Steroid-associated osteonecrosis of the femoral head (SANFH) is a progressive osteoarticular disorder associated with prolonged or high-dose glucocorticoid exposure. Its development involves local ischemia, oxidative stress, dysregulated bone metabolism, and disruption of the osteoimmune microenvironment. Macrophages exhibit marked phenotypic plasticity, and their polarization is essential for maintaining the dynamic balance among inflammation, angiogenesis, and bone remodeling. Persistent glucocorticoid stimulation, hypoxia, excessive reactive oxygen species, and damage-associated signals released from necrotic tissues can shift macrophages toward a pro-inflammatory phenotype. Classically activated macrophages (M1 macrophages) predominantly mediate inflammatory responses. By releasing tumor necrosis factor-α, interleukin-1β, interleukin-6, and other mediators, promoting osteoclast activation, suppressing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and impairing vascular endothelial function, M1 macrophages accelerate trabecular destruction and expansion of the necrotic lesion. In contrast, alternatively activated macrophages (M2 macrophages) contribute to inflammation resolution, neovascularization, osteogenic repair, and tissue remodeling, thereby supporting regeneration within the necrotic region. Macrophage-derived exosomes further influence disease progression through intercellular communication. Exosomes from different macrophage phenotypes can differentially regulate adipogenic differentiation, neutrophil extracellular trap formation, and endothelial phenotypic transition, thereby affecting the repair capacity of the necrotic area. These findings indicate that macrophage polarization shapes the local microenvironment not only through soluble mediators but also through vesicle-mediated communication with BMSCs, neutrophils, endothelial cells, and other cell populations. At the molecular level, the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3) inflammasome, nuclear factor kappa B (NF‑κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathways jointly regulate macrophage polarization and its downstream osteoimmune effects. Dysregulation of these pathways may sustain inflammatory activation, aggravate oxidative and vascular injury, inhibit osteogenesis, and impair tissue repair. NLRP3 inflammasome activation links danger signals and oxidative stress to inflammatory cytokine maturation and pyroptotic injury; NF-κB signaling promotes pro-inflammatory gene transcription and M1 polarization; JAK/STAT signaling participates in the balance between inflammatory and reparative macrophage programs; and PI3K/Akt/mTOR signaling regulates cellular metabolism, survival, autophagy, and regeneration. Notably, the biological effects of PI3K/Akt/mTOR signaling are cell-type dependent, and Akt-mediated repair signaling should be distinguished from mTOR-related autophagy regulation. The pathological significance of macrophage polarization in SANFH is not determined simply by an increase or decrease in a single phenotype. Rather, disease progression appears to result from an imbalance between persistent pro-inflammatory activity and insufficient reparative responses at different stages of the disease. Such an imbalance disrupts the coordinated coupling of inflammation resolution, vascular regeneration, and bone remodeling, ultimately contributing to structural deterioration of the femoral head. This review summarizes the pathological roles, signaling regulation, and exosome-mediated intercellular communication associated with macrophage polarization imbalance in SANFH. A more precise understanding of these mechanisms may clarify the osteoimmune basis of SANFH and support the development of macrophage-targeted interventions. However, most available evidence is derived from cellular and animal studies, and the temporal evolution of macrophage phenotypes in patients remains insufficiently characterized. Therapeutic strategies should therefore move beyond the simple suppression of M1 macrophages or enhancement of M2 macrophages and instead aim to restore a stage-appropriate balance between inflammatory control and tissue repair while promoting angiogenesis and bone reconstruction.

