NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome mediates inflammation, induces pyroptosis, and regulates periodontal tissue remodeling through the maturation and secretion of its downstream cysteine protease 1 (Caspase-1)-dependent pro-inflammatory cytokines, interleukin (IL)-1β and IL-18. Orthodontic force mediates the aseptic inflammation of periodontal tissues and triggers adaptive alteration of periodontal tissues, thereby promoting the movement and stability of orthodontic teeth. NLRP3 inflammasome plays an important role in orthodontic tooth movement and causes periodontal tissue inflammation and orthodontic inflammatory root resorption in orthodontic patients. Literature review suggests that NLRP3 inflammasome is involved in the activation and differentiation of periodontal ligament fibroblasts, periodontal ligament stem cells, macrophages, osteoblasts, and osteoclasts in orthodontic tooth mobile tissue remodeling. Additionally, it targets the upstream nuclear factor kappa-B signaling pathway; downstream effectors, such as Caspase-1, IL-1β, and IL-18; and the NLRP3 inflammasome components for regulating tooth movement as well as treating and preventing orthodontics-associated periodontitis and orthodontic-induced inflammatory root resorption. Future studies can be focused on the specific mechanism of NLRP3 inflammasome tissue modification during orthodontic tooth movement. This article reviews the effects and regulatory mechanisms of the NLRP3 inflammasome signaling pathway on the corresponding tissue remodeling during orthodontic tooth movement.

OBJECTIVE To explore the willingness to pay （WTP） of Urumqi residents for community pharmacies’ medication guidance services and its influencing factors， so as to provide data support for the optimization of community pharmacy services and the establishment of a fee structure for medication guidance services. METHODS A stratified quota sampling method was employed to select 14 communities in Urumqi City. From April to June 2025， a combined offline and online questionnaire survey was conducted among adult residents in these communities. The contingent valuation method was used to construct three hypothetical scenarios （namely， basic， enhanced and extended services） of medication counselling in community pharmacies to assess residents’ WTP for these services. Binary Logistic regression was employed to analyze the influencing factors of WTP. RESULTS A total of 576 valid questionnaires were obtained. Under the scenarios of basic， enhanced and extended services， 38.54%， 49.65% and 67.19% of the respondents expressed WTP for the services， respectively. Occupational type， type of basic medical insurance， annual income， perception of pharmacists’ profession， and acceptance level of the service were identified as major influencing factors for WTP （P＜0.05）. CONCLUSIONS The willingness of residents in Urumqi to pay for medication counseling services provided by pharmacists in community pharmacies significantly increases with the enrichment of service content. It is recommended to incorporate basic medication counselling services provided by pharmacists in community pharmacies into medical insurance payment， while value-added services should be partially or fully self-paid by residents. Additionally， efforts should be made to strengthen the promotion of the professional and service value of licensed pharmacists， so as to facilitate the high-quality development of pharmaceutical care.

Ovulatory dysfunction (OD) is one of the main causes of infertility in women of childbearing age, which not only affects their reproductive ability, but also physical and mental health. Traditional treatment strategies have limited efficacies, and the emergence of biomedicines provides a promising alternative solution via the strategies of combining engineered design with modern advanced technology. This review explores the pathophysiological characteristics and related induction mechanisms of OD, and evaluates the current cutting-edge advances in its treatments. It emphasizes the potentials of biomedicines strategies such as hydrogels, nanoparticles and extracellular vesicles in improving therapeutic precision and efficacy. By mimicking natural physiological processes, and achieving controlled drug release, these advanced drug carriers are expected to address the challenges in ovarian microenvironment reprogramming, tissue repair, and metabolic and immune regulation. Despite the promising progress, there are still challenges in terms of biomedical complexity, differences between animal models and human physiology, and the demand for intelligent drug carriers in the therapy of OD. Future researches are mainly dedicated to developing precise personalized biomedicines in OD therapy through interdisciplinary collaboration, promoting the development of reproductive regenerative medicine.

