BACKGROUND:The local immune microenvironment plays an important regulatory role in the process of bone formation,and the immune system is intricately linked to the skeletal system.OBJECTIVE:To systematically review the promotion of bone regeneration from three aspects:immune cell regulation of microenvironment,regulation of immune response by small extracellular vesicles,and induction of immune response by bone biomaterials,and to elucidate the immune regulatory mechanisms involved in bone regeneration.METHODS:Relevant literature was retrieved from PubMed,CNKI,WanFang Database,and VIP Database,using the search terms of"osteoimmunology,immune microenvironment,small extracellular vesicles,bone regeneration,bone tissue repair,biomaterials,and tissue engineering"in English and Chinese.Repeat and irrelevant literature was screened and removed,and 92 articles that met the criteria were selected for intensive reading and review.RESULTS AND CONCLUSION:Multiple immune cells and bone cells are in the same microenvironment,and immune cells can regulate the differentiation and activity of bone cells,collectively forming an immune microenvironment that affects bone regeneration.Neutrophils can significantly reduce local inflammatory responses in the early stages of bone injury,creating a favorable microenvironment for bone regeneration.M1 macrophages can clear foreign bodies and reduce early inflammatory responses,while M2 macrophages can promote the expression of osteogenic markers and factors,playing an important role in the repair process of bone injury.B cells and T cells can directly or indirectly affect the generation and activity of osteoblasts and osteoclasts,regulate bone metabolism,and promote bone regeneration.Extracellular vesicles of small cells regulate the local immune microenvironment through paracrine secretion,promoting bone formation and angiogenesis at the site of bone injury.The metal ions,surface hydrophilicity,porosity,pore size,surface morphology,and surface roughness on the surface of biomaterials can directly regulate local immune responses,and have anti-inflammatory,angiogenic,and osteogenic effects,thereby accelerating bone regeneration.

BACKGROUND:The local immune microenvironment plays an important regulatory role in the process of bone formation,and the immune system is intricately linked to the skeletal system.OBJECTIVE:To systematically review the promotion of bone regeneration from three aspects:immune cell regulation of microenvironment,regulation of immune response by small extracellular vesicles,and induction of immune response by bone biomaterials,and to elucidate the immune regulatory mechanisms involved in bone regeneration.METHODS:Relevant literature was retrieved from PubMed,CNKI,WanFang Database,and VIP Database,using the search terms of"osteoimmunology,immune microenvironment,small extracellular vesicles,bone regeneration,bone tissue repair,biomaterials,and tissue engineering"in English and Chinese.Repeat and irrelevant literature was screened and removed,and 92 articles that met the criteria were selected for intensive reading and review.RESULTS AND CONCLUSION:Multiple immune cells and bone cells are in the same microenvironment,and immune cells can regulate the differentiation and activity of bone cells,collectively forming an immune microenvironment that affects bone regeneration.Neutrophils can significantly reduce local inflammatory responses in the early stages of bone injury,creating a favorable microenvironment for bone regeneration.M1 macrophages can clear foreign bodies and reduce early inflammatory responses,while M2 macrophages can promote the expression of osteogenic markers and factors,playing an important role in the repair process of bone injury.B cells and T cells can directly or indirectly affect the generation and activity of osteoblasts and osteoclasts,regulate bone metabolism,and promote bone regeneration.Extracellular vesicles of small cells regulate the local immune microenvironment through paracrine secretion,promoting bone formation and angiogenesis at the site of bone injury.The metal ions,surface hydrophilicity,porosity,pore size,surface morphology,and surface roughness on the surface of biomaterials can directly regulate local immune responses,and have anti-inflammatory,angiogenic,and osteogenic effects,thereby accelerating bone regeneration.

