Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

ObjectiveTo investigate the molecular mechanisms of Mahuang Fuzi Gancao Tang and its pungent single herbs， Ephedrae Herba and Aconiti Lateralis Radix Praeparaia， in repairing podocyte injury based on the sweat pore theory， with a focus on the podocyte cytoskeletal transient receptor potential canonical 5 （TRPC5）-Ras-related C3 botulinum toxin substrate 1 （RAC1） feedforward loop. MethodsAn animal model with puromycin aminonucleoside （PAN）-induced overexpression of TRPC5 was established. Interventions included Mahuang Fuzi Gancao Tang， Ephedrae Herba alone， and Aconiti Lateralis Radix Praeparaia alone. Biochemical parameters ， histopathological changes， and podocyte ultrastructure were analyzed. Western blotting was performed to determine the expression of cytoskeletal protein synaptopodin and mechanism-related proteins TRPC5， RAC1-GTP， and RAC1 in the kidney. Primary podocytes were isolated and cultured for three-dimensional imaging of foot processes， cytoskeletal fluorescence analysis， and TRPC5-RAC1 co-staining via immunofluorescence. ResultsCompared with the model group， Mahuang Fuzi Gancao Tang， Ephedrae Herba alone， and Aconiti Lateralis Radix Praeparaia alone increased serum albumin （ALB）， decreased UPCR， reduced podocyte foot process fusion rate， upregulated synaptopodin expression， and downregulated TRPC5， RAC1-GTP， and RAC1 expression （P<0.05）. Moreover， the interventions increased the phalloidin fluorescence area/field area ratio （P<0.01） and mean fluorescence intensity （P<0.05）， while decreasing the proportion of TRPC5-RAC1 co-stained double-positive cells/total cells per field （P<0.01） in primary podocytes. ConclusionMahuang Fuzi Gancao Tang and its pungent single herbs， Ephedrae Herba and Aconiti Lateralis Radix Praeparaia， ameliorated podocyte injury in the model with PAN-induced TRPC5 overexpression by reducing proteinuria and suppressing the TRPC5-RAC1 feedforward loop-mediated podocyte cytoskeletal damage.

ObjectiveTo investigate the molecular mechanisms of Mahuang Fuzi Gancao Tang and its pungent single herbs， Ephedrae Herba and Aconiti Lateralis Radix Praeparaia， in repairing podocyte injury based on the sweat pore theory， with a focus on the podocyte cytoskeletal transient receptor potential canonical 5 （TRPC5）-Ras-related C3 botulinum toxin substrate 1 （RAC1） feedforward loop. MethodsAn animal model with puromycin aminonucleoside （PAN）-induced overexpression of TRPC5 was established. Interventions included Mahuang Fuzi Gancao Tang， Ephedrae Herba alone， and Aconiti Lateralis Radix Praeparaia alone. Biochemical parameters ， histopathological changes， and podocyte ultrastructure were analyzed. Western blotting was performed to determine the expression of cytoskeletal protein synaptopodin and mechanism-related proteins TRPC5， RAC1-GTP， and RAC1 in the kidney. Primary podocytes were isolated and cultured for three-dimensional imaging of foot processes， cytoskeletal fluorescence analysis， and TRPC5-RAC1 co-staining via immunofluorescence. ResultsCompared with the model group， Mahuang Fuzi Gancao Tang， Ephedrae Herba alone， and Aconiti Lateralis Radix Praeparaia alone increased serum albumin （ALB）， decreased UPCR， reduced podocyte foot process fusion rate， upregulated synaptopodin expression， and downregulated TRPC5， RAC1-GTP， and RAC1 expression （P<0.05）. Moreover， the interventions increased the phalloidin fluorescence area/field area ratio （P<0.01） and mean fluorescence intensity （P<0.05）， while decreasing the proportion of TRPC5-RAC1 co-stained double-positive cells/total cells per field （P<0.01） in primary podocytes. ConclusionMahuang Fuzi Gancao Tang and its pungent single herbs， Ephedrae Herba and Aconiti Lateralis Radix Praeparaia， ameliorated podocyte injury in the model with PAN-induced TRPC5 overexpression by reducing proteinuria and suppressing the TRPC5-RAC1 feedforward loop-mediated podocyte cytoskeletal damage.