OBJECTIVES: To investigate the active components and possible mechanisms of n-butanol fraction of Periploca forrestii Schltr. ethanol extract for treating Alzheimer's disease (AD). METHODS: The active components of n-butanol fraction of Periploca forrestii Schltr. ethanol extract were analyzed using UPLC-QE-MS technique. In a SD rat model of AD induced by treatment with AlCl₃ and D-gal, the therapeutic effects of low, moderate and high doses of the n-butanol fraction, saline, and donepezil hydrochloride were evaluated using ELISA, HE and Nissl staining, immunohistochemistry and Western blotting. The therapeutic mechanisms of the n-butanol fraction were explored using network pharmacology and molecular docking. RESULTS: Seventeen active components were identified from the n-butanol fraction of Periploca forrestii Schltr. ethanol extract, including phenylpropanoids, flavonoids, anthraquinones, triterpenoids, steroids, and volatile oils. In the rat models of AD, treatment with the n-butanol fraction significantly lowed AChE content in the hippocampus, increased the contents of ACh, SOD, CAT, and GSH-Px, enhanced the expressions of neuronal apoptotic factors Bcl-2, PI3K, Akt, p-PI3K, and p-Akt, and reduced the expressions of Bax and caspase-3 proteins. The treatment also dose-dependently up-regulated hippocampal expressions of Nrf-2, HO-1 and BDNF and down-regulated Keap-1, Aβ and Tau expressions. Bioinformatics analysis identified 14 key intersected targets (including TNF, AKT1 and ESR1) between the n-butanol fraction and AD. CONCLUSIONS The therapeutic effect of n-butanol fraction of Periploca forrestii Schltr. ethanol extract in AD mice is mediated by its multiple active components that regulate multiple targets and pathways.
Animals ; Rats, Sprague-Dawley ; Rats ; 1-Butanol/chemistry* ; Plant Extracts/pharmacology* ; Periploca/chemistry* ; Ethanol/chemistry* ; Alzheimer Disease/drug therapy* ; Male ; Molecular Docking Simulation ; Apoptosis/drug effects*

Objective To investigate the expression and clinical significance of B7-H5 in patients with chro-nic hepatitis B and hepatitis B virus(HBV)-related hepatocellular carcinoma.Methods Enzyme-linked immu-nosorbent assay(ELISA)was used to detect the serum levels of B7-H5 in 104 patients with chronic hepatitis B,28 patients with HBV-related hepatocellular carcinoma and 35 healthy controls.And statistical methods were used to analyze the difference,correlation and diagnostic value of the results.Results The serum levels of B7-H5 in patients with HBV-related hepatocellular carcinoma,patients with chronic hepatitis B and healthy subjects were statistically different(P＜0.05),and the level from high to low was HBV-related liver cancer patients,chronic hepatitis B patients,healthy subjects.The serum level of B7-H5 in chronic hepatitis B pa-tients with negative HBV-DNA was significantly higher than that in healthy subjects(P＜0.01).The level of B7-H5 in patients with chronic hepatitis B was positively correlated with HBV-DNA load(P＜0.05).And the level of B7-H5 in patients with HBV-related hepatocellular carcinoma was positively correlated with HBsAg,HBeAg and AFP levels(P＜0.05).In addition,B7-H5 had diagnostic value for chronic hepatitis B and HBV-related hepatocellular carcinoma(P＜0.01),and the diagnostic value for HBV-related hepatocellular carcino-ma was higher than that for chronic hepatitis B.The level of B7-H5 in patients with HBV-related hepatocellu-lar carcinoma after surgery was significantly lower than that before surgery(P＜0.05).Conclusion Serum levels of B7-H5 is related to the progression of CHB and HBV-related hepatocellular carcinoma,and can be considered as an effective detection index for the auxiliary diagnosis and the judgment of postoperative condi-tion of CHB and HBV-related hepatocellular carcinoma.

Objective To investigate the effects of BMSCs treatment on neuropathic pain in rats with SCI and explore the underlying mechanism.Methods The rats were randomly divided into the following groups(n=15 per group):sham-operated(sham)group,spinal cord injury model(SCI)group,SCI+BMSCs group,and SCI+BMSCs+LY294002 group.An SCI model was established using Sprague-Dawley rats,followed by intraspinal administration of BMSCs and the PI3K inhibitor LY294002 to the injured spinal cord of SCI rats.The BBB score,pMWT,and pTWL values under thermal stimulation were measured.Hematoxylin-eosin staining was used to observe pathological changes in the injured spinal cord of rats.The effects of BMSCs transplantation on SCI rats were explored through hematoxylin-eosin staining,immunofluorescence staining,ELISA,and Western Blot experiments.RSCN were induced using LPS and co-cultured with BMSCs and their exosomes.The effects of BMSCs and their exosomes on RSCN were investigated through Annexin V-FITC/PI kit,ELISA,and Western Blot assays.Results The SCI model was considered successfully established when the following criteria were met on post-operative day 5:BBB locomotor score≤5,accompanied by a BBB score<10 on day 20,along with histopathological evidence of spinal cord tissue loosening,extensive vacuolation,and neuronal atrophy observed via HE staining.Compared with the sham group,the SCI group exhibited significantly lower BBB scores,pMWT,and pTWL values(P<0.001).Concurrently,increased immunofluorescence intensity of IBA1,elevated levels of pro-inflammatory cytokines,and pain-related factors were detected in the spinal cord(P<0.001).Furthermore,activation of the PI3K/AKT signaling pathway was significantly suppressed.BMSCs transplantation protected SCI rats by activating the PI3K/AKT pathway(P<0.001).BMSC-mediated spinal cord repair was attenuated by LY294002 administration.LPS-induced RSCNs showed increased apoptosis and pro-inflammatory cytokine release(P<0.001).Co-culture with MSCs or BMSCs-derived exosomes activated the PI3K/AKT signaling pathway,thereby reducing LPS-induced apoptosis and proinflammatory cytokine production(P<0.05).Conclusion BMSCs activate the PI3K/AKT signaling pathway in neurons through exosomes,suppressing the levels of TNF-α,SP,NE,and 5-HT,and promoting functional recovery in SCI rats.

