Alveolar bone reconstruction simulation is an effective means for quantifying orthodontics, but currently, it is not possible to directly obtain human alveolar bone material models for simulation. This study introduces a prediction method for the equivalent shear modulus of three-dimensional random porous materials, integrating the first-order Ogden hyperelastic model to construct a computed tomography (CT) based porous hyperelastic Ogden model (CT-PHO) for human alveolar bone. Model parameters are derived by combining results from micro-CT, nanoindentation experiments, and uniaxial compression tests. Compared to previous predictive models, the CT-PHO model shows a lower root mean square error (RMSE) under all bone density conditions. Simulation results using the CT-PHO model parameters in uniaxial compression experiments demonstrate more accurate prediction of the mechanical behavior of alveolar bone under compression. Further prediction and validation with different individual human alveolar bone samples yield accurate results, confirming the generality of the CT-PHO model. The study suggests that the CT-PHO model proposed in this paper can estimate the material properties of human alveolar bone and may eventually be used for bone reconstruction simulations to guide clinical treatment.
Humans ; Tomography, X-Ray Computed/methods* ; Porosity ; Alveolar Process/physiology* ; Bone Density ; Computer Simulation ; Elasticity ; X-Ray Microtomography ; Stress, Mechanical ; Finite Element Analysis ; Models, Biological

OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

Objective To study the efficacy of hemoperfusion(HP)in series with continuous renal replace-ment therapy(CRRT)integrated combined blood purification under extracorporeal citrate anticoagulation in the treatment of severe hypertriglyceridemic acute pancreatitis(HTG-AP).Methods A total of 62 patients with severe HTG-AP admitted to the Affiliated Hospital of Xuzhou Medical University from June 2022 to May 2024 were selected and randomly divided into control group and observation group,with 31 cases in each group.The control group was treated with conventional medical treatment+HP combined with CRRT staged combined blood purifica-tion treatment,and the observation group was treated with conventional medical treatment+HP in series with CRRT integrated combined blood purification treatment under extracorporeal citrate anticoagulation.The indexes and clinical efficacy before and 7 days after treatment were compared between the two groups.Results The single CRRT time of the observation group was longer than that of the control group,and the frequency of CRRT was less than that of the control group(P<0.05).There were no significant differences in the total CRRT time,single HP time,HP frequency and total HP time between the two groups(P>0.05).The blood routine,inflammatory factors,blood biochemistry and clinical scores of the two groups after treatment were improved compared with those before treatment(P<0.05).After treatment,the hemoglobin(Hb)and platelet count(Plt)of the observation group were higher than those of the control group(P<0.05),and there were no significant differences in other indexes of blood routine,inflammatory factors,blood biochemistry and clinical scores between the two groups(P>0.05).There were no significant differences in clinical indexes,prognosis and complications between the two groups(P>0.05).Conclusions Without affecting the efficacy,HP in series with CRRT integrated combined blood purification under extracorporeal citrate anticoagulation in the treatment of severe HTG-AP can prolong the use time of CRRT blood filter and pipeline,reduce the use of consumables,reduce the risk of bleeding,and avoid multiple catheter removal of HP and CRRT operation separately,and reduce the risk of related infection.It is worthy of clinical application.

Aim To infer novel therapeutic and phar-macological targets related to lung cancer treatment through multiomics approaches,so as to provide new directions for developing more personalized and effec-tive treatment strategies.Methods Genome-wide as-sociation study(GWAS)data analysis,pan-cancer,single-cell,transcriptomics,and protein-protein interac-tion analysis were employed in this study.Results We analyzed biomarkers and therapeutic targets associ-ated with lung cancer.The study identified key bio-markers closely related to lung cancer progression and explored the interrelationships between these biomark-ers and viral infections.According to KEGG pathway annotation,the number of genes related to metabolic processes increased significantly.In particular,metab-olites such as alanine and isoleucine emerged as pivotal factors in therapeutic interventions.The IgD+CD24+and IgD+CD24-B cell subsets were identified as cen-tral elements in immune evasion and treatment re-sponse.Concurrently,the Lachnospiraceae and Prevo-tella were shown to modulate host immune responses and the tumor microenvironment by regulating short-chain fatty acid levels,thereby opening novel avenues for cancer research.Conclusions Through mul-tiomics analysis combined with transcriptomics and pro-teomics analysis,we identify several potential therapeu-tic targets for lung cancer,providing key insights for developing novel treatment strategies.

