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Background and objectives: This case report investigates the application of intermittent Theta-Burst Stimulation (iTBS) in aphasia rehabilitation following a right hemisphere stroke. Case presentation: A 52-year-old Chinese male with Broca's aphasia post-stroke was treated with iTBS. His progress was evaluated using Functional Near-Infrared Spectroscopy (fNIRS) and behavioral assessments. Significant language function improvement was noted, with fNIRS showing increased activation in right hemisphere language-related cortical areas and altered functional connectivity patterns. Conclusion: The findings indicate that iTBS is effective in facilitating language recovery in right hemisphere stroke-induced aphasia, highlighting the importance of personalized neurorehabilitation strategies. Despite focusing on a single case, the study contributes to understanding neural plasticity mechanisms in right hemisphere stroke-induced aphasia.
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OBJECTIVE: Daridorexant, a novel dual orexin receptor antagonist, was approved by the FDA in 2022 for the treatment of insomnia in adults. The aim of this study is to delve into the adverse events (AEs) of daridorexant by analyzing data from the FAERS database, to assess its safety and effectiveness in clinical applications. METHODS: This study selected data from the FAERS database from the first quarter of 2022 to the third quarter of 2023. Various data analysis methods were used, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), to assess AEs related to daridorexant. RESULTS: The study analyzed a total of 2,624,030 AE reports, of which 1318 were related to daridorexant. It identified 59 preferred terms (PTs) involving 23 system organ classes (SOCs). Signal mining identified new potential AEs related to daridorexant, including sleep-related psychiatric symptoms (nightmare, abnormal dreams, sleep terror, etc.), emotional and perceptual abnormalities (hallucination, depression, agitation), physiological and behavioral responses (palpitations, dry mouth, energy increased, etc.), suicide risk (suicidal ideation, intentional overdose), and other special concern AEs (tachyphrenia, sleep-related eating disorder, hypersensitivity). CONCLUSION: Although some new potential AEs have been identified, these findings need further verification in broader datasets and long-term studies due to limitations in data sources and analysis methods. Future research should comprehensively assess the safety and effectiveness of daridorexant, providing more accurate guidance for medical professionals in the treatment of insomnia.
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Antagonistas de los Receptores de Orexina , Trastornos del Inicio y del Mantenimiento del Sueño , United States Food and Drug Administration , Humanos , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Trastornos del Inicio y del Mantenimiento del Sueño/inducido químicamente , Estados Unidos , Antagonistas de los Receptores de Orexina/efectos adversos , Antagonistas de los Receptores de Orexina/uso terapéutico , Masculino , Adulto , Femenino , Persona de Mediana Edad , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Teorema de Bayes , Pirrolidinas/efectos adversos , Pirrolidinas/uso terapéutico , Anciano , ImidazolesRESUMEN
BACKGROUND: Accurate evaluation of level of disorder of consciousness (DOC) is clinically challenging. OBJECTIVE: This study aimed to establish a distinctive DOC-related pattern (DOCRP) for assessing disease severity and distinguishing unresponsive wakefulness syndrome (UWS) from minimally conscious state (MCS). METHODS: Fifteen patients with DOC and eighteen health subjects with F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET) were enrolled in this study. All patients were assessed by Coma Recovery Scale-Revised (CRS-R) and all individuals were randomly divided into two cohorts (Cohort A and B). DOCRP was identified in Cohort A and subsequently validated in Cohort B and A+B. We also assessed the discriminatory power of DOCRP between MCS and UWS. RESULTS: The DOCRP was characterized bilaterally by relatively decreased metabolism in the medial and lateral frontal lobes, parieto-temporal lobes, cingulate gyrus and caudate, associated with relatively increased metabolism in the cerebellum and brainstem. DOCRP expression exhibited high accuracy in differentiating DOC patients from controls (P<0.0001, AUC=1.000), and furthermore could effectively distinguish MCS from UWS (P=0.037, AUC=0.821, sensitivity: 85.7â¯%, specificity: 75.0â¯%). Particularly in the subgroup of DOC patients survived global hypoxic-ischemic brain injury, DOCRP expression exhibited even better discriminatory power between MCS and UWS (P=0.046, AUC=1.000). CONCLUSIONS: DOCRP might serve as an objective biomarker in distinguishing between UWS and MCS, especially in patients survived global hypoxic-ischemic brain injury. TRIAL REGISTRATION NUMBER: ChiCTR2300073717 (Chinese clinical trial registry site, http://www.chictr.org).