Objective: To establish aNBR1-knockout lung cancer mouse model through CRISPR-Cas9 technology by using adeno-associated virus(AAV) as a vector to specifically inhibitNBR1expression and to investigate the impact ofNBR1knockout on tumor growth and immune cell infiltration and regulation. Methods: sgRNAs targeting mouseNBR1(Gene ID: 17966) was designed using the online tool CRISPOR(http://crispor.tefor.net/crispor.py). AAV6 was utilized as the vector for sgRNA delivery, and the efficiency of gene knockout was confirmed using PCR and DNA sequencing methods. To determine the best AAV infection approach in mice, 6 C57BL/6J mice were randomly divided into intranasal and endotracheal groups. After 28 days, lung tissue sections were assessed for enhanced green fluorescent protein expression to identify the more efficient infection method for subsequent experiments. Lung tumor growth, as well as immune cell infiltration and activation status in tumor tissues, were detected using methods including HE staining, immunohistochemistry, immunofluorescence, and flow cytometry. Results: DNA sequencing and immunofluorescence results indicated successful construction of the AAV6-U6-sgNBR1-CAG-Cre-GFP vector with stable knockout efficiency. Fluorescence microscopy showed higher efficiency of lung infection in mice through intratracheal administration(P<0.05). HE staining revealed reduced tumor area in mouse lungs after targetedNBR1knockout compared to the control group(P<0.01). Immunofluorescence and flow cytometry results demonstrated enhanced functional activity of CD8+T lymphocytes in lung cancer tissues of mice with targetedNBR1knockout, characterized by increased effector T lymphocytes and decreased exhausted T lymphocytes(P<0.01). Conclusion Using CRISPR/Cas9 technology, we construct a lung cancer mouse model with targetedNBR1knockout. We verify that targeted inhibition of NBR1 expression significantly enhances the functional activity of CD8+T lymphocytes in lung tissues, resulting in suppressed tumor growth, reduced tumor burden, and extended survival in lung cancer mice. This study lays an experimental foundation for investigations into the mechanisms and functions ofNBR1and other genes in lung adenocarcinoma cells.

Psychiatric comorbidity is common in symptom-based diagnoses like autism spectrum disorder (ASD), attention/deficit hyper-activity disorder (ADHD), and obsessive-compulsive disorder (OCD). However, these co-occurring symptoms mediated by shared and/or distinct neural mechanisms are difficult to profile at the individual level. Capitalizing on unsupervised machine learning with a hierarchical Bayesian framework, we derived latent disease factors from resting-state functional connectivity data in a hybrid cohort of ASD and ADHD and delineated individual associations with dimensional symptoms based on canonical correlation analysis. Models based on the same factors generalized to previously unseen individuals in a subclinical cohort and one local OCD database with a subset of patients undergoing neurosurgical intervention. Four factors, identified as variably co-expressed in each patient, were significantly correlated with distinct symptom domains (r = -0.26-0.53, P < 0.05): behavioral regulation (Factor-1), communication (Factor-2), anxiety (Factor-3), adaptive behaviors (Factor-4). Moreover, we demonstrated Factor-1 expressed in patients with OCD and Factor-3 expressed in participants with anxiety, at the degree to which factor expression was significantly predictive of individual symptom scores (r = 0.18-0.5, P < 0.01). Importantly, peri-intervention changes in Factor-1 of OCD were associated with variable treatment outcomes (r = 0.39, P < 0.05). Our results indicate that these data-derived latent disease factors quantify individual factor expression to inform dimensional symptom and treatment outcomes across cohorts, which may promote quantitative psychiatric diagnosis and personalized intervention.
Humans ; Male ; Female ; Attention Deficit Disorder with Hyperactivity ; Obsessive-Compulsive Disorder ; Adult ; Autism Spectrum Disorder ; Bayes Theorem ; Adolescent ; Young Adult ; Magnetic Resonance Imaging ; Middle Aged ; Child ; Brain/metabolism* ; Cohort Studies ; Comorbidity

