OBJECTIVE To investigate the effect of astragaloside Ⅳ（AST） on the injury of arterial endothelial tissue in rats with intracranial aneurysms （IA）， and to explore its mechanism of action based on the nuclear factor κB （NF-κB）/nucleotide- binding domain leucine-rich repeat and pyrin domain-containing protein 3 （NLRP3） signaling pathway. METHODS Rats were divided into Sham group （intragastric administration and intraperitoneal injection of the same volume of normal saline）， IA group （intragastric administration and intraperitoneal injection of the same volume of normal saline）， AST low-dose group （AST-L group， intragastric administration of 40 mg/kg AST）， AST high-dose group （AST-H group， intragastric administration of 80 mg/kg AST）， AST-H+HY-N2485 group [intragastric administration of 80 mg/kg AST and intraperitoneal injection of 25 mg/kg HY-N2485 （activator of NF-κB/NLRP3 signaling pathway）]. They were given relevant medicine， once a day， for 8 consecutive weeks. After last medication， the levels of inflammatory factors [serum tumor necrosis factor-α （TNF-α）， interleukin-18 （IL-18）， IL-6] and vascular endothelial growth factor （VEGF） and endothelin （ET） were detected； the morphology of IA was observed； the expressions of von Willebrand factor （vWF）， vascular cell adhesion molecule-1 （VCAM-1）， endothelial nitric oxide synthase （eNOS）， and NF-κB/NLRP3 pathway related proteins in vascular tissue were also determined. RESULTS Compared with the Sham group， the basilar arterial ring of rats in the IA group had obvious protrusions， and the arterial vascular endothelial cells were significantly damaged. The levels of inflammatory factors， VEGF and ET in serum， as well as the expression levels of vWF， VCAM-1 and NLRP3 proteins and the phosphorylation level of NF-κB protein in vascular tissues were increased significantly （P＜ 0.05）. Aneurysms and ruptures of the internal elastic layer were significantly increased （P＜0.05）， while the expression level of eNOS protein was significantly decreased （P＜0.05）. Compared with IA group， the morphology of IA and the levels of above indexes were all improved significantly in AST-L and AST-H groups （P＜0.05），and the improvement in the AST-H group was more significant than that in the AST-L group （P＜0.05）； HY-N2485 could attenuate the improvement effect of AST on vascular endothelial tissue damage in IA rats （P＜0.05）. CONCLUSIONS AST may inhibit the expression of inflammatory factors， alleviate inflammation and vascular endothelial tissue damage in IA rats by inhibiting NF- κB/NLRP3 signaling pathway，thereby inhibiting the formation of IA. active_999@sina.com

ObjectiveTo observe the neuroprotective effects of ginsenoside Rb₁ on lipopolysaccharide （LPS）-induced neuroinflammation in mice and to preliminarily investigate its mechanism of action. MethodSeventy ICR mice were randomly divided into blank group， model group， dexamethasone sodium phosphate injection group， and low-dose， high-dose ginsenoside Rb₁ groups， with 14 mice in each group. A mouse brain neuroinflammation model was prepared using the LPS dose escalation method， starting with a dose of 1 mg·kg^-1 and administered via intraperitoneal injection every 48 h （every other morning）. Each subsequent dose increased by 2 mg·kg^-1， for a total of 7 injections， culminating in a final dose of 13 mg·kg^-1. The dexamethasone sodium phosphate injection group received an intraperitoneal injection at 5 mg·kg^-1·d^-1. The low-dose and high-dose ginsenoside Rb₁ groups were given intraperitoneal injections at 10 mg·kg^-1·d^-1 and 20 mg·kg^-1·d^-1， respectively， while the blank and model groups received the same volume of normal saline for 14 days. The behavioral activity of LPS mice was observed， anxiety-like behavior was assessed using the Y-maze and elevated plus maze， and brain levels of monocyte chemoattractant protein-1 （MCP-1）， tumor necrosis factor-α （TNF-α）， and interleukin-1β （IL-1β） were measured by enzyme-linked immunosorbent assay （ELISA）. Neuronal damage of microglia， and the activation status of microglia and astrocytes in the brain were assessed using immunofluorescence staining. The protein expression of phosphatidylinositol-3-kinase （PI3K）， protein kinase B （Akt）， and nuclear factor-κB （NF-κB） in mouse brain were detected by Western blot. ResultCompared with the blank group， the model group showed significantly increased anxiety-like behavior in the Y-maze and elevated plus maze （P<0.05， P<0.01）， significantly elevated levels of MCP-1， TNF-α， and IL-1β in the brain （P<0.01）， a significant decrease in the number of neuronal positive cells in the somatosensory cortex and hippocampus CA1 region （P<0.01）， significant activation of microglia and astrocytes （P<0.01）， and a significant increase in the expression of phosphorylated PI3K， Akt， and NF-κB proteins （P<0.01）. Compared with the model group， the ginsenoside Rb₁ low-dose and high-dose groups showed significantly reduced anxiety-like behavior in the Y-maze and elevated plus maze （P<0.05， P<0.01）， significantly decreased levels of MCP-1， TNF-α， and IL-1β in the brain （P<0.01）， a significant increase in the number of neuronal positive cells in the somatosensory cortex and hippocampus CA1 region （P<0.01）， significant inhibition of microglia and astrocyte activation （P<0.05， P<0.01）， and a significant decrease in the expression of phosphorylated PI3K， Akt， and NF-κB proteins （P<0.05， P<0.01）. ConclusionGinsenoside Rb₁ has neuroprotective effects on LPS-induced inflammation in mice， which may involve the regulation of the PI3K/Akt signaling pathway.

