Aromatherapy refers to the method of using the aromatic components of plants in appropriate forms to act on the entire body or a specific area to prevent and treat diseases. Essential oils used in aromatherapy are hydrophobic liquids containing volatile aromatic molecules， such as limonene， linalool， linalool acetate， geraniol， and citronellol. These chemicals have been extensively studied and shown to have a variety of functions， including reducing anxiety， relieving depression， promoting sleep， and providing pain relief. Terpenoids are a class of organic molecules with relatively low lipid solubility. After being inhaled， they can pass through the nasal mucosa for transfer or penetrate the skin and enter the bloodstream upon local application. Some of these substances also have the ability to cross the blood-brain barrier， thereby exerting effects on the central nervous system. Currently， the academic community generally agrees that products such as essential oils and aromatherapy from aromatic plants have certain health benefits. However， the process of extracting a single component from it and successfully developing it into a drug still faces many challenges. Its safety and efficacy still need to be further verified through more rigorous and systematic experiments. This article systematically elaborated on the efficacy of aromatic substances， including plant extracts and natural small molecule compounds， in antibacterial and antiviral fields and the regulation of nervous system activity. As a result， a deeper understanding of aromatherapy was achieved. At the same time， the potential of these aromatic substances for drug development was thoroughly explored， providing important references and insights for possible future drug research and application.

Cancer immunotherapy has emerged as a promising strategy. However, low response rates and immune-related side effects have plagued immunotherapy. Metallic nanoparticles, utilizing metals as their framework, are gaining prominence in cancer immunotherapy. Metal ions have shown the ability to modulate immune status by activating the cGAS-STING pathway and inducing immunogenic cell death (ICD), thereby enabling multidimensional activation of immunotherapy. Metallic nanoparticles offer significant advantages in cancer immunotherapy, leading to their increasing use in enhancing therapeutic outcomes. In view of the ever-increasing research on metallic nanoparticles, this review presents the construction, characterization, and enhanced cancer immunotherapeutic effects of different types of metal nanosystems from the perspective of the immunoregulatory mechanisms of metal ions. We delve into the current limitations and future directions of metallic nanoparticles in this rapidly evolving field. To the best of our knowledge, this review offers the most up-to-date and systematic analysis of metallic nanoparticles in immunotherapeutic applications. It is anticipated that this review of metallic nanoparticles will inspire a more refined and intelligent design of metallic nanoparticles for future research, paving the way for advancing their clinical applications.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

The translation of genetic findings from genome-wide association studies into actionable therapeutics persists as a critical challenge in Alzheimer's disease (AD) research. Here, we present PI4AD, a computational medicine framework that integrates multi-omics data, systems biology, and artificial neural networks for therapeutic discovery. This framework leverages multi-omic and network evidence to deliver three core functionalities: clinical target prioritisation; self-organising prioritisation map construction, distinguishing AD-specific targets from those linked to neuropsychiatric disorders; and pathway crosstalk-informed therapeutic discovery. PI4AD successfully recovers clinically validated targets like APP and ESR1, confirming its prioritisation efficacy. Its artificial neural network component identifies disease-specific molecular signatures, while pathway crosstalk analysis reveals critical nodal genes (e.g., HRAS and MAPK1), drug repurposing candidates, and clinically relevant network modules. By validating targets, elucidating disease-specific therapeutic potentials, and exploring crosstalk mechanisms, PI4AD bridges genetic insights with pathway-level biology, establishing a systems genetics foundation for rational therapeutic development. Importantly, its emphasis on Ras-centred pathways-implicated in synaptic dysfunction and neuroinflammation-provides a strategy to disrupt AD progression, complementing conventional amyloid/tau-focused paradigms, with the future potential to redefine treatment strategies in conjunction with mRNA therapeutics and thereby advance translational medicine in neurodegeneration.