ObjectiveThis study aimed to investigate the anti-Mycoplasma pneumoniae (MP) activity of luteolin and elucidate its underlying mechanisms. MethodsLuteolin was identified as the primary active compound from the polyphenol extract ofF. diotrys using network pharmacology. Its efficacy was evaluated against two MP strains: the standard strain M129 and the multidrug-resistant strain M19. A modified culture medium with visual characteristics was employed to determine the minimum inhibitory concentration (MIC) of luteolin. The expression of key proteins involved in MP growth and pathogenicity was assessed by qRT-PCR following luteolin treatment. Additionally, the viability of A549 cells infected with MP was compared between luteolin-treated and untreated groups. In vivo anti-MP activity was evaluated using a mouse model, and the expression of inflammatory cytokines in lung tissues was analyzed. ResultsLuteolin effectively inhibited both MP strains, with MIC₉₀ values of 100 mg/L for M19 and M129. Treatment with luteolin significantly downregulated the expression of adhesion proteins P1 and P30 in both strains. However, the expression of P65, HMW3, TrmB, and CARDS TX was reduced only in the M19 strain following luteolin intervention. Luteolin also enhanced the growth and viability of A549 cells infected with MP. In the mouse model, luteolin treatment resulted in steady weight gain and was well tolerated. The bacteriostatic rate of luteolin in lung tissues was 50.7%, significantly higher than the 25.2% observed in the roxithromycin group. Furthermore, luteolin reduced the expression of inflammatory factors, including IL-6, TNF-α, and HMGB1, in MP-infected mice. ConclusionLuteolin effectively and safely inhibits the proliferation and pathogenicity of MP, particularly the drug-resistant M19 strain, by downregulating the expression of toxicity-associated proteins (P1, P30, P65, HMW3, TrmB, CARDS TX) and modulating host inflammatory responses. These findings suggest that luteolin may offer a novel therapeutic strategy for treating MP infections, especially those caused by drug-resistant strains.

ObjectiveThis study aimed to investigate the anti-Mycoplasma pneumoniae (MP) activity of luteolin and elucidate its underlying mechanisms. MethodsLuteolin was identified as the primary active compound from the polyphenol extract ofF. diotrys using network pharmacology. Its efficacy was evaluated against two MP strains: the standard strain M129 and the multidrug-resistant strain M19. A modified culture medium with visual characteristics was employed to determine the minimum inhibitory concentration (MIC) of luteolin. The expression of key proteins involved in MP growth and pathogenicity was assessed by qRT-PCR following luteolin treatment. Additionally, the viability of A549 cells infected with MP was compared between luteolin-treated and untreated groups. In vivo anti-MP activity was evaluated using a mouse model, and the expression of inflammatory cytokines in lung tissues was analyzed. ResultsLuteolin effectively inhibited both MP strains, with MIC₉₀ values of 100 mg/L for M19 and M129. Treatment with luteolin significantly downregulated the expression of adhesion proteins P1 and P30 in both strains. However, the expression of P65, HMW3, TrmB, and CARDS TX was reduced only in the M19 strain following luteolin intervention. Luteolin also enhanced the growth and viability of A549 cells infected with MP. In the mouse model, luteolin treatment resulted in steady weight gain and was well tolerated. The bacteriostatic rate of luteolin in lung tissues was 50.7%, significantly higher than the 25.2% observed in the roxithromycin group. Furthermore, luteolin reduced the expression of inflammatory factors, including IL-6, TNF-α, and HMGB1, in MP-infected mice. ConclusionLuteolin effectively and safely inhibits the proliferation and pathogenicity of MP, particularly the drug-resistant M19 strain, by downregulating the expression of toxicity-associated proteins (P1, P30, P65, HMW3, TrmB, CARDS TX) and modulating host inflammatory responses. These findings suggest that luteolin may offer a novel therapeutic strategy for treating MP infections, especially those caused by drug-resistant strains.

Background/Aims: Recent advances in computer-aided diagnosis (CADx) systems have demonstrated expert-level accuracy in the optical diagnosis of colorectal polyps. High-confidence (HC) diagnoses have been defined as those made within 3 seconds without hesitation, and these systems have been shown to improve diagnostic accuracy. We aimed to evaluate the performance of endoscopists with varying levels of experience in diagnosing colorectal polyps with the assistance of a new CADx system applying the 3-second rule and without artificial intelligence assistance. Methods: In this multicenter ex vivo study, 35 endoscopists assessed 100 polyps (51 adenomas, 39 hyperplastic polyps, 10 sessile serrated lesions) using narrow-band imaging video clips on an online platform. Assessments consisted of individual endoscopist diagnosis and CADx-assisted diagnosis. HC assignments followed the 3-second rule in both phases. Performance metrics included HC accuracy, HC rate, and adherence to the Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) and Simple Optical Diagnosis Accuracy (SODA) thresholds. Results: HC diagnostic accuracy improved from 78.3% (95% confidence interval [CI], 76.6% to 80.0%) to 89.8% (95% CI, 88.6% to 90.9%) with CADx assistance (p<0.001). The proportion of HC predictions increased from 64.2% to 75.4% (p<0.001). Novice endoscopists showed marked improvement with CADx (74.1% vs 88.8%; p<0.001). CADx-assisted diagnoses nearly met SODA and PIVI thresholds under the 3-second rule. Additional analysis demonstrated that CADx assistance significantly improved interobserver agreement and ground truth, particularly for novices (κ=0.37 to κ=0.65; p<0.001). Conclusions Integrating CADx with the 3-second rule significantly enhances the performance of endoscopists in the optical diagnosis of colorectal polyps, with the greatest benefit observed among novice endoscopists.