OBJECTIVE To establish HPLC fingerprint of Shuangdong capsules， and to study the spectral effect relationship of its anti-inflammatory effect. METHODS The fingerprints of 15 batches of Shuangdong capsules were established by HPLC，and the similarity evaluation was carried out； the foot swelling model was established to investigate the anti-inflammatory activity of Shuangdong capsules. The gray correlation analysis method was used to construct the spectral effect relationship for the anti- inflammatory effect of Shuangdong capsules using the swelling rate of rat foot and the levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， prostaglandin E2 （PGE2）， interleukin-6 （IL-6）， IL-8， IL-1β and tumor necrosis factor-α （TNF-α） in right hindfoot tissues as the pharmacodynamic indexes of anti-inflammatory effects. RESULTS Overall 15 batches of Shuangdong capsules identified 20 common peaks， the similarities were all greater than 0.97， and a total of 8 chromatographic peaks were identified. According to the gray correlation analysis， the correlation degrees between the peak area and the foot swelling rate and the levels of MDA， SOD， PGE2， IL-6， IL-8， IL-1β and TNF-α in 15 batches of Shuangdong capsules were 0.621 1- 0.783 5， 0.564 3-0.827 9， 0.581 0-0.845 3， 0.564 9-0.855 0， 0.583 1-0.856 4， 0.576 5-0.863 5， 0.564 1-0.838 0 and 0.572 5- 0.851 3， respectively. Among them， the chemical components represented by peak 4 （geniposidic acid）， peak 10 （chlorogenic acid） and the chemical composition represented by peak 2 were strongly correlated with anti-inflammatory efficacy indicators. CONCLUSIONS In this study， HPLC fingerprints of 15 batches of Shuangdong capsules were successfully established. Among them， geniposidic acid， chlorogenic acid may be its anti-inflammatory ingredients.

Objective:To design a fully integrated multi-channel implantable brain-computer interface electrical stimulation system.Methods:The human-computer interaction interface of the upper computer was set by users, and the data was packaged via a self-built protocol. When parameters were transmitted to the field programmable gate array (FPGA) chip through the Bluetooth module, the stimulation chip was controlled after the parameter analysis was completed. Eventually the user-set current stimulation was output. To verify the system feasibility, the accuracy of the single-channel stimulation waveform, the multi-channel output capability, and the adjustable range of the parameter were tested separately.Results:It realized 16 channels of time-sharing differential stimulation current output, the output stimulation current waveform was dual-phase equal-width pulse, the amplitude ranged within 4~1 000 μA, the pulse single-phase width range was 10~1 000 μs, the cycle time was 1~1 000 ms, thus the current parameters could be accurately adjusted.Conclusions:A fully integrated multi-channel implantable brain-computer interface electrical stimulation system was completed.

