BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To investigate the efficacy of antiviral therapy and influencing factors of hepatitis B surface antigen(HBsAg) negative conversion for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB) in children.Methods:The clinical data of 38 children with CHB who received antiviral treatment in Children's Hospital Affiliated to Xi'an Jiaotong University from January 2019 to August 2024 were collected.All patients were treated with interferon alpha monotherapy or combined with nucleoside analogues for 48 weeks.The patients were divided into HBsAg negative group and HBsAg non-negative group according to the therapeutic results at 48 weeks.Multivariate Logistic regression were used to identify influencing factors of HBsAg negative conversion at 48 weeks.The receiver operator characteristic（ROC）curve was used to analyze the predictive value of each factor to HBsAg negative conversion.Results:The alanine aminotransferase normalization rate，hepatitis B virus DNA negative rate，HBeAg negative rate and HBsAg negative rate were 76.3%，94.7%，39.5% and 47.4%，respectively at 48 weeks.There were 18 cases in HBsAg negative group and 20 cases in HBsAg non-negative group.There were statistical significant differences in age and HBsAg decline level at 12 and 24 weeks of antiviral treatment between HBsAg negative group and HBsAg non-negative group（ P<0.05）.Multivariate Logistic regression analysis showed that age and HBsAg decline level at 12 and 24 weeks of antiviral treatment were independent predictors of HBsAg negative conversion at 48 weeks（ OR=0.664，95% CI 0.473-0.932， P=0.018； OR=8.719，95% CI 1.920-39.604， P=0.005； OR=6.182，95% CI 2.083-18.347， P=0.001）.The area under the curve of age and HBsAg decline level at 12 and 24 weeks were 0.737（95% CI 0.576-0.899， P=0.012），0.847（95% CI 0.725-0.969， P<0.001）and 0.939（95% CI 0.811-0.991， P<0.001），respectively.When the age was less than 4.625 years，the sensitivity，specificity，positive predictive value and negative predictive value of HBsAg negative conversion at 48 weeks were 83.3%，65.0%，68.2% and 81.3%，respectively.A decrease in HBsAg level of >1.07 lg IU/mL at 12 weeks of treatment had a sensitivity，specificity，positive predictive value，and negative predictive value of 72.2%，90.0%，86.7%，and 78.3%，respectively，for predicting HBsAg seroclearance at 48 weeks.A reduction in HBsAg of >1.92 lg IU/mL at 24 weeks of treatment showed a sensitivity，specificity，positive predictive value，and negative predictive value of 83.3%，90.0%，88.2%，and 85.7%，respectively，in predicting HBsAg seroclearance at 48 weeks. Conclusion:The children with CHB have a higher rate of HBsAg negative conversion after antiviral therapy at 48 weeks.Age and HBsAg decline level at 12 and 24 weeks of antiviral treatment can serve as early predictors for HBsAg negative conversion in children with CHB.

Purpose To explore the value of 18F-FDG PET/CT for assessing the therapeutic effect of RANKL monoclonal antibody for vertebral giant cell tumors.Materials and Methods PET/CT data of 11 patients with vertebral giant cell tumors treated with RANKL monoclonal antibody in Peking University Third Hospital from October 2020 to September 2021 were retrospectively collected.Imaging characteristics such as the number,location and type of bone destruction were analyzed,the maximum standardized uptake value(SUVmax)and the longest diameter of the lesions were measured.The objective tumor response was evaluated based on the modified European organization for research and treatment of cancer(EORTC)criteria,response evaluation criteria in solid tumors(RECIST)1.1 and inverse Choi density/size(ICDS)criteria.Results The skeletal lesions of 11 patients were all single,with lytic destruction and incomplete bone cortex,and marginal bone sclerosis was observed after treatment.The lesions had a baseline SUVmax of 12.12±3.64 and a post-treatment SUVmax of 4.39±2.10,with a%ΔSUVmax ranging from 31.81%to 80.52%.Based on the modified EORTC criteria,two cases had complete response and nine cases showed partial response.The median longest diameter was 46.21(33.84,85.93)mm at baseline and 42.25(32.44,79.29)mm after medication,with a decrease ranging from 0.71%to 22.90%.Based on the modified RECIST 1.1 criteria,11 cases showed stable disease.Based on ICDS criteria,two cases had partial response and nine cases had stable disease.Conclusion PET/CT can be used to assess the efficacy of RANKL monoclonal antibody therapy for vertebral giant cell tumors,with a high objective response based on the modified EORTC criteria.

