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:In vitro construction of tissue-engineered intestinal models plays an important role in intestinal regeneration and intestinal disease research.The interaction of intestinal nervous system and intestinal epithelial barrier to maintain body homeostasis is a hot topic in the bionic construction of tissue-engineered intestinal tract.OBJECTIVE:To construct a bionic model that can mimic the enteric nervous system in vivo.METHODS:Using fibroin protein with villus structure as scaffold,human induced neural stem cells solidified with collagen were added to intestinal epithelial cells(Caco-2 and HT29-MTX-E12)for 3-day culture to construct a co-culture system of intestinal epithelial cells and nerve cells(co-culture group).Human induced neural stem cells or intestinal epithelial cells cultured alone that were inoculated with fibroin scaffolds were set as controls.Cell morphology was observed by scanning electron microscopy and hematoxylin-eosin staining.Cell activity was detected by Live/Dead cell staining.Human induced neural stem cell differentiation was detected by β-microtubulin immunofluorescence staining.Intestinal epithelial histological properties and barrier function were detected by microvillin,sucrase-isomaltase,tight junction protein 1,E-calmodulin,and mucin-2 immunofluorescence staining.The function of mucus secretion from intestinal epithelial cells was detected by Alcian blue staining.Alkaline phosphatase staining was performed to detect differentiation of intestinal epithelial cells,at the same time,sucrase-isomaltase,tight junction protein 1,and alkaline phosphatase mRNAs were detected by RT-qRCR.RESULTS AND CONCLUSION:The neuralized intestinal mucosal co-culture model with villi structure was successfully constructed,and neural stem cells and intestinal epithelial cells on the fibroin scaffold showed good cellular activities.After neuralization,the activity of alkaline phosphatase and sucrase-isomaltase in intestinal epithelial cells was enhanced,while the expression level of tight junction protein 1 was up-regulated.To conclude,the neuralized bionic intestinal epithelial model is beneficial to the maturation of intestinal mucosal epithelial cells and the formation of barrier function.

BACKGROUND:Triptolide,a bioactive component of the traditional Chinese medicine Tripterygium wilfordii,has a certain protective effect on neurons.OBJECTIVE:To investigate the effect of triptolide on cerebral ischemia/reperfusion injury.METHODS:(1)Cell experiment:Hippocampal neurons(HT22 cells)were randomly divided into control group,glucose oxygen deprivation/reoxygenation(OGD/R)group,OGD/R+triptolide group,OGD/R+triptolide+si-TIGAR group,OGD/R+si-TIGAR group,and OGD/R+triptolide+rapamycin group.HT22 cell viability was detected by cell counting kit 8.Tp53-induced glycolysis and apoptosis factors,glutathione peroxidase 4,7 members of the solsolic vector family 11,sphingosine kinase 1(SPHK1)and(mTOR)were detected by western blot assay.Glutathione,malondialdehyde and iron level were detected using the biochemical kit.(2)Animal experiment:Rats were randomly divided into sham surgery group,model group,and triptolide group.Cerebral artery occlusion/reperfusion rat models were prepared in the latter two groups.Rats in the triptolide group were orally administered 50 mg/kg triptolide for 7 days.Twenty-four hours after administration,LONGA method was used to evaluate the neurological impairment of rats,TTC method was used to observe the conditions of cerebral infarction,TUNEL staining was used to detect cell apoptosis,and western blot was performed to detect the expression level of related proteins.RESULTS AND CONCLUSION:(1)At the cellular level,triptolide promoted cell viability and inhibited apoptosis in HT22 cells treated with OGD/R.Triptolide also increased the expression levels of Tp53-induced glycolysis and apoptosis factors,glutathione peroxidase 4,and 7 members of the solsolic vector family 11,activated the SPHK1/mTOR pathway,increased glutathione content,inhibited malondialdehyde content and iron levels.Rapamycin treatment counteracted the protective effect of triptolide on HT22 cells.(2)At the animal level,triptolide significantly reduced neurological deficits,infarct volume,and cell apoptosis,and inhibited neuronal ferroptosis in brain tissue of rats.To conclude,triptolide can inhibit ferroptosis by upregulating the expression level of Tp53-induced glycolysis and apoptosis factors and activating the SPHK1/mTOR signaling,and thereby reduced cerebral ischemia/reperfusion injury.These findings suggest that triptolide may be a candidate drug for the treatment of cerebral ischemia/reperfusion injury.

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.