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Trastornos de la Conciencia , Fluorodesoxiglucosa F18 , Estado Vegetativo Persistente , Tomografía de Emisión de Positrones , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estado Vegetativo Persistente/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Adulto , Trastornos de la Conciencia/diagnóstico por imagen , Anciano , Encéfalo/diagnóstico por imagen , Diagnóstico Diferencial , Vigilia/fisiologíaRESUMEN
To comprehensively investigate the molecular transmission patterns of HIV-1 genotypes among men who have sex with men (MSM) in Chongqing, we employed 392 pol sequences of MSM to construct a phylogenetic tree and gene transmission network. Among the viral subtypes, CRF07_BC accounted for 73.2% (287/392) and CRF01_AE accounted for 20.7% (81/392), emerging as the predominant subtypes in this investigation. Additionally, we observed the presence of CRF55_01B, subtype B, CRF08_BC and other circulating recombinant forms. The HIV-1 molecular network was constructed with a gene distance threshold of 1.5%, resulting in an entry rate of 61.4% (241/392). Within the network, we identified a total of 23 molecular clusters, with the largest cluster being the CRF07_BC molecular cluster comprising 148 node values. Transmitted drug-resistance (TDR) mutations were found in 4.34% of the cases, with 1.79% associated with protease inhibitors (PIs), 0.51% with nucleoside reverse transcriptase inhibitors (NRTIs), and 2.55% with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Statistical analysis indicated a higher enrollment rate in the HIV-1 molecular network among infected individuals with the CRF07_BC subtype, those identifying with same-sex sexual roles as "vers," and individuals with higher education levels. This suggests the need for strengthened investigation and intervention in this population to prevent the formation of larger transmission clusters. Furthermore, continuous monitoring of the HIV-1 molecular dynamics network is necessary to promptly and accurately track changes in molecular epidemic characteristics.
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Farmacorresistencia Viral , Infecciones por VIH , VIH-1 , Homosexualidad Masculina , Filogenia , Humanos , Masculino , China/epidemiología , Homosexualidad Masculina/estadística & datos numéricos , VIH-1/genética , VIH-1/efectos de los fármacos , Farmacorresistencia Viral/genética , Adulto , Infecciones por VIH/epidemiología , Infecciones por VIH/genética , Infecciones por VIH/transmisión , Genotipo , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/transmisión , Persona de Mediana Edad , MutaciónRESUMEN
Focal malformations of cortical development (FMCDs) are brain disorders mainly caused by hyperactive mTOR signaling due to both inactivating and activating mutations of genes in the PI3K-AKT-mTOR pathway. Among them, mosaic and somatic activating mutations of the mTOR pathway activators are more frequently linked to severe form of FMCDs. A human stem cell-based FMCDs model to study these activating mutations is still lacking. Herein, we genetically engineer human embryonic stem cell lines carrying these activating mutations to generate cortical organoids. Mosaic and somatic expression of AKT3 activating mutations in cortical organoids mimicking the disease presentation with overproliferation and the formation of dysmorphic neurons. In parallel comparison of various AKT3 activating mutations reveals that stronger mutation is associated with more severe neuronal migratory and overgrowth defects. Together, we have established a feasible human stem cell-based model for FMCDs that could help to better understand pathogenic mechanism and develop novel therapeutic strategy.
