As a pivotal strategy to alleviate the shortage of organ donors, xenotransplantation has achieved remarkable advances in both pre-clinical and clinical studies in recent years, driven by continuous optimization of gene modification techniques and immunosuppressive regimens. Nevertheless, clinical translation still confronts formidable challenges, including rejection and heightened infection risks, which severely compromise long-term graft survival. Consequently, the role of immunosuppressive regimens in xenotransplantation has become increasingly prominent. This article summarizes the mechanisms underlying xenogeneic immune rejection, the latest developments in immunosuppressive regimens, cutting-edge strategies for inducing immune tolerance and the major hurdles facing clinical xenotransplantation. It delves into potential optimization strategies and directions for future clinical research, aiming to offer theoretical insights and practical guidance for the safe and effective application of clinical xenotransplantation.

Hygroscopicity research has long been a key focus and hot topic in Chinese materia medica（CMM）. Elucidating hygroscopic mechanisms plays a vital role in formulation design， process optimization， and storage condition selection. Hygroscopic models serve as essential tools for characterizing CMM hygroscopic mechanisms， with various types available. The double exponential model is a kinetic mathematical model constructed based on the law of conservation of energy and Fick's first law of diffusion， tailored to the physical properties of CMM extracts. In recent years， this model has been extensively applied to simulate the dynamic moisture absorption behavior of CMM extracts and solid dosage forms under varying humidity conditions. It has revealed the correlation between moisture absorption kinetic parameters and material properties， offering a new perspective for characterizing the moisture uptake behavior of CMM. This paper systematically reviews the application progress of this model in the field of CMM， analyzes its advantages， disadvantages， and challenges in this domain， and explores its potential application trends in other fields. It aims to provide references for elucidating the moisture absorption mechanisms of CMM and researching moisture-proofing technologies， while also offering insights for its broader application in food and polymer materials.

ObjectiveTo analyze the research status and development trends of non-pharmacological therapies for post-stroke spasticity (PSS) over the past two decades. MethodsRelevant literatures on non-pharmacological rehabilitation of PSS published from January, 2004 to June, 2024 were retrieved from Web of Science Core Collection. CiteSpace 6.3.R6 and VOSviewer 1.6.18 were used for visualization analysis. ResultsA total of 780 publications were included. The annual number of publications showed an overall upward trend. China, the USA, and Italy contributed the highest number of publications. The Hong Kong Polytechnic University and researcher Noureddin Nakhostin Ansari were identified as the most influential institution and author, respectively. High-frequency keywords and cluster labels included electric stimulation, transcranial magnetic stimulation, robot and acupuncture. ConclusionOver the past 20 years, researches on non-pharmacological therapies for PSS have remained active, with hotspots focusing on diverse interventions such as electrical stimulation, magnetic stimulation and robot-assisted therapy.

ObjectiveTo investigate the present situation of input, output, outcome and impact of all registered community-based rehabilitation stations in Inner Mongolia in China, and analyze how the input predict the output, outcome and impact. MethodsFrom March 1st to April 30th, 2025, a questionnaire survey was conducted on all registered community-based rehabilitation stations in Inner Mongolia, covering four dimensions: input, output, outcome and impact. A total of 1 365 questionnaires were distributed. The input included four items: laws and policies, human resources, equipment and facilities, and rehabilitation information management. The output included two items: technical paths and benefits/effectiveness. The outcome included three items: coverage rates, rehabilitation interventions and functional results. The impact included two items: health and sustainability. Each item contained several questions, all of which were described in a positive way. Each question was scored from one to five. A lower score indicated that the situation of the community-based rehabilitation station was more in line with the content described in the question. Regression analysis was performed using the total score of each item of input dimension as independent variables, and the total scores of the output, outcome and impact dimensions as dependent variables. ResultsA total of 1 262 valid questionnaires were collected. The mean values of input, output, outcome and impact of community-based rehabilitation stations were 1.827 to 1.904, with coefficient of variation of 45.892% to 49.239%. The regression analysis showed that, rehabilitation information management, human resources, and laws and policies significantly predicted the output dimension (R² = 0.910, P < 0.001). Meanwhile, all four items in the input dimension predicted both the outcome (R² = 0.850, P < 0.001) and impact dimensions (R² = 0.833, P < 0.001). ConclusionInput, output, outcome and impact of the community-based rehabilitation stations in Inner Mongolia were generally in line with the content of the questions, although some imbalances were observed. Additionally, the input of community-based rehabilitation stations could significantly predict their output, outcome and impact.