Janus kinase (JAK) inhibitors are an important treatment option for ulcerative colitis, providing rapid onset of action, oral administration, and efficacy even after biologic failure. The 3 approved agents—tofacitinib, filgotinib, and upadacitinib—differ in JAK isoform selectivity, leading to clinically meaningful differences in efficacy and safety. Evidence from network meta-analyses, clinical trials, and real-world studies consistently shows that upadacitinib provides the highest efficacy for induction and maintenance of remission, whereas filgotinib demonstrates the most favorable safety profile. The strong efficacy of upadacitinib and tofacitinib is particularly relevant in patients with severe disease, including acute severe ulcerative colitis, and upadacitinib maintains high efficacy regardless of prior advanced therapy exposure. JAK inhibitors also benefit extraintestinal manifestations. Although risks such as herpes zoster, serious infection, thromboembolism, and major cardiovascular events differ among agents, long-term data suggest generally acceptable safety when used appropriately. Intraclass JAK-to-JAK cycling is feasible, with about half of patients achieving steroid-free clinical remission in retrospective cohorts. Based on mechanistic, clinical, and real-world evidence, filgotinib may be a first-line option for patients with lower disease activity or when safety is a priority, whereas upadacitinib or tofacitinib may be preferred in higher disease activity. Strategically selecting agents may improve durability and outcomes.

Objective: To analyze the epidemiological characteristics of pulmonary tuberculosis (PTB) among college students in Yangzhou from 2020 to 2024, so as to provide a scientific basis for developing prevention and control strategies. Methods: An epidemiological investigation was conducted among 162 college students with PTB, and 7 134 of their contacts were screened. Data were obtained from the tuberculosis information management system and on campus screening records. Using descriptive epidemiological methods, trends in incidence, seasonal distribution, and bacteriological characteristics were analyzed. Results: From 2020 to 2024, the annual average incidence of pulmonary tuberculosis among college students in Yangzhou was 29.42 per 100 000, showing an overall fluctuating downward trend ( χ 2=12.36, P <0.01). Cases were mainly concentrated in summer and autumn, with the highest proportion in autumn (41.36%, 67/162), followed by summer (23.46%, 38/162). The proportion of etiologically positive cases increased from 37.21% in 2020 to 71.43% in 2024; among positive cases, the proportion of latent tuberculosis infection (LTBI) decreased from 66.67% (10/15) to 26.67% (4/15). The etiological positive rate was higher in females than in males ( χ 2= 11.76 , P <0.01). Comparison of screening methods showed that among index cases, the LTBI detection rate of the recombinant Mycobacterium tuberculosis fusion protein skin test (C-TST) was higher than that of the tuberculin skin test (TST), but the difference was not statistically significant ( χ 2=0.65, P =0.42); among close contacts, the detection rate of TST was higher than that of C-TST (15.1%,10.1%; χ 2=5.23, P <0.05). Conclusion From 2020 to 2024, the annual average incidence of pulmonary tuberculosis among college students in Yangzhou showed an overall fluctuating downward trend, with differences in TB infection screening methods and gender.

Objective To investigate the current status of cognitive impairment and its influencing factors in patients with Alzheimer's disease (AD) and to explore effective intervention strategies. Methods A total of 380 patients with AD diagnosed in the Qingdao Central Hospital were retrospectively enrolled between January 2023 and January 2025. According to scores of Montreal Cognitive Assessment (MoCA), the patients were divided into a mild cognitive impairment group (21-25 points) and a moderate to severe impairment group (<21 points). The general clinical data in the two groups were collected. The influencing factors of moderate to severe cognitive impairment were analyzed by univariate and multivariate logistic regression analysis. Results Among the 380 AD patients, 157 cases (41.32%) had mild cognitive impairment, and 223 cases (58.68%) had moderate to severe cognitive impairment. Compared with the mild cognitive impairment group, the moderate to severe cognitive impairment group had a higher proportion of patients who were aged ≥ 75 years, engaged in physical labor, had a disease course of ≥5 years, and had moderate to severe atrophy on head CT examination (P < 0.05). Age ≥75 years, disease course ≥5 years, and moderate to severe atrophy on head CT were independent risk factors of moderate to severe cognitive impairment in AD patients (P<0.05). Conclusion Cognitive impairment is closely related to age, disease course and head CT manifestations in AD patients. Interventions targeting these key factors are expected to delay cognitive decline and improve patients' quality of life.

