Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies.

Epilepsy is a severe, relapsing, and multifactorial neurological disorder. Studies regarding the accurate diagnosis, prognosis, and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy. The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression, protein expression, ion channel activity, energy metabolites, and gut microbiota composition. Satisfactory results are lacking for conventional treatments for epilepsy. Surgical resection of lesions, drug therapy, and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy. Non-pharmacological treatments, such as a ketogenic diet, gene therapy for nerve regeneration, and neural regulation, are currently areas of research focus. This review provides a comprehensive overview of the pathogenesis, diagnostic methods, and treatments of epilepsy. It also elaborates on the theoretical basis, treatment modes, and effects of invasive nerve stimulation in neurotherapy, including percutaneous vagus nerve stimulation, deep brain electrical stimulation, repetitive nerve electrical stimulation, in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation. Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures. Additionally, many new technologies for the diagnosis and treatment of epilepsy are being explored. However, current research is mainly focused on analyzing patients' clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level, which has led to a lack of consensus regarding the mechanisms related to the disease.

Circ_0004592: An auxiliary diagnostic biomarker for gastric cancer.

BACKGROUND: Gastric cancer (GC) has a high mortality rate, and robust diagnostic biomarkers are currently lacking. However, the clinical relevance of circular RNAs (circRNAs) as GC biomarkers remains largely unexplored. AIM: To evaluate the potential of novel circRNA circ_0004592 in the early screening and prognosis of GC. METHODS: High-throughput sequencing of circRNAs was performed to screen for potential target molecules. Circ_0004592 expression was examined in GC tissues, cells, and plasma. Plasma samples were collected from healthy subjects' patients, as well as from patients with benign lesions, precancerous lesions, and GC, whereafter the diagnostic accuracy of circ_0004592 was evaluated. The correlation between circ_0004592 levels in plasma and clinicopathological data of patients with GC was further analyzed. RESULTS: Circ_0004592 was upregulated in both the tissue and plasma of patients with GC. Further, circ_0004592 expression was higher in patients with precancerous lesions than in healthy controls while being highest in patients with GC. In the same patient, the postoperative plasma level of circ_0004592 was lower than that in the preoperative period. Moreover, circ_0004592 level was significantly correlated with tumor differentiation, tumor depth, and lymph node metastasis. The area under the curve (AUC) of plasma circ_0004592 exhibited high sensitivity and specificity for differentiating patients with GC from healthy donors. Diagnosis based on circ_0004592, carcinoembryonic antigen, and cancer antigen 199 achieved a superior AUC and was highly sensitive. CONCLUSION: Plasma circ_0004592 may represent a potential non-invasive auxiliary diagnostic biomarker for patients with GC.

Palladium-Catalyzed Carbonylative Sonogashira Coupling of Aryl Thianthrenium Salts with Arylalkynes.

Alkynones are valuable compounds with applications in various areas. In this work, we developed an efficient carbonylation procedure for the carbonylative cross-coupling of aryl thianthrenium salts with aromatic alkynes. Various useful alkynones were produced in moderate to excellent yields under mild conditions. Notably, among the various tolerated functional groups, the bromide group can be maintained, which is ready for further coupling reactions.

Stable inhibition of choroidal neovascularization by adeno-associated virus 2/8-vectored bispecific molecules.

Neovascular age-related macular degeneration (nAMD) causes severe visual impairment. Pigment epithelium-derived factor (PEDF), soluble CD59 (sCD59), and soluble fms-like tyrosine kinase-1 (sFLT-1) are potential therapeutic agents for nAMD, which target angiogenesis and the complement system. Using the AAV2/8 vector, two bi-target gene therapy agents, AAV2/8-PEDF-P2A-sCD59 and AAV2/8-sFLT-1-P2A-sCD59, were generated, and their therapeutic efficacy was investigated in laser-induced choroidal neovascularization (CNV) and Vldlr-/- mouse models. After a single injection, AAV2/8-mediated gene expression was maintained at high levels in the retina for two months. Both AAV2/8-PEDF-P2A-sCD59 and AAV2/8-sFLT-1-P2A-sCD59 significantly reduced CNV development for an extended period without side effects and provided efficacy similar to two injections of current anti-vascular endothelial growth factor monotherapy. Mechanistically, these agents suppressed the extracellular signal-regulated kinase and nuclear factor-κB pathways, resulting in anti-angiogenic activity. This study demonstrated the safety and long-lasting effects of AAV2/8-PEDF-P2A-sCD59 and AAV2/8-sFLT-1-P2A-sCD59 in CNV treatment, providing a promising therapeutic strategy for nAMD.

