ObjectiveTo explore the mechanism of Huoxue Rongluo prescription （HXRLP） in repairing the blood-brain barrier （BBB） after ischemic stroke （IS）. MethodsMale C57BL/6 mice were randomly divided into sham operation （Sham） group， cerebral infarction model （MCAO） group， environmental circadian disruption with cerebral infarction model （ECD-MCAO） group， low-， medium-， and high-dose HXRLP （HXRLP-L， M， and H） groups （8.5， 17， 34 g·kg^-1·d^-1， respectively）， and positive drug butylphthalide （NBP） group （0.23 mL·d^-1）. In the Sham group， only the exposed blood vessels were isolated without suture insertion. In the other groups， the middle cerebral artery occlusion （MCAO） model of mice was prepared. In the ECD-MCAO group， HXRLP groups， and NBP group， the environmental circadian disruption （ECD） model was prepared. The mice in the Sham group， MCAO group， and ECD-MCAO group were given the same volume of soybean oil by gavage， while those in the other groups were given the corresponding drugs by gavage. Samples were collected after 7 consecutive days of administration. The mNSS score was used to evaluate the repair effect of HXRLP on neurological deficits after IS. Hematoxylin-eosin （HE） staining was used to assess the impact of HXRLP on the pathological damage of brain tissue after IS. 2，3，5-Triphenyltetrazolium chloride （TTC） staining and cerebral blood perfusion status were used to evaluate the repair effect of HXRLP on brain tissue damage after IS. Evans blue staining and transmission electron microscopy were used to evaluate the improvement effect of HXRLP on the permeability injury of BBB after IS. Immunofluorescence （IF） staining was used to observe the expression of von Willebrand Factor （vWF）， brain and muscle Arnt-like 1 （Bmal1）， and Occludin in brain tissue. Western blot was used to detect the protein expression of Bmal1， Occludin， tight junction protein （Claudin-5）， vascular endothelial growth factor （VEGF）， and angiopoietins（Ang）， and related analysis was conducted. ResultsCompared with the Sham group， the MCAO group exhibited significantly aggravated neurological deficits， cerebral infarction volume， brain pathological damage， and BBB leakage （P0.01） and significantly reduced cerebral blood perfusion （P0.01）. The expression of Bmal1， vWF， vascular endothelial growth factor A （VEGFA）， and Ang in brain tissue was significantly enhanced （P0.01）， while the expression of Occludin and Claudin-5 was significantly weakened （P0.01）. Compared with the MCAO group， the ECD-MCAO group showed significantly aggravated neurological deficits， cerebral infarction volume， and BBB leakage （P0.01）， obviously worsened brain pathological damage （P0.05）， significantly reduced cerebral blood perfusion （P0.01）， and significantly decreased expression of Bmal1， vWF， VEGFA， Ang， Occludin， and Claudin-5 in brain tissue （P0.01）. Compared with the ECD-MCAO group， the HXRLP groups of all doses presented significantly improved neurological deficits， cerebral infarction volume， brain pathological damage， and BBB leakage （P0.01）， significantly increased cerebral blood perfusion （P0.01）， and enhanced expression levels of Bmal1， vWF， VEGFA， Ang， Occludin， and Claudin-5 in brain tissue （P0.01）. ConclusionHXRLP can regulate the clock protein Bmal1 and promote the expression of VEGFA， Ang， Occludin， and Claudin-5， thereby improving BBB damage after IS.

Alzheimer's disease (AD) is the leading cause of dementia, and no effective treatment has been developed for it thus far. Recently, the use of natural compounds in the treatment of neurodegenerative diseases has garnered significant attention owing to their minimal adverse reactions. Accordingly, the potential therapeutic effect of pterostilbene (PTS) on AD has been demonstrated in multiple in vivo and in vitro experiments. In this study, we systematically reviewed and summarized the results of these studies investigating the use of PTS for treating AD. Analysis of the literature revealed that PTS may play a role in AD treatment through various mechanisms, including anti-oxidative damage, anti-neuroinflammation, anti-apoptosis, cholinesterase activity inhibition, attenuation of β-amyloid deposition, and tau protein hyperphosphorylation. Moreover, PTS interferes with the progression of AD by regulating the activities of peroxisome proliferator-activated receptor alpha (PPAR-α), monoamine oxidase B (MAO-B), silent information regulator sirtuin 1 (SIRT1), and phosphodiesterase 4A (PDE4A). Furthermore, to further elucidate the potential therapeutic mechanisms of PTS in AD, we employed network pharmacology and molecular docking technology to perform molecular docking of related proteins, and the obtained binding energies ranged from -2.83 to -5.14 kJ/mol, indicating that these proteins exhibit good binding ability with PTS. Network pharmacology analysis revealed multiple potential mechanisms of action for PTS in AD. In summary, by systematically collating and summarizing the relevant studies on the role of PTS in treatment of AD, it is anticipated that this will serve as a reference for the precise targeted prevention and treatment of AD, either using PTS or other developed drug interventions.