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Malformaciones del Desarrollo Cortical , Organoides , Proteínas Proto-Oncogénicas c-akt , Humanos , Organoides/metabolismo , Organoides/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Malformaciones del Desarrollo Cortical/genética , Malformaciones del Desarrollo Cortical/patología , Malformaciones del Desarrollo Cortical/metabolismo , Células Madre Embrionarias Humanas/metabolismo , Transducción de Señal/genética , Corteza Cerebral/patología , Corteza Cerebral/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Mutación , Neuronas/metabolismo , Neuronas/patología , Línea CelularRESUMEN
BACKGROUND: This study aims to compare antimicrobial drug usage in our hospital to Jiangsu Province and China from 2020 to 2022. RESEARCH DESIGN AND METHODS: A detailed analysis was performed using data from the National Antimicrobial Drug Clinical Application Monitoring Network. Several parameters were studied: the rate of antimicrobial drug use, number and types of drugs used, the rate of combined use, rate of microbiological examinations, drug use intensity, and cumulative Defined Daily Doses (DDDs). RESULTS: From 2020 to 2022, our hospital's antimicrobial drug usage rate was consistently lower than Jiangsu Province and China. The average number of drug types and the combined drug use rate were higher in 2020 but fell below those in Jiangsu Province and China in 2021 and 2022. Our microbiological examination rate consistently surpassed that of Jiangsu Province and China. Furthermore, our Antimicrobial Usage Density and cumulative DDDs were notably lower. While AUD remained stable, DDDs showed a decreasing trend. The most dominant drug in DDDs was cefditoren, a third-generation cephalosporin. CONCLUSIONS: During the pandemic years, our hospital not only met the requirements for antimicrobial drug usage, microbiological examination, AUD, and cumulative DDDs but also demonstrated a consistent year-by-year decrease in drug usage and DDDs.
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Nowadays, immunotherapy is one of the most promising anti-tumor therapeutic strategy. Specifically, immune-related targets can be used to predict the efficacy and side effects of immunotherapy and monitor the tumor immune response. In the past few decades, increasing numbers of novel immune biomarkers have been found to participate in certain links of the tumor immunity to contribute to the formation of immunosuppression and have entered clinical trials. Here, we systematically reviewed the oncogenesis and progression of cancer in the view of anti-tumor immunity, particularly in terms of tumor antigen expression (related to tumor immunogenicity) and tumor innate immunity to complement the cancer-immune cycle. From the perspective of integrated management of chronic cancer, we also appraised emerging factors affecting tumor immunity (including metabolic, microbial, and exercise-related markers). We finally summarized the clinical studies and applications based on immune biomarkers. Overall, immune biomarkers participate in promoting the development of more precise and individualized immunotherapy by predicting, monitoring, and regulating tumor immune response. Therefore, targeting immune biomarkers may lead to the development of innovative clinical applications.
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Analyze the adverse event (AE) signals of istradefylline based on the FAERS database. By extracting large-scale data from the FAERS database, this study used various signal quantification techniques such as ROR, PRR, BCPNN, and MGPS to calculate and evaluate the ratio and association between istradefylline and specific AEs. In the FAERS database, this study extracted data from the third quarter of 2019 to the first quarter of 2023, totaling 6,749,750 AE reports. After data cleansing and drug screening, a total of 3633 AE reports related to istradefylline were included for analysis. Based on four calculation methods, this study unearthed 25 System Organ Class (SOC) AE signals and 82 potential preferred terms (PTs) related to istradefylline. The analysis revealed new AEs during istradefylline treatment, including reports of Parkinsonism hyperpyrexia syndrome (n = 3, ROR 178.70, PRR 178.63, IC 1.97, EBGM 165.63), Compulsions (n = 5, ROR 130.12, PRR 130.04, IC 2.53, EBGM 123.02), Deep brain stimulation (n = 10, ROR 114.42, PRR 114.27, IC 3.33, EBGM 108.83), and Freezing phenomenon (n = 60, ROR 97.52, PRR 96.76, IC 5.21, EBGM 92.83). This study provides new risk signals and important insights into the use of istradefylline, but further research and validation are needed, especially for those AE that may occur in actual usage scenarios but are not yet explicitly described in the instructions.
