Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

Alzheimer's disease (AD), characterized by β-amyloid (Aβ) aggregation and neuroinflammation, remains a formidable clinical challenge. Herein, we present an innovative nose-to-brain delivery platform utilizing lactoferrin (Lf)-functionalized lipid nanoparticles (LNPs) co-encapsulating α-mangostin (α-M) and β-site APP cleaving enzyme 1 (BACE1) siRNA (siB). This dual-modal therapeutic system synergistically combines the neuroprotective and microglia-reprogramming capabilities of α-M with the transcriptional silencing of BACE1 via siB, thereby simultaneously inhibiting Aβ production and enhancing its clearance. Fabricated via a microfluidic approach, the LNPs exhibited uniform particle size distribution, great encapsulation efficiency, and robust colloidal stability. Upon intranasal administration, Lf-functionalization enabled superior brain-targeting efficacy through receptor-mediated transcytosis. In vitro studies demonstrated that α-M reversed Aβ-induced low-density lipoprotein receptor downregulation, promoting microglial phagocytosis and autophagic degradation of Aβ, while siB effectively suppressed BACE1 expression, abrogating Aβ synthesis. In vivo investigations in APP/PS1 transgenic mice revealed remarkable cognitive recovery, substantial Aβ plaque reduction, and alleviation of neuroinflammation and oxidative stress. This intricately designed LNP system, exploiting a non-invasive and efficient nose-to-brain delivery route, provides a biocompatible, synergistic, and transformative therapeutic strategy for the multifaceted management of AD.

Objective:To investigate the diagnostic value of different conventional ultrasound-based radiomics models and their combination with clinical ultrasound features in the pathological subtyping of renal cell carcinoma.Methods:Retrospective data from 286 patients diagnosed with renal cell carcinoma by pathology at the Tenth Affiliated Hospital of Southern Medical University between May 1，2017 and June 7，2024 were collected. Among the 286 patients，203 were clear cell carcinoma，44 were papillary renal cell carcinoma，and 39 were chromophobe renal cell carcinoma. The patients were randomly divided into a training group（201 cases）and a validation group（85 cases）in a ratio of 7 to 3. Regions of interest（ROI）were delineated on conventional ultrasound images，and the radiomics features were extracted. Feature selection was performed using Student's t-test，Pearson correlation，and the least absolute shrinkage and selection operator（LASSO）. Six different machine learning methods included category gradient boosting（CatBoost），light gradient boosting machine（LightGBM），Logistic regression（LR），random forest（RF），support vector machine（SVM）and extreme gradient boosting（XGBoost）were used to establish radiomics models. Weight balancing was applied to correct for sample imbalance，and an imaging genomics model was constructed after balancing the samples. Independent predictors of renal cell carcinoma subtyping were selected from clinical ultrasound features using univariate and multivariate logistic regression analyses，and a clinical imaging model was constructed. The best-performing radiomics model was combined with the clinical independent predictors to construct a combined model. Receiver operating characteristic curves and the obuchowski index were plotted to evaluate model performance. Results:Among the radiomics models，the model constructed using Random Forest（RS RF）after balancing the samples exhibited the best predictive performance，with area under the curve（AUCs）of 0.918（micro-average ROC）and 0.903（macro-average ROC），and the obuchowski index was 0.885 in the validation group. The long and short axes of ultrasound image tumor masses were used as imaging independent predictors to construct a clinical imaging model. In the validation group，the AUCs of the clinical model were 0.886（micro-average ROC）and 0.606（macro-average ROC），and the obuchowski index was 0.569. The combined model achieved AUCs of 0.888（micro-average ROC）and 0.967（macro-average ROC），with an obuchowski index of 0.933，outperforming any single model. Conclusions:The combination of conventional ultrasound-based radiomics models with clinical ultrasound features demonstrates high diagnostic value in differentiating clear cell carcinoma，papillary renal cell carcinoma，and chromophobe renal cell carcinoma. It may serve as an auxiliary tool for providing timely and effective clinical guidance.

