Objective To evaluate the predictive value of different machine learning models constructed in a multicenter environment for potential organ donors and verify their clinical application feasibility. Methods The study included 2 000 inpatients admitted to five domestic tertiary hospitals from January 2020 to December 2023, who met the criteria for potential organ donation assessment. They were randomly divided into a training set and an internal validation set (7∶3). Another 300 similar patients admitted to the First Affiliated Hospital of Harbin Medical University from January 2024 to April 2025 were included as an external validation set. The area under the curve (AUC), sensitivity, specificity, accuracy and F1-score of three models were compared, and the consistency of the potential organ donor determination process was tested. Multivariate logistic regression analysis was used to identify predictive factors of potential organ donors. Decision curve analysis (DCA) was employed to verify the resource efficiency of each model, and the threshold interval and intervention balance point were assessed. Results Apart from age, there were no significant differences in other basic characteristics among the centers (all P>0.05). The consistency of the potential organ donor determination process among researchers in each center was good [all 95% confidence interval (CI) lower limits >0]. In the internal validation set, the XGBoost model had the best predictive performance (AUC=0.92, 95% CI 0.89-0.94) and the best calibration (P=0.441, Brier score 0.099). In the external validation set, the XGBoost model also had the best predictive performance (AUC=0.91, 95% CI 0.88-0.94), outperforming logistic regression and random forest models. Multivariate logistic regression showed that mechanical ventilation had the greatest impact (odds ratio=2.06, 95% CI 1.54-2.76, P<0.001). DCA indicated that the XGBoost model had the highest net benefit in the threshold interval of 0.2-0.6. The “treat all” strategy only had a slight advantage at extremely low thresholds. The recommended threshold interval, which balances intervention costs and clinical benefits, considers ≥50% positive predictive value (PPV) and ≤50 referrals per 100 high-risk patients. Conclusions The XGBoost model established in a multicenter environment is accurate and well-calibrated in predicting potential organ donors. Combined with DCA, it may effectively guide the timing of clinical interventions and resource allocation, providing new ideas for the assessment and management of organ donation after brain death.

Peripheral neurotoxicity represents one of the most severe dose-limiting adverse reactions associated with oxaliplatin， with genetic polymorphisms playing a significant role in oxaliplatin-induced peripheral neuropathy （OIPN）. OIPN can be categorized as acute or chronic based on onset timing. The former presents clinically as sensory abnormalities or even motor disorders， while the latter presents clinically as limb sensory disorders that persist， numbness or pain in the hands and feet. The transporter genes OCT2， OCTN2， and NHE1 may be implicated in OIPN； drug-metabolizing enzyme gene GSTP1 Ile105Val， DPYD rs1801265， voltage-gated sodium channel （NaV） gene SCN4A rs2302237， SCN9A rs6746030， SCN10A rs12632942， and other associated genes such as HLA-G rs1610696， rs371194629 and CCNH rs2230641， rs3093816 are associated with severe OIPN. Conversely， DNA repair-related gene XRCC1 rs23885， NaV gene SCN9A rs3750904， rs12478318 and rs6754031 are associated with reduced OIPN risk. In the future， the genetic research findings on OIPN can be translated into clinical applications， ultimately achieving individualized precision medicine for patients.

OBJECTIVE To investigate the effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats. METHODS Eighteen male SD rats were randomly divided into control group， clopidogrel normal-dose group and clopidogrel high-dose group， with 6 rats in each group. Among them， rats in the normal-dose group and high-dose group were given 7.5 mg/kg and 15 mg/kg clopidogrel by gavage， respectively， and rats in the control group were given the same volume of 0.5% sodium carboxymethyl cellulose solution， once a day， for 14 consecutive days. Afterward， 2.4 mg/kg ciprofol was injected by tailvein and blood samples were collected from the inner canthus of the eye at 2， 4， 8， 12， 16， 20， 30， 45 and 60 min after the end of the administration. During this period， the duration of the loss of righting reflex （LORR） in rats was counted. After the proteins were precipitated by acetonitrile， the rat plasma sample was analyzed by LC-MS/MS using deuterated ciprofol as the internal standard， Symmetry C18 as the chromatographic column， and acetonitrile-0.01% ammonia solution containing 5 mmol/L ammonium acetate （gradient elution） as the mobile phase to detect the concentration of ciprofol in the plasma. The pharmacokinetic parameters in rats were calculated by using DAS 2.0 software. RESULTS Compared with control group， area under the drug concentration-time curve and mean residence time of ciprofol increased or prolonged significantly， while plasma clearance decreased significantly in clopidogrel normal-dose and high-dose groups； the duration of LORR in rats was prolonged by 19.5% and 23.9%， with statistical difference （P＜0.05）. However， there was no statistically significant difference in the pharmacokinetic parameters or LORR duration of ciprofol between the different dose groups of clopidogrel （P＞0.05）. CONCLUSIONS Clopidogrel could inhibit the metabolism of ciprofol in rats and prolong the duration of LORR.