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Conducta Compulsiva , Purinas , Estados Unidos , Bases de Datos Factuales , Evaluación Preclínica de Medicamentos , Purinas/efectos adversos , United States Food and Drug AdministrationRESUMEN
OBJECTIVE: Bupropion, a monocyclic antidepressant, aids in smoking cessation, treats major depression, and prevents severe depression in seasonal affective disorder patients. Yet, its adverse reactions remain insufficiently studied. METHODS: All data from the raw data packages for 78 quarters from the 1st quarter of 2004 to the 2nd quarter of 2023 were extracted from the FDA Adverse Event Reporting System (FAERS) database and imported into the SAS9.4 software for data cleaning and analysis. The Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) methods were used to analyze drug adverse events and assess their compliance with various screening criteria. RESULTS: The results showed a total of 36,862 reports related to Bupropion use, identifying 364 positive reaction terms (PT) covering 23 System Organ Classes (SOCs). In addition to known side effects, some new potential adverse reactions were found, such as Stool analysis abnormal, Oculocephalogyric reflex absent, Suspected suicide, and so on. At the same time, reactions like Encephalopathy neonatal, Hyponatraemic coma, and Electrocardiogram QRS complex prolonged were prominently ranked. Notably, occurrences such as Urine amphetamine positive and Amphetamines positive were relatively high, suggesting extra caution for these potential adverse reactions during clinical use of Bupropion. CONCLUSION: These findings highlight the potential health risks of long-term Bupropion use, especially concerning efficacy, positive drug tests, and suicidal tendencies. Therefore, it is recommended to monitor and assess patients using Bupropion more stringently to use this therapeutically potential drug more safely and effectively.
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Bupropión , Cese del Hábito de Fumar , Recién Nacido , Humanos , Bupropión/efectos adversos , Teorema de Bayes , Antidepresivos/uso terapéutico , Cese del Hábito de Fumar/psicología , Programas InformáticosRESUMEN
Objective: To investigate the antidepressant effect and potential mechanism of the Chufan Yishen Formula (CFYS) through network pharmacology, molecular docking, and experimental verification. Methods: The active ingredients and their target genes of CFYS were identified through Traditional Chinese Medicine Systems Pharmacology (TCMSP) and TCM-ID. We obtained the differentially expressed genes in patients with depression from the GEO database and screened out the genes intersecting with the target genes of CFYS to construct the PPI network. The key pathways were selected through STRING and KEGG. Then, molecular docking and experimental verification were performed. Results: A total of 113 effective components and 195 target genes were obtained. After intersecting the target genes with the differentially expressed genes in patients with depression, we obtained 37 differential target genes, among which HMOX1, VEGFA, etc., were the key genes. After enriching the differential target genes by KEGG, we found that the "chemical carcinogenesis-reactive oxygen species" pathway was the key pathway for the CFYS antidepressant effect. Besides, VEGFA might be a key marker for depression. Experimental verification found that CFYS could significantly improve the behavioral indicators of rats with depression models, including improving the antioxidant enzyme activity and increasing VEGFA levels. The results are consistent with the network pharmacology analysis. Conclusions: CFYS treatment for depression is a multicomponent, multitarget, and multipathway complex process, which may mainly exert an antidepressant effect by improving the neuron antioxidant stress response and regulating VEGFA levels.
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Ecological compensation is an effective means to reconcile the imbalance of eco-social development between regions and promote enthusiasm for ecological environmental protection. There is some conformity between the theory of ecosystem service flow and ecological compensation, which provides new technical support for the formulation of ecological compensation policy. This study took the Qinghai-Tibet Plateau as the research area, adopted the breaking point model to obtain the spatial characteristics of carbon sequestration flow, and formulated a multilevel ecological compensation policy with Tibet as the design object. The results showed that most of the Qinghai-Tibet Plateau has a carbon sequestration surplus; the central and eastern Qinghai-Tibet Plateau, western Sichuan are successively carbon sequestration supply areas; the Chengdu Plain and Xinjiang were listed as carbon sequestration benefit areas; and the carbon sequestration tended to flow more closely between supply and benefit areas in proximity to each other. Nyingchi, Chamdo, Naqu and Shannan in Tibet need to receive a total ecological compensation of 393.21 million USD, of which 93.71 % is from the national level, 6.02 % is from carbon sequestration benefit areas in other provinces; furthermore, Lhasa and Shigatse in Tibet need to provide the remaining ecological compensation. This study offers innovations for the formulation of ecological compensation policies and provide a new theory for ecological environment management.
