Correction of Ito in human induced pluripotent stem Cell-derived cardiomyocyte carrying DPP6 mutation in early repolarization syndrome by CRISPR/Cas9 genome editing.

Early repolarization syndrome (ERS) is defined as occurring in patients with early repolarization pattern who have survived idiopathic ventricular fibrillation with clinical evaluation unrevealing for other explanations. The pathophysiologic basis of the ERS is currently uncertain. The objective of the present study was to examine the electrophysiological mechanism of ERS utilizing induced pluripotent stem cells (iPSCs) and CRISPR/Cas9 genome editing. Whole genome sequencing was used to identify the DPP6 (c.2561T > C/p.L854P) variant in four families with sudden cardiac arrest induced by ERS. Cardiomyocytes were generated from iPSCs from a 14-year-old boy in the four families with ERS and an unrelated healthy control subject. Patch clamp recordings revealed more significant prolongation of the action potential duration (APD) and increased transient outward potassium current (Ito) (103.97 ± 18.73 pA/pF vs 44.36 ± 16.54 pA/pF at +70 mV, P < 0.05) in ERS cardiomyocytes compared with control cardiomyocytes. Of note, the selective correction of the causal variant in iPSC-derived cardiomyocytes using CRISPR/Cas9 gene editing normalized the Ito, whereas prolongation of the APD remained unchanged. ERS cardiomyocytes carrying DPP6 mutation increased Ito and lengthen APD, which maybe lay the electrophysiological foundation of ERS.

Serum electrolyte concentrations and risk of atrial fibrillation: an observational and mendelian randomization study.

BACKGROUND: Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the relationship between AF and serum electrolytes remains unclear. METHODS: A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association. RESULTS: In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively. CONCLUSIONS: Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.

Incidence and influencing factors of post-stroke cognitive impairment in convalescent young patients with first-ever stroke.

OBJECTIVE: To investigate the occurrence of post-stroke cognitive impairment (PSCI) and its influencing factors in convalescent young patients with first-ever stroke. METHODS: A total of 300 first-ever young stroke patients (age ≤45 years) were collected. The Mini-Mental State Examination (MMSE) was used to assess the cognitive status. The sociodemographic data, clinical symptoms, social environment, and behavior-related information were collected and analyzed. RESULTS: The incidence of PSCI in young stroke patients was 62.33 %. Through univariate analysis, there were statistical differences in different levels of education, smoking status and hypertension (P < 0.05). With subsequently multivariate logistic regression analysis, it was found that junior high school (OR=8.58,95 %CI:2.25∼32.70) and high school (OR=10.50,95 %CI:2.69∼41.00) education levels, lesion volume >3.00 cm3 (OR=8.03,95 %CI:2.28∼28.36), stroke in the frontal-parietal-temporal region (OR=7.26,95 %CI:1.58∼33.40) and the basal ganglia area (OR=6.13,95 %CI:1.24∼30.43), high NIHSS score (OR=1.17,95 %CI: 1.06∼1.29), and high diastolic blood pressure variability coefficient (OR=1.43,95 %CI: 1.02∼2.01) were risk factors for PSCI. Meanwhile, 24≤BMI<28 (OR=0.06,95 %CI:0.02∼0.23) and BMI<24 (OR=0.18,95 %CI:0.06∼0.53), hospitalization cost >20,000/month (OR=0.22,95 %CI:0.09∼0.56), and stroke onset in spring and summer (OR=0.37,95 %CI:0.14∼0.96) were protective factors. CONCLUSION: The incidence of PSCI is relatively high in young stroke patients. Junior high and high school education, stroke lesions >3.00cm3, strokes in the frontal-parietal-temporal and basal ganglia regions, high NIHSS scores, and high DBPV are risk factors for PSCI in young stroke patients. Meanwhile, BMI<28, treatment cost >20,000/month, and stroke onset in spring and summer are protective factors for PSCI in young stroke patients.

Diagnosing Orthotopic Lung Tumor Using a NTR-Activatable Near-Infrared Fluorescent Probe by Tracheal Inhalation.