The general models for intermediates quality analysis in the production process of Yaobitong capsule were established by near infrared spectroscopy (NIRS) combined with chemometrics, realizing the rapid determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, ginsenoside Rd and moisture. The spray-dried fine powder and total mixed granule were selected as research objects. The contents of five saponins were determined by high performance liquid chromatography and the moisture content was determined by drying method. The measured contents were used as reference values. Meanwhile, NIR spectra were collected. After removing abnormal samples by Monte Carlo cross validation (MCCV), Monte Carlo uninformative variables elimination (MC-UVE) and competitive adaptive reweighted sampling (CARS) were used to select feature variables respectively. Based on the feature variables, quantitative models were established by partial least squares regression (PLSR), extreme learning machine (ELM) and ant lion optimization least squares support vector machine (ALO-LSSVM). The results showed that CARS-ALO-LSSVM model had the optimum effect. The correlation coefficients of the six index components were greater than 0.93, and the relative standard errors were controlled within 6%. ALO-LSSVM was more suitable for a large number of samples with rich information, and the prediction effect and stability of the model were significantly improved. The general models with good predicting effect can be used for the rapid quality determination of Yaobitong capsule intermediates.

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 analyze the efficacy and safety of decitabine-based myeloablative preconditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML). METHODS: The clinical characteristics and efficacy of 115 AML patients who underwent allo-HSCT at the First Medical Center of Chinese PLA General Hospital from August 2018 to August 2022 were retrospectively analyzed, including 37 patients treated with decitabine conditioning regimen (decitabine group) and 78 patients without decitabine conditioning regimen (non-decitabine group). The cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM) and graft versus host disease (GVHD) were analyzed. RESULTS: For the patients in first complete remission (CR1) state before allo-HSCT, the 1-year relapse rates of decitabine group(22 cases) and non-decitabine group(69 cases) were 9.1% and 29.6%, respectively, the difference was statistically significant(P =0.042). The 1-year cumulative incidence of acute graft-versus-host disease (aGVHD) in decitabine group and non-decitabine group was 62.2% and 70.5%, respectively, and the 1-year cumulative incidence of chronic inhibitor-versus-host disease (cGVHD) was 18.9% and 14.1%, respectively, there were no significant differences in the incidence of aGVHD and cGVHD between the two groups (P >0.05). Of the 115 patients, there were no significantly differences in the 1-year CIR(21.7% vs 28.8%, P =0.866), NRM(10.9% vs 3.9%, P =0.203), OS(75.2% vs 83.8%, P =0.131) and LFS(74.6% vs 69.1%, P =0.912) between the decitabine group(37 cases) and the non-decitabine group(78 cases). CONCLUSION Decitabine-based conditioning regimen could reduce the relapse rate of AML CR1 patients with good safety.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation/methods* ; Decitabine/therapeutic use* ; Transplantation Conditioning/methods* ; Retrospective Studies ; Graft vs Host Disease ; Transplantation, Homologous ; Male ; Female ; Adult ; Middle Aged ; Adolescent ; Young Adult