ObjectiveTo investigate the characteristics of gray matter structure and clinical symptoms in patients with Alzheimer's disease （AD） comorbid with apathy （AD-A）. MethodsThe study included 30 patients with AD-A， 30 AD disease patients without apathy （AD without apathy， AD-NA）， and 30 healthy controls （HCs） matched in gender， age， and years of education. All participants underwent a comprehensive neuropsychological assessment and magnetic resonance imaging （MRI） scans. Voxel-based morphometry （VBM） was used to analyze changes in gray matter volume among the three groups. Additionally， the correlation between the identified abnormal brain regions and apathy scale scores was analyzed. ResultsThere were no statistically significant differences among the three groups in terms of age， gender， years of education， or total intracranial volume. Compared with the HCs group， both the AD-A and AD-NA groups showed significantly lower scores in cognitive function （P<0.001）. The AD-A group exhibited significantly higher apathy scale scores compared with the AD-NA group （P<0.001）. Compared with the AD-NA group， the AD-A group showed reduced gray matter volume in the bilateral caudate nucleus， left orbitofrontal cortex， lingual gyrus， inferior frontal gyrus， superior frontal gyrus， entorhinal cortex， right middle frontal gyrus and posterior cingulate cortex （FWE-corrected， P<0.05 for all）. Compared with the HCs group， the AD-A group exhibited reduced gray matter volume in the bilateral middle temporal gyrus， left fusiform gyrus， calcarine sulcus， postcentral gyrus， right inferior frontal gyrus and supramarginal gyrus （FWE-corrected， P<0.05 for all）. Compared with the HCs group， the AD-NA group showed reduced gray matter volume in the left precuneus， inferior temporal gyrus， and right inferior temporal gyrus （FWE-corrected， P<0.05 for all）. In the AD-A group， changes in the gray matter volume of the left caudate nucleus （r= -0.557， P=0.002） and right middle frontal gyrus （r=-0.620， P=0.001） were negatively correlated with the apathy evaluation scale （AES） scores. ConclusionPatients in the AD-A group exhibited significant atrophy in the frontal-temporal-basal ganglia circuit， and the degree of gray matter atrophy was correlated with the severity of apathy.

ObjectiveTo explore the effect and mechanism of Taishan Panshi powder （TSPSP） on inhibiting oxidative stress injury in human chorionic trophoblast cells （HTR-8/SVneo）， and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion （SA）. MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus （GEO） database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP， and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments， HTR-8/SVneo cells were divided into blank group， model group， TSPSP-containing serum 2.5%， 5%， 10% groups， and nuclear factor E₂-related factor 2 （Nrf2） inhibitor group （ML385， 30 μmol·L^-1）. Except for the blank group， other groups were stimulated with 150 μmol·L^-1 H₂O₂ for 3 h to establish a cell oxidative stress injury model. After successful modeling， the blank group and model group were given 10% blank serum， each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum， and the Nrf2 inhibitor group was additionally given 30 μmol·L^-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h， and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde （MDA）， Fe²⁺， and Glutathione （GSH） were detected by enzyme-linked immunosorbent assay （ELISA）. Intracellular reactive oxygen species （ROS） level was detected by a fluorescent probe （DCF-DA）. The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 （KEAP1）， Nrf2， and forkhead box protein O3 （FoxO3） in cells were detected by immunofluorescence （IF） and real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of KEAP1， Nrf2， FoxO3， Glutathione peroxidase 4 （GPX4）， and superoxide dismutase （SOD） in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1， Nrf2， and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway， nine significantly differential pathways were identified （P<0.05）， among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology， and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response， FOXO and MAPK signaling pathways， etc. In in vitro experiments， compared with the blank group， the cell viability in the model group was significantly decreased （P<0.01）. Compared with the model group， the cell viability in each TSPSP-containing serum group was significantly increased （P<0.01）. Compared with the 10% TSPSP-containing serum group， the cell viability in the ML385 group decreased to approximately 70% （P<0.01）. Compared with the blank group， the model group showed significantly increased contents of MDA， Fe²⁺， and ROS， decreased GSH expression （P<0.01）， significantly reduced cell migration rate （P<0.01）， and increased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.01）， while decreased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.01）. Compared with the model group， each TSPSP-containing serum group showed significantly decreased contents of MDA， Fe²⁺， and ROS， increased GSH expression （P<0.01）， significantly increased migration rate （P<0.01）， significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.05， P<0.01）， and significantly increased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.05， P<0.01）. Compared with the 10% TSPSP-containing serum group， the ML385 group showed reversed trends in all indicators （P<0.05， P<0.01）. ConclusionTSPSP can inhibit H₂O₂-induced oxidative stress injury of trophoblast cells， and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.