Nitroreductase (NTR) is an enzyme that is upregulated under tumor-depleted oxygen conditions. The majority of studies have been conducted on NTR, but many existing fluorescent imaging tools for monitoring NTR inevitably suffer from weak targeting, low sensitivity, and simple tumor models. Research on diagnosing lung tumors has been very popular in recent years, but targeting assays in orthotopic lung tumors is still of great research value, as such models better mimic the reality of cancer in the organism. Here, we developed a novel near-infrared (NIR) fluorescent probe IR-ABS that jointly targets NTR and carbonic anhydrase IX (CAIX). IR-ABS has excellent sensitivity and selectivity and shows exceptional NTR response in spectroscopic tests. The measurements ensured that this probe has good biosafety in both cells and mice. A better NTR response was found in hypoxic tumor cells at the cellular level, distinguishing tumor cells from normal cells. In vivo experiments demonstrated that IR-ABS achieves a hypoxic response at the zebrafish level and enables rapid and accurate tumor margin distinguishment in different mouse tumor models. More importantly, we successfully applied IR-ABS for NTR detection in orthotopic lung tumor models, further combined with tracheal inhalation drug delivery to improve targeting. To the best of our knowledge, we present for the first time a near-infrared imaging method for targeting lung cancerous tumor in situ via tracheal inhalation drug delivery, in contrast to the reported literature. This NIR fluorescence diagnostic strategy for targeting orthotopic lung cancer holds exciting potential for clinical aid in cancer diagnosis.

Bidirectional causal association between ischemic stroke and five mental disorders.

OBJECTIVE: To explore the bidirectional causal association between ischemic stroke and five mental disorders from a genetic perspective using two-sample Mendelian randomization (TSMR). METHODS: Single-nucleotide polymorphisms (SNPs) associated with ischemic stroke were obtained from the genome-wide association study (GWAS) database, and those closely related to the exposure phenotype and satisfying the three core assumptions of Mendelian randomization were selected as instrumental variables (IVs). The main TSMR analysis was conducted using the inverse variance-weighted (IVW) method, and the robustness of the results was assessed using the weighted median, weighted mode, and MR Egger methods. Heterogeneity test, pleiotropy test, and sensitivity analysis were also conducted to further ensure the accuracy and stability of the research results. RESULTS: This study found a positive correlation between ischemic stroke and depression [IVW method (FEM): OR = 1.002, 95%CI: 1.000-1.003, P = 0.023<0.05], but no significant causal association with schizophrenia, bipolar disorder, insomnia, or anxiety (P > 0.05). Reverse TSMR analysis showed no causal association between depression, schizophrenia, bipolar disorder, insomnia, anxiety, and ischemic stroke (P > 0.05). CONCLUSION: This study used TSMR to demonstrate from a genetic perspective that there is a positive correlation between ischemic stroke and depression, which increases the risk of depression. Proactive intervention for ischemic stroke might reduce the risk of depression.

Combined effects of transcranial direct current stimulation and aerobic exercise on inhibitory control function in healthy young adults: An event-related potential study.

Transcranial direct current stimulation (tDCS) and aerobic exercise (AE) have been demonstrated to enhance inhibitory control function in healthy individuals separately. However, the potential benefits of combining these two interventions have yet to be fully explored. In this study, we aimed to use multiple event-related potential (ERP) components (P200, N200, and N450) to investigate the combined effects of tDCS and AE on the improvement of inhibitory control ability in healthy young adults. We evaluated the influence of this combined intervention on cognitive tasks involving inhibitory control function and basic information processing by performing the Stroop Word Color task. Our results showed that compared to the application of tDCS or AE alone, the combined intervention of tDCS and AE had a greater effect on improving inhibitory control function in healthy young adults. The amplitude of P200, N200, and N450 ERP components also changed more significantly during the Stroop Word Color task. We concluded that the mechanism of tDCS combined with AE in improving inhibitory control ability may involve synergistic effects on brain structures at different levels, such as regulating interactions at the reticular activating system level and activating corresponding brain regions at the medial frontal lobe and frontal lobe levels.

