GFAP astrocytopathy may be positive for anti-NMDAR and sulfatide-IgG, and immunotherapy may be effective in patients with severe conditions. LESSONS: Autoimmune GFAP astrocytopathy with nonspecific symptoms is rarely reported and is easy to be missed and misdiagnosed. GFAP astrocytopathy should be considered in patients with fever, headache, disturbance of consciousness, convulsions, and central infections that do not respond to antibacterial and viral agents. Autoimmune encephalopathy-related antibody testing should be performed as soon as possible, early diagnosis should be confirmed, and immunomodulatory therapy should be administered promptly.

The cooperative migration dynamics of particles correlates to the nature of hexatic-isotropic phase transition in 2D systems of corner-rounded hexagons.

In the two-dimensional (2D) melting transition of colloidal systems, the hexatic-isotropic (H-I) transition can be either first-order or continuous. However, how particle dynamics differs at the single-particle level during these two different melting transitions remains to be disclosed. In this work, by Brownian dynamics (BD) simulations, we have systematically studied the dynamic behavior of corner-rounded hexagons during the H-I transition, for a range of corner-roundness ζ = 0.40 to 0.99 that covers the crossover from the continuous to first-order nature of H-I transition. The results show that hexagons with ζ ≤ 0.5 display a continuous H-I transition, whereas those with ζ ≥ 0.6 demonstrate a first-order H-I transition. Dynamic analysis shows different evolution pathways of the dominant cluster formed by migrating particles, which results in a droplet-like cluster structure for ζ = 0.40 hexagons and a tree-like cluster structure for ζ = 0.99 hexagons. Further investigations on the hopping activities of particles suggest a cooperative origin of migrating clusters. Our work provides a new aspect to understand the dependence of the nature of H-I transition on the roundness of hexagons through particle dynamic behavior.

[Spatial distribution patterns and intraspecific and interspecific spatial associations of Quercus myrsinifolia population in Shennongjia, China]. / ç¥žå†œæž¶å°å¶é’å†ˆç§ç¾¤çš„ç©ºé—´åˆ†å¸ƒæ ¼å±€åŠç§å† ç§é—´ç©ºé—´å ³è”.

Quercus myrsinifolia is one of the dominant species in the evergreen broad-leaf forest on the southern slope of Shennongjia. The study of spatial distribution pattern and spatial correlation of Q. myrsinifolia population will help to understand population development and potential ecological processes, as well as the structure and biodiversity maintenance mechanism of evergreen broad-leaf forests at the northern edge of the subtropics. Based on forest dynamic monitoring data from one 1 hm2 permanent plot on the southern slope of Shennongjia, we employed pair correlation functions g(r) and marked correlation functions to analyze the diameter structure of the Q. myrsinifolia population, spatial distribution patterns at different diameter classes, and intraspecific and interspecific spatial associations. The results showed that diameter structure of Q. myrsinifolia population exhibited an inverted 'J'-shaped distribution, suggesting a healthy regeneration status and belonging to a growing population type. The spatial distribution showed a decreasing trend in aggregation with increasing diameter. Positive correlations among individuals strengthened with closer diameter classes, while weakening with larger diameter differences. Interspecific spatial associations showed an increasing correlation of Q. myrsinifolia with understory dominant species with increasing spatial scales, but no correlation was observed with canopy-dominant species. Our results suggested that the spatial pattern of Q. myrsinifolia populations on the southern slope of Shennongjia was mainly influenced by habitat filtering, seed dispersal limitation, and intraspecific and interspecific competition. Furthermore, the adaptive strategies of Q. myrsinifolia varied when they coexisted with different species.

Longitudinal associations of air pollution and green space with cardiometabolic risk factor clustering among children in the Netherlands.