Objective: To evaluate the safety and efficacy of therapeutic whole blood exchange combined with lymphoplasmapheresis in the treatment of refractory autoimmune hemolytic anemia (AIHA). Methods: A retrospective analysis was performed on the clinical data of AIHA patients who underwent therapeutic whole blood exchange combined with lymphoplasmapheresis at our hospital from March 2022 to May 2025. Efficacy was assessed by comparing changes in hemoglobin, platelet count, and bilirubin levels before and after treatment. Safety was evaluated by analyzing vital signs before and after the procedure, parameters during the exchange, and adverse reactions. Results: A total of 12 AIHA patients were enrolled, completing 19 exchange procedures. The number of procedures per patient ranged from 1 to 3. The median treatment duration was 67 (65-73) minutes, with a median exchange volume of 2 025 (1 851-2 121) mL, comprising 4.5 (4-6) units of red blood cells and 1 350 (1 200-1 400) mL of plasma. Ten patients achieved partial remission, one achieved complete remission, and one showed no response, yielding an response rate of 91% (11/12). After a single session, hemoglobin increased significantly by 17.58±9.85 g/L (P<0.01), while platelets counts decreased by 45 (17.5, 79)×10 /L (P<0.05), and both systolic and diastolic blood pressure showed a significant elevation (P<0.05). However, no statistically significant differences were observed in total bilirubin, indirect bilirubin, white blood cell count, or heart rate. During the procedures, 4 adverse reactions occurred in 3 patients: one child experienced severe heart rate fluctuation twice consecutively, and two adults developed plasma allergies. All reactions resolved spontaneously without pharmacological intervention. Conclusion: The combination of therapeutic whole blood exchange and lymphoplasmapheresis appears to be a safe and effective treatment for refractory AIHA patients.

Objective: To investigate the factors affecting pre-exposure prophylaxis (PrEP) use among men who have sex with men (MSM), so as to provide a basis for improving PrEP uptake among MSM and optimizing HIV prevention and control strategies. Methods: The MSM were recruited at a HIV testing site of the "Danlan Public Welfare" organization in Beijing Municipality using the convenient sampling method from March to May 2024. Sociodemographic information, awareness of basic AIDS knowledge, sexual orientation and behaviors, the use of PrEP and post-exposure prophylaxis (PEP) in the past six months were collected using the questionnaire survey. Multivariable logistic regression model and decision tree model were used to analyze the influencing factors for PrEP use among MSM. Results: A total of 414 participants were surveyed, with a mean age of (33.52±8.50) years. Among them, 345 individuals (83.33%) had a college degree and above. The predominant sexual orientation was homosexual, with 265 individuals, accounting for 64.01%. The majority reported having 1 to 2 same-sex partners in the past six months, with 182 individuals (43.96%). A total of 39 individuals (9.42%) had used PEP in the past six months. A total of 68 individuals (16.43%) had used PrEP during the same period. Multivariable logistic regression analysis revealed that educational attainment (college degree and above, OR=28.200, 95%CI: 3.162-251.519), the number of same-sex partners in the past six months (3-5 partners, OR=3.963, 95%CI: 1.065-14.755; ≥6 partners, OR=7.518, 95%CI: 1.829-30.910), and the use of PEP in the past six months (OR=18.606, 95%CI: 7.587-45.631) were significant factors associated with PrEP use among MSM. The decision tree model identified educational level, sexual orientation, and the number of same-sex partners in the past six months as factors affecting PrEP use among MSM. Among these, the number of same-sex partners in the past six months emerged as the primary influencing factor. The use of PrEP was 38.46% among MSM who had ≥3 same-sex partners in the past six months and identified as homosexual or heterosexual. Conclusion The use of PrEP among MSM is primarily associated with educational level, the number of same-sex partners in the past six months, use of post-exposure prophylaxis (PEP) in the past six months, and sexual orientation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement (OTM) model. Firstly, bone formation was activated after the 3rd day of OTM, coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor (NGF), highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells (hPDLCs) within 24 hours. Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.
Humans ; Bone Remodeling ; Cell Differentiation ; Osteogenesis ; Semaphorin-3A/pharmacology* ; Trigeminal Ganglion/metabolism*