Effect of interactive, multimedia-based home-initiated education on preoperative anxiety inchildren and their parents: a single-center randomized controlled trial.

BACKGROUND: Anesthesiologists need to appreciate the impact of preoperative anxiety in children. The present study aimed to explore whether interactive multimedia-based home-initiated interventions could effectively relieve preoperative anxiety in pediatric patients. METHODS: In this prospective study, we compared preoperative anxiety between two groups of children aged 4-9 years. Children in the control group received a question-and-answer (Q&A) introduction, and children in the intervention group received multimedia-based home-initiated preoperative education using comic booklets, videos, and coloring game books. Differences in anxiety between the two groups were evaluated by the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF) at four time points: in the ophthalmology outpatient clinic before intervention as the baseline (T0); in the preoperative waiting area (T1); at the time of separating from their parents and moving to the operating room (T2); and at the time of anesthesia induction (T3). Parental anxiety was assessed by the Self-rating Anxiety Scale (SAS) and Visual Analog Scale (VAS) at T0 and T2. Other related information was collected by questionnaire. RESULTS: Eighty-four children who underwent pediatric strabismus in our center between November 2020 and July 2021 were included in this study. An intention-to-treat (ITT) analysis was performed on data from 78 enrolled children. Children in the intervention group exhibited lower m-YPAS-SF scores at T1, T2, and T3 than those in the control group (all p < 0.001). By using a mixed-effect model with repeated measurement (MMRM) after adjusting the m-YPAS score at T0 as a covariate, the interventional effect in terms of themYPAS-SF score was also significant over time (p < 0.001). The percentage of children with perfect induction compliance (ICC = 0) in the intervention group was significantly higher than that in the control group [18.4% vs. 7.5%], and poor induction compliance (ICC>4) was lower (2.6% vs. 17.5%, p = 0.048). The mean parental VAS score at T2 in the intervention group was significantly lower than that in the control group (p = 0.021). CONCLUSIONS: Interactive multimedia-based home-initiated intervention could reduce preoperative anxiety in children and improve the quality of anesthesia induction based on ICC scores, which may in turn impose a positive impact on parental anxiety.

Opportunistic osteoporosis screening using chest CT with artificial intelligence.

Osteoporosis has a high incidence and a low detection rate. If it is not detected in time, it will cause osteoporotic fracture and other serious consequences. This study showed that the attenuation values of vertebrae on chest CT could be used for opportunistic screening of osteoporosis. This will be beneficial to improve the detection rate of osteoporosis and reduce the incidence of adverse events caused by osteoporosis. INTRODUCTION: To explore the value of the attenuation values of all thoracic vertebrae and the first lumbar vertebra measured by artificial intelligence on non-enhanced chest CT to do osteoporosis screening. METHODS: On base of images of chest CT, using artificial intelligence (AI) to measure the attenuation values (HU) of all thoracic and the first vertebrae of patients who underwent CT examination for lung cancer screening and dual-energy X-ray absorptiometry (DXA) examination during the same period. The patients were divided into three groups: normal group, osteopenia group, and osteoporosis group according to the results of DXA. Clinical baseline data and attenuation values were compared among the three groups. The correlation between attenuation values and BMD values was analyzed, and the predictive ability and diagnostic efficacy of attenuation values of thoracic and first lumbar vertebrae on osteopenia or osteoporosis risk were further evaluated. RESULTS: CT values of each thoracic vertebrae and the first lumbar vertebrae decreased with age, especially in menopausal women and presented high predictive ability and diagnostic efficacy for osteopenia or osteoporosis. After clinical data correction, with every 10 HU increase of CT values, the risk of osteopenia or osteoporosis decreased by 32 ~ 44% and 61 ~ 80%, respectively. And the combined diagnostic efficacy of all thoracic vertebrae was higher than that of a single vertebra. The AUC of recognizing osteopenia or osteoporosis from normal group was 0.831and 0.972, respectively. CONCLUSIONS: The routine chest CT with AI is of great value in opportunistic screening for osteopenia or osteoporosis, which can quickly screen the population at high risk of osteoporosis without increasing radiation dose, thus reducing the incidence of osteoporotic fracture.