BACKGROUND: This study examines longitudinal associations of air pollution and green space with cardiometabolic risk among children in the Netherlands. METHODS: Three Dutch prospective cohorts with a total of 13,822 participants aged 5 to 17 years were included: (1) the Amsterdam Born Children and their Development (ABCD) study from Amsterdam (n = 2,547), (2) the Generation R study from Rotterdam (n = 5,431), and (3) the Lifelines study from northern Netherlands (n = 5,844). Air pollution (PM2.5, PM10, NO2, and elemental carbon (EC)) and green space exposures (density in multiple Euclidean buffer sizes) from 2006 to 2017 at home address level were used. Cardiometabolic risk factor clustering was assessed by a MetScore, which was derived from a confirmatory factor analysis of six cardiometabolic risk factors to assess the overall risk. Linear regression models with change in Metscore as the dependent variable, adjusted for multiple confounders, were conducted for each cohort separately. Meta-analyses were used to pool cohort-specific estimates. RESULTS: Exposure to higher levels of NO2 and EC was significantly associated with increases in MetScore in Lifelines (per SD higher exposure: ßNO2 = 0.006, 95 % CI = 0.001 to 0.010; ßEC = 0.008, 95 % CI = 0.002 to 0.014). In the other two cohort studies, these associations were in the same direction but these were not significant. Higher green space density in 500-meter buffer zones around participants' residential addresses was not significantly associated with decreases of MetScore in all three cohorts. Higher green space density in 2000-meter buffer zones was significantly associated with decreases of MetScore in ABCD and Lifelines (per SD higher green space density: ßABCD = -0.008, 95 % CI = -0.013 to -0.003; ßLifelines = -0.002, 95 % CI = -0.003 to -0.00003). The pooled estimates were ßNO2 = 0.003 (95 % CI = -0.001 to 0.006) for NO2, ßEC = 0.003 (95 % CI = -0.001, 0.007) for EC, and ß500m buffer = -0.0014 (95 % CI = -0.0026 to -0.0001) for green space. CONCLUSIONS: More green space exposure at residence was associated with decreased cardiometabolic risk in children. Exposure to more NO2 and EC was also associated with increased cardiometabolic risk.

Systematic evaluation with practical guidelines for single-cell and spatially resolved transcriptomics data simulation under multiple scenarios.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (SRT) have led to groundbreaking advancements in life sciences. To develop bioinformatics tools for scRNA-seq and SRT data and perform unbiased benchmarks, data simulation has been widely adopted by providing explicit ground truth and generating customized datasets. However, the performance of simulation methods under multiple scenarios has not been comprehensively assessed, making it challenging to choose suitable methods without practical guidelines. RESULTS: We systematically evaluated 49 simulation methods developed for scRNA-seq and/or SRT data in terms of accuracy, functionality, scalability, and usability using 152 reference datasets derived from 24 platforms. SRTsim, scDesign3, ZINB-WaVE, and scDesign2 have the best accuracy performance across various platforms. Unexpectedly, some methods tailored to scRNA-seq data have potential compatibility for simulating SRT data. Lun, SPARSim, and scDesign3-tree outperform other methods under corresponding simulation scenarios. Phenopath, Lun, Simple, and MFA yield high scalability scores but they cannot generate realistic simulated data. Users should consider the trade-offs between method accuracy and scalability (or functionality) when making decisions. Additionally, execution errors are mainly caused by failed parameter estimations and appearance of missing or infinite values in calculations. We provide practical guidelines for method selection, a standard pipeline Simpipe ( https://github.com/duohongrui/simpipe ; https://doi.org/10.5281/zenodo.11178409 ), and an online tool Simsite ( https://www.ciblab.net/software/simshiny/ ) for data simulation. CONCLUSIONS: No method performs best on all criteria, thus a good-yet-not-the-best method is recommended if it solves problems effectively and reasonably. Our comprehensive work provides crucial insights for developers on modeling gene expression data and fosters the simulation process for users.

Integrating bulk RNA-seq and scRNA-seq analyses revealed the function and clinical value of thrombospondins in colon cancer.