Cold sub-mucosal injection versus traditional cold snare polypectomy for diminutive and small colorectal polyps: A systematic review and meta-analysis.

BACKGROUND: The guidelines recommend conventional cold snare polypectomy (C-CSP) for diminutive and small colorectal polyps (≤ 10 mm). However, it remains unclear whether CSP with sub-mucosal injection (SI-CSP) achieves comparable efficacy to C-CSP for managing these lesions. This study compares SI-CSP with C-CSP for patients with diminutive and small colorectal polyps. METHODS: An electronic literature search was conducted to retrieve articles comparing resection outcomes between SI-CSP and C-CSP in diminutive and small colorectal polyps (registration number INPLASY2023100096). Our primary outcomes of interest were the complete resection rate (CRR), complications (namely immediate bleeding, delayed bleeding and perforation) and polypectomy time. Mean differences with 95% confidence intervals (CI) were employed for continuous variables, while odds ratios (OR) with 95% CI were calculated for categorical variables. Data was analyzed using a random effects model and the I2 test was utilized to assess heterogeneity. RESULTS: Eight studies involving 1470 patients with 2223 polyps were included in our analysis. The CRR was not significantly higher in the SI-CSP group, with an OR of 95% CI 0.50 (0.22, 1.15). The incidences of immediate bleeding (OR 95% CI 0.60 [0.26-1.40]) and delayed bleeding (OR 95% CI 0.88 [0.32-2.42]) did not differ significantly between the two groups. On average, the mean polypectomy time was 64.75 seconds shorter in the C-CSP group (95% CI, - 102.96 to - 26.53). Notably, no perforation events were reported in the included studies. CONCLUSIONS: The use of SI-CSP was not superior to C-CSP in managing diminutive and small colorectal polyps and the procedure required significantly more time.

Fuzheng Huayu recipe inhibits bleomycin-induced pulmonary fibrosis in rats by inhibiting M2 polarization of macrophages via the oxidative phosphorylation pathway.

Fuzheng Huayu recipe (FZHYR) is a Chinese patent medicine for the treatment of fibrosis. The effects of FZHYR on pulmonary fibrosis and macrophage polarization were investigated in vitro. FZHYR inhibited pulmonary inflammation and fibrosis and M2 polarization of macrophages in bleomycin-induced pulmonary fibrosis (BPF) of rat model. Differentially expressed genes were screened by high-throughput mRNA sequencing and GSEA showed that oxidative phosphorylation (OXPHOS) was correlated with BPF. FZHYR inhibited expressions of Ndufa2 and Ndufa6 in lung tissues of BPF rats. These findings suggest that OXPHOS pathway serves as a possible target for pulmonary fibrosis therapy by FZHYR.

Gestational valproic acid exposure enhances facial stimulation-evoked cerebellar mossy fiber-granule cell transmission via GluN2A subunit-containing NMDA receptor in offspring mice.

Valproic acid (VPA) is one of the most effective antiepileptic drugs, and exposing animals to VPA during gestation has been used as a model for autism spectrum disorder (ASD). Numerous studies have shown that impaired synaptic transmission in the cerebellar cortical circuits is one of the reasons for the social deficits and repetitive behavior seen in ASD. In this study, we investigated the effect of VPA exposure during pregnancy on tactile stimulation-evoked cerebellar mossy fiber-granule cell (MF-GC) synaptic transmission in mice anesthetized with urethane. Three-chamber testing showed that mice exposed to VPA mice exhibited a significant reduction in social interaction compared with the control group. In vivo electrophysiological recordings revealed that a pair of air-puff stimulation on ipsilateral whisker pad evoked MF-GC synaptic transmission, N1, and N2. The evoked MF-GC synaptic responses in VPA-exposed mice exhibited a significant increase in the area under the curve (AUC) of N1 and the amplitude and AUC of N2 compared with untreated mice. Cerebellar surface application of the selective N-methyl-D-aspartate (NMDA) receptor blocker D-APV significantly inhibited facial stimulation-evoked MF-GC synaptic transmission. In the presence of D-APV, there were no significant differences between the AUC of N1 and the amplitude and AUC of N2 in the VPA-exposed mice and those of the untreated mice. Notably, blockade of the GluN2A subunit-containing, but not the GluN2B subunit-containing, NMDA receptor, significantly inhibited MF-GC synaptic transmission and decreased the AUC of N1 and the amplitude and AUC of N2 in VPA-exposed mice to levels similar to those seen in untreated mice. In addition, the GluN2A subunit-containing NMDA receptor was expressed at higher levels in the GC layer of VPA-treated mice than in control mice. These results indicate that gestational VPA exposure in mice produces ASD-like behaviors, accompanied by increased cerebellar MF-GC synaptic transmission and an increase in GluN2A subunit-containing NMDA receptor expression in the offspring.

