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 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.

Polatuzumab vedotin (Pola) is a novel antibody-drug conjugate targeting CD79b, which has been shown to be effective in treating newly diagnosed and relapsed/refractory diffuse large B cell lymphoma (DLBCL) during clinical trials. This study aims to conduct a retrospective analysis of the clinical characteristics, diagnosis, and treatment of a patient with refractory secondary central nervous system lymphoma at Beijing Hospital, alongside a review of relevant literature. This study included a 79-year-old female patient who was diagnosed with DLBCL affecting the ilium, sacrum, spinal cord, and nerve roots and had an IPI score of 5 and a high-risk score according to MSKCC. She showed a geriatric comprehensive assessment (IACA) score of 2, which was categorized under the unfit group. Her initial treatment comprised chemo-free therapy and radiotherapy, followed by progression. In the second-line treatment, a Pola-based regimen was applied, and the patient achieved a complete response, suggesting that this regimen may be a therapeutic option for patients with DLBCL involving the central nervous system.

Objective The biomechanical model for the musculoskeletal system of a human knee joint was established using a numerical simulation method.The kinematic and dynamic information captured during jumping motion simulated by the human dynamic model was used as driven data of the knee biomechanical model,followed by further analysis of the stress field distribution characteristics of the meniscus under different thermal-force coupling knee brace conditions.Methods Based on computed tomography and magnetic resonance imaging of the subject,a realistic human knee model,including bone,articular cartilage,meniscus,ligaments and peripheral soft tissues of the knee joint,was constructed.Furthermore,two gaits,namely taking-off and landing-on,of jumping motion with an increased risk of meniscus injuries were selected according to mechanical features in full-cycle jumping motion.Subsequently,the stress field characteristics of the knee meniscus under four different thermal-force coupling knee braces were analyzed,the changes of the peak stress of the meniscus and its stress concentration area were discussed,and the protective efficacy and mechanical basis of meniscal injuries and wearing knee braces were explored.Results The anterior part of the medial knee meniscus was a vulnerable area under concentrated stress.Under the knee brace thermal-force coupling condition,the stress concentration area of the medial meniscus was transferred from its narrow and weak anterior part to its wide and thick middle part,and the peak stress was also significantly reduced.The peak stress on the medial meniscus and that on the lateral meniscus were similar,indicating that the two parts of the meniscus bore the external load evenly,and the meniscus stress concentration area decreased.Conclusions Thermal-force coupling knee braces have good protective effects against knee meniscus injury.The numerical simulation provides theoretical support and technical guidance for the design of multifunctional thermal knee braces.

Objective:To evaluate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on tourniquet-induced hypertension (TIH) in the patients undergoing anterior cruciate ligament reconstruction.Methods:Seventy-four patients of either sex, aged 18-60 yr, of American Society of Anesthesiologists Physical Status classification I or II, with body mass index of 18-30 kg/m 2, undergoing elective anterior cruciate ligament reconstruction under general anesthesia combined with preoperative femoral nerve block, were divided into 2 groups ( n=37 each) using a random number table method: sham stimulation group (group SS) and group taVNS. Group SS received stimulation on the ear lobe and the tail of the helix of the left ear. Group taVNS received stimulation on the cymba concha and the earlobe of the left ear. Both groups received stimulation from 1 h before induction of anesthesia until the end of the procedure (frequency of 30 Hz, pulse width of 300 μs, and amplitude of the strongest current that could be tolerated by the patient in the absence of pain). The tourniquet inflation pressure was 280 mmHg, with an inflation time of 60-90 min. Systolic blood pressure, diastolic blood pressure and heart rate were recorded before tourniquet inflation to assess the development of intraoperative TIH. The consumption of intraoperative propofol, remifentanil, nitroglycerin, esmolol, norepinephrine and atropine was recorded, and the occurrence of postoperative nausea and vomiting, skin itching and headache and dizziness was also recorded. Results:Compared with group SS, the incidence of TIH and the number of patients used nitroglycerin were significantly reduced ( P<0.05), and no significant changes were found in the other parameters in group taVNS ( P>0.05). Conclusions:taVNS can decrease the occurrence of TIH in the patients undergoing anterior cruciate ligament reconstruction.

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.

Objectives:To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions.Methods:Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set ( n=284) and a validation set ( n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training ( n=243), validation ( n=105), and test ( n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results:We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression ( P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions:Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.