Background: Acting as mediators in cell-matrix and cell-cell communication, matricellular proteins play a crucial role in cancer progression. Thrombospondins (TSPs), a type of matricellular glycoproteins, are key regulators in cancer biology with multifaceted roles. Although TSPs have been implicated in anti-tumor immunity and epithelial-mesenchymal transition (EMT) in several malignancies, their specific roles to colon cancer remain elusive. Addressing this knowledge gap is essential, as understanding the function of TSPs in colon cancer could identify new therapeutic targets and prognostic markers. Methods: Analyzing 1981 samples from 10 high-throughput datasets, including six bulk RNA-seq, three scRNA-seq, and one spatial transcriptome dataset, our study investigated the prognostic relevance, risk stratification value, immune heterogeneity, and cellular origin of TSPs, as well as their influence on cancer-associated fibroblasts (CAFs). Utilizing survival analysis, unsupervised clustering, and functional enrichment, along with multiple correlation analyses of the tumor-microenvironment (TME) via Gene Set Variation Analysis (GSVA), spatial localization, Monocle2, and CellPhoneDB, we provided insights into the clinical and cellular implications of TSPs. Results: First, we observed significant upregulation of THBS2 and COMP in colon cancer, both of which displayed significant prognostic value. Additionally, we detected a significant positive correlation between TSPs and immune cells, as well as marker genes of EMT. Second, based on TSPs expression, patients were divided into two clusters with distinct prognoses: the high TSPs expression group (TSPs-H) was characterized by pronounced immune and stromal cell infiltration, and notably elevated T-cell exhaustion scores. Subsequently, we found that THBS2 and COMP may be associated with the differentiation of CAFs into pan-iCAFs and pan-dCAFs, which are known for their heightened matrix remodeling activities. Moreover, THBS2 enhanced CAFs communication with vascular endothelial cells and monocyte-macrophages. CAFs expressing THBS2 (THBS2+ CAFs) demonstrated higher scores across multiple signaling pathways, including angiogenic, EMT, Hedgehog, Notch, Wnt, and TGF-ß, when compared to THBS2- CAFs. These observations suggest that THBS2 may be associated with stronger pro-carcinogenic activity in CAFs. Conclusions: This study revealed the crucial role of TSPs and the significant correlation between THBS2 and CAFs interactions in colon cancer progression, providing valuable insights for targeting TSPs to mitigate cancer progression.

A case of scrub typhus with meningitis as the onset: Case report and literature review.

RATIONALE: Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon. PATIENT CONCERNS: A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation. DIAGNOSES: The patient was diagnosed with a central nervous system infection. INTERVENTIONS: Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders. OUTCOMES: Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided. CONCLUSIONS: The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective. LESSION: Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly.

Analyzing factors causing deadlock events of bi-directional pedestrian flow when moving on stairs using a personal space model.

Comprehending crowd dynamics on staircases is imperative for preventing accidents, particularly in emergency scenarios. In this context, our study delves into bi-directional pedestrian flow. When confronted with limited staircase space, the occurrence of two distinct lanes-one for upstairs and another for downstairs-is a common observation. However, there has been no quantitative investigation conducted to understand this phenomenon. To facilitate such an analysis, we employ a velocity-based personal space model that accurately reproduces the formation of upstairs and downstairs lanes in bi-directional staircases. The study of lane formation mechanisms and the exploration of factors influencing deadlock are essentially two sides of the same coin. This is due to the fact that, the occurrence of deadlock signifies a disruption in the anticipated lane behavior during counter flow. As a result, we have devised various scenarios to meticulously analyze the factors contributing to both deadlock formation and its subsequent performance. This involves manipulating parameters such as speed, speed dispersion, pedestrian count, initial density, right-hand preference weight, minimum personal space size, same-direction following intensity, and time step. The findings hold the potential to enhance the overall quality of service in stairway movement and offer significant contributions to the understanding and management of pedestrian behavior in such settings.

PDLIM3 knockdown promotes ferroptosis in endometriosis progression via inducing Gli1 degradation and blocking Hedgehog signaling pathway.

