Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

In order to accurately capture the respiratory muscle movement and extract the synchronization signals corresponding to the breathing phases, a comprehensive signal sensing system for sensing the movement of the respiratory muscle was developed with applying the thin-film varistor FSR402 IMS-C07A in this paper. The system integrated a sensor, a signal processing circuit, and an application program to collect, amplify and denoise electronic signals. Based on the respiratory muscle movement sensor and a STM32F107 development board, an experimental platform was designed to conduct experiments. The respiratory muscle movement data and respiratory airflow data were collected from 3 healthy adults for comparative analysis. In this paper, the results demonstrated that the method for determining respiratory phase based on the sensing the respiratory muscle movement exhibited strong real-time performance. Compared to traditional airflow-based respiratory phase detection, the proposed method showed a lead times ranging from 33 to 210 ms [(88.3 ± 47.9) ms] for expiration switched into inspiration and 17 to 222 ms [(92.9 ± 63.8) ms] for inspiration switched into expiration, respectively. When this system is applied to trigger the output of the ventilator, it will effectively improve the patient-ventilator synchrony and facilitate the ventilation treatment for patients with respiratory diseases.
Humans ; Respiratory Muscles/physiology* ; Signal Processing, Computer-Assisted ; Movement/physiology* ; Respiration ; Monitoring, Physiologic/methods* ; Adult

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Gelsemium elegans (G. elegans) is an extremely poisonous plant that is widely distributed in southern China and southeastern Asia. G. elegans poisoning events occur frequently in southern China, and are therefore an urgent public health problem requiring multidisciplinary action. However, the toxic components and toxicological mechanisms remain unclear. Here, we describe a systematic investigation on the toxic components of G. elegans, resulting in the isolation and identification of 120 alkaloids. Based on acute toxicity screening, the structure-toxicity relationship of Gelsemium alkaloids was proposed for the first time. Moreover, gelsedine- and humantenine-type alkaloids were detected in the clinical blood sample, and were confirmed to be causative in the poisoning. The most toxic compound, gelsenicine (1), had selective inhibitory effects toward ventral respiratory group (VRG) neurons in the medulla, which is the main brain region controlling respiration in the central nervous system. Gelsenicine (1) strongly inhibited the firing of action potentials in VRG neurons through its ability to stimulate GABA_A receptors, the main receptors involved in inhibitory neurotransmission. Application of GABA_A receptor antagonists successively reversed action potential firing in gelsenicine (1)-treated VRG neurons. Importantly, the GABA_A receptor antagonists securinine and flumazenil significantly increased the survival of poisoned animals. Our findings provide insight into the components and mechanisms of G. elegans toxicity, and should assist the development of effective emergency treatments for G. elegans poisoning.

Objective:To summarize the HRCT and MRI appearances of stapical footplate fistula related to inner ear malformation (SFF-Re-IEM).Methods:The HRCT and MRI materials of 48 cases (53 ears) SFF-Re-IEM were retrospectively analyzed. Among them, 25 SFF-Re-IEM ears were confirmed by surgery. Their CT and MRI findings including associated IEM type, internal auditory canal (IAC) malformation, tympanic fluid, its density and signal features, and accompanied labyrinthitis were recorded.Results:Among 48 cases (53 ears) with SFF-Re-IEM, 17 ears with incomplete partition type Ⅰ, accounting for 32.1%, 13 ears with common cavity for 24.5%, 13 ears with cochlear aplasia for 24.5%, 7 ears with cochlear dysplasia Ⅱ for 13.2%, and 3 ears with Mondini for 5.7%,were found respectively. 94.3% of them were associated with a defect or dysplasia in the found of the IAC. They were divided into 4 types according to the intact of the stapical footplate and accompanied CSF otorrhea: 22 ears were diagnosed as the stapical footplate leaking, of them, 2 ears might come from the stapical footplate bony defect, 6 ears were from the stapical footplate hernia. 1 ear belonged to the peristapical footplate leaking. 30 ears with the isolated the stapical footplate hernia were another found. The bony defect in 2 ears with the stapical footplate bony defect were not presented on CT and MRI.The focal bony defect of the affected stapical footplate of 36 ears with the stapical footplate hernia were demonstrated, which presented the hemispherical protruding into the tympana, the soft-tissue density on CT, and CSF-like signal on the MR heaved-T2WI images. Among 22 ears with the stapical footplate leaking, their imaging appearances varied from the different amount of the leaking CSF. Besides the focal bony defects of the affected stapical footplates, there were much more CSF-like density or signal in the ipsilateral tympanic cavity in 17 affected ears connecting with the vestibule through the defect area. In the CSF leaking ears with less CSF leaking in 5 ears, the CSF-like cysts like SFH were shown on the stapical footplate defect area, but their outer edges were irregular, and the CSF-like signal scattering in the tympanic cavity did not connect with the protruding cysts at the stapical area.Conclusion:The variable appearances of the SFF-Re-IEM ears based on the different subtypes are its characteristic HRCT and MRI appearances. This is helpful for the SFF-Re-IEM diagnosing to grasp its imaging features.