Fucoidan alleviates doxorubicin-induced cardiotoxicity by inhibiting ferroptosis via Nrf2/GPX4 pathway.

Doxorubicin (Dox), a chemotherapeutic agent frequently used to treat cancer, elicits cardiotoxicity, a condition referred to as Dox-induced cardiotoxicity (DIC), and ferroptosis plays a contributory role in its pathophysiology. Fucoidan, a polysaccharide with various biological activities and safety profile, has potential therapeutic and pharmaceutical applications. This study aimed to investigate the protective effects and underlying mechanisms of fucoidan in DIC. Echocardiography, biomarkers of cardiomyocyte injury, serum creatine kinase, creatine kinase isoenzyme and lactate dehydrogenase, as well as histological staining results, revealed that fucoidan significantly reduced myocardial damage and improved cardiac function in DIC mice. Transmission electron microscopy; levels of lipid reactive oxygen species, glutathione, and malondialdehyde; ferroptosis-related markers; and regulatory factors such as glutathione peroxidase 4 (GPX4), transferrin receptor protein-1, ferritin heavy chain-1, heme oxygenase-1 in the heart tissue were measured to explore the effect of fucoidan on Dox-induced ferroptosis. These results suggested that fucoidan could inhibit cardiomyocyte ferroptosis caused by Dox. In vitro experiments revealed that silencing nuclear factor-erythroid 2-related factor 2 (Nrf2) in cardiomyocytes reduced the inhibitory effect of fucoidan on ferroptosis. Hence, fucoidan has the potential to ameliorate DIC by inhibiting ferroptosis via the Nrf2/GPX4 pathway.

An Atlas on Multitudinous Risk Factors Associated with Incident Hypertension: Comprehensive Exposome-Wide Association and Wide-angled Genetic Analyses.

BACKGROUND: Despite numerous risk factors being associated with hypertension, the breadth of research remains constrained, with a notable absence of systematic, data-driven exploration into established and novel factors across a broad spectrum of exposures. This study aims to construct an atlas on known and emerging factors for hypertension through comprehensive epidemiological and genetic analyses. METHODS: We conducted exposome-wide association studies (ExWAS) via Cox regression models on two equally sized datasets for discovery and replication in UK Biobank, a large prospective cohort study. A maximum of 10,806 exposome variables were included in ExWAS and were grouped into 13 categories: genomics, sociodemographic, lifestyle, physical measure, biomarkers, medical history, imaging markers, sex-specific factors, psychosocial factors, cognitive function indicators, local environment, family history, and early life factors. The credibility of epidemiological associations was assessed through meta-analyses. The genetic underpinnings were explored through linkage-disequilibrium score regression (LDSC), quantifying global genetic correlation. Two-sample Mendelian randomization (MR) studies were conducted to investigate the causal effects of each exposure on hypertension, with co-analyses undertaken to identify associations supported by both epidemiological and genetic evidence. RESULTS: This study included 214,957 UK Biobank participants, hypertension-free at baseline. In our ExWAS analyses, 964 significant exposome variables were replicated. In meta-analyses, 462 were backed by convincing and highly suggestive evidence. Among 10,765 exposures in LDSC, 1923 had global genetic correlations with hypertension. The MR analyses yielded robust evidence for a causal relationship with 125 phenotypes, probable evidence for 270 phenotypes, and suggestive evidence for 718 phenotypes. Co-analyses identified 146 associations supported by strong epidemiological and genetic evidence. These primarily encompassed traits like anthropometry, lung function, lipids, and factors such as urate and walking pace. This coverage further extended from well-studied factors (like BMI and physical activity) to less explored exposures (including high light scatter reticulocyte count and age at first live). All study results are compiled in a webserver for user-friendly exploration of exposure-hypertension associations. CONCLUSION: This study provides an atlas on established and novel risk factors for hypertension, underpinned by epidemiological and causal evidence. Our findings present a multiple perspective to prioritize hypertension prevention strategies, encompassing modifiable risk factors like television watching time and walking pace. The study also emphasized the roles of urate in hypertension pathogenesis. Consequently, our study may serve as a critical guide for hypertension prevention and bear significant clinical implications.