AIMS: Current evidence suggests that there is no completely effective method for endometriosis (EMS) without trauma due to diverse adverse effects. Reliable evidence illustrates that inhibiting ferroptosis is a potential strategy for EMS. We sufficiently verified that the expression of endogenous protein PDZ and LIM domain 3 (PDLIM3) was significantly increased in EMS. METHODS: PDLIM3 knockdown reduced primary ectopic endometrial stromal cells' (EESCs) viability and migration, and elevated ferroptosis signaling indicators including Fe2+, malondialdehyde (MDA), and reactive oxygen species (ROS) in EESCs. RESULTS: Mechanistic studies revealed that inhibition of PDLIM3 accelerated glioma-associated oncogene-1 (Gli1) degradation and further deactivated Hedgehog signaling. Gli1 inhibitor, GANT61, abrogated the impact of PDLIM3 deletion on EESC growth, migration, and ferroptosis. In vivo experiments suggested that PDLIM3 reduction repressed the growth of endometrial lesions. Likewise, repression of PDLIM3 promoted ferroptosis and attenuated Hedgehog signaling in endometrial lesions. CONCLUSIONS: Collectively, silencing of PDLIM3 facilitates ferroptosis in EMS by inducing Gli1 degradation and blocking Hedgehog signaling. It may provide an alternative strategy for developing therapeutic agents of EMS in the future.

Impact of green space exposure on blood pressure in Guangzhou, China: Mediation by air pollution, mental health, physical activity, and weight status.

Green space exposure has been inversely associated with blood pressure (BP) levels and hypertension risk. However, empirical evidence on the underlying mechanisms are lacking. This study examined the association of green space exposure with BP and hypertension, and assessed the mediating effects by air pollution, mental health, physical activity, and weight status. Survey data from 719 adults, who lived in Guangzhou (China) in 2016, were used. Three area-level green space indicators, including network distance to the nearest park, percentage of green space and Normalized Difference Vegetation Index within a 1 km Euclidean buffer around residence and workplace, were calculated and linked to individual-level BP measurements. Structural equation models were applied to estimate the direct and indirect associations of the various green space indicators on systolic BP (SBP), diastolic BP (DBP), and hypertension, respectively. After adjusting for multiple covariates, longer network distance to green space was directly associated with higher SBP. Compared to the reference group (0-500m), the differences were 0.11 mmHg (95% CI = 0.03 to 0.19, P = 0.006) for 500-1000m, 0.03 mmHg (95% CI = -0.05 to 0.12, P = 0.45) for 1000-1500m, and 0.16 mmHg (95% CI = 0.09 to 0.23, P < 0.001) for >1500m, respectively. The overall and direct associations were significant for all three indicators (distance or density) with or without considering workplace exposure. The association between network distance to green and SBP was partially (18.4%, 95% CI = 0-42.1%) mediated by mental health. There was no statistical evidence that air pollution, physical activity, or weight status mediate the association. Secondary analyses for other indicators and other outcomes showed similar results. Both distance to green space and more green space around residence and workplace were associated with lower BP and lower risk of hypertension in adults living in a Chinese metropolitan. Mental health partly mediated the association.

PPanG: a precision pangenome browser enabling nucleotide-level analysis of genomic variations in individual genomes and their graph-based pangenome.

Graph-based pangenome is gaining more popularity than linear pangenome because it stores more comprehensive information of variations. However, traditional linear genome browser has its own advantages, especially the tremendous resources accumulated historically. With the fast-growing number of individual genomes and their annotations available, the demand for a genome browser to visualize genome annotation for many individuals together with a graph-based pangenome is getting higher and higher. Here we report a new pangenome browser PPanG, a precise pangenome browser enabling nucleotide-level comparison of individual genome annotations together with a graph-based pangenome. Nine rice genomes with annotations were provided by default as potential references, and any individual genome can be selected as the reference. Our pangenome browser provides unprecedented insights on genome variations at different levels from base to gene, and reveals how the structures of a gene could differ for individuals. PPanG can be applied to any species with multiple individual genomes available and it is available at https://cgm.sjtu.edu.cn/PPanG .

Case report of recurrent epistaxis caused by a live leech in the nasal cavity.