Purpose To explore the value of 18F-FDG PET/CT for assessing the therapeutic effect of RANKL monoclonal antibody for vertebral giant cell tumors.Materials and Methods PET/CT data of 11 patients with vertebral giant cell tumors treated with RANKL monoclonal antibody in Peking University Third Hospital from October 2020 to September 2021 were retrospectively collected.Imaging characteristics such as the number,location and type of bone destruction were analyzed,the maximum standardized uptake value(SUVmax)and the longest diameter of the lesions were measured.The objective tumor response was evaluated based on the modified European organization for research and treatment of cancer(EORTC)criteria,response evaluation criteria in solid tumors(RECIST)1.1 and inverse Choi density/size(ICDS)criteria.Results The skeletal lesions of 11 patients were all single,with lytic destruction and incomplete bone cortex,and marginal bone sclerosis was observed after treatment.The lesions had a baseline SUVmax of 12.12±3.64 and a post-treatment SUVmax of 4.39±2.10,with a%ΔSUVmax ranging from 31.81%to 80.52%.Based on the modified EORTC criteria,two cases had complete response and nine cases showed partial response.The median longest diameter was 46.21(33.84,85.93)mm at baseline and 42.25(32.44,79.29)mm after medication,with a decrease ranging from 0.71%to 22.90%.Based on the modified RECIST 1.1 criteria,11 cases showed stable disease.Based on ICDS criteria,two cases had partial response and nine cases had stable disease.Conclusion PET/CT can be used to assess the efficacy of RANKL monoclonal antibody therapy for vertebral giant cell tumors,with a high objective response based on the modified EORTC criteria.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To investigate the efficacy of antiviral therapy and influencing factors of hepatitis B surface antigen(HBsAg) negative conversion for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB) in children.Methods:The clinical data of 38 children with CHB who received antiviral treatment in Children's Hospital Affiliated to Xi'an Jiaotong University from January 2019 to August 2024 were collected.All patients were treated with interferon alpha monotherapy or combined with nucleoside analogues for 48 weeks.The patients were divided into HBsAg negative group and HBsAg non-negative group according to the therapeutic results at 48 weeks.Multivariate Logistic regression were used to identify influencing factors of HBsAg negative conversion at 48 weeks.The receiver operator characteristic（ROC）curve was used to analyze the predictive value of each factor to HBsAg negative conversion.Results:The alanine aminotransferase normalization rate，hepatitis B virus DNA negative rate，HBeAg negative rate and HBsAg negative rate were 76.3%，94.7%，39.5% and 47.4%，respectively at 48 weeks.There were 18 cases in HBsAg negative group and 20 cases in HBsAg non-negative group.There were statistical significant differences in age and HBsAg decline level at 12 and 24 weeks of antiviral treatment between HBsAg negative group and HBsAg non-negative group（ P<0.05）.Multivariate Logistic regression analysis showed that age and HBsAg decline level at 12 and 24 weeks of antiviral treatment were independent predictors of HBsAg negative conversion at 48 weeks（ OR=0.664，95% CI 0.473-0.932， P=0.018； OR=8.719，95% CI 1.920-39.604， P=0.005； OR=6.182，95% CI 2.083-18.347， P=0.001）.The area under the curve of age and HBsAg decline level at 12 and 24 weeks were 0.737（95% CI 0.576-0.899， P=0.012），0.847（95% CI 0.725-0.969， P<0.001）and 0.939（95% CI 0.811-0.991， P<0.001），respectively.When the age was less than 4.625 years，the sensitivity，specificity，positive predictive value and negative predictive value of HBsAg negative conversion at 48 weeks were 83.3%，65.0%，68.2% and 81.3%，respectively.A decrease in HBsAg level of >1.07 lg IU/mL at 12 weeks of treatment had a sensitivity，specificity，positive predictive value，and negative predictive value of 72.2%，90.0%，86.7%，and 78.3%，respectively，for predicting HBsAg seroclearance at 48 weeks.A reduction in HBsAg of >1.92 lg IU/mL at 24 weeks of treatment showed a sensitivity，specificity，positive predictive value，and negative predictive value of 83.3%，90.0%，88.2%，and 85.7%，respectively，in predicting HBsAg seroclearance at 48 weeks. Conclusion:The children with CHB have a higher rate of HBsAg negative conversion after antiviral therapy at 48 weeks.Age and HBsAg decline level at 12 and 24 weeks of antiviral treatment can serve as early predictors for HBsAg negative conversion in children with CHB.