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OBJECTIVE: This study explores the causal relationship between diabetes and depression using a two-sample Mendelian Randomization (TSMR) method. METHODS: The study selected single nucleotide polymorphisms (SNPs) closely associated with diabetes and depression in European populations from the Genome-Wide Association Study (GWAS) database, to serve as instrumental variables (IVs). The main evaluation method was inverse variance weighted analysis (IVW), supplemented by verification using Weighted median, Weighted mode, and MR Egger methods. The Odds Ratio (OR) and 95 % Confidence Interval (CI) were used as the main evaluation indicators, along with sensitivity analysis. RESULTS: This study found a negative correlation between diabetes and depression, suggesting that diabetes may reduce the risk of depression [IVW(FE): OR: 0.901, 95 % CI: 0.823 to 0.987; P = 0.025 < 0.05]. This finding was further confirmed by the Weighted median [OR: 0.844, 95 % CI: 0.730 to 0.974; P = 0.021 < 0.05] and Weighted mode method [OR: 0.766, 95 % CI: 0.637 to 0.921; P = 0.006 < 0.05]. However, the reverse showed no causal relationship between depression and diabetes (P > 0.05). Sensitivity analysis found no pleiotropy, and there were no large influences from individual SNPs on the result's robustness; the results are stable and reliable. CONCLUSION: For the first time, this study using TSMR analysis found a negative correlation between diabetes and the risk of depression onset in European populations, suggesting that diabetes might reduce the risk of depression. But as the mechanisms are still unclear, these findings warrant further study.
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Depresión , Diabetes Mellitus , Humanos , Depresión/epidemiología , Depresión/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Diabetes Mellitus/epidemiología , Diabetes Mellitus/genética , Análisis de VarianzaRESUMEN
BACKGROUND AND OBJECTIVES: Aimed to investigate the safety, accuracy, and efficacy of stereo electroencephalography (SEEG) in children of various ages, with particular emphasis on those younger than 3 years. There is limited guidance regarding whether SEEG can conducted on very young children. METHODS: This retrospective study was conducted between July 2018 and August 2022. It involved 88 patients who underwent 99 robot-assisted SEEG procedures at our center. The patients were categorized into 3 groups based on their age at the time of the robot-assisted SEEG procedures: group 1 (3 years and younger, n = 28), group 2 (age 3-6 years, n = 27), and group 3 (older than 6 years, n = 44). Clinical data, SEEG demographics, complications, and seizure outcomes were analyzed. RESULTS: A total of 675 electrodes were implanted, with an average of 6.82 ± 3.47 (2.00-16.00) electrodes per patient (P = .052). The average target point error for the 675 electrodes was 1.93 ± 1.11 mm, and the average entry point error was 1.30 ± 0.97 mm (P = .536 and P = .549, respectively). The overall percentage of complications was 6.06% (P = .879). No severe or long-term neurologic impairment was observed. Of the total 99 procedures included in this study, 78 were admitted for epilepsy surgery for the first time, while 9 patients were treated twice and 1 patient was treated 3 times. There were 21 radiofrequency thermocoagulation and 78 second-stage resective procedures performed after SEEG. There was no statistically significant difference in Engel class I outcomes among the patients who underwent SEEG in the 3 age groups (P = .621). CONCLUSION: Robot-assisted SEEG were demonstrated to be safe, accurate, and efficient across different age groups of children. This technique is suitable for children younger than 3 years who have indications for SEEG placement.
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Antibody-drug conjugates (ADCs)-a groundbreaking class of agents for targeted oncological therapies-consist of monoclonal antibodies with strong antigenic specificity coupled with highly active cytotoxic agents (also referred to as "payloads"). Over the past 2 decades, breast cancer research has evolved into a focal point for the research and development of ADCs, leading to several recent landmark publications. These advancements are ushering in a transformative era in breast cancer treatment and redefining conventional classifications by introducing a prospective subtype termed "HER2-low." The latest iterations of ADCs have demonstrated enhanced efficacy in disease management through the optimization of various factors, notably the incorporation of the bystander effect. These conjugates are no longer limited to the oncogenic driver human epidermal growth factor receptor 2 (HER2). Other antigens, including human epidermal growth factor receptor 3 (HER3), trophoblast cell surface antigen 2 (Trop-2), zinc transporter ZIP6 (LIV-1), and folate receptor α (FRα), have recently emerged as intriguing tumor cell surface nondriver gene targets for ADCs, each with one or more specific ADCs that showed encouraging results in the breast cancer field. This article reviews recent advances in the application of ADCs in the treatment of HER2-low breast cancer. Additionally, this review explores the underlying factors contributing to the impact of target selection on ADC efficacy to provide new insights for optimizing the clinical application of ADCs in individuals with low HER2 expression in advanced breast cancer.