Objective: To explore the latent profiles of psychological help seeking intentions among adolescents in Wuhan, and to investigate their association with non suicidal self injury (NSSI), in order to provide a theoretical basis for constructing an early intervention system for adolescents NSSI. Methods: From October to December 2022, a convenient sampling method was used to select 3 975 students from grades 7 to 12 in Wuhan. A self administered questionnaire assessed psychological help seeking intentions, followed by a post survey interview using the Ottawa Self injury Inventory to evaluate NSSI behaviors. Latent profile analysis(LPA) was used to explore the potential categories of help seeking intentions in adolescents. Multinomial Logistic regression was used to analyze factors associated with the latent profiles of help seeking intentions and multiple Logistic regression was used to analyze the association between latent profiles of help seeking intentions and NSSI. Results: Based on latent profile analysis, four latent profiles of help seeking intentions in adolescents were identified, namely overall low, moderate, and high help seeking group, as well as family/friendfocused help seeking group, accouting for 14.1%, 20.9%, 43.1% and 21.8%, respectively. Multinomial Logistic regression analysis showed that compared to senior high school students, junior high school students were more willing to seek help from family and friends ( OR =1.56); compared to males, females were more likely to exhibit moderate help seeking intentions( OR =1.37); students with extroverted or balanced personalities were more likely to exhibit high level help seeking intentions( OR =1.50, 1.49); students with average or good family economic status, better parental relationships, and adequate mental health knowledge were more likely to exhibit moderate and high level help seeking intentions( OR =1.59, 2.02; 1.80, 2.64; 1.44, 1.55; 1.34, 1.58) (all P <0.05). Students with moderate or severe family dysfunction were less likely to seek help from family and friends or to exhibit moderate and high level help seeking intentions( OR =0.51, 0.60, 0.25; 0.22, 0.27, 0.06, all P <0.01). Students whose parents exhibited stigma towards mental illness were less likely to show high level help seeking intentions( OR= 0.78 , P <0.05). Multivariable Logistic regression analysis results indicated that compared to the overall low help seeking intentions group, reduced risk of NSSI was observed among students in the overall moderate and overall high groups, as well as in the family/friend focused help seeking group( OR =0.73, 0.60, 0.70, all P <0.05). Conclusions Active psychological help seeking intentions can reduce NSSI behaviors in adolescents. Interventions should focus on improving family support environment to enhance adolescents intentions to seek psychological help.

ObjectiveTo explore the mechanism of action of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata （CSFZ） in the treatment of acute-on-chronic liver failure （ACLF） through network pharmacology， molecular docking， and animal experiments. MethodsNetwork pharmacology was used to identify potential targets and related signaling pathways for the treatment of ACLF with CSFZ. Molecular docking was used to examine the binding activity of the core components with corresponding key targets. An ACLF rat model was established by subcutaneous and tail vein injections of bovine serum albumin combined with lipopolysaccharide （LPS） + D-galactosamine （D-GalN） intraperitoneal injection. A normal control group （NC）， a model group， a CSFZ group （CSFZ， 5.85 g·kg^-1）， and a hepatocyte growth-promoting granule group （HGFG， 4.05 g·kg^-1） were set up in this study. Pathological changes in rat liver tissue were observed using hematoxylin and eosin （HE） and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of interleukin-6 （IL-6）， B-cell lymphoma-2 （Bcl-2）， Caspase-3， and albumin （ALB）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to measure the mRNA and protein expression levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， phosphorylated PI3K （p-PI3K）， and phosphorylated Akt （p-Akt）. ResultsNetwork pharmacology screening identified 49 active ingredients of CSFZ， 103 action targets， and 3 317 targets related to ACLF. Among these， 74 targets overlapped with CSFZ drug targets. Key nodes in the protein-protein interaction （PPI） network included Akt1， tumor necrosis factor （TNF）， IL-6， Bcl-2， and Caspase-3. Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis identified multiple signaling pathways， with the PI3K/Akt signaling pathway being the most frequent. Molecular docking showed that the core components of the drug exhibited good binding activity with the corresponding key targets. Animal experiments confirmed that CSFZ significantly improved liver tissue pathological damage in ACLF rats， reduced the release of inflammatory factors and liver cell apoptosis， and upregulated the expression levels of the PI3K/Akt signaling pathway. ConclusionThrough network pharmacology， molecular docking， and in vivo experiments， this study confirms the effect of CSFZ in reducing liver cell inflammatory damage and inhibiting liver cell apoptosis. The specific mechanism may be related to its involvement in regulating the PI3K/Akt signaling pathway.

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.