RATIONALE: Epistaxis is one of the common emergencies in otolaryngology. There are many causes of epistaxis, but reports of epistaxis due to nasal foreign bodies like leeches are rare. PATIENT CONCERNS: A 55-year-old male presented with "repeated epistaxis for over 20 days." Nasal endoscopy revealed a live leech in the olfactory area of the left nostril. DIAGNOSES: The patient was diagnosed with epistaxis caused by a live leech in the nasal cavity. INTERVENTIONS: Under nasal endoscopy, the leech was grasped with a vascular clamp and removed from the nasal cavity. The leech measured 8 cm in length. Hemostasis was achieved using a gelatin sponge at the wound site, and the nasal cavity was packed with Vaseline gauze. OUTCOMES: The live leech was removed via nasal endoscopy. Two days later, the Vaseline gauze packing was removed, and the patient experienced no further nasal bleeding. CONCLUSION: Live leeches in the nasal cavity can cause epistaxis. Nasal endoscopic removal of the live leech is an effective treatment. LESSON: There are many causes of epistaxis, which are nonspecific and prone to missed or incorrect diagnosis. In patients with a history of fieldwork or direct contact with leeches who present with recurrent nasal bleeding, the possibility of epistaxis caused by a live leech should be considered, and timely and effective treatment should be provided.

Influence of the Original Concrete Strength and Initial Moisture Condition on the Properties Improvement of Recycled Coarse Aggregate via Accelerated Carbonation Reactions.

The physical and mechanical properties of recycled coarse aggregate (RCA) are worse than those of natural coarse aggregate (NCA), and the overall performance of recycled concrete prepared from RCA is worse than that of natural aggregate concrete. Treatment of RCA by CO2-accelerated carbonation effectively improves the macroscopic properties of RCA. The degree of influence of raw material factors, i.e., the original concrete strength (OCS) and initial moisture content (IMC) of RCA, on the carbonation of RCAs is very complex. Herein, an accelerated carbonation experiment for RCA with different material factors as variables was carried out to explore the influence of the abovementioned factors on the physical properties of carbonated recycled coarse aggregate (CRCA). By analyzing the microstructure of the RCA with the best modification effect before and after carbonation, the carbonation modification mechanism of the RCA was revealed. The physical performance indexes, including the apparent density, water absorption and carbonation rate, of the dried RCA with an OCS of C40 and C50 were significantly improved. The research results can provide basic data and theoretical support for promoting the popularization and application of RCA and recycled concrete in practical engineering.

Rhabdomyolysis caused by Botrychium ternatum intoxication: Case report and literature review.

RATIONALE: Botrychium ternatum ((Thunb.) Sw.), a traditional Chinese medicine, is known for its therapeutic properties in clearing heat, detoxifying, cough suppression, and phlegm elimination. It has been extensively used in clinics for the treatment of many inflammation-related diseases. Currently, there are no documented cases of rhabdomyolysis resulting from Botrychium ternatum intoxication. PATIENT CONCERNS: A 57-year-old male presented with a complaint of low back discomfort accompanied by tea-colored urine lasting for 4 days. The patient also exhibited markedly increased creatine phosphate kinase and myoglobin levels. Prior to the onset of symptoms, the patient consumed 50 g of Botrychium ternatum to alleviate pharyngodynia. DIAGNOSES: The patient was diagnosed with rhabdomyolysis due to Botrychium ternatum intoxication. INTERVENTIONS: The patient underwent a substantial volume of fluid resuscitation, diuresis, and alkalization of urine, as well as correction of the acid-base balance and electrolyte disruption. OUTCOMES: Following a 10-day treatment plan involving massive fluid resuscitation, diuresis, and alkalization of urine, the patient showed notable improvement in his lower back pain and reported the absence of any discomfort. Following reexamination, the levels of creatine phosphate kinase and myoglobin were restored to within the normal ranges. Additionally, no abnormalities were detected in liver or renal function. As a result, the patient was considered eligible for discharge and was monitored. CONCLUSIONS: Botrychium ternatum intoxication was associated with the development of rhabdomyolysis. To manage this condition, it is recommended that patients provide massive fluid resuscitation, diuresis, alkalization of urine, and other appropriate therapeutic interventions. LESSON: Currently, there are no known cases of rhabdomyolysis resulting from Botrychium ternatum intoxication. However, it is important to consider the potential occurrence of rhabdomyolysis resulting from Botrychium ternatum intoxication when there is a correlation between the administration of Botrychium ternatum and the presence of muscular discomfort in the waist or throughout the body, along with tea-colored urine. Considering the levels of creatine phosphate kinase and myoglobin, the diagnosis or exclusion of rhabdomyolysis caused by Botrychium ternatum intoxication should be made, and suitable treatment should be administered accordingly.