Researchers have created a comprehensive map that identifies and analyses a wide array of risk factors linked to the development of high blood pressure, using extensive data from the UK Biobank. The study revealed 964 significant factors related to lifestyle, environment, and genetics that could influence the risk of developing hypertension, with 462 of these factors showing strong evidence of a link.Key lifestyle-related findings include the impact of behaviors such as television watching and walking pace on hypertension risk, suggesting that modifiable habits can be targeted for prevention strategies.

Sophora subprostrate polysaccharide targets LncRNA MSTRG.5823.1 to suppress PCV2-mediated immunosuppression via TNF/NF-κB signaling.

Current evidence suggests that porcine circovirus type 2 (PCV2) infection induces immunosuppression in piglets. Sophora subprostrate polysaccharide (SSP) exhibits various pharmacological activities, including immunoregulatory, anti-inflammatory, antiviral, and antioxidant properties. However, the acts of lncRNAs in regulating the therapeutic effects of SSP on PCV2-infected RAW264.7 cells remains poorly understood. This study aimed to investigate the molecular mechanisms by which lncRNAs regulate PCV2-induced immunosuppression during SSP treatment. Our findings revealed that 1699 mRNAs, 373 lncRNAs, and 129 miRNAs were differentially expressed in PCV2-infected RAW264.7 cells. Additionally, 359 mRNAs, 271 lncRNAs, and 79 miRNAs exhibited differential expression in SSP-treated PCV2-infected RAW264.7 cells. GO and KEGG analyses indicated that the candidate genes were enriched in the TNF/NF-κB signaling pathway. Furthermore, based on GO and KEGG pathway analysis, a ceRNA network involving chemokine (C-X-C motif) ligand 2 (CXCL2), miR-217-x, and MSTRG.5823.1 was constructed. We demonstrated that lncRNA MSTRG.5823.1 localized to the cytoplasm. Moreover, we found that silencing or overexpressing lncRNA MSTRG.5823.1 significantly modulated PCV2-induced immunosuppression by regulating the activation of the TNF/NF-κB signaling pathway. Specifically, lncRNA MSTRG.5823.1 overexpression increased the expression of TNF/NF-κB signaling pathway-related genes and proteins in PCV2-infected RAW264.7 cells. Conversely, silencing lncRNA MSTRG.5823.1 decreased their expression. Rescue assays further revealed that the suppressive effects of miR-217-x overexpression on TNF/NF-κB signaling pathway-related genes and proteins could be reversed by MSTRG.5823.1 overexpression. These findings highlight the critical role of lncRNA MSTRG.5823.1 in PCV2 infection progression and suggest a new strategy for the prevention and treatment of PCV2 infection.

Equilibrative nucleoside transporter 3 supports microglial functions and protects against the progression of Huntington's disease in the mouse model.

Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by involuntary movements, cognitive deficits, and psychiatric symptoms. Currently, there is no cure, and only limited treatments are available to manage the symptoms and to slow down the disease's progression. The molecular and cellular mechanisms of HD's pathogenesis are complex, involving immune cell activation, altered protein turnover, and disturbance in brain energy homeostasis. Microglia have been known to play a dual role in HD, contributing to neurodegeneration through inflammation but also enacting neuroprotective effects by clearing mHTT aggregates. However, little is known about the contribution of microglial metabolism to HD progression. This study explores the impact of a microglial metabolite transporter, equilibrative nucleoside transporter 3 (ENT3), in HD. Known as a lysosomal membrane transporter protein, ENT3 is highly enriched in microglia, with its expression correlated with HD severity. Using the R6/2 ENT3-/- mouse model, we found that the deletion of ENT3 increases microglia numbers yet worsens HD progression, leading to mHTT accumulation, cell death, and disturbed energy metabolism. These results suggest that the delicate balance between microglial metabolism and function is crucial for maintaining brain homeostasis and that ENT3 has a protective role in ameliorating neurodegenerative processes.