Objective To explore the correlation of baseline CCL19+dendritic cell(CCL19+DC)infiltration in lung adenocarcinoma microenvironment with immunotherapy efficacy and CD8+T cell infiltration.Methods We retrospectively analyzed the data of patients with lung adenocarcinoma hospitalized at First Affiliated Hospital of Henan University of Science and Technology from January,2020 to December,2023,and collected tissue samples from 96 patients undergoing immunotherapy for assessing CCL19+DC and CD8+T cell infiltration using immunofluorescence assay.We evaluated the predictive value of baseline CCL19+DCs for patient responses to immunotherapy using receiver-operating characteristics(ROC)curves and analyzed the correlations of baseline CCL19+DC expression with immunotherapy efficacy and CD8+T cell and cytotoxic T lymphocyte(CTL)infiltrations.In co-culture systems of lung adenocarcinoma PC9 cells,CD8+T cells and DCs(overexpressing CCL19 with or without anti PD-1 antibody treatment),the expressions of granzyme B,perforin,IFN-γ,and Ki-67 in T cells were analyzed using flow cytometry.Results The patients with partial or complete remission following immunotherapy had a significantly higher baseline CCL19+DC infiltration level in lung adenocarcinoma tissues than those with poor responses.CCL19+DC infiltration had an area under ROC curve of 0.785,a sensitivity of 75.6%,and a specificity of 62.8%for predicting immunotherapy efficacy.The expression of CD8+T cell surface molecules Granzyme B(P<0.01),Perforin(P<0.01),IFN-γ(P<0.01)and Ki-67(P<0.001)in patients with high expression of CCL19+DC were higher than those in patients with low expression of CCL19+DC.The baseline CCL19+DC infiltration level was positively correlated with immunotherapy efficacy(P=0.003),CTL infiltration of(r=0.6657,P<0.001)and CD8+T cell infiltration(P=0.007).In the co-cultured cells,CCL19 overexpression combined with anti-PD1 treatment of the DCs more strongly enhanced cytotoxicity and proliferation of CD8+T lymphocytes than either of the single treatments(P<0.01 or 0.001).Conclusion The baseline CCL19+DC infiltration level in lung adenocarcinoma microenvironment is positively correlated with immunotherapy efficacy and CTL infiltration and can thus predict the response to immunotherapy.

Objective:To retrospectively analyze the clinical characteristics and prognosis of 85 newly diagnosed patients with follicular lymphoma (FL), as well as the prognostic value of comprehensive geriatric assessment (CGA) in patients with FL aged ≥ 60 years old.Methods:The clinical data and prognosis of 85 newly diagnosed FL patients admitted from August 2011 to June 2022 were collected. The clinical features, laboratory indicators, therapeutic efficacy, survival and prognostic factors of patients were statistically analyzed, and the prognosis of patients was stratified using various geriatric assessment tools.Results:① The patients with FL were mostly middle-aged and older, with a median age of 59 (20-87) years, including 41 patients (48.2%) aged ≥60 years. The ratio of male to female was 1∶1.36. Overall, 77.6% of the patients were diagnosed with Ann Arbor stage Ⅲ-Ⅳ, and 17 cases (20.0%) were accompanied by B symptoms. Bone marrow involvement was the most common (34.1%). ②Overall, 71 patients received immunochemotherapy. The overall response rate was 86.6%, and the complete recovery rate was 47.1% of 68 evaluated patients. Disease progression or relapse in the first 2 years was observed in 23.9% of the patient. Overall, 14.1% of the patients died during follow-up. ③Of the 56 patients receiving R-CHOP-like therapies, the 3-year and 5-year progression-free survival (PFS) rates were 85.2% and 72.8%, respectively, and the 3-year and 5-year overall survival (OS) rates were 95.9% and 88.8%, respectively. The univariate analysis showed that age ≥60 years old ( HR=3.430, 95% CI 1.256-9.371, P=0.016), B symptoms ( HR=5.030, 95% CI 1.903-13.294, P=0.016), Prognostic Nutritional Index (PNI) <45.25 ( HR=3.478, 95% CI 1.299-9.310, P=0.013), Follicular Lymphoma International Prognostic Index (FLIPI) high-risk ( HR=2.918, 95% CI 1.074-7.928, P=0.036), and PRIMA-prognostic index (PRIMA-PI) high-risk ( HR=2.745, 95% CI 1.057-7.129, P=0.038) significantly predicted PFS. Moreover, age ≥60 years old and B symptoms were independent risk factors for PFS. Progression of disease within 24 months (POD24) significantly predicted OS in the univariate analysis. Conclusions:FL is more common among middle-aged and older women. Age, B symptoms, PNI score, FLIPI high-risk, PRIMA-PI high-risk, and POD24 influenced PFS and OS. The CGA can be used for treatment selection and risk prognostication in older patients with FL.