Objective:To investigate the different expression levels of programmed cell death 1 ligand 1 (PD-L1) in non-small cell carcinoma (NSCLC) of distribution characteristics of TCM constitutions and prognosis.Methods:The clinical data of 355 NSCLC patients who had been treated with immune checkpoint inhibitors (ICIs) from January 2019 to June 2023 in the Cancer Medical Center of the First Affiliated Hospital of Hunan University of Chinese Medicine were retrospectively analyzed, and their TCM constitutions were determined. According to the expression level of PD-L1, they were divided into three groups: low expression group (TPS≤1%), medium expression group (1% < TPS < 49%) and high expression group (TPS≥50%). Overall survival (OS) of patients was followed up, and the median OS were compared. Kaplan-Meier method was used to draw survival curves, and Log-rank test was used to compare the difference of survival curves. The independent risk factors of OS were analyzed by COX regression.Results:The distribution of different TCM constitutions showed statistical significance across the three groups ( P<0.05). The median OS for the medium and high expression groups were 21.082 months and 25.714 months, respectively, both significantly higher than the 14.437 months for the low expression group ( P<0.05). The survival curve of TCM constitutions showed that the constitutions significantly correlated with the prognosis of ICIs treatment were qi deficiency, phlegm dampness, and blood stasis ( P<0.05 or P<0.01). The median OS from high to low was 44.971 months for phlegm-dampness constitution, 23.297 months for qi-deficiency constitution, and 11.763 months for blood-stasis constitution. COX regression analysis indicated that medium PD-L1 expression ( HR=0.622, 95% CI=0.459,0.844, P=0.002), high PD-L1 expression ( HR=0.509, 95% CI=0.361,0.718, P<0.001), phlegm-dampness constitution ( HR=0.556, 95% CI=0.335,0.924, P=0.024), and blood-stasis constitution ( HR=2.952, 95% CI=1.929,4.518, P<0.001) were independent prognostic factors. Conclusions:The higher the expression level of PD-L1 in NSCLC patients, the better the prognosis of ICIs treatment. The prognosis of ICIs treatment is better for people with phlegm-dampness constitution and poor for those with blood stasis constitution.

Objective To evaluate the effectiveness of different non-pharmacological interventions in relieving post-transcatheter arterial chemoembolization(post-TACE)pain in patients with liver neoplasm.Methods A computerized retrieval of randomized controlled trials(RCT)concerning the non-pharmacological interventions for relieving post-TACE pain in patients with liver neoplasm from the Chinese and English databases of CNKI,VIP,Wanfang,CBM,PubMed,Embase,Web of Science,the Cochrane Library,etc.was conducted.The retrieval time period was from the establishment of the database to May,2024.Review Manager 5.4 software was used to make meta-analysis.Two investigators independently screened the literature,extracted the data and evaluated the quality of the included literature using the RCT risk of bias assessment tool recommended by the Cochrane Handbook for Systematic Evaluation 5.1.0,and RevMan 5.3 software and Stata 17 software were used to perform traditional and network meta-analysis respectively.Results A total of 29 studies,including 2 866 patients and involving 10 non-pharmacologic intervention measures,were included in this analysis.The results of network meta-analysis showed that acupressure combined with music therapy was the most effective method for relieving post-TACE pain in patients with liver neoplasm.According to the area under the cumulative ranked probability map,the order of the effects of various intervention measures from best to poor was as follows:acupressure plus music therapy(88.9％),exercise rehabilitation therapy(76.8％),acupressure(76.0％),abdominal breathing training(66.4％),music therapy(54.5％),psychological relaxation therapy(47.9％),ear acupoint pressure bean(45.3％),systematic health education(35.2％),wrist and ankle needle therapy(25.7％),ear acupoint pressure bean plus acupressure(25.6％),and conventional nursing care(7.4％).Conclusion A variety of non-pharmacological intervention measures can effectively relieve post-TACE pain in patients with liver neoplasm,and acupressure plus music therapy is the best way for relieving pain.Due to the limitation of the quality and quantity of the collected literature,more high-quality,multicenter,large-sample studies need to be conducted before the pain-relief effect of non-pharmacological intervention measures can be further verified.

Objective To explore the effect of prominent cortical vein(PCV)sign on the clinical prognosis of patients undergoing endovascular recanalization for acute anterior circulation cerebral infarction.Methods A total of 102 patients with acute anterior circulation large-vessel occlusion in Zhongshan Municipal Hospital of Tradiontional Chinese Medicine from January 1,2020 to December 21,2022,who received endovascular recanalization,were enrolled in this study.The clinical data and radiographic materials were collected.According to whether PCV sign was present or not,the patients were divided into PCV group and non-PCV group.The clinical data were compared between the two groups.Logistic regression analysis was used to analyze the correlation between the postoperative 90-day mRS score and the occurrence of PCV.Results Compared with non-PCV group,in PCV group the incidence of atrial fibrillation was even higher,and the good rate of collateral compensation was even lower,and the postoperative(7±2)-day NIHSS score was even lower;the differences in above indexes between the two groups were statistically significant(all P＜0.05).Ninety days after treatment,the proportion of patients having modified Rankin Scale(mRS)score ≤2 points in the non-PCV group was 76.3％,which was higher than 58.6％in the PCV group,but the difference was not statistically significant(P=0.074).Logistic regression analysis indicated that a positive correlation existed between the presence of PCV sign and atrial fibrillation(OR=9.679,95％CI=1.264-74.364)and a negative correlation existed between the presence of PCV sign and good collateral compensation(OR=0.015,95％CI=0.033-0.331).No relationship existed between the postoperative 90-day good prognosis and the presence of preoperative PCV sign(OR=2.078,95％CI=0.680-6.348),but patient's age,preoperative intravenous thrombolysis were negatively correlated with the preoperative Alberta Stroke Program Early CT(ASPECT)score(P＜0.005).Conclusion In patients with anterior circulation acute ischemic stroke(AIS),the occurrence of PCV sign is associated with the impaired collateral compensation and atrial fibrillation,but its impact on the clinical outcomes of patients after receiving reperfusion therapy remains uncertain.PCV sign may be used as a potential evaluation indicator for inadequate cerebrovascular collateral compensation.