Aim To infer novel therapeutic and phar-macological targets related to lung cancer treatment through multiomics approaches,so as to provide new directions for developing more personalized and effec-tive treatment strategies.Methods Genome-wide as-sociation study(GWAS)data analysis,pan-cancer,single-cell,transcriptomics,and protein-protein interac-tion analysis were employed in this study.Results We analyzed biomarkers and therapeutic targets associ-ated with lung cancer.The study identified key bio-markers closely related to lung cancer progression and explored the interrelationships between these biomark-ers and viral infections.According to KEGG pathway annotation,the number of genes related to metabolic processes increased significantly.In particular,metab-olites such as alanine and isoleucine emerged as pivotal factors in therapeutic interventions.The IgD+CD24+and IgD+CD24-B cell subsets were identified as cen-tral elements in immune evasion and treatment re-sponse.Concurrently,the Lachnospiraceae and Prevo-tella were shown to modulate host immune responses and the tumor microenvironment by regulating short-chain fatty acid levels,thereby opening novel avenues for cancer research.Conclusions Through mul-tiomics analysis combined with transcriptomics and pro-teomics analysis,we identify several potential therapeu-tic targets for lung cancer,providing key insights for developing novel treatment strategies.

Objective To study the efficacy of hemoperfusion(HP)in series with continuous renal replace-ment therapy(CRRT)integrated combined blood purification under extracorporeal citrate anticoagulation in the treatment of severe hypertriglyceridemic acute pancreatitis(HTG-AP).Methods A total of 62 patients with severe HTG-AP admitted to the Affiliated Hospital of Xuzhou Medical University from June 2022 to May 2024 were selected and randomly divided into control group and observation group,with 31 cases in each group.The control group was treated with conventional medical treatment+HP combined with CRRT staged combined blood purifica-tion treatment,and the observation group was treated with conventional medical treatment+HP in series with CRRT integrated combined blood purification treatment under extracorporeal citrate anticoagulation.The indexes and clinical efficacy before and 7 days after treatment were compared between the two groups.Results The single CRRT time of the observation group was longer than that of the control group,and the frequency of CRRT was less than that of the control group(P<0.05).There were no significant differences in the total CRRT time,single HP time,HP frequency and total HP time between the two groups(P>0.05).The blood routine,inflammatory factors,blood biochemistry and clinical scores of the two groups after treatment were improved compared with those before treatment(P<0.05).After treatment,the hemoglobin(Hb)and platelet count(Plt)of the observation group were higher than those of the control group(P<0.05),and there were no significant differences in other indexes of blood routine,inflammatory factors,blood biochemistry and clinical scores between the two groups(P>0.05).There were no significant differences in clinical indexes,prognosis and complications between the two groups(P>0.05).Conclusions Without affecting the efficacy,HP in series with CRRT integrated combined blood purification under extracorporeal citrate anticoagulation in the treatment of severe HTG-AP can prolong the use time of CRRT blood filter and pipeline,reduce the use of consumables,reduce the risk of bleeding,and avoid multiple catheter removal of HP and CRRT operation separately,and reduce the risk of related infection.It is worthy of clinical application.