Dual-target synergistic antithrombotic mechanism of a dabigatran etexilate analogue (HY023016).

Thrombin has long been considered a desirable antithrombotic target, but anti-thrombin therapy without anti-platelet therapy has never achieved the ideal effect. HY023016, derived from dabigatran etexilate, exhibited a potent antithrombotic efficacy. In the present study, mechanisms underlying this effect were explored. HY023016 strongly decreased the binding of thrombin to recombinant GPIbα N-terminal sequence, which was confirmed by surface plasmon resonance. Flow cytometry revealed that HY023016 selectively decreased the binding of antibody to GPIbα and inhibited the washed human platelet aggregation induced by thrombin. Fluorescence experiment showed that HY023016 remarkably inhibited exosite II by a loss of affinity for the γ'-peptide of fibrinogen. Using intravital microscopy, we observed and recorded the dynamic process of thrombus formation and found that HY023016 effectively prevented thrombus formation in rat arteriovenous shunt thrombosis model. On the basis of these findings, we propose that HY023016 provides a novel insight into the antithrombotic mechanism, which exerts synergistic anticoagulant and antiplatelet effects through thrombin and GPIbα.

Reevaluation of adverse drug reactions of psychiatric drugs under the chinese drug volume-based procurement policy.

BACKGROUND: The "4 + 7" volume-based procurement is a "large group purchase" led by the Chinese government, with the aim of reducing the price of medicines by trading volume for price. Although the "4 + 7" drugs had passed the national consistency evaluation, the adverse drug reactions need to be further evaluated to ensure the safety of the "4 + 7" drugs with low prices. We aimed to analyze the occurrence characteristics and related influencing factors of adverse reactions of psychiatric drugs under the chinese drug volume-based procurement policy(4 + 7 policy), and provide references for clinical medication. METHODS: 137 cases of adverse drug reactions of four psychotropic drugs reported under the "4 + 7" policy in Wuxi Mental Health Center in 2020 were collected. The gender and age of patients, related "4 + 7" drugs, involving organs / systems, clinical manifestations, distribution of new / serious adverse reactions, clinic outcomes were analyzed. RESULTS: Among the 137 cases of adverse drug reactions, the incidence of adverse drug reactions was the highest in patients aged 61-70 (25.38%). Mainly involved 4 "4 + 7" psychiatric drugs, of which olanzapine tablets caused the most adverse reactions (54, 39.24%). The adverse reactions mainly involved the digestive system, nervous system, cardiovascular system, blood and lymphatic system, among which the digestive system was the most common (61, 44.53%). A total of 8 cases (6.16%) of new and 26 cases of serious adverse reactions were reported, all of which led to the prolongation of disease course. Except for the transient side effects, most of that were improved or cured with no death, disability or teratogenicity after stopping or reducing the dose with symptomatic treatment. CONCLUSION: Since more and more drugs will be included in "4 + 7" for clinic, clinical pharmacists should strengthen the publicity and training of the knowledge of "4 + 7" drugs, strengthen the monitoring of adverse drug reactions, and provide timely feedback to the clinic, in order to achieve early prevention, early identification, timely diagnosis and reasonable intervention of the adverse drug reactions under the context of "4 + 7" policy.

Gamma-Glutamyl Transpeptidase to Platelet Ratio: A New Inflammatory Marker Associated with Outcomes after Cardiac Arrest.