Objective To analyze the correlations between the thoracic electrical impedance tomography(EIT)-derived parameters global inhomogeneity(GI),center of ventilation(COV),regional ventilation delay(RVD),and atelectasis in hospitalized patients,and to explore their effectiveness in evaluating atelectasis.Methods The clinical data of 140 hospitalized patients monitored by thoracic EIT between Sep.2024 and Jan.2025 were retrospectively analyzed.Patients were assigned to 2 groups based on chest computed tomography confirmation of atelectasis within the preceding short-term period during EIT monitoring:non-atelectasis group or atelectasis group.The algorithm software designed with MATLAB was used to acquire GI and COV.RVD was obtained through analysis with the Dr?ger EIT Data Analysis Tool 6.3 software,and patients'general data were concurrently documented.Comparative analysis of EIT-derived parameters between groups was conducted.Multivariate logistic regression analysis was employed to investigate the correlations of GI,COV,and RVD with atelectasis,while receiver operating characteristic curve analysis was performed to assess the efficacy of EIT-derived parameters in evaluating atelectasis.Results A total of 140 patients were enrolled,with 19(13.6%)cases presenting atelectasis.Compared to the non-atelectasis group,the atelectasis group demonstrated significantly higher proportions of male patients and cardiovascular disease and thoracic surgery(non-pulmonary)histories,lower body mass index(BMI),and alongside elevated GI and RVD values with reduced COV(all P＜0.05).Multivariate logistic regression analysis revealed that GI,COV,and RVD maintained independent associations with atelectasis after adjusting for age,gender,BMI,pleural effusion,and emphysema(odds ratio[OR]=1.39,95%confidence interval[CI]1.20-1.67;OR=0.85,95%CI 0.75-0.96;OR=1.22,95%CI 1.09-1.39;all P＜0.05).The area under curve(AUC)values of GI,COV,and RVD for evaluating atelectasis in hospitalized patients were 0.82,0.80,and 0.82,respectively(while RVD demonstrated a higher AUC,its clinical applicability was influenced by respiratory patterns).Conclusion Thoracic EIT-derived parameters GI and COV demonstrate significant correlations with atelectasis and may serve as valuable indicators for evaluating atelectasis in hospitalized patients.

OBJECTIVE: To investigate the clinical phenotypes and genetic variant characteristics in children with epilepsy. METHODS: A total of 91 children with epilepsy admitted to the Women's and Children's Hospital Affiliated to Ningbo University from July 2021 to October 2022 were selected as the study subjects. Peripheral blood samples were collected from the children for whole exome sequencing. Candidate genetic variants were validated by Sanger sequencing and copy number variation sequencing (CNV-seq). The clinical phenotypes and treatment outcomes of the children with epilepsy were followed up, and an analysis of the relationship between genotype and phenotype was conducted. This study was approved by the Women's and Children's Hospital Affiliated to Ningbo University (Ethics No.: EC2020-048). RESULTS: Among the 91 children with epilepsy, 21 cases (23.08%, 21/91) were found to carry pathogenic or likely pathogenic variants. Of these, 18 cases had involved single base variant or insertional deletion, while 3 cases involved copy number variations. The gene with the highest detection rate was PRRT2 (38.10%, 8/21). Among the children with genetic variants, 47.62% (10/21) had onset during infancy, with 8 diagnosed with Benign familial infantile epilepsy (BFIE), 8 with Developmental epileptic encephalopathy (DEE), and 3 with Epileptic encephalopathy (EE). One case of Dravet syndrome (DS) and one case of Infantile spasms (IS) were also noted. The clinical manifestations of children were diverse and primarily included generalized tonic-clonic seizures and focal seizures. Among them, 52.38% (11/21) had exhibited cluster seizures, 23.81% (5/21) showed fever sensitivity, and 14.29% (3/21) experienced status epilepticus. After pharmacological treatment, 42.86% (9/21) of children had achieved complete seizure control, while 61.90% (13/21) had intellectual disability and 19.05% (4/21) had co-morbid autism spectrum disorder. CONCLUSION Pathogenic or likely pathogenic variants were identified in 23.08% of the pediatric epilepsy cases, with the PRRT2 gene being the most frequently involved. Among children carrying genetic variants, 47.62% had seizure onset during infancy. Genetic factors are an important cause of epilepsy, and early genetic testing may facilitate precise diagnosis, treatment, and prognostic evaluation.
Humans ; Female ; Male ; Epilepsy/genetics* ; Child, Preschool ; Child ; Phenotype ; Genotype ; DNA Copy Number Variations/genetics* ; Infant ; Membrane Proteins/genetics* ; Nerve Tissue Proteins/genetics* ; Adolescent ; Exome Sequencing