Robotic-assisted anatomic anterior cruciate ligament reconstruction: a comparative analysis of modified transtibial and anteromedial portal techniques in cadaveric knees.

Introduction: This study employed surgical robot to perform anatomic single-bundle reconstruction using the modified transtibial (TT) technique and anteromedial (AM) portal technique. The purpose was to directly compare tunnel and graft characteristics of the two techniques. Methods: Eight cadaveric knees without ligament injury were used in the study. The modified TT and AM portal technique were both conducted under surgical robotic system. Postoperative data acquisition of the tunnel and graft characteristics included tibial tunnel position, tunnel angle, tunnel length and femoral tunnel-graft angle. Results: The mean tibial tunnel length of the modified TT technique was significantly shorter than in the AM portal technique (p < 0.001). The mean length of the femoral tunnel was significantly longer for the modified TT technique than for the AM portal technique (p < 0.001). The mean coronal angle of the tibial tunnel was significantly lower for the modified TT technique than for the AM portal technique (p < 0.001). The mean coronal angle of the femoral tunnel was significantly lower for the AM portal technique than for the modified TT technique (p < 0.001). The AM portal technique resulted in a graft bending angle that was significantly more angulated in the coronal (p < 0.001) and the sagittal planes (p < 0.001) compared with the modified TT technique. Discussion: Comparison of the preoperative planning and postoperative femoral tunnel positions showed that the mean difference of the tunnel position was 1.8 ± 0.4 mm. It suggested that the surgical navigation robot could make predictable tunnel position with high accuracy. The findings may support that the modified TT technique has benefits on femoral tunnel length and obliquity compared with AM portal technique. The modified TT technique showed a larger femoral tunnel angle in the coronal plane than the AM portal technique. Compared with the modified TT technique, the more horizontal trajectory of the femoral tunnel in the AM portal technique creates a shorter femoral tunnel length and a more acute graft bending angle.

Maternal history of Alzheimer's disease predisposes to altered serum cholesterol levels in adult offspring.

Controversial findings regarding the association between serum cholesterol levels and Alzheimer's disease (AD) have been identified through observational studies. The genetic basis shared by both factors and the causality between them remain largely unknown. The objective of this study is to examine the causal impact of maternal history of AD on changes in serum cholesterol levels in adult offspring. By retrieving genetic variants from summary statistics of large-scale genome-wide association study of maternal history of AD (European-based: Ncase = 27 696, Ncontrol = 260 980). The causal association between genetically predicted maternal history of AD and changes in serum cholesterol levels in adult offspring was examined using the two-sample Mendelian randomization (MR) method. Causal impact estimates were calculated using single-nucleotide polymorphisms in both univariable MR (UMR) and multivariable MR (MVMR) analyses. Additionally, other approaches, such as Cochran's Q test and leave-one-out variant analysis, were employed to correct for potential biases. The results of UMR presented that genetically predicted maternal history of AD was positively associated with hypercholesterolemia (OR = 1.014; 95% CI: 1.009-1.018; p < 0.001), total cholesterol (OR = 1.29; 95% CI: 1.134-1.466; p < 0.001) and low-density lipoprotein (OR = 1.525; 95% CI: 1.272-1.828; p < 0.001) among adult offspring. Genetic predisposition for maternal history of AD to be negatively associated with high-density lipoprotein (OR = 0.889; 95% CI: 0.861-0.917; p < 0.001). The MVMR analysis remained robust and significant after adjusting for diabetes and obesity in offspring. Sufficient evidence was provided in this study to support the putative causal impact of maternal history of AD on the change of serum cholesterol profile in adult offspring. In clinical practice, priority should be given to the detection and monitoring of cholesterol levels in individuals with a maternal history of AD, particularly in the early stages.