Mediation of FOXA2/IL-6/IL-6R/STAT3 signaling pathway mediates benzo[a]pyrene-induced airway epithelial mesenchymal transformation in asthma.

Benzo [a]pyrene (BaP), a toxic pollutant, increases the incidence and severity of asthma. However, the molecular mechanisms underlying the effects of BaP in asthma remain unclear. In terms of research methods, we used BaP to intervene in the animal model of asthma and the human bronchial epithelial (16HBE) cells, and the involved mechanisms were found from the injury, inflammation, and airway epithelial to mesenchymal transition (EMT) in asthma. We also constructed small interfering RNAs and overexpression plasmids to knockdown/overexpress IL-6R and FOXA2 in 16HBE cells and a serotype 9 adeno-associated viral vector for lung tissue overexpression of FOXA2 in mice to determine the mechanism of action of BaP-exacerbated asthma airway EMT. We observed that BaP aggravated inflammatory cell infiltration into the lungs, reduced the Penh value, increased collagen fibres in the lung tissue, and increased serum IgE levels in asthmatic mice. After BaP intervention, the expression of FOXA2 in the lung tissue of asthmatic mice decreased, the production and secretion of IL-6 were stimulated, and STAT3 phosphorylation and nuclear translocation increased, leading to changes in EMT markers. However, EMT decreased after increasing FOXA2 expression and decreasing that of IL-6R and was further enhanced after low FOXA2 expression. Our results revealed that BaP exacerbated airway epithelial cell injury and interfered with FOXA2, activating the IL-6/IL-6R/STAT3 signaling pathway to promote airway EMT in asthma. These findings provide toxicological evidence for the mechanism underlying the contribution of BaP to the increased incidence of asthma and its exacerbations.

Exploring symptom clusters in Chinese patients with peritoneal dialysis: a network analysis.

BACKGROUND: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management. METHODS: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis. RESULTS: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients. CONCLUSIONS: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms.

The Myopia Prevalence and Association With Physical Activity Among Primary School Students Aged 6-12 Years: A Cross-Sectional Study in Tianjin, China.

Purpose: This study aimed to investigate the prevalence of myopia and determine the association between physical activity and risk of myopia among primary school students in Tianjin, China. Methods: A cross-sectional study was conducted among subjects from nine primary schools. All of the subjects underwent visual acuity and spherical equivalent (SE) with noncycloplegic autorefraction measurement. Myopia was defined as an SE refraction ≤-0.50D and an uncorrected visual acuity <5.0 in either eye. Physical activity was measured via the Physical Activity Questionnaire for Children. Data were analyzed using the Pearson χ2 test and binary logistic regression. Stratification analysis by sex was also performed. Results: A total of 2976 participants (1408 boys and 1568 girls) aged six to 12 years (mean age 8.82 years) were included in this study. The overall prevalence of myopia was 52.92%. When stratified according to physical activity, myopia prevalence significantly decreased with increasing physical activity levels (χ2 trend test = 127.63, P < 0.001). In the binary logistic regression analysis, after adjusting for age, sex, and school region, the odds ratio for the association between physical activity and myopia was 0.762 (95% confidence interval, 0.675-0.862, P < 0.001). When stratified by sex, the significant statistical association between physical activity and myopia both can be found in two groups (P < 0.05). Conclusions: Higher levels of physical activity were independently associated with decreased risk of myopia. The significant reverse statistical association between physical activity and myopia can be found in male or female groups. Translational Relevance: Taking part in physical activities may be an effective way to reduce the prevalence of myopia.

Postmortem Diffusion of Aconitum Alkaloids and Their Metabolites in Rabbits.