INTRODUCTION: In recent years, gamma-glutamyl transpeptidase to platelet ratio (GPR) has been proposed as a new inflammatory marker. We aimed to evaluate the association between GPR and outcomes after cardiac arrest (CA). METHODS: A total of 354 consecutive patients with CA were included in this retrospective study. Patients were divided into three groups according to tertiles of GPR (low, n = 119; middle, n = 117; and high, n = 118). To determine the relationship between GPR and prognosis, a logistic regression analysis was performed. The ability of GPR to predict the outcomes was evaluated by receiver operating characteristic (ROC) curve analysis. Two prediction models were established, and the likelihood ratio test (LRT) and the Akaike Information Criterion (AIC) were utilized for model comparison. RESULTS: Among the 354 patients (age 62 [52, 74], 254/354 male) who were finally included in the analysis, those in the high GPR group had poor outcomes. Multivariate logistic regression analysis revealed that GPR was independently associated with the three outcomes, for ICU mortality (odds ratios (OR) = 1.738, 95% confidence interval (CI): 1.221-2.474, P = 0.002), hospital mortality (OR = 1.676[1.164 - 2.413], P = 0.005), and unfavorable neurologic outcomes (OR = 1.623[1.121 - 2.351], P = 0.010). The area under the ROC curve was 0.611 (95% Cl: 0.558-0.662) for ICU mortality, 0.600 (95% CI: 0.547-0.651) for hospital mortality, and 0.602 (95% CI: 0.549-0.653) for unfavorable neurologic outcomes. Further, the LRT analysis showed that compared with the model without GPR, the GPR-combined model had a higher likelihood ratio χ 2 score and smaller AIC. CONCLUSION: GPR, as an inflammatory indicator, was independently associated with outcomes after CA. GPR is helpful in estimating the clinical outcomes of patients with CA.

Usefulness of fibrinogen-to-albumin ratio to predict no-reflow and short-term prognosis in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

No-reflow is one of the major complications of primary percutaneous coronary artery intervention (pPCI) in the treatment of acute ST-segment elevation myocardial infarction (STEMI). Fibrinogen-to-albumin ratio (FAR) has currently emerged as a novel inflammatory marker to predict inflammation in chronic diseases. This study aimed to investigate whether admission FAR values predicts angiographic no-reflow and short-term prognosis in all STEMI patients. A total of 510 consecutive STEMI patients who underwent successful pPCI between September 2016 and May 2018 were included in this study. Patients were divided into groups based on thrombolysis in myocardial infarction (TIMI) flow grades after pPCI. No-reflow was defined as a post-PCI TIMI flow grade of 0, 1, or 2. Angiographic success was defined as TIMI flow grade 3. Fibrinogen, hs-CRP, and admission FAR values were significantly higher among patients with no-reflow. On multivariate analysis, admission FAR was an independent predictor of angiographic no-reflow (p < 0.001). Receiver-operating characteristics analysis revealed the cut-off value of admission FAR was a predictor of no-reflow with a sensitivity of 79.59% and a specificity of 69.42%. In multivariable Cox regression models adjusted for potential confounders, admission FAR values, and LVEF, hs-CRP was independently and positively associated with the 30-day all-cause mortality. Admission FAR was associated independently and significantly with angiographic no-reflow and short-term mortality in patients with STEMI undergoing pPCI.

Bcl-2 silencing attenuates hypoxia-induced apoptosis resistance in pulmonary microvascular endothelial cells.

Pulmonary arterial hypertension (PAH) is a life-threatening disorder that ultimately causes heart failure. While the underlying causes of this condition are not well understood, previous studies suggest that the anti-apoptotic nature of pulmonary microvascular endothelial cells (PMVECs) in hypoxic environments contributes to PAH pathogenesis. In this study, we focus on the contribution of Bcl-2 and hypoxia response element (HRE) to apoptosis-resistant endothelial cells and investigate the mechanism. PMVECs obtained from either normal rats or apoptosis-resistant PMVECs obtained from PAH rats were transduced with recombinant lentiviral vectors carrying either Bcl-2-shRNA or HRE combined Bcl-2-shRNA, and then cultured these cells for 24 h under hypoxic (5% O2) or normoxic (21% O2) conditions. In normal PMVECs, Bcl-2-shRNA or HRE combined with Bcl-2-shRNA transduction successfully decreased Bcl-2 expression, while increasing apoptosis as well as caspase-3 and P53 expression in a normoxic environment. In a hypoxic environment, the effects of Bcl-2-shRNA treatment on cell apoptosis, and on Bcl-2, caspase-3, P53 expression were significantly suppressed. Conversely, HRE activation combined with Bcl-2-shRNA transduction markedly enhanced cell apoptosis and upregulated caspase-3 and P53 expression, while decreasing Bcl-2 expression. Furthermore, in apoptosis-resistant PMVECs, HRE-mediated Bcl-2 silencing effectively enhanced cell apoptosis and caspase-3 activity. The apoptosis rate was significantly depressed when Lv-HRE-Bcl-2-shRNA was combined with Lv-P53-shRNA or Lv-caspase3-shRNA transduction in a hypoxic environment. These results suggest that HRE-mediated Bcl-2 inhibition can effectively attenuate hypoxia-induced apoptosis resistance in PMVECs by downregulating Bcl-2 expression and upregulating caspase-3 and P53 expression. This study therefore reveals critical insight into potential therapeutic targets for treating PAH.