Objective To optimize the preparation process of hydroxysafflor yellow A(HSYA)nanoparticle and conduct in vitro release evaluation.Methods HSYA nanoparticles were prepared with PLGA as carrier by modified compound emulsion method.The optimal preparation process of the experiment was selected by Plackett-Burman and Box-Behnken response surface method.The nanoparticles were characterized by using particle size analyzer,TEM scanning electron microscope,Fourier transform infrared spectroscopy(FT-IR),X-ray diffraction(XRD).Frozen(4℃)storage stability,stability in physiological medium,lyophilized protective agent and in vitro release rate were investigated.Results The optimal process prescription of nanoparticle is as follow:pH value is 6.95,the dosage is 2.8 mg,and carrier dosage is 18.2 mg.The size of nanoparticles obtained at optimum condition is(176.4±1.29)nm,the polydiseperse index(PDI)is 0.152±0.014,the Zeta potential is(-17.6±0.46)mV,the encapsulation rate is(78.5±0.49)％,drug loading is(7.3±0.07)％.These nanoparticles showed round and good dispersion.Good stability in 4℃ storage environment and different physiological media of nanoparticles were observed.The best lyophilized protective agent was 1％glucose and the in vitro release rate of nanoparticles at 48 hours was 85％.Conclusion The optimization method is reasonable and reliable.The obtained nanoparticles have good stability and sustained-release effect.The in vitro release behavior conformed to first-order kinetic model.

Objective To explore the potential mechanism of Babao Dan on primary liver cancer based on network pharmacology. Methods First, the diethylnitrosamine-induced hepatocellular carcinoma rat（HCC）model was used to observe the effects of Babao Dan. Then, the effective components in Babao Dan were detected by UPLC-MS, and the potential target sites of these effective components were predicted in the Swiss Target Prediction databases, etc. The corresponding target sites for HCC were screened using GeneCards, OMIM and Therapeutic Target Database, and the common target sites between Babao Dan and HCC were obtained after getting the intersection. The protein-protein interaction network was drawn by Cytoscape software and the STRING database, and the key molecules regulating HCC by Babao Dan were screened out. The effective target sites were subjected to GO analysis in the DAVID database and enrichment analysis in the Pathway’s KEGG. Finally, the clinical relevance of key molecules to liver cancer patients was verified by the TCGA database. Results Babao Dan could slow down the tumor development. 851 chemical components were detected in BaBao Dan by UPLC-MS , 9 major active components and 285 target sites were identified. 637 hepatocellular carcinoma-related targets were screened out, and 16 targets of Babao Dan regulating HCC were identified. GO enrichment analysis showed 802 biological processes, 11 cell compositions, and 43 molecular functions, while KEGG pathway enrichment analysis identified a total of 90 pathways. Correlation analysis of TCGA identified three key molecules associated with the survival of liver cancer patients. Conclusion In the primary rat liver cancer model, Babao Dan was found to significantly prolong the survival of cancer-induced rats and reduce tumor burden. The initial prediction of the mechanism by which Babao Dan regulating liver cancer was made through UPLC-MS analysis and network pharmacology methods, indicating that Babao Dan has the characteristics of multi-component, multi-pathway, and multi-target regulation of primary liver cancer, which could provide a reference for further relevant experimental research.