OBJECTIVES: To explore the postmortem diffusion rule of Aconitum alkaloids and their metabolites in poisoned rabbits, and to provide a reference for identifying the antemortem poisoning or postmortem poisoning of Aconitum alkaloids. METHODS: Twenty-four rabbits were sacrificed by tracheal clamps. After 1 hour, the rabbits were administered with aconitine LD50 in decocting aconite root powder by intragastric administration. Then, they were placed supine and stored at 25 ℃. The biological samples from 3 randomly selected rabbits were collected including heart blood, peripheral blood, urine, heart, liver, spleen, lung and kidney tissues at 0 h, 4 h, 8 h, 12 h, 24 h, 48 h, 72 h and 96 h after intragastric administration, respectively. Aconitum alkaloids and their metabolites in the biological samples were analyzed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). RESULTS: At 4 h after intragastric administration, Aconitum alkaloids and their metabolites could be detected in heart blood, peripheral blood and major organs, and the contents of them changed dynamically with the preservation time. The contents of Aconitum alkaloids and their metabolites were higher in the spleen, liver and lung, especially in the spleen which was closer to the stomach. The average mass fraction of benzoylmesaconine metabolized in rabbit spleen was the highest at 48 h after intragastric administration. In contrast, the contents of Aconitum alkaloids and their metabolites in kidney were all lower. Aconitum alkaloids and their metabolites were not detected in urine. CONCLUSIONS: Aconitum alkaloids and their metabolites have postmortem diffusion in poisoned rabbits, diffusing from high-content organs (stomach) to other major organs and tissues as well as the heart blood. The main mechanism is the dispersion along the concentration gradient, while urine is not affected by postmortem diffusion, which can be used as the basis for the identification of antemortem and postmortem Aconitum alkaloids poisoning.

Accuracy of 12 Intraocular Lens Power Formulas After Corneal Myopic Refractive Surgery.

PURPOSE: To assess the predictive accuracy of new-generation online intraocular lens (IOL) power formulas in eyes with previous myopic laser refractive surgery (LRS) and to evaluate the influence of corneal asphericity on the predictive accuracy. METHODS: The authors retrospectively evaluated 52 patients (78 eyes) with a history of laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) who subsequently underwent cataract surgery. Refractive prediction errors were calculated for 12 no-history new online formulas: 8 formulas with post-LRS versions (Barrett True-K, EVO 2.0, Hoffer QST, and Pearl DGS) using keratometry and posterior/total keratometry measured by IOLMaster 700 and 4 formulas without post-LRS versions (Cooke K6 and Kane) using keratometry and total keratometry. The refractive prediction error, mean absolute error (MAE), and percentages of eyes with prediction errors of ±0.25, ±0.50, ±0.75, ±1.00, and ±1.50 diopters (D) were compared. RESULTS: The MAEs of the 12 formulas were significantly different (F = 83.66, P < .001). The MAEs ranged from 0.62 to 0.94 D and from 1.07 to 1.84 D in the formulas with and without post-LRS versions, respectively. The EVO formula produced the lowest MAE (0.60) and MedAE (0.47), followed by the Barrett True-K (0.69 and 0.50, respectively). Each percentage of eyes with refractive prediction error was also significantly different among the 12 formulas (P < .001). CONCLUSIONS: The EVO and Barrett True-K formulas demonstrate comparable performance to the other existing formulas in eyes with a history of myopic LASIK/PRK. Surgeons should use these formulas with post-LRS versions and input keratometric values whenever possible. [J Refract Surg. 2024;40(6):e354-e361.].

Metabolomics reveals that ferroptosis participates in bisphenol A-induced testicular injury.

Objective: Bisphenol A (BPA) is a common environmental endocrine disruptor that negatively impairs male reproductive ability. This study aimed to explore the alterations in serum metabolomics that occur following BPA exposure and the mechanism via which BPA induces the death of testicular cells in a male mouse model. Methods: The mice were classified into two groups: BPA-exposed and control groups, and samples were collected for metabolomic determination, semen quality analysis, electron microscopy, enzyme-linked immunosorbent assay, quantitative real-time PCR, pathological staining, and Western blot analysis. Results: BPA exposure caused testicular damage and significantly decreased sperm quality in mice. Combined with non-target metabolomic analysis, this was closely related to ferroptosis induced by abnormal metabolites of arachidonic acid and phosphatidylcholine, and the expression of its related genes, acyl CoA synthetase 4, glutathione peroxidase 4, lysophosphatidylcholine acyltransferase 3, and phosphatidylethanolamine-binding protein 1 were altered. Conclusion: BPA induced ferroptosis, caused testicular damage, and reduced fertility by affecting lipid metabolism in male mice. Inhibiting ferroptosis may potentially function as a therapeutic strategy to mitigate the male reproductive toxicity induced by BPA.

