1.Screening of biomarkers for fibromyalgia syndrome and analysis of immune infiltration
Yani LIU ; Jinghuan YANG ; Huihui LU ; Yufang YI ; Zhixiang LI ; Yangfu OU ; Jingli WU ; Bing WEI
Chinese Journal of Tissue Engineering Research 2025;29(5):1091-1100
BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.
2.Research progress in mechanisms of kidney-tonifying traditional Chinese medicine in promoting healing of osteoporotic fractures.
Jun WU ; Ou-Ye LI ; Ken QIN ; Xuan WAN ; Wang-Bing XU ; Yong LI ; Jia-Wei ZHONG ; Yong-Xiang YE ; Rui XU
China Journal of Chinese Materia Medica 2025;50(15):4166-4177
Osteoporotic fractures(OPF) refer to the fractures caused by minor violence in the state of osteoporosis, seriously threatening the life and health of elderly patients. Drug and surgical therapies have limitations such as single targets, diverse adverse reactions, and poor prognosis. Kidney-tonifying traditional Chinese medicine(TCM) has good potential in the treatment of OPF. TCM can promote the healing of OPF by promoting angiogenesis in the early stage of bone healing, promoting osteogenic differentiation of bone marrow mesenchymal stem cells in the stage of bone repair, maintaining the balance of osteogenic and osteoclastic system in the stage of bone remodeling, and regulating the oxidative stress responses throughout the process of OPF healing. TCM can alleviate the pathological state of osteoporosis and promote fracture healing in OPF patients via multiple pathways and targets, demonstrating the advantages and potential of biphasic regulation.
Humans
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Drugs, Chinese Herbal/therapeutic use*
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Osteoporotic Fractures/metabolism*
;
Animals
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Fracture Healing/drug effects*
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Medicine, Chinese Traditional
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Kidney/metabolism*
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Osteogenesis/drug effects*
3.Generalized Functional Linear Models: Efficient Modeling for High-dimensional Correlated Mixture Exposures.
Bing Song ZHANG ; Hai Bin YU ; Xin PENG ; Hai Yi YAN ; Si Ran LI ; Shutong LUO ; Hui Zi WEIREN ; Zhu Jiang ZHOU ; Ya Lin KUANG ; Yi Huan ZHENG ; Chu Lan OU ; Lin Hua LIU ; Yuehua HU ; Jin Dong NI
Biomedical and Environmental Sciences 2025;38(8):961-976
OBJECTIVE:
Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects.
METHODS:
We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies.
RESULTS:
We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity.
CONCLUSION
GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans
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Environmental Exposure/analysis*
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Linear Models
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Nutrition Surveys
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Environmental Pollutants
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Body Mass Index
5.Analysis of the Impact of Early Diabetic Kidney Disease on Brain Function and Cognitive Abilities via Resting-state Functional Magnetic Resonance Imaging
Miao HE ; Bing JI ; Liqing CHENG ; Lan OU ; Rui XIE ; Jian WANG
Chinese Journal of Medical Imaging 2025;33(2):133-140
Purpose To analyze the impact of early renal complication on brain function in diabetes using the amplitude of low frequency fluctuations(ALFF)and functional connectivity(FC).Materials and Methods A total of 39 early diabetic kidney disease patients and 49 diabetic patients without kidney disease were included at the First Affiliated Hospital of Army Medical University from September 2023 to June 2024.Cognitive assessments were conducted using the Montreal cognitive assessment(MoCA)and mini-mental state examination(MMSE).All subjects underwent resting-state functional magnetic resonance imaging.Differences in brain function between the two groups were analyzed by ALFF and FC.In the early diabetic kidney disease group,the correlation and stepwise multiple linear regression analysis were performed between imaging difference indicators and clinical variables.Results In the early diabetic kidney disease patients,there was a decrease in ALFF values in the left calcarine(P<0.05,corrected for FWE),but an increase in FC with the left putamen(P<0.05,corrected for FWE).The ALFF values showed a negative correlation with urinary albumin-to-creatinine ratio and total cholesterol(r=-0.595,-0.351,both P<0.05)and a positive correlation with MoCA and MMSE scores(r=0.596,0.591,both P<0.001).The FC values were positively correlated with urinary albumin-to-creatinine ratio(r=0.552,P<0.001),while negatively correlated with MoCA and MMSE scores(r=-0.497,P=0.011;r=-0.529,P<0.001).Conclusion Early renal complications can affect changes in brain function and cognitive abilities in diabetic patients;alterations in the ALFF of the left calcarine and its FC with left putamen may serve as imaging biomarkers for monitoring cognitive impairment and brain injury in early diabetic kidney disease.