A Novel Cu(II) Loaded Polypeptide SO2 Prodrug Nanoformulation Combining Chemodynamic and Gas Anticancer Therapies.

Sulfur dioxide (SO2)-based gas therapy and chemodynamic therapyare both reactive oxygen species (ROS)-mediated anticancer strategies, but there are few reports of their combined application. To this end, a novel graft-type copolymeric SO2 prodrug, PLG-g-mPEG-DNs, is designed and synthesized in this work. The amphiphilic polypeptides can self-assemble into nanoparticles (NPs) and encapsulated Cu(II) ions by metal-carboxyl coordination. In vitro release results showed that the obtained NPs-Cu can respond to the acidic pH and high glutathione levels typical of a tumor microenvironment to release Cu(II) and SO2 simultaneously. Both a Cu(II)-triggered Fenton-like reaction and the SO2 gas would promote ROS production and upregulate the oxidative stress in tumor cells, leading to an enhanced killing effect towards 4T1 cancer cells compared to either Cu(II) or the NPs alone. Furthermore, the in vitro hemolysis of NPs-Cu is less than 1.0% at a high concentration of 8 mg/mL, indicating good blood compatibility and the potential for in vivo tumor inhibition application.

Safety assessment of Brexpiprazole: Real-world adverse event analysis from the FAERS database.

OBJECTIVE: This study aims to analysis adverse drug events (ADE) related to Brexpiprazole from the third quarter of 2015 to the first quarter of 2023 from FAERS database. METHODS: The ADE data related to Brexpiprazole from 2015 Q3 to 2023 Q1 were collected. After standardizing the data, a variety of signal quantification techniques, including ROR, PRR, BCPNN, and MGPS were used for analysis. RESULTS: Among the 8559 ADE reports with Brexpiprazole as the primary suspected drug, 178 preferred terms (PT) of adverse reactions spanning 27 different system organ classes (SOC) were identified. Specifically, Metabolism and nutrition disorders and Reproductive system and breast disorders were unique adverse reactions to Brexpiprazole, with the latter not mentioned in the official drug label. Moreover, uncommon but significantly strong ADE signals, such as Egocentrism, Pharmacophobia, and Compulsions were observed. Notably, Tardive dyskinesia (n = 317, ROR 103.87, PRR 102.21, IC 6.21, EBGM 96.17) and Extrapyramidal disorder (n = 104, ROR 31.17, PRR 31.00, IC 4.57, EBGM 30.44) exhibited relatively high occurrence rates and signal strengths. Additionally, Lactation disorder (n = 6, ROR 48.09, PRR 48.07, IC 2.63, EBGM 46.71) and Breast discharge (n = 10, ROR 23.18, PRR 23.17, IC 2.94, EBGM 22.86) were observed, both presenting strong ADE signals. CONCLUSION: Brexpiprazole poses risks of various adverse reactions while providing therapeutic effects. In clinical applications, practitioners should closely monitor occurrences of Psychiatric disorders, Metabolism and nutrition disorders, Reproductive system and breast disorders, and other events.

Unveiling potential adverse events associated with escitalopram oxalate: A real-world analysis based FDA adverse event reporting system database.