Five saponins were isolated from the kernels of Momordica cochinchinensis, by macroporous resin, silica gel, ODS column chromatography, and semi preparative HPLC. Based on MS and NMR analysis, combining with alkaline hydrolysis and acid hydrolysis, their structures were identified as: gypsogenin-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (1), quillaic acid-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (2), gypsogenin-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (3), quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (4), 18α-quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside (5). Compounds 1-5 were new compounds, and named as mubezhisides A, B, C, D, E, respectively. They all could obviously inhibited the growth of Candida albicans, C. parapsilosis, and C. tropicalis.

Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

Objective To investigate the effects of a 100 mT static magnetic field(SMF)on emotional behavior and brain damage-related molecules in mice.Methods Fifty-eight C57BL/6N mice were randomly divided into control group(n=25)and observation group(n=33).Mice in observation group were exposed to a 100 mT SMF for 0.5 h/d over 14 consecutive days,while mice in control group underwent pseudo-exposure.On the 7 and 14 days of exposure,anxiety-like behavior was assessed using open field and elevated plus maze tests.Cerebral blood flow was monitored using laser speckle imaging,and the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-4,central nervous system specific protein β(S100β),neuron-specific enolase(NSE),and brain-derived neurotrophic factor(BDNF)were measured by radioimmunoassay.BDNF expression in the brain was detected by immunofluorescence.Results On the 7 and 14 days of SMF exposure,the open field and elevated plus maze tests showed no statistically significant differences between observation and control groups in the frequencies,durations,and distance entering the central area of the open field and the open arm of the elevated plus maze(P>0.05).Laser speckle imaging revealed no significant difference in cerebral cortical perfusion compared with pre-exposure period(P>0.05).The results of radioimmunoassay showed that compared with control group,on the 7 d of SMF exposure,the serum IL-1β,NSE and S100β levels were significantly increased(P<0.05),the serum BDNF level was significantly decreased(P<0.05),and the IL-1β and TNF-α contents in brain tissues were significantly increased in observation group(P<0.01).On the 14 d of SMF exposure,serum IL-1β,TNF-α,NSE,and S100β levels were significantly increased(P<0.05,P<0.0001),and the brain IL-1β and TNF-α levels were significantly increased(P<0.01)in observation group.No statistically significant differences were found in anti-inflammatory cytokine IL-4 level of serum and brain tissue or BDNF content of brain tissue between the two groups(P>0.05).Conclusion Continuous exposure to a 100 mT SMF for 14 d at 0.5 h/d induces neuroinflammation and brain damage in mice,without inducing anxiety-like behavior.

Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*

By employing the analytic hierarchy process(AHP), the CRITIC method(a weight determination method based on indicator correlations), and the AHP-CRITIC hybrid weighting method, the weight coefficients of evaluation indicators were determined, followed by a comprehensive score comparison. The grey correlation analysis was then performed to analyze the results calculated using the hybrid weighting method. Subsequently, a backpropagation-artificial neural network(BP-ANN) model was constructed to predict the extraction process parameters and optimize the extraction process for Shenxiong Huanglian Jiedu Granules(SHJG). In the extraction process, an L_9(3~4) orthogonal experiment was designed to optimize three factors at three levels, including extraction frequency, water addition amount, and extraction time. The evaluation indicators included geniposide, berberine, ginsenoside Rg_1 + Re, ginsenoside Rb_1, ferulic acid, and extract yield. Finally, the optimal extraction results obtained by the orthogonal experiment, grey correlation analysis, and BP-ANN method were compared, and validation experiments were conducted. The results showed that the optimal extraction process involved two rounds of aqueous extraction, each lasting one hour; the first extraction used ten times the amount of added water, while the second extraction used eight times the amount. In the validation experiments, the average content of each indicator component was higher than the average content obtained in the orthogonal experiment, with a higher comprehensive score. The optimized extraction process parameters were reliable and stable, making them suitable for subsequent preparation process research.
Drugs, Chinese Herbal/analysis* ; Neural Networks, Computer

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*