ObjectiveTo investigate the role of paraventricular nucleus (PVN) corticotropin releasing hormone (CRH) neurons in chronic restraint stress (CRS)-induced anxiety-like behavior. And whether exercise relieves chronic restraint stress-induced anxiety through PVN CRH neurons. MethodsTwenty 8-week-old male C57BL/6J mice were randomly divided into control (Ctrl) group and chronic restraint stress (CRS) group. The open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behavior of the mice. Food intake was recorded after CRS. Immunofluorescence staining was used to label the expression of c-Fos expression in PVN and calculate the co-expression of c-Fos and CRH neurons. We used chemogenetic activation of PVN CRH neurons to observed the anxiety-like behavior. 8-week treadmill training (10-16 m/min, 60 min/d, 6 d/week) were used to explore the role of exercise in ameliorating CRS-induced anxiety behavior and how PVN CRH neurons involved in it. ResultsCompared with Ctrl group, CRS group exhibited significant anxiety-like behavior. In OFT, the mice in CRS groups spent less time in center area (P<0.001). In EPM, the time in open arm in CRS group were significantly decreased (P<0.001). Besides, food intake was also suppressed in CRS group compared with Ctrl group (P<0.05). Compared with Ctrl group, CRS significantly increase c-Fos expression in PVN and most of CRH neurons co-express c-Fos (P<0.001). Chemogenetic activation of PVN CRH neurons induced anxiety-like behavior (P<0.05) and inhibited feeding behavior (P<0.01). Exercise relieves chronic restraint stress-induced anxiety (P<0.001) and relieved the anorexia caused by chronic restraint stress (P<0.05). Aerobic exercise inhibited the CRS labeled c-Fos in PVN CRH neurons (P<0.001). Furthermore, ablation of PVN CRH neurons attenuated CRS induced anxiety-like behavior. ConclusionCRS activated PVN CRH neurons, induced anxiety-like behavior and reduced food intake. 8-week exercise attenuated CRS-induced anxiety-like behavior through inhibiting PVN CRH neuron. Ablation of CRH PVN neurons ameliorated CRS-induced anxiety-like behavior. These finding reveals a potential neural mechanism of exercise-relieving CRS-induced anxiety-like behavior. This provides a new idea and theoretical basis for the treatment of anxiety and related mental disorders.

Objective: To investigate the effect of auricular therapy on sleep improvement and the GABAergic system pathway in a rat model of insomnia and to explore its possible mechanism. Methods: According to the random number table, 60 male SD rats were randomly divided into blank control, model, auricular point sticking, auricular bloodletting, and auricular bloodletting combined with sticking groups, with 12 rats per group. Insomnia was induced by intraperitoneal injection of p-chlorophenylalanine. After establishing the insomnia model, 36 rats were treated once a day with auricular point sticking or bloodletting for 5 consecutive days. After the intervention, the general condition and body weight of rats were observed; the righting reflex test was used to detect the sleep latency and duration; HE staining was used to observe the morphology of hypothalamic neuron cells; and an enzyme-linked immunosorbent assay was used to detect the GABA and glutamate content in rat serum. Immunohistochemistry(IHC) and real-time fluorescence quantitative PCR were used to detect GABA ARα1 and GABA ARγ2 protein and mRNA expression in the hypothalamus of rats, and Western blotting(WB) was used to detect GABA ARα1, GABA ARγ2, GAD65/67, GAT-1, and GABA-T protein expression in the hypothalamus of rats. Results: Compared with the blank control group, the model group had a lower body weight, a significantly shorter sleep duration (P<0.05), severe damage to the morphological structure of hypothalamic neurons with disordered cell arrangement, larger intercellular gaps, enlarged cell bodies, and a vacuolated appearance. All the intervention groups had significantly higher body weight and longer sleep duration than the model group (P<0.05). Compared with the other intervention groups, the auricular point sticking group had a longer sleep duration (P<0.05), and the hypothalamic neuron cells in all intervention groups improved, with the auricular point sticking group showing more apparent improvement. The model group had a lower GABA and higher glutamate contents, and GABA ARα1, GABA ARγ2, and GAD65/67 protein expression in the hypothalamus were lower than in the blank control group. In contrast, GAT-1 and GABA-T protein expression was higher, and GABA ARα1 and GABA ARγ2 mRNA expression was lower (P<0.05). The serum GABA content in the auricular point sticking and auricular bloodletting groups was higher, and the serum glutamate content in the auricular point sticking and auricular bloodletting combined sticking groups was lower than in the model group. GABA ARα1 mRNA expression in the hypothalamus of each intervention group was significantly increased, and GABA ARγ2 mRNA expression in the hypothalamus of the auricular point sticking and auricular bloodletting combined sticking groups increased. GABA ARα1(IHC, WB), GABA ARγ2(WB), and GAD65/67 protein expression in the hypothalamus of the auricular point sticking group increased, whereas GAT-1 and GABA-T protein expression decreased. GABA ARα1 and GABA ARγ2 protein expression(IHC, WB) in the hypothalamus of the auricular bloodletting group increased, whereas GABA-T protein expression decreased. GABA ARγ1(IHC) and GABA ARγ2(WB) protein expression in the hypothalamus of the auricular bloodletting combined sticking group increased, whereas GAT-1 and GABA-T protein expression decreased (P<0.05). Compared with in the inventation groups, the serum GABA content in the auricular point sticking group increased, the serum glutamate content decreased, GABA ARα1 and GABA ARγ2 mRNA expression in the hypothalamus increased, and GABA ARα1(IHC), GAD65/67 protein expression increased. In contrast, GABA-T protein expression decreased (P<0.05), and GABA ARγ2 protein expression(IHC) in the hypothalamus of the auricular bloodletting group increased (P<0.05). Conclusion Auricular therapy, particularly auricular point sticking, may have modulated the GABAergic system pathway by upregulating hypothalamic GABA ARα1, GABA ARγ2, and GAD65/67 protein expression while downregulating GAT-1 and GABA-T protein expression to alleviate symptoms in an insomnia rat model.