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective Based on the acupuncture literature data set,a named entity recognition method of acupuncture literature based on dictionary and deep learning model is proposed to improve the effect of acupuncture literature entity recognition.Methods In this paper,the entity recognition methods of acupuncture literature were explored,and the vector representation effects based on word2vec and ALBERTmodels and ALBERT+domain dictionary were compared.On this basis,a named entity extraction method combining domain dictionary and ALBERT-BiLSTM-CRF deep learning model was proposed.Results According to the extraction effect of three model entities,the P value of word2vec-BiLSTM-CRF is 81.82%,the R value is 70.76%,and the F1 value is 75.48%;ALBERT-BiLSTM-CRF has an P value of 83.10%,a R value of 81.14%and a F1 value of 81.98%."ALBERT-BiLSTM-CRF+dictionary"is 92.57%,91.42%and 91.85%.In terms of entity categories,the top three entities with the highest accuracy rate are acupuncture,needling and needling site,which are 98%,ninety-seven percent and ninety-seven percent respectively,while the three entities with the lowest accuracy rate are acupoint matching corresponding symptoms,disease names and sample size,which are 50.00%,50.68%and 52.43%respectively.Conclusion Compared with the original ALBERT-BiLSTM-CRF model,the precision rate,recall rate and F1 value increased after adding the dictionary,and the convergence speed of the model after adding the dictionary was twice that without adding the dictionary.It is effective to use"ALBERT-BiLSTM-CRF+dictionary"model to identify named entities in acupuncture literature.

Objective:To evaluate the effect of sleep deprivation on the expression of sirtuin 6 (SIRT6) in the cerebellum of immature mice.Methods:Fifty SPF healthy male C57BL/6 mice, aged 4 weeks, weighing 14-16 g, were divided into 2 groups ( n=25 each) using a random number table method: control group (Con group) and sleep deprivation group (SD group). The chronic sleep deprivation model was prepared by using the multi-platform water environment method, with 20 h of sleep deprivation per day for 10 consecutive days. After sleep deprivation, a balance beam experiment was performed to test the balance and coordination ability of mice. The mice were sacrificed after anesthesia and cerebellar lobular IV-VI (4-6 cb) tissues were taken for microscopic examination of the ultrastructure (with a transmission electron microscope) and for determination of the dendritic spine density of cerebellar 4-6cb Purkinje neurons (by Golgi staining), co-expression of SIRT6 and Calbindin D-28k (CbD-28k) and expression of glucose transporter Glut3 of cerebellar 4-6cb (by immunofluorescence staining). Results:Compared with group Con, the duration of passage through the balance beam was significantly prolonged, and the number of posterior foot slips was increased, the synaptic gap of cerebellar 4-6cb neurons was increased, the thickness of postsynaptic density was increased, the density of dendritic spines of Purkinje cells and the number of positive cells co-expressing SIRT6 and CbD-28k were decreased, and the expression of Glut3 was down-regulated in group SD ( P<0.05). Conclusions:The mechanism by which sleep deprivation decreases the abilities of balance and coordination is related to down-regulating SIRT6 expression in cerebellar Purkinje cells and decreasing neuronal glucose metabolism, thus damaging the synaptic plasticity of cerebellum in immature mice.

Objective:To summarize the clinical characteristics and prognosis of severe infant botulism and evaluate the therapeutic effect of botulinum antitoxin in the pediatric intensive care unit (PICU).Methods:The clinical data of 8 cases diagnosed with infantile botulism were retrospectively analyzed in the PICU of Beijing Children′s Hospital from October 2019 to August 2023. Data of basic demographic information, clinical manifestations, laboratory tests, treatment and prognosis of each child were collected and analyzed using descriptive statistical methods.Results:Eight laboratory-confirmed cases of infant botulism were included in this study, all of which were male infants with an age of 6.0 (3.3,6.8) months. Three of the children were from Inner Mongolia Autonomous Region, 2 of them were from Hebei, and the other 3 were from Beijing, Shandong and Xinjiang Uyghur Autonomous Region, respectively. All the patients were previously healthy. In 4 of these cases, the possible cause was the ingestion of either honey and its products or sealed pickled food by the mother or child before the onset of the disease. The first symptom was poor milk intake (4 cases), followed by shallow shortness of breath (7 cases), limb weakness (7 cases) and so on. The typical signs were bilateral dilated pupils (8 cases) and decreased limb muscle strength (8 cases). The main subtype was type B (7 cases), and only 1 case was classified as type A. Six of the children were treated with antitoxin therapy for a duration of 24 (19, 49) d. Seven of them had invasive mechanical ventilation. All the patients survived upon discharge with a follow-up period of 29 d to 3 years and 8 months. Six patients had fully recovered, and 2 recently discharged patients were gradually recovering.Conclusions:For infants with suspected contact or ingestion of botulinum and presented with bilateral pupillary paralysis, muscle weakness and clear consciousness, the stool should be collected for diagnostic testing using a mouse bioassay as soon as possible. Type B was the most common type. The antitoxin treatment was effectiveness and the prognosis was well.