Aim To study the effect of Guben Yanling pills on liver aging in aging mice and the related mech-anism.Methods The mice were randomly divided in-to blank control group,model group,vitamin E group(0.1 g·kg-1)and low,medium and high dose groups(0.59,1.17,2.34 g·kg-1)of Guben Yan-ling pills.The aging mouse model was established by subcutaneous injection of D-galactose(150 mg·kg-1)into the back of neck.At the same time of mod-eling,the corresponding drugs were given by gavage once a day for six weeks.The main organ indexes were calculated.HE staining was used to observe the mor-phology of liver tissue.Colorimetry was used to detect the activity of β-galactosidase in liver.ELISA was used to detect the content of TNF-α,IL-1 β,IL-6,IL-4,IL-10.Western blot was used to detect the protein relative expression level of IKKβ,Iκ Bα,NF-κB p65.Immunofluorescence was used to detect the expression level of NF-κB p65.Results Compared with the blank control group,the organ index of the brain,liv-er,kidney,spleen,and thymus in the model group decreased(P＜0.05,P＜0.01),the activity of β-galactosidase increased(P＜0.01),liver tissue mor-phology and structure were significantly damaged,the content of TNF-α,IL-1 β and IL-6 increased(P＜0.01),the content of IL-4 and IL-10 decreased(P＜0.01),the levels of IKKβ,NF-κB p65 in-creased(P＜0.01),the levels of IKBα decreased(P＜0.01),and the levels of NF-κB p65 in nucleus increased(P＜0.01).Compared with the model group,the organ indexes of brain,liver,kidney,spleen,and thymus in each dose group of Guben Yan-ling pills increased(P＜0.05,P＜0.01),the activity of β-galactosidase decreased(P＜0.01),the morpho-logical and structural damage of liver tissue was signifi-cantly improved,the content of TNF-α,IL-1 β and IL-6 decreased(P＜0.01),the content of IL-4 and IL-10 increased(P＜0.01),the levels of IKKβ,NF-κB p65 decreased(P＜0.01),the levels of IκBα in-creased(P＜0.01),and the levels of NF-κB p65 in nucleus decreased(P＜0.01).Conclusions Guben Yanling pills can antagonize liver aging in mice,and its mechanism may be related to inhibiting the activa-tion of NF-κB signaling pathway in liver,downregulat-ing downstream pro-inflammatory factor levels,upregu-lating anti-inflammatory factor levels,and alleviating inflammation in liver.

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC₅₀ value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

Objectives: To investigate the factors influencing the height of anterior peritoneal reflection (APR) for patients with rectal cancer, and to analyze the relationship between the APR and the lateral lymph node metastasis. Methods: Clinical data of 432 patients with tumor located within and below APR were retrospectively collected from the rectal cancer database at the Department of General Surgery, Peking Union Medical College Hospital from August 2020 to September 2022. Ninty-eight non-rectal cancer patients were also enrolled as a control group. There were 308 males and 124 females in the tumor group, aged (M(IQR)) 62 (16) years (range: 24 to 85 years) and 53 males and 45 females in the control group, aged 60 (22) years (range: 27 to 87 years). The APR height, pelvis, and tumor-related parameters were measured by MRI. A multifactor linear regression model was established to analyze the dependent correlation factors of APR height. These factors of the two groups were matched by propensity score matching and their APR heights were compared after matching. An ordinal Logistic regression model was established to explore the relationship between APR-related parameters and radiographic lateral lymph node metastasis. Results: The APR height of the tumor group was (98.7±14.4) mm (range: 43.3 to 154.0 mm) and the control group was (95.1±12.7) mm (range: 68.0 to 137.9 mm). Multivariable linear regression revealed that the greater the weight (B=0.519, 95%CI: 0.399 to 0.640, P<0.01), the anterior pelvic depth (B=0.109, 95%CI: 0.005 to 0.213, P=0.039) and the smaller the bi-ischial diameter (B=-0.172, 95%CI:-0.294 to -0.049, P=0.006), the higher the APR height. The tumor group had a higher APR height than the control group after propensity score matching ((98.3±14.2) mm vs. (95.1±12.7) mm, t=-1.992, P=0.047). Ordinal Logistic regression indicated that the longer segment of the tumor invade the nonperitoneal rectum was an independent influencing factor of radiographic lateral lymph node metastasis (OR=1.016, 95%CI: 1.002 to 1.030, P=0.021), while the distance between the anal verge and the tumor was not (OR=0.986, 95%CI: 0.972 to 1.000, P=0.058). Conclusions: The higher the weight, the deeper and narrower the pelvis, the higher the APR height. There is a certain relationship between APR and lateral lymph node metastasis on imaging.