Objective:To explore the role of lactate in Superoxide dismutase 2 (SOD2) lactylation in cerebral ischemia-reperfusion injury in mice.Methods:Male C57BL/6 mice were randomLy (random number) divided into 4 groups: sham operation group (Sham group), Middle Cerebral Artery Occlusion/Reperfusion group (MCAO/R group), Middle Cerebral Artery Occlusion/Reperfusion+2-Deoxy-D-glucose group (MCAO/R+2-DG group), Middle Cerebral Artery Occlusion/Reperfusion+sodium lactate group (MCAO/R+Nala group). Cerebral ischemia reperfusion injury model was established in the mice of MCAO/R group using the thread occlusion. In the MCAO/R+2-DG group, mice received an intraperitoneal injection of 250 mg/kg of 2-DG 90 min before ischemia. Mice in the MCAO/R+ Nala group was given an intraventricular injection of 2 μL of 100 mmol/L Nala 24 h before ischemia. Commercial kits was used to detect lactate levels, Hematoxylin & Eosin Staining (HE) was employed to observe cell morphology, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was performed to assess cell apoptosis, and immunofluorescence was utilized to detect reactive oxygen species (ROS). Western blot was conducted to measure SOD2, Superoxide Dismutase 2 Lysine 114 Lactylation(SOD2-K114la), Iron regulatory protein 2(IRP2) and transferrin receptor protein 1(TFR1) levels. The above indicators were analyzed and compared by one-way variance.Results:Compared with the Sham group, the MCAO/R group showed increased levels of lactate, SOD2-K114la, TUNEL positive rate, ROS, IRP2 and TFR1[lactate: (0.608±0.064) vs. (0.376±0.030), P<0.005; SOD2-K114la: (2.311±0.146) vs. (1.009±0.073), P<0.0005; TUNEL positive rate: (35.420±2.832) vs. (0.294±0.147), P<0.0001; ROS: (3.415±0.229) vs. (1.166±0.155), P<0.0001; IRP2: (1.735±0.125) vs. (1.000±0.000), P<0.0001; TFR1: (1.611±0.058) vs. (1.000±0.000), P<0.0001], while SOD2 decreased[(0.545±0.062) vs. (1.082±0.088), P<0.0001]. HE staining indicated brain damage. Compared with the MCAO/R group, the MCAO/R+2-DG group showed reduced levels of lactate, SOD2-K114la, TUNEL positive rate, ROS, IRP2, and TFR1[lactate: (0.453±0.047) vs. (0.608±0.064), P<0.05; SOD2-K114la: (1.764±0.188) vs. (2.311±0.146), P<0.05; TUNEL positive rate: (23.800±3.168) vs. (35.420±2.832), P<0.005; ROS: (2.640±0.213) vs. (3.415±0.229), P<0.005; IRP2: (1.463±0.055) vs. (1.735±0.125), P<0.05; TFR1: (1.252±0.081) vs. (1.611±0.058), P<0.005], with higher level of SOD2 [(0.727±0.026) vs. (0.545±0.062), P<0.05]. Meanwhile, HE staining indicated reduced damage. Compared with the MCAO/R group, the MCAO/R+Nala group showed increased levels of lactate, SOD2-K114la, TUNEL positive rate, ROS, IRP2 and TFR1[lactate: (1.021±0.051) vs. (0.608±0.064), P<0.0001; SOD2-K114la: (3.479±0.275) vs. (2.311±0.146), P<0.0005; TUNEL positive rate: (53.430±3.551) vs. (35.420±2.832), P<0.0001; ROS: (4.687±0.253) vs. (3.415±0.229), P<0.0001; IRP2: (2.463±0.117) vs. (1.735±0.125), P<0.0001; TFR1: (2.209±0.094) vs. (1.611±0.058), P<0.0001], with decreased levels of SOD2 [(0.286±0.040) vs. (0.545±0.062), P<0.0001]. And HE staining revealed worsened braindamage. Conclusions:Increased lactate levels can enhance the lactylation of SOD2, exacerbating brain damage after Cerebral ischemia reperfusion injury(CIRI). Inhibiting lactate production may alleviate brain injury by regulating iron Metabolism.