Based on the theory of "shaoyang（少阳） resembling the pivot" and collateral diseases， this article proposes that pulmonary fibrosis （PF） can be divided into three stages including wind bi （痹）， constraint bi， and atrophy bi. The core pathogenesis of PF is the obstruction of the pivot and pulmonary collateral obstruction. In terms of treatment， the basic principles are to harmonize and regulate the pivot， and to promote the circulation of the lung collaterals. Depending on the different characteristics of the "essence-attribute-function"， treatment methods such as harmonizing and regulating the pivot， resolving phlegm and removing stasis， supplementing deficiency and harmonizing collaterals are suggested. This approach ensures the regulation of the pivot， smooth circulation of qi and blood， unblocking of the lung collaterals and nourishing the lung body， achieving the goals of balancing the ascending and descending of qi， removing phlegm and stasis， and relieving cough and wheezing.

BACKGROUND:In vitro construction of tissue-engineered intestinal models plays an important role in intestinal regeneration and intestinal disease research.The interaction of intestinal nervous system and intestinal epithelial barrier to maintain body homeostasis is a hot topic in the bionic construction of tissue-engineered intestinal tract.OBJECTIVE:To construct a bionic model that can mimic the enteric nervous system in vivo.METHODS:Using fibroin protein with villus structure as scaffold,human induced neural stem cells solidified with collagen were added to intestinal epithelial cells(Caco-2 and HT29-MTX-E12)for 3-day culture to construct a co-culture system of intestinal epithelial cells and nerve cells(co-culture group).Human induced neural stem cells or intestinal epithelial cells cultured alone that were inoculated with fibroin scaffolds were set as controls.Cell morphology was observed by scanning electron microscopy and hematoxylin-eosin staining.Cell activity was detected by Live/Dead cell staining.Human induced neural stem cell differentiation was detected by β-microtubulin immunofluorescence staining.Intestinal epithelial histological properties and barrier function were detected by microvillin,sucrase-isomaltase,tight junction protein 1,E-calmodulin,and mucin-2 immunofluorescence staining.The function of mucus secretion from intestinal epithelial cells was detected by Alcian blue staining.Alkaline phosphatase staining was performed to detect differentiation of intestinal epithelial cells,at the same time,sucrase-isomaltase,tight junction protein 1,and alkaline phosphatase mRNAs were detected by RT-qRCR.RESULTS AND CONCLUSION:The neuralized intestinal mucosal co-culture model with villi structure was successfully constructed,and neural stem cells and intestinal epithelial cells on the fibroin scaffold showed good cellular activities.After neuralization,the activity of alkaline phosphatase and sucrase-isomaltase in intestinal epithelial cells was enhanced,while the expression level of tight junction protein 1 was up-regulated.To conclude,the neuralized bionic intestinal epithelial model is beneficial to the maturation of intestinal mucosal epithelial cells and the formation of barrier function.

BACKGROUND:Triptolide,a bioactive component of the traditional Chinese medicine Tripterygium wilfordii,has a certain protective effect on neurons.OBJECTIVE:To investigate the effect of triptolide on cerebral ischemia/reperfusion injury.METHODS:(1)Cell experiment:Hippocampal neurons(HT22 cells)were randomly divided into control group,glucose oxygen deprivation/reoxygenation(OGD/R)group,OGD/R+triptolide group,OGD/R+triptolide+si-TIGAR group,OGD/R+si-TIGAR group,and OGD/R+triptolide+rapamycin group.HT22 cell viability was detected by cell counting kit 8.Tp53-induced glycolysis and apoptosis factors,glutathione peroxidase 4,7 members of the solsolic vector family 11,sphingosine kinase 1(SPHK1)and(mTOR)were detected by western blot assay.Glutathione,malondialdehyde and iron level were detected using the biochemical kit.(2)Animal experiment:Rats were randomly divided into sham surgery group,model group,and triptolide group.Cerebral artery occlusion/reperfusion rat models were prepared in the latter two groups.Rats in the triptolide group were orally administered 50 mg/kg triptolide for 7 days.Twenty-four hours after administration,LONGA method was used to evaluate the neurological impairment of rats,TTC method was used to observe the conditions of cerebral infarction,TUNEL staining was used to detect cell apoptosis,and western blot was performed to detect the expression level of related proteins.RESULTS AND CONCLUSION:(1)At the cellular level,triptolide promoted cell viability and inhibited apoptosis in HT22 cells treated with OGD/R.Triptolide also increased the expression levels of Tp53-induced glycolysis and apoptosis factors,glutathione peroxidase 4,and 7 members of the solsolic vector family 11,activated the SPHK1/mTOR pathway,increased glutathione content,inhibited malondialdehyde content and iron levels.Rapamycin treatment counteracted the protective effect of triptolide on HT22 cells.(2)At the animal level,triptolide significantly reduced neurological deficits,infarct volume,and cell apoptosis,and inhibited neuronal ferroptosis in brain tissue of rats.To conclude,triptolide can inhibit ferroptosis by upregulating the expression level of Tp53-induced glycolysis and apoptosis factors and activating the SPHK1/mTOR signaling,and thereby reduced cerebral ischemia/reperfusion injury.These findings suggest that triptolide may be a candidate drug for the treatment of cerebral ischemia/reperfusion injury.