OBJECTIVE: The study aimed to conduct a multidimensional evaluation of potential adverse events (AEs) of escitalopram oxalate based on the FDA adverse event reporting system (FAERS) database. METHODS: This study utilized the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma-poisson shrinker (MGPS) to mine and analyze data from the FAERS database from the first quarter of 2004 to the second quarter of 2023. RESULTS: There was a total of 19,854 AE reports related to escitalopram oxalate, extracting 625 preferred terms (PTs), and covering 27 system organ classes (SOCs). The results showed that the number of reports by females was significantly higher than males, accounting for 57.68%. The reporting number was higher in 2018 and 2019, accounting for 9.50% and 10.18% of the total reports, respectively. The main reporters were consumers and other health professionals, accounting for 26.99% and 26.75% respectively. The majority of the reports were primarily from the United States. Newly emerging AE signals such as intentional overdose (n = 691, ROR 8.51, PRR 8.45, IC 3.05, Empirical Bayesian Geometric Mean (EBGM) 8.35), suicide attempt (n = 665, ROR 8.58, PRR 8.52, IC 3.06, EBGM 8.42), serum serotonin (n = 5, ROR 1044.78, PRR 1044.71, IC 2.56, EBGM 392.39), anti-actin antibody positive (n = 5, ROR 626.87, PRR 626.83, IC 2.56, EBGM 313.91), among others, were not mentioned in the drug's label. CONCLUSION: While escitalopram oxalate has clear benefits in the treatment of depression and other mental health disorders, the presence of AEs also suggests risks associated with its use. Particularly concerning are risks of suicide and changes in serum serotonin levels.

Construction of a diagnostic model for osteoarthritis based on transcriptomic immune-related genes.

Background: Osteoarthritis (OA) is a leading cause of disability globally, affecting over 500 million individuals worldwide. However, accurate and early diagnosis of OA is challenging to achieve. Immune-related genes play an essential role in OA development. Therefore, the objective of this study was to develop a diagnostic model for OA based on immune-related genes identified in synovial membrane. Methods: The gene expression profile of OA were downloaded based on four datasets. The significantly differentially expressed genes (DEGs) between OA and control groups were selected. The differential immune cells were analyzed, followed by immune-related DEGs screening. WGCNA was used to screen module genes and these genes were further selected through optimization algorithm. Then, nomogram model was constructed. Chemical drug small molecule related to OA was predicted. Finally, expression levels of several key genes were validated by qRT-PCR through construction of OA rat models. Results: The total 656 DEGs were obtained. Eight immune cells were significantly differential between two groups, and 317 immune-related DEGs were obtained. WGCNA identified three modules. The genes in modules were significantly involved in 15 pathways, involving in 65 genes. Then 12 DEGs were screened as the final optimal combination of DEGs, such as CEBPB, CXCL1, JUND, GABARAPL2 and PDGFC. The Nomogram model was also constructed. Furthermore, the chemical small molecules, such as acetaminophen, aspirin, and caffeine were predicted. The expression levels of CEBPB, CXCL1, GABARAPL2 and PDGFC were validated in OA rat models. Conclusion: A diagnostic model based on twelve immune related genes was constructed. These model genes, such as CEBPB, CXCL1, GABARAPL2, and PDGFC, may serve as diagnostic biomarkers and immunotherapeutic targets.

Development of hypertension models for lung cancer screening cohorts using clinical and thoracic aorta imaging factors.