Objective:To systematically search, evaluate, and summarize evidence-based findings related to postoperative oral health management for orthognathic surgery patients, with the goal of providing clinical care professionals with evidence-based guidance for postoperative care, infection prevention, and functional recovery.Methods:Using the "6S" evidence hierarchy model, a systematic search was conducted in databases such as UpToDate, BMJ Best Practice, DynaMed, The Cochrane Library, World Health Organization (WHO), National Institute for Health and Care Excellence (NICE), Guidelines International Network (GIN), Registered Nurses′Association of Ontario (RNAO), Chinese Stomatological Association (CSA), American Association of Oral and Maxillofacial Surgeons (AAOMS), PubMed, and Scopus. The search included literature on postoperative oral health management for orthognathic surgery patients, such as guidelines, clinical decision-making tools, expert consensus, evidence summaries, and systematic reviews, covering publications from database inception to November 12, 2024. Two researchers independently assessed the quality of the included literature and extracted, summarized, and synthesized the evidence.Results:A total of 18 studies were included, consisting of 7 guidelines, 7 systematic reviews, 2 expert consensus documents and 2 randomized controued trials. Twenty-two best evidence statements were summarized, addressing six key areas: oral hygiene and infection prevention, wound care, oral functional recovery, dietary and nutritional support, oral comfort management, and long-term oral health maintenance.Conclusions:This study provides a comprehensive summary of the best available evidence for postoperative oral health management in orthognathic surgery patients. It offers theoretical support for clinical nursing practices and evidence-based recommendations for postoperative care specific to this patient population.

Objective:To construct a triple pre-rehabilitation intervention program for patients undergoing radical prostatectomy, to provide a basis for promoting pre-rehabilitation in patients undergoing radical prostatectomy.Methods:Literature analysis was used to search domestic and foreign databases such as China National Knowledge Infrastructure, Wanfang, PubMed, etc, on triple pre-rehabilitation and rapid rehabilitation of patients undergoing radical prostatectomy, with a search time frame from January 1, 2013 to December 31, 2023. The Delphi expert letter consultation was conducted later, and the final draft of the triple pre-rehabilitation intervention program for patients with radical prostatectomy was finally formed.Results:A total of 20 experts completed 2 rounds of inquiries, all were female, with an age of (40.85 ± 5.40) years old. The response rates for the 2 rounds of expert inquiries were both 100%(20/20). The authority coefficients of the experts were 0.87 and 0.90, respectively. Kendall coordination coefficients were 0.11 and 0.21, respectively. The coefficient of variation for each item in the second round of inquiries ranged from 0 to 0.15. The triple pre-rehabilitation intervention program for patients with radical resection of prostate cancer was constructed, including 4 primary indexes, 8 secondary indexes and 25 tertiary indexes.Conclusions:It is scientific, targeted and feasible to construct a triple pre-rehabilitation intervention program for patients undergoing radical prostatectomy based on Delphi method, which can provide clinical basis for pre-rehabilitation of elderly patients undergoing prostate cancer surgery.

Objective:To systematically search, evaluate, and summarize evidence-based findings related to postoperative oral health management for orthognathic surgery patients, with the goal of providing clinical care professionals with evidence-based guidance for postoperative care, infection prevention, and functional recovery.Methods:Using the "6S" evidence hierarchy model, a systematic search was conducted in databases such as UpToDate, BMJ Best Practice, DynaMed, The Cochrane Library, World Health Organization (WHO), National Institute for Health and Care Excellence (NICE), Guidelines International Network (GIN), Registered Nurses′Association of Ontario (RNAO), Chinese Stomatological Association (CSA), American Association of Oral and Maxillofacial Surgeons (AAOMS), PubMed, and Scopus. The search included literature on postoperative oral health management for orthognathic surgery patients, such as guidelines, clinical decision-making tools, expert consensus, evidence summaries, and systematic reviews, covering publications from database inception to November 12, 2024. Two researchers independently assessed the quality of the included literature and extracted, summarized, and synthesized the evidence.Results:A total of 18 studies were included, consisting of 7 guidelines, 7 systematic reviews, 2 expert consensus documents and 2 randomized controued trials. Twenty-two best evidence statements were summarized, addressing six key areas: oral hygiene and infection prevention, wound care, oral functional recovery, dietary and nutritional support, oral comfort management, and long-term oral health maintenance.Conclusions:This study provides a comprehensive summary of the best available evidence for postoperative oral health management in orthognathic surgery patients. It offers theoretical support for clinical nursing practices and evidence-based recommendations for postoperative care specific to this patient population.