ObjectiveTaking the cuproptosis/oxidative stress pathway as the entry point， this study investigated the effect and mechanism of Liangyi Paste on hepatic lipid deposition in naturally aged mice fed with a high-fat diet. MethodsAfter adaptive feeding， 80 ten-week-old male C57BL/6 mice were used. Thirty of them were randomly divided into three groups （10 mice per group）： The 12-month-old control group （12MCON）， the 15-month-old control group （15MCON）， and the 15-month-old group with a high-fat diet （15MHFD）. The 12MCON and 15MCON groups were continuously fed a standard diet， while the 15MHFD group started receiving a high-fat diet at 12 months of age. Tissue samples were collected at the corresponding time points for each group. The remaining 50 mice were randomly divided into five groups （10 mice per group）： the 20-month-old control group （20MCON）， the model group， and the low-， medium-， and high-dose Liangyi Paste groups （2.91 ， 5.82 ， 11.64 g·kg^-1·d^-1， respectively）. The 20MCON group was continuously fed a standard diet， while the other groups started receiving a high-fat diet at 15 months of age. At 18 months of age， the Liangyi Paste groups were administered the corresponding doses of Liangyi Paste by gavage， while the 20MCON and model groups were given an equal volume of saline by gavage. After 8 weeks of continuous gavage （when the mice reached 20 months of age）， tissue samples were collected. Hepatic TG levels were measured using assay kits； liver histology and lipid deposition were observed via hematoxylin-eosin （HE） and oil red O staining； reactive oxygen species （ROS） were detected by enzyme-linked immunosorbent assay （ELISA）； Cu²⁺， superoxide dismutase （SOD）， and malondialdehyde （MDA） levels were measured by colorimetry； mRNA and protein expression of genes related to cuproptosis and oxidative stress pathways were analyzed by Real-time polymerase chain reaction（Real-time PCR） and Wes automated protein expression system. ResultsCompared with 12MCON， the 15MCON group showed significantly increased hepatic TG， Cu²⁺， ROS， and MDA levels （P<0.01）， decreased SOD （P<0.01）， hepatocyte swelling， and disordered arrangement. The mRNA and protein levels of ferredoxin 1 （FDX1）， dihydrolipoamide S-acetyltransferase （DLAT）， heat shock protein 70 （HSP70）， dihydrolipoamide dehydrogenase （DLD）， pyruvate dehydrogenase E1 subunit-β （PDHB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and peroxisome proliferator-activated receptor γ （PPARγ） were significantly elevated （P<0.05， P<0.01）. Compared with 15MCON group， the 15MHFD and 20MCON groups exhibited further increases in TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， and aggravated hepatocyte swelling and disorder. There were increased lipid droplets with mild vacuolization in the 15MHFD group， and no significant lipid deposition was observed in the 20MCON group. FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and protein levels were significantly increased （P<0.05， P<0.01）. Compared with 20MCON group， the model group demonstrated markedly elevated TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， severe hepatic steatosis， and upregulated expression of FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and proteins （P<0.05， P<0.01）. All abnormalities were significantly reversed after Liangyi Paste treatment. ConclusionLiangyi paste can ameliorate hepatic lipid deposition in naturally aged mice with a high-fat diet by modulating the cuproptosis/oxidative stress pathway.