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Antineoplásicos , Neoplasias de la Mama , Inmunoconjugados , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Inmunoconjugados/uso terapéutico , Estudios Prospectivos , Anticuerpos Monoclonales/uso terapéutico , Oncología Médica , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: Cerebral ischemic stroke (CIS) is a common cerebrovascular disease. The purpose of this study was to investigate the potential mechanism of hypoxia and immune-related genes in CIS. METHODS: All data were downloaded from public databases. Hub mRNAs was identified by differential expression analysis, WGCNA analysis and machine learning. Hub mRNAs were used to construct the classification models. Pearson correlation analysis was used to analyze the correlation between hub mRNAs and immune cell infiltration. Finally, the SAP30 was selected for verification in HMC3 cells. RESULTS: The SVM, RF and DT classification models constructed based on 6 hub mRNAs had higher area under the curve values, which implied that these classification models had high diagnostic accuracy. Pearson correlation analysis found that Macrophage has the highest negative correlation with CCR7, while Neutrophil has the highest positive correlation with SLC2A3. Drug prediction found that ruxolitinib, methotrexate, resveratrol and resatorvid may play a role in disease treatment by targeting different hub mRNAs. Notably, inhibition of SAP30 expression can reduce the apoptosis of HMC3 cells and inhibit the production of ROS and MDA. CONCLUSION: The identification of hub miRNAs and the construction of classification diagnosis models provide a theoretical basis for the diagnosis and management of CIS.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Apoptosis/genética , Histona Desacetilasas , Hipoxia , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/genética , Especies Reactivas de Oxígeno , Accidente Cerebrovascular/genética , Malondialdehído/metabolismoRESUMEN
Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder whose etiology involves multiple genetic and environmental factors. Sphingomyelin (SM) is a type of sphingolipid found in cell membranes, and recent evidence suggests a potential link between SM and AD. However, the nature of this relationship remains unclear. Objective: To elucidate the potential causal relationship between SM levels and the risk of developing AD using a two-sample Mendelian randomization approach. Methods: The study utilized data extracted from the genome wide association study database. The primary analysis method was the inverse variance weighted (IVW) method, which was supplemented by weighted median, weighted mode, and MR Egger methods. The study specifically investigated the bidirectional causal relationship between SM and AD, evaluating odds ratios (OR) with a 95% confidence interval (95% CI). Results: Elevated levels of SM were found to be a risk factor for AD, as shown by IVW(MRE) [OR: 1.001, 95% CI: 1.000 to 1.002; pâ=â0.020â<â0.05], IVW(FE) [OR: 1.001, 95% CI: 1.001 to 1.002; pâ=â3.36e-07â<â0.05], and MR Egger. Conversely, AD was demonstrated to lead to an increase in SM levels [IVW(MRE): OR: 5.64e+08, 95% CI: 1.69e+05 to 1.89e+12; pâ=â1.14e-06â<â0.05], with consistent findings across the IVW(FE), MR Egger, weighted median, and weighted mode methods. Conclusions: The study establishes a bidirectional positive correlation between SM and AD. Increased SM levels are associated with a higher risk of developing AD, and the presence of AD can further elevate SM levels, potentially exacerbating the disease's progression.
