Alzheimer’s disease (AD) is pathologically characterized by cerebral amyloid β‑protein (Aβ) aggregation, neurofibrillary tangles and progressive cognitive deterioration. There is an urgent clinical demand for targeted therapeutic agents against AD, whereas the blood-brain barrier (BBB) acts as a critical physical barrier that blocks over 98% small-molecule drugs and nearly all biomacromolecules from entering brain parenchyma. Nanomedicine-based drug delivery systems (NDDSs) with tunable physicochemical properties can cross the BBB via multiple transcytosis pathways including adsorptive-mediated, receptor-mediated and transporter-mediated routes, opening a promising avenue for targeted AD treatment. A core academic viewpoint proposed herein is that robust in vitro endothelial penetration of nanocarriers cannot guarantee effective accumulation in brain target cells. Comprehensive evaluation of BBB-crossing delivery efficiency should not merely rely on in vitro permeability tests, but cover the full multi-step transcytosis cascade, cellular tropism in brain tissues and in vivo therapeutic outcomes. This review systematically sorts out diverse nanoplatforms applicable to BBB penetration for AD intervention. Inorganic nanomaterials such as gold and ceria nanoparticles possess large specific surface areas and intrinsic antioxidant capacity, which eliminate reactive oxygen species and hinder Aβ fibrillization. Liposomal formulations and solid lipid nanoparticles exhibit superior biocompatibility with biomimetic phospholipid bilayer architectures, capable of co-loading hydrophilic nucleic acids for Tau regulation and lipophilic Aβ inhibitors; relying on receptor-mediated transcytosis, they achieve sustained drug retention in the brain. Polymeric nanocarriers including nanogels and polyamidoamine dendrimers enable multi-target combinatorial therapy, and can be engineered to release cargo in response to inflammatory microenvironments, thereby suppressing excessive microglial activation and protecting neuronal mitochondria. Beyond conventional nanocarriers, this work elaborates two cutting-edge BBB-crossing delivery platforms: biomimetic nanosystems and metal-organic frameworks (MOFs). Biomimetic nanoparticles camouflaged with erythrocyte, platelet or macrophage membranes, as well as natural exosomes, evade immune clearance, prolong systemic circulation and inherently home to inflammatory lesions. Serving as “nano-decoys”, they neutralize Aβ neurotoxins and remodel cerebral inflammatory microenvironments simultaneously. MOFs feature high porosity and customizable pore channels for co-delivery of multiple therapeutics, and can be integrated with near-infrared photothermal and photooxidation modalities to facilitate focal brain lesion therapy. This review highlights a transformative paradigm shift in the field of BBB-targeted AD therapy: research focus has shifted from simply maximizing cerebral drug penetration toward active modulation and functional restoration of the BBB. Impaired BBB transporters intrinsically impede endogenous Aβ clearance. Accordingly, BBB-regulating nanocarriers are designed to remodel the low-density lipoprotein receptor-related protein 1 (LRP1) trafficking cascade, redirecting endocytic vesicles from lysosomal degradation to non-degradable transcytosis and restoring the intrinsic Aβ efflux capacity of the BBB. Distinct from conventional strategies that only exert local lesion inhibition, this systemic clearance strategy eliminates cerebral Aβ deposits by accelerating peripheral excretion.

Objective To study the oral health status of officers and soldiers in a certain unit,so as to provide a basis for the formulation and implementation of oral health support plans.Methods A total of 437 officers and soldiers in a certain unit were enrolled to assess their oral health status through questionnaire survey and clinical examination.Results The prevalences of dental caries and periodontal diseases were 87.6%(383/437)and 90.4%(395/437),respectively;the detection rates of impacted third molars,recurrent aphthous stomatitis,other mucosal diseases,and temporomandibular joint disorders were 12.6%(55/437),54.2%(237/437),29.5%(129/437),and 19.2%(84/437),respectively.In terms of oral medical needs,23.3%(102/437)patients did not need treatment,66.1%(289/437)required elective treatment,9.2%(40/437)required early treatment,and 1.4%(6/437)required urgent treatment.Conclusion Officers and soldiers in this study have a variety of oral diseases,with periodontal diseases having the highest prevalence.Supportting plans should be formulated based on the characteristics of the prevalence of oral diseases among them,and regular oral diagnosis and treatment should be carried out to prevent the development and progression of oral diseases.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