OBJECTIVE To investigate the effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats. METHODS Eighteen male SD rats were randomly divided into control group， clopidogrel normal-dose group and clopidogrel high-dose group， with 6 rats in each group. Among them， rats in the normal-dose group and high-dose group were given 7.5 mg/kg and 15 mg/kg clopidogrel by gavage， respectively， and rats in the control group were given the same volume of 0.5% sodium carboxymethyl cellulose solution， once a day， for 14 consecutive days. Afterward， 2.4 mg/kg ciprofol was injected by tailvein and blood samples were collected from the inner canthus of the eye at 2， 4， 8， 12， 16， 20， 30， 45 and 60 min after the end of the administration. During this period， the duration of the loss of righting reflex （LORR） in rats was counted. After the proteins were precipitated by acetonitrile， the rat plasma sample was analyzed by LC-MS/MS using deuterated ciprofol as the internal standard， Symmetry C18 as the chromatographic column， and acetonitrile-0.01% ammonia solution containing 5 mmol/L ammonium acetate （gradient elution） as the mobile phase to detect the concentration of ciprofol in the plasma. The pharmacokinetic parameters in rats were calculated by using DAS 2.0 software. RESULTS Compared with control group， area under the drug concentration-time curve and mean residence time of ciprofol increased or prolonged significantly， while plasma clearance decreased significantly in clopidogrel normal-dose and high-dose groups； the duration of LORR in rats was prolonged by 19.5% and 23.9%， with statistical difference （P＜0.05）. However， there was no statistically significant difference in the pharmacokinetic parameters or LORR duration of ciprofol between the different dose groups of clopidogrel （P＞0.05）. CONCLUSIONS Clopidogrel could inhibit the metabolism of ciprofol in rats and prolong the duration of LORR.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

[Objective] To analyze the prevalence of human T-lymphocyte leukemia virus (HTLV) among blood donors in Guangzhou from 2016 to 2021, and provide a basis for blood collection and supply management in this region. [Methods] A total of 2 116 951 voluntary blood donors were screened for anti-HTLV by enzyme-linked immunosorbent assay (ELISA) from March 2016 to December 2021 in Guangzhou, and the reactive cases were further confirmed by Western blotting (WB). Qualitative data were analyzed by χ2 with spss19 software. The trend of the total positive rate of HTLV confirmation test by WB from 2016 to 2021 was analyzed with the Joinpoint software, and the annual percent change (APC) was used to determine whether the trend changes were statistically significant. [Results] From March 2016 to December 2021, the total positive rate for anti-HTLV by ELISA among voluntary blood donors in Guangzhou was 0.019 7% (416/ 2116 951), and the WB confirmed positive rate was 0.001 1% (23/2 116 951). The total positive rate of HTLV among individual voluntary blood donors in the six main districts (0.002 12%, 19/895 301) was higher than that among group voluntary blood donors (0.000 32%, 3/951 947) (P<0.05). There was no significant difference in the total positive rate of HTLV confirmation between the six main districts (0.001 19%) and the three non-main districts (0.000 37%) (P>0.05). The trend of the total positive rate of HTLV infection in the six main districts and the Guangzhou area(including the six main districts and three non-main districts) showed no significant increase or decrease. [Conclusion] The prevalence of HTLV among blood donors in Guangzhou remains at a low level.

Ulcerative colitis（UC） is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulceration of the colonic mucosa and submucosa， and its complex pathogenesis involves immune abnormality， oxidative stress and other factors. The nuclear transcription factor E₂-related factor 2（Nrf2）， encoded by the Nfe212 gene， plays a central role in antioxidant responses. It not only activates various antioxidant response elements such as heme oxygenase-1（HO-1） and quinone oxidoreductase 1（NQO1）， but also enhances the activity of glutathione-S-transferase（GST） and superoxide dismutase 1（SOD1）， effectively eliminating reactive oxygen species（ROS） accumulated in the body， and mitigating oxidative stress-induced damage to intestinal mucosa. In addition， Nrf2 can reduce the release of inflammatory factors and infiltration of immune cells by regulating immune response， cell apoptosis and autophagy pathways， thereby alleviating intestinal inflammation and promoting the repair and regeneration of damaged mucosa. Based on this， this paper reviews the research progress of Chinese materia medica in the prevention and treatment of UC by modulating the Nrf2 signaling pathway. It deeply explores the physiological role of Nrf2， the molecular mechanism of activation， the protective effect in the pathological process of UC， and how active ingredients in Chinese materia medica regulate the Nrf2 signaling pathway through multiple pathways to exert their potential mechanisms. These studies have revealed in depth that Chinese materia medica can effectively combat oxidative stress by regulating the Nrf2 signaling pathway. It can also play a role in anti-inflammatory， promoting autophagy， inhibiting apoptosis， protecting the intestinal mucosal barrier， and promoting intestinal mucosal repair， providing new ideas and methods for the multi-faceted treatment of UC.