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OBJECTIVE: This study aimed to investigate the role of immune dysfunction in the pathogenesis of schizophrenia through single-cell transcriptome and bulk RNA data analyses. METHODS: The single-cell RNA sequencing (scRNA-seq) was selected to assess the cellular composition and gene expression profiles of the brain tissue. Further, bulk RNA sequencing data was utilized to corroborate findings from the single-cell analyses and provide additional insights into the molecular changes associated with the disease. Gene-drug interaction data was also included to identify potential therapeutic drugs targeting these dysregulated immune-related genes in schizophrenia. RESULTS: We discovered significant differences in cellular composition within schizophrenia tissue, including increased infiltration of fibroblasts, horizontal basal cells, monocytes, mesenchymal cells, and smooth muscle cells. The investigation of immune-related genes revealed significantly different expression of genes such as S100A2, CCL14, IGHA1, BPIFA1, GDF15, IL32, BPIFB2, HLA-DRA, S100A8, PTX3, TPM2, TNFRSF12A, GREM1 and others. These genes possibly contribute to the progression of schizophrenia through various pathways such as humoral immune response, IL-17 signaling pathway, adaptive immune response, antigen processing and presentation, and gut IgA production. Our findings also suggest possible transcriptional regulation in schizophrenia's immune dysfunction by transcription factors in monocytes, neutrophils, endothelial cells, and epithelial cells. Lastly, potential therapeutic drugs were identified through gene-drug interaction data, such as those targeting HLA-A and HLAB. CONCLUSION: The cellular heterogeneity and immune-related gene dysregulation play important roles in schizophrenia, which provides a foundation for understanding the pathogenesis and developing new treatment methods.
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Background: The overexpression of human epidermal growth factor receptor 2 (HER2) is strongly correlated with an elevated risk of developing distant metastases, particularly brain metastases, in breast cancer (BC) cases. RC48 (also known as Disitamab vedotin), represents a promising antibody-drug conjugate (ADC), that comprises three well-defined components: hertuzumab against the prominent tumor target-HER2, monomethyl auristatin E (MMAE) and a cleavable linker. Preclinical studies have demonstrated its robust antitumor activity in BC patient-derived xenograft models with HER2-positive or HER2-low expression. Additionally, antiangiogenic drugs like bevacizumab have shown potential efficacy on advanced BC via inhibiting pathological neovascularizationits. Case presentation: Here, we will share our experience in treating a 49-year-old woman initially diagnosed with stage IV breast cancer characterized by hormone receptor (HR)-negativity and HER2-positivity. This complex case entailed brain and liver metastases, and the patient exhibited resistance to various HER2-targeted treatment regimens. Finally, the patient received RC48 plus bevacizumab as the advanced forth-line treatment, which was well tolerated with no observed toxicities. Subsequent radiological assessments revealed remarkable regression in the brain metastatic lesions, classified as having partial response based on the RECIST 1.1 system. The period of progression-free survival (PFS) was 7 months. Conclusion: The present study underscores the efficacy of systemic treatment with RC48 in conjunction, showcasing substantial enhancement in both radiographic indicators and clinical symptomatology among patients with brain metastatic breast cancer (BMBC). More specifically, the sequential application of ADCs in combination with antiangiogenics presents a novel avenue for advancing the treatment landscape of metastatic BC.
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Objective: To study the practice of pharmaceutical services in internet-based psychiatric hospitals, and to analyze the prescriptions to ensure the safety and efficacy of internet-based medication in Wuxi, China. Methods: All 1,259 internet-based prescriptions from our hospital in 2022 were collected, and data on patients' age, gender, diagnosis, medications used, medication types, dosage forms, rationality of medication use, and reasons for irrationality were analyzed through descriptive statistics. Results: In the electronic prescriptions of internet-based psychiatric hospitals, females accounted for the majority (64.50%), with a female-to-male ratio of 1.82:1. Middle-aged and young adults accounted for the majority of patients (57.50%). There were 47 diagnosed diseases involved, with 89 types of medications used and 1,938prescriptions issued. Among them, there were 78 types of western medicine with 1,876 prescriptions (96.80%), and 11 types of traditional Chinese medicine with 62 prescriptions (3.20%). The main medications used were anti-anxiety and antidepressant medications (44.94%) and psychiatric medications (42.21%). The dosage forms were all oral, with tablets (78.53%), capsules (17.54%), and solution preparations (2.17%) being the top three in frequency. According to the prescription review results, the initial pass rate of internet-based system review was 64.26%. After intervention by the internet-based system and manual review by pharmacist reviewers, the final pass rate of internet-based prescriptions reached 99.76%. Conclusion: The practice of pharmaceutical services and prescription analysis in internet-based psychiatric hospitals could significantly improve medication rationality, which fills the research gap in this field. In addition, it promotes the transformation of pharmaceutical service models.