Objective:To identify candidate strains of Nontoxigenic Clostridioides difficile (NTCD) with potential for intervention in Clostridioides difficile infection (CDI) and analyze their phenotypic characteristics. Methods:A total of 713 Clostridioides difficile strains from various sources were systematically collected nationwide between 2015 and 2023. This included 649 strains isolated from human fecal samples and 64 strains isolated from the fecal samples of farmed animals. NTCD strains were preliminarily screened through toxin gene detection and antibiotic sensitivity test, and then NTCD candidate strains with potential for intervention in CDI were screened by a series of in vitro experiments, including MLST, sporulation, germination, adhesion, motility, and biofilm formation ability. Ultimately, the virulence genes and antimicrobial resistance genes of the candidate strains were comprehensively analyzed to rigorously assess their safety profiles. Results:Among 713 strains of C. difficile from different sources, 10 strains were initially screened out, which were non-toxin-producing and sensitive to antibiotics. MLST showed that seven strains were from the Clade1 branch and three strains were of a novel type. The results of sporulation and germination showed that SD59, SD178, SJZ17, and WZ142 had stronger sporulation and germination abilities. The adhesion of 10 strains was high, and the adhesion rate was between 72.93% and 99.32%. The motility of all strains was different, and the motility of SD178, SD59 and SJZ17 was stronger. The biofilm-forming ability of all strains was weak. SD59, SD178 and SJZ17 carried a limited number of virulence and resistance genes, thereby posing a relatively low safety risk. Conclusion:Three NTCD strains are successfully selected as potential effective NTCD strains to interfere with CDI.

Objective:To identify factors associated with depressive symptoms in maintenance hemodialysis patients and to examine the relationship between these symptoms and mortality.Methods:Between January and December 2019, patients who received maintenance hemodialysis in the Blood Purification Center of the Second Affiliated Hospital of Nanjing Medical University were enrolled in a prospective cohort study. Depressive symptoms were assessed using the internationally validated patient health questionnaire-8 (PHQ-8). Sleep quality and anxiety were measured with the Pittsburgh sleep quality index (PSQI) and the generalized anxiety disorder-7 (GAD-7) scale, respectively. Follow-up continued until December 31, 2022, with all-cause mortality as the primary outcome. Ordinal logistic regression was used to identify independent predictors of depression severity. Cox proportional hazards models evaluated the association between depressive symptoms and mortality.Results:A total of 532 maintenance hemodialysis (MHD) patients completed the study. Among them, 177 (33.3%) exhibited depressive symptoms. Compared with patients without depression, those with mild or moderate-to-severe depression were older [median age: 58 (50, 66) vs. 60 (55, 65) vs. 55 (46, 64)], more likely to smoke [35.9% (51/142) vs. 40.0% (14/35) vs.26.2% (93/355)], had poorer sleep quality [PSQI: 9 (6, 13) vs. 12 (9, 17) vs. 5 (3, 9)], and higher anxiety levels [GAD-7: 1 (0, 3) vs. 3 (1, 6) vs. 0 (0, 1)], the differences among the three groups were statistically significant (all P<0.05). Ordinal logistic regression identified smoking status, history of diabetes or cardiovascular disease, hemoglobin level, PSQI score, and GAD-7 score as independent predictors of depression severity ( OR=1.60, 1.80, 1.81, 0.98, 3.67, 8.67; all P<0.05). After a median follow-up of 40 (35, 44) months, 109 patients died, including 66 (60.6%) from cardio-cerebrovascular causes and 24 (22.0%) from infections. Kaplan-Meier analysis revealed significantly lower cumulative survival in the depression group compared to the non-depression group ( P<0.001). Cox regression analysis demonstrated that depressive symptoms remained independently associated with all-cause mortality after adjusting for confounders ( HR=1.06, 95% CI 1.00-1.13, P=0.048), with an even stronger association observed for patients with PHQ-8 scores≥2.9 ( HR=1.10, 95% CI 1.03-1.16, P=0.005). However, the associations between depression and cardio-cerebrovascular mortality ( P=0.111) or infection-related mortality ( P=0.509) were not statistically significant. Conclusions:Depressive symptoms are prevalent among maintenance hemodialysis patients and are independently associated with increased all-cause mortality. Smoking, comorbid diabetes or cardiovascular disease, low hemoglobin level, poor sleep quality, and anxiety are risk factors contributing to depression. Maintenance hemodialysis patients with PHQ-8 scores≥3 should be considered at heightened risk for mortality.