Objective To explore the application effect of the dual-track nursing intervention model in the treatment process of children with lobar pneumonia.Methods A total of 186 children with lobar pneumonia were selected and randomly divided into control group and intervention group u-sing a double-blind method,with 93 cases in each group.The control group received conventional nursing intervention,while the intervention group implemented the dual-track nursing intervention model on the basis of conventional nursing.This model included the establishment and training of nurs-ing teams,personalized nursing plans,health education,and psychological support.Outside the hos-pital,it emphasized family support,regular follow-up guidance,and community-based collaborative ed-ucation.Both groups received a 3-week intervention.The improvement times of clinical symptoms,hos-pital stay,pulmonary function indicators before and after nursing,treatment compliance,and family members' satisfaction with nursing were compared and analyzed between the two groups.Results The fever resolution time[(3.89±0.96)d],cough relief time[(6.21±1.34)d],disappearance time of pulmonary rales[(7.89±1.56)d],and hospital stay duration[(9.45±1.89)d]in the intervention group were all shorter than those in the control group[(5.23±1.14),(7.45±1.67),(9.32±2.01),and(11.28±2.35)d,respectively],with statistically significant differences(P＜0.05).After nursing,the forced expiratory volume in one second(FEV1)[(1.51±0.22)L],forced vital capacity(FVC)[(1.75±0.25)L],and FEV1/FVC[(94.12±5.65)％]in the intervention group were all higher than those in the control group[(1.42±0.15)L,(1.66±0.22)L,and(85.73±8.41)％,respectively],with statistically significant differences(P＜0.05).The scores for exami-nation cooperation[(23.91±3.82)points],nursing cooperation[(24.19±4.03)points],standardized medication use[(24.26±3.94)points],and rational diet[(23.77±3.62)points]in the intervention group were higher than those in the control group[(20.16±3.53),(19.64±3.46),(23.05±3.68),and(18.85±3.41)points,respectively],with statistically significant differences(P＜0.05).The satisfaction rate of family members with nursing work in the intervention group was higher than that in the control group,with a statistically significant difference(98.92％versus 89.25％,P＜0.05).Conclusion The dual-track nursing intervention model has a signifi-cant application effect in children with lobar pneumonia.It can accelerate their recovery process,improve treatment compliance,promote pulmonary function improvement,and enhance family mem-bers' satisfaction.

Objective To evaluate the protective effect of Schistosoma japonicum cystatin(rSj-Cystatin)in a mouse mode of"two-hit"sepsis.Methods Sixty male C57BL/6 mice randomized equally into sham-operated group,protein group,"two-hit"modeling group,and protein intervention group.In the former two groups,the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later;In the latter two groups,100 μL PBS containing LPS(5 mg/kg)was injected intraperitoneally 24 h before cecal ligation and puncture(CLP),and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP.At 12 h after rSj-Cystatin treatment,6 mice from each group were sacrificed for detection of TNF-α,IL-6,IL-10,TGF-β,iNOS and Arg-1 in the serum,spleen,liver,lung and kidney tissues using ELISA,for examinations of liver,lung and kidney pathologies with HE staining,and for analysis of CD3+CD4+CD25+Foxp3+T cell percentage in the spleen using flow cytometry.The remaining mice were observed for general condition and 72-h survival.Results The 72-h survival rates in the 4 groups were 100％,100％,0％and 20％,respectively,showing significant differences between the latter two groups.The mouse models of"two-hit"sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate,which were significantly ameliorated by rSj-Cystatin treatment.Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3+CD4+CD25+Foxp3+T cell percentage.The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney,and these changes were obviously improved by rSj-Cystatin treatment.Conclusion rSj-Cystatin has a protective effect against"two-hit"sepsis in mice by regulating the inflammatory microenvironment.