ObjectiveBased on the zebrafish model， the hepatotoxicity and anti-osteoporotic activity of evodiamine （EVO） were studied. The mechanism of EVO in treating osteoporosis was explored by using network pharmacology and real-time polymerase chain reaction（Real-time PCR）. MethodsThree days after fertilization （3 dpf）， zebrafish were randomly selected and exposed to different concentrations of EVO solution for 96 hours. The mortality rate of zebrafish at different concentrations was calculated at the exposure endpoint， and a "dose-toxicity" curve was drawn. The 10% lethal concentration （LC₁₀） was calculated. Liver phenotype， acridine orange staining， and pathological tissue sections of liver-transgenic zebrafish ［CZ16 （gz15Tg.Tg （fabp 10a： ds Red； ela31： EGFP））］ were used to confirm hepatotoxicity of EVO. On this basis， prednisolone was used to create a model of osteoporosis in zebrafish. The skull development， area of the skull stained by alizarin red， and cumulative optical density were used as indicators to evaluate the anti-osteoporotic activity of EVO in a safe dose. Based on network pharmacology， the mechanism of action of EVO in the treatment of osteoporosis was predicted and verified through Real-time PCR. ResultsThe LC₁₀ of EVO on zebrafish （7 dpf） was determined to be 0.4 mg·L^-1. Compared with the control group， sublethal concentrations （10=0.36 mg·L^-1 and 1/2LC₁₀=0.18 mg·L^-1） significantly decreased the fluorescence area of zebrafish liver （P<0.05，P<0.01） and increased the number of liver cell apoptosis. The arrangement of liver tissue was disordered and loose， and the vacuole was obvious， especially in the 0.36 mg·L^-1 group. Compared with the control group， under safe dose conditions， 0.08 and 0.02 mg·L^-1 of EVO had no significant effect on the liver. Prednisolone administration significantly reduced the mineralization area and cumulative optical density of zebrafish skulls （P<0.01） compared with the control group. The mineralization area and cumulative optical density of zebrafish skulls in the 0.08 and 0.02 mg·L^-1 groups of EVO were significantly increased compared with the model group （P<0.01）. Network pharmacology prediction suggested that EVO may regulate key targets such as avian sarcoma viral oncogene homolog （SRC）， signal transducer and activator of transcription 3 （STAT3）， interleukin-8 （CXCL8） and tyrosine kinase receptor 2 （ERBB2） to regulate signaling pathways related to lipid and atherosclerosis in diabetic complications， as well as the regulation of inflammatory mediators of tryptophan （TRP） channels. Real-time PCR experiment results indicated that EVO could regulate the above-mentioned targets， as well as genes related to osteoblasts and osteoclasts. ConclusionExcessive doses of EVO can lead to hepatotoxicity in zebrafish. Under safe dosage conditions， EVO can regulate relevant targets to exert anti-osteoporotic activity， providing a reference for the clinical safe use of EVO and ideas for the development of new drugs for osteoporosis.

Brain’s neural activities encompass both periodic rhythmic oscillations and aperiodic neural fluctuations. Rhythmic oscillations manifest as spectral peaks of neural signals, directly reflecting the synchronized activities of neural populations and closely tied to cognitive and behavioral states. In contrast, aperiodic fluctuations exhibit a power-law decaying spectral trend, revealing the multiscale dynamics of brain neural activity. In recent years, researchers have made notable progress in studying brain aperiodic dynamics. These studies demonstrate that aperiodic activity holds significant physiological relevance, correlating with various physiological states such as external stimuli, drug induction, sleep states, and aging. Aperiodic activity serves as a reflection of the brain’s sensory capacity, consciousness level, and cognitive ability. In clinical research, the aperiodic exponent has emerged as a significant potential biomarker, capable of reflecting the progression and trends of brain diseases while being intricately intertwined with the excitation-inhibition balance of neural system. The physiological mechanisms underlying aperiodic dynamics span multiple neural scales, with activities at the levels of individual neurons, neuronal ensembles, and neural networks collectively influencing the frequency, oscillatory patterns, and spatiotemporal characteristics of aperiodic signals. Aperiodic dynamics currently boasts broad application prospects. It not only provides a novel perspective for investigating brain neural dynamics but also holds immense potential as a neural marker in neuromodulation or brain-computer interface technologies. This paper summarizes methods for extracting characteristic parameters of aperiodic activity, analyzes its physiological relevance and potential as a biomarker in brain diseases, summarizes its physiological mechanisms, and based on these findings, elaborates on the research prospects of aperiodic dynamics.