Rodenticide poisoning leading to cerebral hemorrhage: A case report.

RATIONALE: Anticoagulant rodenticides (ARs) are a substantial fraction of murine types. AR poisoning causes bleeding from the skin, mucous membranes, and multiple organs. However, reports of AR-induced cerebral hemorrhage are scarce. PATIENT CONCERNS: A 40-year-old male presented with dizziness, headache, and limb weakness for 5 days and with coagulopathy. Two days prior to the onset of these symptoms, the patient was exposed to dead mice. DIAGNOSES: Rodenticide intoxication-induced cerebral hemorrhage. INTERVENTIONS: Vitamin K1 infusion, administration of dehydrating agents to reduce intracranial pressure, and correction of acid-base and electrolyte imbalances. OUTCOMES: After 9 days of treatment, the patient's symptoms were relieved, and reexamination revealed that coagulation parameters returned to normal levels. The patient was eventually discharged for observation with oral vitamin K1. CONCLUSIONS: Rodenticide poisoning can lead to intracerebral hemorrhage, and treatment with vitamin K1 infusion is effective. LESSON: Rodenticide poisoning-induced cerebral hemorrhage is rarely reported. Because its symptoms are nonspecific, it is easy to miss the diagnosis or misdiagnose. When patients present with direct and indirect symptoms such as dizziness, headache, and limb weakness, rodenticide poisoning should be considered. Coagulation function and head computed tomography or magnetic resonance imaging examination should be performed at the earliest to confirm the diagnosis and provide timely treatment.

Analysis and identification of oxidative stress-ferroptosis related biomarkers in ischemic stroke.

Studies have shown that a series of molecular events caused by oxidative stress is associated with ferroptosis and oxidation after ischemic stroke (IS). Differential analysis was performed to identify differentially expressed mRNA (DEmRNAs) between IS and control groups. Critical module genes were identified using weighted gene co-expression network analysis (WGCNA). DEmRNAs, critical module genes, oxidative stress-related genes (ORGs), and ferroptosis-related genes (FRGs) were crossed to screen for intersection mRNAs. Candidate mRNAs were screened based on the protein-protein interaction (PPI) network and the MCODE plug-in. Biomarkers were identified based on two types of machine learning algorithms, and the intersection was obtained. Functional items and related pathways of the biomarkers were identified using gene set enrichment analysis (GSEA). Finally, single-sample GSEA (ssGSEA) and Wilcoxon tests were used to identify differential immune cells. An miRNA-mRNA-TF network was created. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the expression levels of biomarkers in the IS and control groups. There were 8287 DE mRNAs between the IS and control groups. The genes in the turquoise module were selected as critical module genes for IS. Thirty intersecting mRNAs were screened for overlaps. Seventeen candidate mRNAs were also identified. Four biomarkers (CDKN1A, GPX4, PRDX1, and PRDX6) were identified using two types of machine-learning algorithms. GSEA results indicated that the biomarkers were associated with steroid biosynthesis. Nine types of immune cells (activated B cells and neutrophils) were markedly different between the IS and control groups. We identified 3747 miRNA-mRNA-TF regulatory pairs in the miRNA-mRNA-TF regulatory network, including hsa-miR-4469-CDKN1A-BACH2 and hsa-miR-188-3p-GPX4-ATF2. CDKN1A, PRDX1, and PRDX6 were upregulated in IS samples compared with control samples. This study suggests that four biomarkers (CDKN1A, GPX4, PRDX1, and PRDX6) are significantly associated with IS. This study provides a new reference for the diagnosis and treatment of IS.

A literature review and meta-analysis of the optimal factors study of repetitive transcranial magnetic stimulation in post-infarction aphasia.