Validation of the China mortality prediction model in trauma based on the ICD-10-CM codes.

The China mortality prediction model in trauma, based on the International Classification of Diseases, Tenth Revision, Clinical Modification lexicon (CMPMIT-ICD-10), is a novel model for predicting outcomes in patients who experienced trauma. This model has not yet been validated using data acquired from patients at other trauma centers in China. This retrospective study used data retrieved from the Peking University People's Hospital discharge database and included all patients admitted for trauma between 2012 and 2022 for model validation. Model performance was categorized into discrimination and calibration. In total, 23,299 patients were included in this study, with an overall mortality rate of 1.2%. CMPMIT-ICD-10 showed good discrimination and calibration, with an area under the curve of 0.84 (95% confidence interval: 0.82-0.87) and a Brier score of 0.02. The performance of the CMPMIT-ICD-10 during validation was satisfactory, and the application of the model will be scaled up in future studies.

Chaos and quantization of the three-particle generic Fermi-Pasta-Ulam-Tsingou model. I. Density of states and spectral statistics.

We study the mixed-type classical dynamics of the three-particle Fermi-Pasta-Ulam-Tsingou (FPUT) model in relationship with its quantum counterpart and present new results on aspects of quantum chaos in this system. First we derive for the general N-particle FPUT system the transformation to the normal mode representation. Then we specialize to the three-particle FPUT case and derive analytically the semiclassical energy density of states, and its derivatives in which different singularies are determined, using the Thomas-Fermi rule. The result agrees with the numerical energy density from the Krylov subspace method, as well as with the energy density obtained by the method of quantum typicality. Here, in paper I, we concentrate on the energy level statistics (level spacing and spacing ratios), in all classical dynamical regimes of interest: the almost entirely regular, the entirely chaotic, and the mixed-type regimes. We clearly confirm, correspondingly, the Poissonian statistics, the Gaussian orthogonal ensemble statistics, and the Berry-Robnik-Brody (BRB) statistics in the mixed-type regime. It is found that the BRB level spacing distribution perfectly fits the numerical data. The extracted quantum Berry-Robnik parameter is found to agree with the classical value within better than one percent. We discuss the role of localization of chaotic eigenstates, and its appearances, in relation to the classical phase space structure (Poincaré and smaller alignment index plots), whose details will be presented in paper II, where the structure and the statistical properties of the Husimi functions in the quantum phase space will be studied.

Chaos and quantization of the three-particle generic Fermi-Pasta-Ulam-Tsingou model. II. Phenomenology of quantum eigenstates.

We undertake a thorough investigation into the phenomenology of quantum eigenstates, in the three-particle Fermi-Pasta-Ulam-Tsingou model. Employing different Husimi functions, our study focuses on both the α-type, which is canonically equivalent to the celebrated Hénon-Heiles Hamiltonian, a nonintegrable and mixed-type system, and the general case at the saddle energy where the system is fully chaotic. Based on Husimi quantum surface of sections, we find that in the mixed-type system, the fraction of mixed eigenstates in an energy shell [E-δE/2,E+δE/2] with δE≪E shows a power-law decay with respect to the decreasing Planck constant ℏ. Defining the localization measures in terms of the Rényi-Wehrl entropy, in both the mixed-type and fully chaotic systems, we find a better fit with the ß distribution and a lesser degree of localization, in the distribution of localization measures of chaotic eigenstates, as the controlling ratio α_{L}=t_{H}/t_{T} between the Heisenberg time t_{H} and the classical transport time t_{T} increases. This transition with respect to α_{L} and the power-law decay of the mixed states, together provide supporting evidence for the principle of uniform semiclassical condensation in the semiclassical limit. Moreover, we find that in the general case which is fully chaotic, the maximally localized state, is influenced by the stable and unstable manifold of the saddles (hyperbolic fixed points), while the maximally extended state notably avoids these points, extending across the remaining space, complementing each other.