Objectives: To investigate whether the protective actions of ginsenoside Rb1 (Rb1) on astrocytes are mediated through the Gs-type G-protein-coupled receptor (GPCR-Gs). Methods: Primary astrocyte cultures derived from neonatal mouse brain were used. Astrocyte injury was induced via oxygen-glucose deprivation/re-oxygenation (OGD/R). Cell morphology, viability, lactate dehydrogenase (LDH) leakage, apoptosis, glutamate uptake, and brain-derived neurotrophic factor (BDNF) secretion were assessed to gauge cell survival and functionality. Western blot was used to investigate the cyclic adenosine monophosphate (cAMP) and protein kinase B (Akt) signaling pathways. GPCR-Gs-specific inhibitors and molecular docking were used to identify target receptors. Results: Rb1 at concentrations ranging from 0.8 to 5 μM did not significantly affect the viability, glutamate uptake, or BDNF secretion in normal astrocytes. OGD/R reduced astrocyte viability, increasing their LDH leakage and apoptosis rate. It also decreased glutamate uptake and BDNF secretion by these cells. Rb1 had protective effects of astrocytes challenged by OGD/R, by improving viability, reducing apoptosis, and enhancing glutamate uptake and BDNF secretion. Additionally, Rb1 activated the cAMP and Akt pathways in these cells. When the GPCR-Gs inhibitor NF449 was introduced, the protective effects of Rb1 completely disappeared, and its activation of cAMP and Akt signaling pathways was significantly inhibited. Conclusion Rb1 protects against astrocytes from OGD/R-induced injury through GPCR-Gs mediation.

Objective:To explore influencing factors of poor prognosis in patients with severe trauma,and to analyze distribu-tion characteristics of adverse prognostic factors in patients with different early peripheral blood lymphocyte levels based on potential categories.Methods:A total of 174 patients with severe trauma treated in Mianyang Central Hospital from September 2020 to Septem-ber 2022 were selected.According to condition of massive blood transfusion or death within 24 hours after admission,patients were divided into:good prognosis group(n=136)and poor prognosis group(n=38).Clinical data of two groups were compared,multivariate Logistic regression analysis was used to analyze factors affecting poor prognosis,and cluster analysis and potential classification were used to analyze distribution characteristics of adverse prognostic factors in patients with different early peripheral blood lymphocyte levels.Results:Multivariate Logistic regression analysis results showed decrease of Glasgow coma scale(GCS),prolongation of acti-vated partial thromboplastin time(APTT),increase of D-dimer(D-D),decrease of fibrinogen(Fib),increase of fibrinogen degrada-tion products(FDP),increase of neutrophil/lymphocyte ratio(NLR)and decrease of lymphocyte level were factors influencing poor prognosis(P<0.05).Cluster analysis results showed that risk of poor prognosis was obviously clustered,and patients could be divided into poor prognosis high risk group(lymphocyte level≤0.90×109 L-1,n=72)and low risk group(lymphocyte level>0.90×109 L-1,n=102).Incidence of poor prognosis in high risk group[33.33%(24/72)]was significantly higher than that in low risk group[13.73%(14/102)](P<0.05).Potential category analysis results showed that there were three potential category distribution patterns in poor prognosis high risk group and low risk group.Proportion of"unelevated distribution of D-D in patients with low GCS score"in high risk group was significantly higher than that in low risk group,and proportion of"distribution of less risk factors"in high risk group was sig-nificantly lower than that in low risk group(P<0.05).There was no significant difference in proportion of elevated D-D distribution in patients with low GCS score between two groups(P>0.05).Conclusion:Decrease of GCS score,prolongation of APTT and increase of D-D are all associated with poor prognosis in patients with severe trauma.Patients with lymphocyte level≤0.90×109 L-1 have a higher risk of poor prognosis,and main influencing factors are"non-elevated distribution of D-D in patients with low GCS score".

BACKGROUND: Weather conditions are a possible contributing factor to age-related macular degeneration (AMD), a leading cause of irreversible loss of vision. The present study evaluated the joint effects of meteorological factors and fine particulate matter (PM_2.5) on AMD. METHODS: Data was extracted from a national cross-sectional survey conducted across 10 provinces in rural China. A total of 36,081 participants aged 40 and older were recruited. AMD was diagnosed clinically by slit-lamp ophthalmoscopy, fundus photography, and spectral domain optical coherence tomography (OCT). Meteorological data were calculated by European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis and were matched to participants' home addresses by latitude and longitude. Participants' individual PM_2.5 exposure concentrations were calculated by a satellite-based model at a 1-km resolution level. Multivariable-adjusted logistic regression models paired with interaction analysis were performed to investigate the joint effects of meteorological factors and PM_2.5 on AMD. RESULTS: The prevalence of AMD in the study population was 2.6% (95% CI 2.42-2.76%). The average annual PM_2.5 level during the study period was 63.1 ± 15.3 µg/m³. A significant positive association was detected between AMD and PM_2.5 level, temperature (T), and relative humidity (RH), in both the independent and the combined effect models. For PM_2.5, compared with the lowest quartile, the odds ratios (ORs) with 95% confidence intervals (CIs) across increasing quartiles were 0.828 (0.674,1.018), 1.105 (0.799,1.528), and 2.602 (1.516,4.468). Positive associations were observed between AMD and temperature, with ORs (95% CI) of 1.625 (1.059,2.494), 1.619 (1.026,2.553), and 3.276 (1.841,5.830), across increasing quartiles. In the interaction analysis, the estimated relative excess risk due to interaction (RERI) and the attributable proportion (AP) for combined atmospheric pressure and PM_2.5 was 0.864 (0.586,1.141) and 1.180 (0.768,1.592), respectively, indicating a synergistic effect between PM_2.5 and atmospheric pressure. CONCLUSIONS This study is among the first to characterize the coordinated effects of meteorological factors and PM_2.5 on AMD. The findings warrant further investigation to elucidate the relationship between ambient environment and AMD.
Humans ; Adult ; Middle Aged ; Cross-Sectional Studies ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; China/epidemiology* ; Macular Degeneration/etiology* ; Meteorological Concepts