Objective:To investigate the clinical phenotypes and genetic variant characteristics in children with epilepsy.Methods:A total of 91 children with epilepsy admitted to the Women′s and Children′s Hospital Affiliated to Ningbo University from July 2021 to October 2022 were selected as the study subjects. Peripheral blood samples were collected from the children for whole exome sequencing. Candidate genetic variants were validated by Sanger sequencing and copy number variation sequencing (CNV-seq). The clinical phenotypes and treatment outcomes of the children with epilepsy were followed up, and an analysis of the relationship between genotype and phenotype was conducted. This study was approved by the Women′s and Children′s Hospital Affiliated to Ningbo University (Ethics No.: EC2020-048).Results:Among the 91 children with epilepsy, 21 cases (23.08%, 21/91) were found to carry pathogenic or likely pathogenic variants. Of these, 18 cases had involved single base variant or insertional deletion, while 3 cases involved copy number variations. The gene with the highest detection rate was PRRT2 (38.10%, 8/21). Among the children with genetic variants, 47.62% (10/21) had onset during infancy, with 8 diagnosed with Benign familial infantile epilepsy (BFIE), 8 with Developmental epileptic encephalopathy (DEE), and 3 with Epileptic encephalopathy (EE). One case of Dravet syndrome (DS) and one case of Infantile spasms (IS) were also noted. The clinical manifestations of children were diverse and primarily included generalized tonic-clonic seizures and focal seizures. Among them, 52.38% (11/21) had exhibited cluster seizures, 23.81% (5/21) showed fever sensitivity, and 14.29% (3/21) experienced status epilepticus. After pharmacological treatment, 42.86% (9/21) of children had achieved complete seizure control, while 61.90% (13/21) had intellectual disability and 19.05% (4/21) had co-morbid autism spectrum disorder. Conclusion:Pathogenic or likely pathogenic variants were identified in 23.08% of the pediatric epilepsy cases, with the PRRT2 gene being the most frequently involved. Among children carrying genetic variants, 47.62% had seizure onset during infancy. Genetic factors are an important cause of epilepsy, and early genetic testing may facilitate precise diagnosis, treatment, and prognostic evaluation.

Objective To investigate the renal function recovery and perioperative risk factors for chronic kidney disease in patients after acute Stanford type A aortic dissection (ATAAD) repair. Methods A retrospective study was conducted on patients who underwent ATAAD repair at the Xiamen Cardiovascular Hospital, Xiamen University from 2020 to 2021, and their clinical data were analyzed. Results A total of 255 patients were included, with 200 males and 55 females, and an average age of (52.80±12.46) years. The incidence of acute kidney injury (AKI) after ATAAD repair was 43.9%. Dissection involving the renal artery [OR=2.144, 95%CI (1.234, 3.765), P=0.007], intraoperative urine output [OR=0.761, 95%CI (0.625, 0.911), P=0.004], and intraoperative red blood cell transfusion [OR=1.288, 95%CI (1.088, 1.543), P=0.004] were significantly associated with early AKI after ATAAD repair. Long-term renal function follow-up data were available for 232 patients, among whom 40 (17.2%) patients developed chronic kidney disease (CKD). Independent predictors for CKD included lower body mass index [OR=0.827, 95%CI (0.723, 0.931), P=0.003], preoperative cardiac tamponade [OR=5.344, 95%CI (1.65, 17.958), P=0.005], preoperative renal hypoperfusion syndrome [OR=12.629, 95%CI (5.003, 35.373), P<0.001], postoperative peak serum creatinine time>3 d [OR=7.566, 95%CI (2.799, 22.731), P<0.001], and AKI grade [grade 1: OR=4.418, 95%CI (1.339, 15.361), P=0.016; grade 2: OR=8.345, 95%CI (1.762, 40.499), P=0.007; grade 3: OR=9.463, 95%CI (2.602, 37.693), P<0.001]. Conclusion AKI related to ATAAD repair can recover in the early postoperative period, but both the duration and severity of AKI will affect long-term renal function. In addition, patients' nutritional status, preoperative cardiac tamponade, and renal hypoperfusion syndrome are also independent risk factors for long-term renal dysfunction.