Objective:To investigate the effects of lipopolysaccharide (LPS)-activated stimulator of interferon genes (STING) signaling on the biological behavior of periodontal ligament cells and its mechanism of action.Methods:Human periodontal ligament cells (hPDLC) were divided into the PBS group and the LPS group by stimulated with phosphate-buffered saline (PBS) and LPS derived from Porphyromonas gingivalis (ATCC 33277) for 12 hours, respectively. The intracellular distribution of 8-hydroxydeoxyguanosine (8-OHdG), a marker of DNA damage, and the activation level of STING signaling were detected by immunofluorescence. The source of intracellular double-stranded DNA was detected by live-cell probes. The levels of osteogenic-related proteins, such as special protein 7 (SP7), bone morphogenetic protein 2 (BMP2), cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), and STING were detected by Western blotting. The cell supernatants of the PBS group and the LPS group were collected, and the levels of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and interferon (IFN)-β, were detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). A total of 12 cgas knockout mice and 12 littermate wild-type mice were constructed. The maxillary second molars of the mice were ligated with silk or sham surgery, respectively. After 7 days of modeling, the mice were divided into littermate control sham surgery group, littermate control periodontitis group, cgas knockout sham surgery group, and cgas knockout periodontitis group, with 6 mice in each group. Micro-CT was used to collect image data, and three-dimensional reconstructions were performed on the maxillary samples of each group. The distance from the cemento-enamel junction to the alveolar bone crest (CEJ-ABC), bone volume fraction (BV/TV), and bone mineral density (BMD) in the model area were statistically analyzed using CTAn and CTVOX software. Frozen sectioning was used to obtain sections of the maxillary molars of each group of mice, and the signal intensities of cGAS and STING proteins were detected by immunofluorescence. Results:Immunofluorescence results showed that the fluorescence signal intensity of 8-OHdG outside the nucleus in the LPS group (4.09±0.24) was significantly higher than that in the PBS group (1.00±0.10) ( t=20.33, P<0.001). The co-localization signal of mitochondrial marker TOM20 and 8-OHdG (8.56±0.53) were significantly higher than that of PBS group (1.00±0.09) ( t=24.37, P<0.001). Live cell DNA probe detection showed that the signal intensity of double-stranded DNA in LPS group (3.23±0.12) was significantly stronger than that in PBS group (1.00±0.17) ( t=18.30, P<0.001). Immunofluorescence demonstrated a significant increase in STING expression in hPDLC of the LPS group ( t=6.42, P<0.001), and it was colocalized with the Golgi marker GM130. ELISA results showed that the abundance of IL-6, IFN-β, and IL-1β in the supernatant of the LPS group were higher than those of the PBS group ( t=12.44, t=11.38, t=9.48, all P<0.001). Animal experiments confirmed that compared with the sham operation group [(207.61±38.09) and (238.97±45.90) μm], the CEJ-ABC in the periodontitis group [(420.31±35.32) and (405.16±35.51) μm] were increased ( P<0.01), while the CEJ-ABC in the cgas knockout periodontitis group [(295.11±35.43) and (309.15±32.22) μm] were significantly lower than those in the control periodontitis group of the same litter ( P<0.01). Compared with the sham operation group (45.84±6.41), the STING fluorescence signal in the periodontitis group (152.44±6.86) was significantly increased ( P<0.001). Compared with the control periodontitis group of the same litter, the STING signal in the cgas knockout periodontitis group was significantly reduced (88.31±9.70) ( P<0.001). Conclusions:LPS stimulation can activate the STING signal by generating mitochondrial-derived double-stranded DNA, stimulating hPDLC to secrete inflammatory cytokines and impairing osteogenic differentiation potential. Suppressing STING activation in animal models can reduce bone destruction in periodontitis.