Objective To observe brain function changes in insomnia disorder(ID)patients and therapeutic effect of repeated transcranial magnetic stimulation(rTMS)based on resting-state functional MRI(rs-fMRI).Methods Totally 37 patients with ID(ID group)and 20 healthy subjects(control group)were prospectively enrolled.The scores of sleep condition and psychological state scales were compared between groups,also within ID group before and after rTMS treatment.Brain regions with amplitude of low frequency fluctuations(ALFF)and regional homogeneity(ReHo)being significantly different between groups were evaluated based on brain rs-fMRI,and voxel-based resting-state functional connectivity(FC)analysis was performed in the above regions and the predefined regions of interest.Results Before treatment,Pittsburgh sleep quality index(PSQI),insomnia severity index(ISI),Epworth sleepiness score(ESS),Beck depression inventory(BDI)score and Beck anxiety inventory(BAI)score in ID group were all higher than those in control group(all P＜0.05).ALFF values and ReHo of the right median cingulate and paracingulate gyrus(Cingulum_Mid_R)were lower in ID group than those in control group(all FWE correctedP＜0.05).FC between Cingulum_Mid_R and the left anterior cingulate gyrus and cingulate gyrus(Cingulum_Ant_L)decreased,so did that between the left hippocampus(Hippocampus_L)and the right frontal gyrus(Frontal_Mid_R)(all FWE corrected P＜0.05).After rTMS,PSQI,ISI and ESS scores of ID patients decreased compared to those before treatment(all P＜0.05),but no significant change of the above neuroimaging indicators was detected(all FWE corrected P＞0.05).Conclusion ID caused synchronous decrease of Cingulum_Mid_R ALFF value and ReHo,as well as weakened FC between frontal cingulate gyrus and frontal with lobe limbic system.rTMS could improve sleep and mental state of ID patients,but its impact on neuroimaging needed further investigation.

Objective To compare the effects of three nickel-titanium file systems,ProTaper Next,TruNatomy,and VDW.RO-TATE,on the morphology of the Danger Zone of the mesial buccal root of mandibular first molar after root canal preparation using Mi-cro-CT and 3D printing technology.Methods 3D-printed mandibular first molars were selected and designed for purpose.They were randomly divided into three groups according to the used NiTi files(n=20).Micro-CT was used to scan the cross-sectional images of the Danger Zone 2 mm below the furcation of the mesial buccal root before and after root canal preparation.The changes in the root ca-nal wall thickness,root canal volume,surface area,cross-sectional area,and root canal transportation in the Danger Zone were ob-served.Statistical analysis was performed using one-way ANOVA(P＜0.05).Results Statistically significant differences were observed before and after root canal preparation in the Danger Zone among the three groups(P＜0.05).Among the three groups,the PTN files caused the largest change before and after preparation,followed by VDW files,and the TRU files had the smallest change.Conclusion The study highlights TruNatomy's conservative shaping capacity,advocating its use in minimally invasive endodontics,whereas Pro-Taper Next may be reserved for cases requiring aggressive canal preparation.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Objective To compare the effects of three nickel-titanium file systems,ProTaper Next,TruNatomy,and VDW.RO-TATE,on the morphology of the Danger Zone of the mesial buccal root of mandibular first molar after root canal preparation using Mi-cro-CT and 3D printing technology.Methods 3D-printed mandibular first molars were selected and designed for purpose.They were randomly divided into three groups according to the used NiTi files(n=20).Micro-CT was used to scan the cross-sectional images of the Danger Zone 2 mm below the furcation of the mesial buccal root before and after root canal preparation.The changes in the root ca-nal wall thickness,root canal volume,surface area,cross-sectional area,and root canal transportation in the Danger Zone were ob-served.Statistical analysis was performed using one-way ANOVA(P＜0.05).Results Statistically significant differences were observed before and after root canal preparation in the Danger Zone among the three groups(P＜0.05).Among the three groups,the PTN files caused the largest change before and after preparation,followed by VDW files,and the TRU files had the smallest change.Conclusion The study highlights TruNatomy's conservative shaping capacity,advocating its use in minimally invasive endodontics,whereas Pro-Taper Next may be reserved for cases requiring aggressive canal preparation.