BACKGROUND: The existing literature indicates that repetitive transcranial magnetic stimulation (rTMS) can potentially enhance the prognosis of poststroke aphasia (PSA). Nevertheless, these investigations did not identify the most effective parameters or settings for achieving optimal treatment outcomes. This study involved a meta-analysis aimed to identify the optimal variables for rTMS in treating post-infarction aphasia to guide the use of rTMS in rehabilitating PSA. METHODS: PubMed, Embase, and Cochrane Library databases were searched from inception to May 2023, and articles were reviewed manually using subject words and free words and supplemented with references from the included literature to obtain additional relevant literature. The search terms included "poststroke aphasia" and "repetitive transcranial magnetic stimulation (rTMS)" repetitive transcranial magnetic stimulation. Additionally, a review of the reference lists of previously published systematic reviews identified through the Cochrane Database of Systematic Reviews (search terms: poststroke aphasia, rTMS; restrictions: none) and PubMed (search terms: poststroke aphasia, rTMSs; restrictions: systematic review or meta-analysis) was performed. Information from studies involving different doses of rTMS in PSA was independently screened and extracted by 2 researchers. RESULTS: This meta-analysis included 387 participants with PSA across 18 randomized controlled trials. The results showed that the total pulse had a trend toward a significant correlation with the treatment effect (P = 0.088), while all other variables did not correlate significantly. When rTMS was not grouped by stimulus parameter and location, our nonlinear results showed that when the total pulses were 40,000 (standardized mean difference (SMD):1.86, 95% credible interval (CrI) 0.50 to 3.33), the pulse/session was 1000 (SMD:1.05, 95% CrI 0.55-1.57), and an RMT of 80% (SMD:1.08, 95% CrI 0.60-1.57) had the best treatment effect. When rTMS was grouped by stimulus parameters and location, our nonlinear results showed that when the total low-frequency (LF)-rTMS-right inferior frontal gyrus (RIFG) pulse was 40,000 (SMD:1.76, 95% CrI:0.36-3.29), the pulse/session was 1000 (SMD:1.06, 95% CrI:0.54-1.59). Optimal results were obtained with an RMT of 80% (SMD:1.14, 95% CrI 0.54 - 1.76). CONCLUSIONS: The optimal treatment effects of rTMS for PSA may be obtained with a total pulse of 40,000, a pulse/session of 1000, and an RMT of 80%. Further rigorous randomized controlled studies are required to substantiate the validity of these results.

A unusual presentation of liver failure caused by Ibuprofen-sustained release capsules: A case report.

RATIONALE: Previous studies have shown that acetaminophen has the potential to induce hepatotoxicity in patients, rendering it a prominent drug implicated in the development of acute hepatic failure. However, there is currently no available literature reporting the impact of ibuprofen-sustained release capsules on liver failure. PATIENT CONCERNS: A 65-year-old man was presented with a 4-day history of tea-colored urine with oil avoidance, jaundiced skin, and anorexia, and impaired liver function. One ibuprofen-sustained release capsule was taken on the day before the onset of the disease due to "headache." DIAGNOSES: A diagnosis of this patient was made of liver failure due to taking ibuprofen-sustained release capsules. INTERVENTIONS: Initially, the patient discontinued the use of hepatotoxic drugs in order to prevent further exposure. Subsequently, the patient underwent a standard therapeutic regimen, which encompassed the administration of hepatoprotective agents, nutritional support drugs, correction of acid-base imbalances, and electrolyte abnormalities, as well as other relevant treatments. OUTCOMES: After 9 days of hepatoprotective and nutritional supplement therapy, the patient saw notable improvement in symptoms, reporting an absence of discomfort, subsided skin jaundice, clear urine, and liver function tests returning to a near normal range. The patient was granted permission to be discharged from the hospital while being prescribed drugs. After 2 weeks of follow-up, the patient reported an absence of discomfort and exhibited normal results in the liver function test. CONCLUSIONS: Liver failure caused by ibuprofen-sustained release capsules has not been reported. It is worth noting that conventional treatments such as suspending offending agents, and administration of hepatoprotective agents and nutritional support drugs have proven to be successful. LESSON: There is currently no known peer-reviewed literature indicating that the administration of ibuprofen-sustained release capsules leads to liver failure. When patients taking ibuprofen-sustained release capsules encounter symptoms such as anorexia, skin jaundice, lack of appetite, and nausea, it is recommended that they undertake a cardiac and liver function tests. In the event that ibuprofen-sustained release capsules induce liver injury, it is imperative to administer timely and immediate medical intervention.