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
Humans ; Epigenesis, Genetic ; Gastric Mucosa/metabolism* ; Chromatin/metabolism* ; Stem Cells ; Epithelium/metabolism* ; Fatty Acid-Binding Proteins/metabolism*

Objective: To clinically validate the feasibility and accuracy of cine images acquired through the multitasking method, with no electrocardiogram gating and free-breathing, in measuring left ventricular (LV) function indices by comparing them with those acquired through the balanced steady-state free precession (bSSFP) method, with multiple breath-holds and electrocardiogram gating. Materials and Methods: Forty-three healthy volunteers (female:male, 30:13; mean age, 23.1 ± 2.3 years) and 36 patients requiring an assessment of LV function for various clinical indications (female:male, 22:14; 57.8 ± 11.3 years) were enrolled in this prospective study. Each participant underwent cardiac magnetic resonance imaging (MRI) using the multiple breath-hold bSSFP method and free-breathing multitasking method. LV function parameters were measured for both MRI methods. Image quality was assessed through subjective image quality scores (1 to 5) and calculation of the contrast-to-noise ratio (CNR) between the myocardium and blood pool. Differences between the two MRI methods were analyzed using the Bland–Altman plot, paired t-test, or Wilcoxon signed-rank test, as appropriate. Results: LV ejection fraction (LVEF) was not significantly different between the two MRI methods (P = 0.222 in healthy volunteers and P = 0.343 in patients). LV end-diastolic mass was slightly overestimated with multitasking in both healthy volunteers (multitasking vs. bSSFP, 60.5 ± 10.7 g vs. 58.0 ± 10.4 g, respectively; P < 0.001) and patients (69.4 ± 18.1 g vs. 66.8 ± 18.0 g, respectively; P = 0.003). Acceptable and comparable image quality was achieved for both MRI methods (multitasking vs. bSSFP, 4.5 ± 0.7 vs. 4.6 ± 0.6, respectively; P = 0.203). The CNR between the myocardium and blood pool showed no significant differences between the two MRI methods (18.89 ± 6.65 vs. 18.19 ± 5.83, respectively; P = 0.480). Conclusion Multitasking-derived cine images obtained without electrocardiogram gating and breath-holding achieved similar image quality and accurate quantification of LVEF in healthy volunteers and patients.

Objective:To explore the application effect of case-based learning (CBL) and lecture-based learning (LBL) in the teaching of image post-processing course in the standardized training system of medical imaging technology.Methods:A total of 34 trainees in the standardized training of imaging technology of Batch 2018 in West China Hospital of Sichuan University were divided into the experimental group and the control group according to their student numbers, with 17 students in each group. CBL teaching was carried out in the experimental group, and LBL teaching was carried out in the control group. According to the standardized training course design, after one year of image post-processing course teaching, the teaching effect was evaluated through closed-book examination, questionnaire survey and post-processing test. SPSS 20.0 was used for t-test and Mann-Whitney U test. Results:The scores of closed-book examinations (74.42±6.10) and post-processing test (73.47±6.03) in the experimental group were higher than those in the control group [(69.11±3.70) and (69.08±6.51)], and the difference was statistically significant ( P<0.05). The questionnaire survey showed that the students in the experimental group recognized CBL teaching in terms of learning interests stimulation, classroom atmosphere mobilization, clinical thinking cultivation, self-study ability training, and analysis of difficult and rare cases, etc. Conclusion:In the image post-processing course of standardized training of medical imaging technology, the rational application of CBL teaching mode is helpful to improve students' learning enthusiasm, self-learning ability, comprehensive analysis of clinical ability, practical ability, innovation consciousness and so on.