Objective:To investigate the effects of lipopolysaccharide (LPS)-activated stimulator of interferon genes (STING) signaling on the biological behavior of periodontal ligament cells and its mechanism of action.Methods:Human periodontal ligament cells (hPDLC) were divided into the PBS group and the LPS group by stimulated with phosphate-buffered saline (PBS) and LPS derived from Porphyromonas gingivalis (ATCC 33277) for 12 hours, respectively. The intracellular distribution of 8-hydroxydeoxyguanosine (8-OHdG), a marker of DNA damage, and the activation level of STING signaling were detected by immunofluorescence. The source of intracellular double-stranded DNA was detected by live-cell probes. The levels of osteogenic-related proteins, such as special protein 7 (SP7), bone morphogenetic protein 2 (BMP2), cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), and STING were detected by Western blotting. The cell supernatants of the PBS group and the LPS group were collected, and the levels of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and interferon (IFN)-β, were detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). A total of 12 cgas knockout mice and 12 littermate wild-type mice were constructed. The maxillary second molars of the mice were ligated with silk or sham surgery, respectively. After 7 days of modeling, the mice were divided into littermate control sham surgery group, littermate control periodontitis group, cgas knockout sham surgery group, and cgas knockout periodontitis group, with 6 mice in each group. Micro-CT was used to collect image data, and three-dimensional reconstructions were performed on the maxillary samples of each group. The distance from the cemento-enamel junction to the alveolar bone crest (CEJ-ABC), bone volume fraction (BV/TV), and bone mineral density (BMD) in the model area were statistically analyzed using CTAn and CTVOX software. Frozen sectioning was used to obtain sections of the maxillary molars of each group of mice, and the signal intensities of cGAS and STING proteins were detected by immunofluorescence. Results:Immunofluorescence results showed that the fluorescence signal intensity of 8-OHdG outside the nucleus in the LPS group (4.09±0.24) was significantly higher than that in the PBS group (1.00±0.10) ( t=20.33, P<0.001). The co-localization signal of mitochondrial marker TOM20 and 8-OHdG (8.56±0.53) were significantly higher than that of PBS group (1.00±0.09) ( t=24.37, P<0.001). Live cell DNA probe detection showed that the signal intensity of double-stranded DNA in LPS group (3.23±0.12) was significantly stronger than that in PBS group (1.00±0.17) ( t=18.30, P<0.001). Immunofluorescence demonstrated a significant increase in STING expression in hPDLC of the LPS group ( t=6.42, P<0.001), and it was colocalized with the Golgi marker GM130. ELISA results showed that the abundance of IL-6, IFN-β, and IL-1β in the supernatant of the LPS group were higher than those of the PBS group ( t=12.44, t=11.38, t=9.48, all P<0.001). Animal experiments confirmed that compared with the sham operation group [(207.61±38.09) and (238.97±45.90) μm], the CEJ-ABC in the periodontitis group [(420.31±35.32) and (405.16±35.51) μm] were increased ( P<0.01), while the CEJ-ABC in the cgas knockout periodontitis group [(295.11±35.43) and (309.15±32.22) μm] were significantly lower than those in the control periodontitis group of the same litter ( P<0.01). Compared with the sham operation group (45.84±6.41), the STING fluorescence signal in the periodontitis group (152.44±6.86) was significantly increased ( P<0.001). Compared with the control periodontitis group of the same litter, the STING signal in the cgas knockout periodontitis group was significantly reduced (88.31±9.70) ( P<0.001). Conclusions:LPS stimulation can activate the STING signal by generating mitochondrial-derived double-stranded DNA, stimulating hPDLC to secrete inflammatory cytokines and impairing osteogenic differentiation potential. Suppressing STING activation in animal models can reduce bone destruction in periodontitis.

Objective To compare the capture performance differences between TruSeq? Exome and NimbleGen SeqCap EZ Human Exome kits in children with cerebral palsy(CP),and to provide a technical selection basis for clinical genetic research and diagnosis.Methods Peripheral blood samples from 48 sporadic CP patients were included.Exome libraries were constructed using TruSeq(DNA probes)and NimbleGen(RNA probes),followed by sequencing on the Illumina HiSeq 2000 platform.Bioinformatics analysis was applied to evaluate mapping rate,target region coverage,variant concordance,and clinical relevance based on a CP-related gene set(2 293 genes).The statistical analysis was performed using a paired t-test with a significance threshold of α=0.05.Results The results showed no significant differences between NimbleGen and TruSeq exome capture kits in basic data quality(alignment rate,insert size)and GC content.However,they exhibited complementary characteristics in key performance metrics:NimbleGen demonstrated superior performance in specific depth coverage(1×coverage rate,P=1.84×10-5;20×coverage rate,P=1.49×10-20).TruSeq,on the other hand,showed higher sensitivity in Indel detection(TruSeq vs.NimbleGen:11 371±1 689 vs.11 274±1 670,P=3.24×10-7)and rare variant capture(TruSeq vs.NimbleGen:3 164±766 vs.3 072±774,P=1.20×10-4),successfully identifying all 11 pathogenic variants(including 2 missed by NimbleGen).Conclusion TruSeq,with its superior variant detection rate,is more suitable for clinical diagnostic applications,while NimbleGen's coverage stability may be advantageous for research-oriented projects.