6.Prognostic Value of Dynamic Monitoring of WT1 Expression Levels for Relapse and Overall Survival in AML Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation During First Complete Remission
Xiao-Ya HE ; Han-Yun REN ; Yu-Jun DONG ; Li JI ; Qing-Yun WANG ; Yuan LI ; Yue YIN ; Ze-Yin LIANG ; Qian WANG ; Wei-Lin XU ; Jin-Ping OU ; Bing-Jie WANG ; Wei LIU
Journal of Experimental Hematology 2025;33(6):1790-1796
Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0%.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1%.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26%(range:0%-23.64%),with an upper quartile value of 0.74%.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels>0.74%at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P<0.001)compared to patients with WT1 levels ≤0.74%.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level>0.74%at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95%CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95%CI:0.749-16.100,P=0.037).Only WT1 level>0.74%at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95%CI:2.402-19.738,P<0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.
7.Prognostic Value of Dynamic Monitoring of WT1 Expression Levels for Relapse and Overall Survival in AML Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation During First Complete Remission
Xiao-Ya HE ; Han-Yun REN ; Yu-Jun DONG ; Li JI ; Qing-Yun WANG ; Yuan LI ; Yue YIN ; Ze-Yin LIANG ; Qian WANG ; Wei-Lin XU ; Jin-Ping OU ; Bing-Jie WANG ; Wei LIU
Journal of Experimental Hematology 2025;33(6):1790-1796
Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0%.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1%.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26%(range:0%-23.64%),with an upper quartile value of 0.74%.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels>0.74%at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P<0.001)compared to patients with WT1 levels ≤0.74%.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level>0.74%at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95%CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95%CI:0.749-16.100,P=0.037).Only WT1 level>0.74%at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95%CI:2.402-19.738,P<0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.
8.Analysis of the Impact of Early Diabetic Kidney Disease on Brain Function and Cognitive Abilities via Resting-state Functional Magnetic Resonance Imaging
Miao HE ; Bing JI ; Liqing CHENG ; Lan OU ; Rui XIE ; Jian WANG
Chinese Journal of Medical Imaging 2025;33(2):133-140
Purpose To analyze the impact of early renal complication on brain function in diabetes using the amplitude of low frequency fluctuations(ALFF)and functional connectivity(FC).Materials and Methods A total of 39 early diabetic kidney disease patients and 49 diabetic patients without kidney disease were included at the First Affiliated Hospital of Army Medical University from September 2023 to June 2024.Cognitive assessments were conducted using the Montreal cognitive assessment(MoCA)and mini-mental state examination(MMSE).All subjects underwent resting-state functional magnetic resonance imaging.Differences in brain function between the two groups were analyzed by ALFF and FC.In the early diabetic kidney disease group,the correlation and stepwise multiple linear regression analysis were performed between imaging difference indicators and clinical variables.Results In the early diabetic kidney disease patients,there was a decrease in ALFF values in the left calcarine(P<0.05,corrected for FWE),but an increase in FC with the left putamen(P<0.05,corrected for FWE).The ALFF values showed a negative correlation with urinary albumin-to-creatinine ratio and total cholesterol(r=-0.595,-0.351,both P<0.05)and a positive correlation with MoCA and MMSE scores(r=0.596,0.591,both P<0.001).The FC values were positively correlated with urinary albumin-to-creatinine ratio(r=0.552,P<0.001),while negatively correlated with MoCA and MMSE scores(r=-0.497,P=0.011;r=-0.529,P<0.001).Conclusion Early renal complications can affect changes in brain function and cognitive abilities in diabetic patients;alterations in the ALFF of the left calcarine and its FC with left putamen may serve as imaging biomarkers for monitoring cognitive impairment and brain injury in early diabetic kidney disease.