This study aims to develop and validate nomogram models utilizing clinical and thoracic aorta imaging factors to assess the risk of hypertension for lung cancer screening cohorts. We included 804 patients and collected baseline clinical data, biochemical indicators, coexisting conditions, and thoracic aorta factors. Patients were randomly divided into a training set (70%) and a validation set (30%). In the training set, variance, t-test/Mann-Whitney U-test and standard least absolute shrinkage and selection operator were used to select thoracic aorta imaging features for constructing the AIScore. Multivariate logistic backward stepwise regression was utilized to analyze the influencing factors of hypertension. Five prediction models (named AIMeasure model, BasicClinical model, TotalClinical model, AIBasicClinical model, AITotalClinical model) were constructed for practical clinical use, tailored to different data scenarios. Additionally, the performance of the models was evaluated using receiver operating characteristic (ROC) curves, calibration curves and decision curve analyses (DCA). The areas under the ROC curve for the five models were 0.73, 0.77, 0.83, 0.78, 0.84 in the training set, and 0.77, 0.78, 0.81, 0.78, 0.82 in the validation set, respectively. Furthermore, the calibration curves and DCAs of both sets performed well on accuracy and clinical practicality. The nomogram models for hypertension risk prediction demonstrate good predictive capability and clinical utility. These models can serve as effective tools for assessing hypertension risk, enabling timely non-pharmacological interventions to preempt or delay the future onset of hypertension.

Inhibiting dissolution strategy achieving high-performance sodium titanium phosphate hybrid anode in seawater-based dual-ion battery.

Aqueous sodium-ion batteries (ASIBs) show great promise as candidates for large-scale energy storage. However, the potential of ASIB is impeded by the limited availability of suitable anode types and the occurrence of dissolution side reactions linked to hydrogen evolution. In this study, we addressed these challenges by developing a Bi-coating modified anode based on a sodium titanium phosphate (NTP)-carbon fibers (CFs) hybrid electrode (NTP-CFs/Bi). The Bi-coating effectively mitigates the localized enrichment of hydroxyl anion (OH-) near the NTP surface, thus addressing the dissolution issue. Notably, the Bi-coating not only restricts the local abundance of OH- to inhibit dissolution but also ensures a higher capacity compared with other NTP-based anodes. Consequently, the NTP-CFs/Bi anode demonstrates an impressive specific capacity of 216.8 mAh/g at 0.2 mV/s and maintains a 90.7 % capacity retention after 1000 cycles at 6.3 A/g. This achievement sets a new capacity record among NTP-based anodes for sodium storage. Furthermore, when paired with a cathode composed of hydroxy nickel oxide directly grown on Ni foam, we assembled a seawater-based cell exhibiting high energy and power densities, surpassing the most recently reported ASIBs. This groundbreaking work lays the foundation for a potential method to develop long-life NTP-based anodes.

Quantitative assessment of airway wall thickness in COPD patients with interstitial lung abnormalities.

Background: Whether the airway is involved in the pathogenesis of interstitial lung abnormalities (ILA) is not well understood. Also the impact of ILA on lung function in COPD patients remains controversial. We aimed to assess the quantitative CT measurements of airway wall thickness (AWT) and lung function according to ILA status in COPD patients. Methods: 157 COPD patients discharged from our hospital from August 1, 2019 through August 31, 2022 who underwent chest CT imagings and pulmonary function tests were retrospectively enrolled. Linear regression analysis and multiple models were used to analyze associations between quantitative assessment of airway wall changes and the presence of ILA. Results: In 157 COPD patients, 23 patients (14.6%) had equivocal ILA, 42 patients (26.8%) had definite ILA. The definite ILA group had the highest measurements of Pi10 (square root of theoretical airway wall area with a lumen perimeter of 10 mm), segmental AWT and segmental WA% (percentage of wall area), whereas the no ILA group had the lowest measurements of Pi10, segmental AWT and segmental WA%. In the adjusted analyses (adjusted by age, sex, body mass index, smoking intensity, COPD GOLD stage, lung function, slice thickness and scanner type), compared to COPD patients without ILA, the measurements of Pi10, segmental AWT and segmental WA% were higher in definite ILA group with differences of 0.225 mm (p = 0.012), 0.152 mm (p < 0.001), 4.8% (p < 0.001) respectively. COPD patients with definite ILA tended to have higher FEV1% predicted, FVC% predicted and lower MMEF75/25% predicted, but there were no statistically differences among the three groups. Conclusion: Our study demonstrates the higher AWT measures in COPD patients with ILA compared to the patients without ILA. These findings suggest that the airway may be involved in the pathogenesis of ILA.