ObjectiveTo provide evidence for strengthening tuberculosis control in Inner Mongolia by analyzing changes and influencing factors in public awareness of tuberculosis prevention and control information among residents between the early stage and 17 years after the implementation of the directly observed treatment， short-course （DOTS） strategy. MethodsBased on the "National Public Knowledge， Belief and Behavior Questionnaire on Tuberculosis Prevention and Control" designed by the Chinese Center for Disease Control and Prevention， a questionnaire survey was conducted among residents in Inner Mongolia using a multi-stage stratified random sampling method. Chi-square test was used for univariate analysis， and binary Logistic regression was employed to explore the influencing factors of public awareness of tuberculosis prevention and control information. ResultsThe overall awareness rate of core information on tuberculosis prevention and control among the public was 67.7% in 2006， and it decreased to 49.2% in 2023 （P<0.05）. Multivariate Logistic regression analysis showed， compared with the groups aged 15-29， illiterate and semi-illiterate， those with public medical care， and those with three or fewer family members， the awareness rate of the groups aged 60 and above （OR=0.689）， those with primary and junior high school education （OR=0.856）， and those with self-paid medical care （OR=0.468） was significantly lower in 2006. The awareness rate was relatively high in groups with more than 3 family members （OR=1.236） （P<0.05）. Compared with the groups aged 15-29， illiterate and semi-illiterate， married， Han ethnicity， employed， and those receiving public medical care， the awareness rate was higher among the groups aged 30-59 （OR=1.976）， 60 and above （OR=2.224）， those with high school education and above （OR=2.801）， and single （OR=2.244） in 2023. However， the awareness rates of ethnic minorities （OR=0.737）， the unemployed （OR=0.557）， and self-funded medical care （OR=0.497） groups were significantly lower （P<0.05）. ConclusionPublic awareness of TB prevention knowledge in Inner Mongolia remains suboptimal. Strengthening diversified health education campaigns， addressing social stigma， and improving healthcare access are critical to enhance regional TB control outcomes.

ObjectiveCleft palate (CP) is a common congenital deformity often associated with velopharyngeal insufficiency (VPI), which disrupts the physiological coupling between respiration and speech. Conventional clinical assessments, such as nasometry and spirometry, provide limited static data and fail to visualize the dynamic spatiotemporal distribution of lung ventilation during phonation. This study introduces spatiotemporal electrical impedance tomography (ST-EIT) to evaluate speech-respiratory functional features in CP patients compared to normal controls (NC). The aim is to characterize multi-domain respiratory patterns and to validate an interpretable machine learning framework for providing objective, quantitative evidence for clinical assessment. MethodsSeventy-five participants were enrolled in this study, comprising 37 patients with surgically repaired CP and 38 healthy volunteers matched for age, gender, and body mass index (BMI). All subjects performed standardized sustained phonation tasks while undergoing synchronous monitoring with a 16-electrode EIT system and a pneumotachograph. A comprehensive feature engineering pipeline was developed to extract physiological parameters across 3 complementary domains. (1) Temporal domain: including inspiratory/expiratory phase duration (tPhase), time constants (Tau), and inspiratory-to-expiratory time ratios (TI/TE); (2) airflow domain: comprising mean flow, peak flow, and instantaneous flow at 25%, 50%, and 75% of tidal volume; and (3) spatial domain: quantifying global and regional tidal impedance variation (TIV), global inhomogeneity (GI), and center of ventilation (CoV). Extreme Gradient Boosting (XGBoost) classifiers were trained using 5 distinct data sources (Spirometry, Nasometry, Inspiratory-EIT, Expiratory-EIT, and fused ST-EIT). Model performance was rigorously evaluated via stratified 5-fold cross-validation, and Shapley additive explanations (SHAP) were employed to quantify global and local feature contributions. ResultsThe CP group exhibited a distinct respiratory phenotype compared to controls. In the temporal domain, CP patients showed significantly shorter inspiratory (1.60 s vs.1.85 s, P<0.001) and expiratory phase durations (2.45 s vs. 3.95 s, P<0.001), indicating a rapid, shallow breathing rhythm. In the airflow domain, while inspiratory flows were comparable, the CP group demonstrated significantly elevated mean and peak flows during the expiratory phase (P<0.001), reflecting compensatory respiratory effort. Spatially, CP patients presented significant ventilation redistribution, characterized by higher regional TIV in the right-anterior (ROI1) and left-posterior (ROI4) quadrants, but lower TIV in the left-anterior (ROI2) quadrant. In terms of diagnostic accuracy, the multi-modal ST-EIT model achieved the highest performance (AUC: 0.915±0.012, Accuracy: 0.843±0.019, F1-score: 0.872±0.017), substantially outperforming models based on spirometry (AUC: 0.721) or nasometry (AUC: 0.625) alone. Interpretability analysis revealed that spatial domain features were the most critical, contributing 53.4% to the model’s decision-making, followed by temporal (25.0%) and airflow (21.6%) features. ConclusionST-EIT successfully captures the temporal, airflow, and spatial deviations in CP speech respiration that are undetectable by conventional methods—specifically, rapid phase transitions, hyperdynamic expiratory airflow, and regional ventilation heterogeneity. This study validates ST-EIT as a robust, non-invasive, and radiation-free tool for characterizing speech-respiratory dysfunction, offering high clinical value for bedside screening, rehabilitation planning, and longitudinal monitoring of patients with cleft palate.