9.Efficacy of stented elephant trunk procedure for right-sided aortic arch with Kommerell's diverticulum
Yongliang ZHONG ; Bing TANG ; Suwei CHEN ; Yipeng GE ; Hai' ; ou HU ; Zhiyu QIAO ; Chengnan LI ; Yongmin LIU ; Junming ZHU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(07):1020-1026
Objective To summarize our experience and the early and midterm outcomes of stented elephant trunk procedure for right-sided aortic arch (RAA) with Kommerell's diverticulum (KD). Methods From April 2013 to July 2020, patients with RAA and KD who underwent stented elephant trunk procedure at our center were collected. Surgery was performed under moderate hypothermic circulatory arrest combined with selective antegrade cerebral perfusion via median sternotomy. Results A total of 8 patients were included, including 7 males and 1 female with a mean age of 51.88±9.61 years. All patients had an aneurysmal KD and aberrant left subclavian artery. Preoperative comorbidities included acute Stanford type B aortic dissection in 1 patient, aortic arch pseudoaneurysm in 1 patient, acute type B intramural hematoma in 2 patients, and coronary artery disease in 1 patient. Concomitant procedures included reconstruction of the left subclavian artery in all patients and coronary artery bypass grafting in 1 patient. The mean time of operation, cardiopulmonary bypass, aortic cross-clamping, and selective cerebral perfusion was 6.25±1.16 h, 157.75±40.07 min, 77.75±33.10 min, and 28.50±5.55 min, respectively. No intraoperative death occurred. There was 1 in-hospital death. Follow-up was completed in all patients with a mean period of 3.58±2.08 years. No late death occurred. A persistent anastomotic leak of the proximal arch was detected in 1 patient, but reintervention was not performed because neither aortic dilatation nor symptoms of tracheal and esophageal compression were observed during the follow-up. The remaining 6 patients showed positive aortic remodeling with complete thrombosis of the aneurysmal KD, and neither aortic event nor tracheal and esophageal compression occurred. Conclusion Stented elephant trunk procedure is a safe and feasible technique for selected patients with RAA and KD, which can achieve favorable early and midterm outcomes.
10.Analysis of the epidemic characteristics of reported pulmonary tuberculosis incidence in Kashgar Prefecture, Xinjiang Uygur Autonomous Region from 2015 to 2022 and establishment of SARIMA prediction
Chong TENG ; Fang XIE ; Bing ZHAO ; Lijie ZHANG ; Hui LI ; Yuanyuan SONG ; Yang ZHENG ; Yang ZHOU ; Jing WANG ; Fei HUANG ; Mingting CHEN ; Xichao OU
Chinese Journal of Preventive Medicine 2024;58(11):1665-1672
Objective:To analyze the epidemic characteristics of reported tuberculosis incidence in Kashgar from 2015 to 2022, and use the seasonal autoregressive integrated moving average (SARIMA) model to predict the incidence, providing references for the local control of pulmonary tuberculosis.Methods:The reported incidence data of tuberculosis in the Kashgar area of Xinjiang from January 2015 to August 2023 were collected through the"Infectious Disease Monitoring System", a subsystem of the "Chinese Disease Prevention and Control Information System". The epidemic characteristics of reported incidence in this area from 2015 to 2022 were analyzed. Two SARIMA models of monthly reported incidence number and rate were established. The prediction performance of the two models was evaluated using the reported incidence data of tuberculosis from January 2023 to August 2023. The χ2 test was used to analyze population characteristics, and the Cochran-Armitage trend test was used to analyze annual incidence. Results:From 2015 to 2022, 133 972 cases of pulmonary tuberculosis were reported in Kashgar, with a yearly reported incidence rate of 383.64/100 000, showing a rising trend ( TCA=77.03, P<0.001) and then a declining trend ( TCA=176.16, P<0.001). The proportion of pathogenic positive pulmonary tuberculosis had increased yearly ( TCA=132.66, P<0.001). The reported onset time was concentrated from January to June each year, with a peak in April. Yengisar County, Zepu County and Yopurga County had the highest reported incidence rate in Kashgar. The sex ratio of men to women was 1.03∶1, and the reported incidence rate of men was higher than that of women ( χ2=27.04, P<0.001). The reported incidence rate of the group aged 60 years and older was the highest. The patient′s occupation was mainly farmers (84.99%). The average relative errors of the SARIMA ( 1, 1, 2) ( 0, 1, 1) 12 model and SARIMA ( 0, 1, 1)( 0, 1, 1) 12 model in predicting the reported monthly incidence number and rate were 11.67% and -9.81%, respectively. Both models had good prediction accuracy (MAPE=33.55%, MAPE=38.22%). Conclusion:The average reported incidence rate of pulmonary tuberculosis in the Kashgar area shows a rising trend first and then a declining trend. The patients are mainly men and farmers, and attention should be paid to the prevention and control of tuberculosis among the elderly in winter and spring. The SARIMA ( 1, 1, 2) ( 0, 1, 1) 12 model and SARIMA ( 0, 1, 1)( 0, 1, 1) 12 model can fit the trend of reported tuberculosis incidence in the Kashgar area well and have good predictive performance.

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