Objective To evaluate the changes in postoperative plasma β-endorphin(β-EP)levels in patients who had received perioperative electroacupuncture(EA)treatment in 10 randomized controlled trials(RCTs)and examine the impact of EA on postoperative pain.Methods This meta-analysis evaluated the changes in plasma β-EP levels and visual analog scale(VAS)12,24 and 48 hours after surgery in patients receiving perioperative EA.It also assessed the changes in plasma serotonin(5-hydroxytryptamine,5-HT)and prostaglandin E2(PGE2)levels at 24 hours postsurgery.A comprehensive search was conducted in the China National Knowledge Infrastructure(CNKI),Wanfang,Chongqing VIP database,Chinese Biomedical Database(CBM),Web of Science,and PubMed databases.RCTs on perioperative EA and β-EP published from the inception of the websites up to July 25,2023,were retrieved.Effect size aggregation,literature quality assessment,and bias analysis were performed using RevMan 5.3 software,and sensitivity analysis was conducted via R 4.3.1.Results A total of 10 RCTs involving 706 patients were included.EA in conjunction with conventional anesthesia significantly increased plasma β-EP levels at 12 hours postsurgery[standard mean difference(SMD)=2.79,95%CI(1.85,3.72),Z=5.81,P＜0.00001],24hours postsurgery[SMD=1.87,95%CI(0.9,2.83),Z=3.79,P=0.0001],and 48 hours postsurgery[SMD=2.02,95%CI(1.49,2.54),Z=7.50,P＜0.00001].EA reduced plasma PGE2 levels at 24 hours postsurgery and plasma 5-HT levels at 24 hours postsurgery,and the VAS at 12,24 and 48 hours after surgery also decreased.Conclusion These findings suggest that perioperative EA markedly elevates plasma β-EP levels,reduces pain-inducing factors in plasma,and effectively alleviates acute postoperative pain.

Objective To compare the capture performance differences between TruSeq? Exome and NimbleGen SeqCap EZ Human Exome kits in children with cerebral palsy(CP),and to provide a technical selection basis for clinical genetic research and diagnosis.Methods Peripheral blood samples from 48 sporadic CP patients were included.Exome libraries were constructed using TruSeq(DNA probes)and NimbleGen(RNA probes),followed by sequencing on the Illumina HiSeq 2000 platform.Bioinformatics analysis was applied to evaluate mapping rate,target region coverage,variant concordance,and clinical relevance based on a CP-related gene set(2 293 genes).The statistical analysis was performed using a paired t-test with a significance threshold of α=0.05.Results The results showed no significant differences between NimbleGen and TruSeq exome capture kits in basic data quality(alignment rate,insert size)and GC content.However,they exhibited complementary characteristics in key performance metrics:NimbleGen demonstrated superior performance in specific depth coverage(1×coverage rate,P=1.84×10-5;20×coverage rate,P=1.49×10-20).TruSeq,on the other hand,showed higher sensitivity in Indel detection(TruSeq vs.NimbleGen:11 371±1 689 vs.11 274±1 670,P=3.24×10-7)and rare variant capture(TruSeq vs.NimbleGen:3 164±766 vs.3 072±774,P=1.20×10-4),successfully identifying all 11 pathogenic variants(including 2 missed by NimbleGen).Conclusion TruSeq,with its superior variant detection rate,is more suitable for clinical diagnostic applications,while NimbleGen's coverage stability may be advantageous for research-oriented projects.

Cells undergo glucose metabolism reprogramming under the influence of the inflammatory microenvironment, changing their primary mode of energy supply from oxidative phosphorylation to aerobic glycolysis. This process is involved in all stages of inflammation-related diseases development. Glucose metabolism reprogramming not only changes the metabolic pattern of individual cells, but also disrupts the metabolic homeostasis of the body microenvironment, which further promotes aerobic glycolysis and provides favourable conditions for the malignant progression of inflammation-related diseases. The metabolic enzymes, transporter proteins, and metabolites of aerobic glycolysis are all key signalling molecules, and drugs can inhibit aerobic glycolysis by targeting these specific key molecules to exert therapeutic effects. This paper reviews the impact of glucose metabolism reprogramming on the development of inflammation-related diseases such as inflammation-related tumours, rheumatoid arthritis and Alzheimer's disease, and the therapeutic effects of drugs targeting glucose metabolism reprogramming on these diseases.