Objective:To construct a triple pre-rehabilitation intervention program for patients undergoing radical prostatectomy, to provide a basis for promoting pre-rehabilitation in patients undergoing radical prostatectomy.Methods:Literature analysis was used to search domestic and foreign databases such as China National Knowledge Infrastructure, Wanfang, PubMed, etc, on triple pre-rehabilitation and rapid rehabilitation of patients undergoing radical prostatectomy, with a search time frame from January 1, 2013 to December 31, 2023. The Delphi expert letter consultation was conducted later, and the final draft of the triple pre-rehabilitation intervention program for patients with radical prostatectomy was finally formed.Results:A total of 20 experts completed 2 rounds of inquiries, all were female, with an age of (40.85 ± 5.40) years old. The response rates for the 2 rounds of expert inquiries were both 100%(20/20). The authority coefficients of the experts were 0.87 and 0.90, respectively. Kendall coordination coefficients were 0.11 and 0.21, respectively. The coefficient of variation for each item in the second round of inquiries ranged from 0 to 0.15. The triple pre-rehabilitation intervention program for patients with radical resection of prostate cancer was constructed, including 4 primary indexes, 8 secondary indexes and 25 tertiary indexes.Conclusions:It is scientific, targeted and feasible to construct a triple pre-rehabilitation intervention program for patients undergoing radical prostatectomy based on Delphi method, which can provide clinical basis for pre-rehabilitation of elderly patients undergoing prostate cancer surgery.

Objective:To investigate the diagnostic value of different conventional ultrasound-based radiomics models and their combination with clinical ultrasound features in the pathological subtyping of renal cell carcinoma.Methods:Retrospective data from 286 patients diagnosed with renal cell carcinoma by pathology at the Tenth Affiliated Hospital of Southern Medical University between May 1，2017 and June 7，2024 were collected. Among the 286 patients，203 were clear cell carcinoma，44 were papillary renal cell carcinoma，and 39 were chromophobe renal cell carcinoma. The patients were randomly divided into a training group（201 cases）and a validation group（85 cases）in a ratio of 7 to 3. Regions of interest（ROI）were delineated on conventional ultrasound images，and the radiomics features were extracted. Feature selection was performed using Student's t-test，Pearson correlation，and the least absolute shrinkage and selection operator（LASSO）. Six different machine learning methods included category gradient boosting（CatBoost），light gradient boosting machine（LightGBM），Logistic regression（LR），random forest（RF），support vector machine（SVM）and extreme gradient boosting（XGBoost）were used to establish radiomics models. Weight balancing was applied to correct for sample imbalance，and an imaging genomics model was constructed after balancing the samples. Independent predictors of renal cell carcinoma subtyping were selected from clinical ultrasound features using univariate and multivariate logistic regression analyses，and a clinical imaging model was constructed. The best-performing radiomics model was combined with the clinical independent predictors to construct a combined model. Receiver operating characteristic curves and the obuchowski index were plotted to evaluate model performance. Results:Among the radiomics models，the model constructed using Random Forest（RS RF）after balancing the samples exhibited the best predictive performance，with area under the curve（AUCs）of 0.918（micro-average ROC）and 0.903（macro-average ROC），and the obuchowski index was 0.885 in the validation group. The long and short axes of ultrasound image tumor masses were used as imaging independent predictors to construct a clinical imaging model. In the validation group，the AUCs of the clinical model were 0.886（micro-average ROC）and 0.606（macro-average ROC），and the obuchowski index was 0.569. The combined model achieved AUCs of 0.888（micro-average ROC）and 0.967（macro-average ROC），with an obuchowski index of 0.933，outperforming any single model. Conclusions:The combination of conventional ultrasound-based radiomics models with clinical ultrasound features demonstrates high diagnostic value in differentiating clear cell carcinoma，papillary renal cell carcinoma，and chromophobe renal cell carcinoma. It may serve as an auxiliary tool for providing timely and effective clinical guidance.

The neurovascular unit (NVU) is highly responsible for cerebral homeostasis and its dysfunction emerges as a critical contributor to Alzheimer's disease (AD) pathology. Hence, rescuing NVU dysfunction might be a viable approach to AD treatments. Here, we fabricated a self-regulated muti-functional nano-modulator (siR/PIO@RP) that can intelligently navigate to damaged blood-brain barrier and release therapeutical cargoes for synergetic AD therapy. The resulting siR/PIO@RP enables self-regulation of its distribution in accordance with the physio/pathological state (low/high RAGE expression) of the target site via a feedback loop. siR/PIO@RP is capable of performing intricate tasks and goes beyond the capabilities of single-target therapeutic agents utilized in AD therapy, such as reducing cerebral Aβ load, relieving neuroinflammation, and alleviating the dysfunction of NVU. Overall, the current study provides proof of concept that normalizing NVU holds promise as a means of alleviating AD symptoms.