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.A survey on the current status of gynecological and breast diseases among 13 031 women in Pudong New Area, Shanghai in 2023
Lu LI ; Xichang ZHAO ; Yuwei ZHANG ; Yufang YE
Shanghai Journal of Preventive Medicine 2025;37(2):160-163
ObjectiveTo investigate the prevalence of gynecological and breast diseases among retired or economically disadvantaged women in part of Pudong New Area of Shanghai under the policy support of screening gynecological diseases and breast diseases for retired and women with economic difficulties in life in Shanghai, to analyze the characteristics of these diseases, so as to provide a scientific basis for the improvement of relevant prevention and treatment strategies. MethodsBased on the gynecological census data of 13 031 cases in five towns, including Xinchang Town, Xuanqiao Town, Laogang Town, Wanxiang Town and Shuyuan Town, conducted by Shanghai Pudong Hospital in 2023, descriptive analysis methods were used to explore the prevalence and age characteristics of common gynecological and breast diseases. ResultsThe total detection rate of gynecological and breast diseases among women in the screening area in this study was 68.29%, with uterine fibroid (22.35%), sarcoidosis of the breast (17.06%), cervicitis (15.37%), vaginitis (8.39%) and ovarian cyst (2.61%) ranking the top 5 in the detection rate among the screening population. The differences of the detection rates in the four major diseases [uterine fibroid (χ2=233.217, P<0.001), breast nodules(χ2=169.896, P<0.001), cervicitis (χ2=388.683, P<0.001), and ovarian cysts (χ2=72.298, P<0.001)] by different age groups were statistically significant (P<0.05) . Moreover, the results of pairwise comparison of different age groups showed that the detection rates in the age group under 45 years old and 45‒55 years old were higher than that in the age group of 55‒65 years old and over 65 years old. ConclusionThe detection rate of gynecological and breast diseases in the younger age group was higher, indicating a certain trend of younger onset of diseases. Uterine fibroid, sarcoidosis of the breast , and reproductive tract diseases such as cervicitis, vaginitis, and ovarian cyst are the main diseases affecting the research subjects. Therefore, medical institutions can combine routine work in screening diseases and carry out corresponding health education and health promotion activities for these key diseases to improve women’s health.
3.Research progress on the pathogenesis of central retinal vein occlusion
Qi HAN ; Xue HAN ; Xingchen GUO ; Yuanhui YANG ; Yuanmin LI ; Yufang TENG
International Eye Science 2025;25(8):1261-1266
Central retinal vein occlusion(CRVO)is a retinal vascular disorder that significantly impairs vision, with its underlying mechanisms involving complex interactions across multiple biological systems. This article provides a systematic review of the pathological mechanisms associated with CRVO, emphasizing critical factors such as endothelial dysfunction, arteriosclerosis, thrombophilia, inflammation, and oxidative stress. The pathological mechanisms of CRVO are characterized by arteriosclerosis, which obstructs venous return through a dual mechanism involving mechanical compression and endothelin-1-mediated contraction; endothelial dysfunction, which exacerbates disturbances in blood flow; genetic and acquired coagulation abnormalities that disrupt hemostatic balance and promote thrombosis; and the synergistic effects of inflammation and oxidative stress that activate cytokines, thereby aggravating ischemia and vascular leakage. Innovatively, this review explores emerging mechanisms such as miRNA-mediated vascular regulation via exosomes, gut microbiota-retina crosstalk through the “gut-eye axis,” and systemic metabolic interactions that link local retinal lesions to broader dysregulation of CRVO. These insights underscore the importance of integrated eye-system interventions and provide a theoretical foundation for advancing early biomarker discovery, multitarget therapeutics, and personalized treatment paradigms. By bridging localized pathology and systemic mechanisms, this work promotes a transformative shift toward an integrative medicine model in the diagnosis and management of CRVO.
4.Nasal-to-Brain Drug Delivery Strategies for Active Ingredients of Traditional Chinese Medicine:A Review
Yang CHEN ; Tiantian WANG ; Yufang HUANG ; Guangdi YANG ; Shengmou HU ; Xiaomeng LEI ; Wenliu ZHANG ; Dongxun LI ; Canjian WANG ; Guosong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):252-261
Central nervous system(CNS) disorders are characterized by complex pathological mechanisms and the presence of the blood-brain barrier(BBB), which significantly limits the effectiveness of drug therapy. Traditional drug delivery modes include oral administration, intravenous injection and transdermal delivery, which have certain advantages, but it is difficult for the drugs to effectively cross the BBB. Therefore, it is crucial to find drug delivery modes that can efficiently traverse the BBB. Nasal drug delivery, as a non-invasive method, can realize the targeted delivery of drugs to the CNS via three pathways, including olfactory neurons, trigeminal neurons and blood circulation, and shows a broad application prospect in the treatment of CNS diseases. Numerous studies have further confirmed that nasal drug delivery combined with novel drug delivery systems such as lipid nanocarriers, nanoparticles, nanoemulsions and composite in situ gels can effectively load the active components of traditional Chinese medicine(TCM), and significantly increase drug concentration in the brain, which provides new strategies for the treatment of CNS diseases. In this paper, the current status of drug delivery for CNS diseases was systematically sorted out, the characteristics of nasal drug delivery were discussed in depth, and the research progress of passive targeting, active targeting, and "guiding the meridian" drug delivery strategies for the nasal-to-brain transport of TCM active components was summarized and analyzed, which was aimed to provide references and insights for the development of drugs for CNS diseases and the application of TCM in nasal-to-brain delivery.
5.Nasal-to-Brain Drug Delivery Strategies for Active Ingredients of Traditional Chinese Medicine:A Review
Yang CHEN ; Tiantian WANG ; Yufang HUANG ; Guangdi YANG ; Shengmou HU ; Xiaomeng LEI ; Wenliu ZHANG ; Dongxun LI ; Canjian WANG ; Guosong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):252-261
Central nervous system(CNS) disorders are characterized by complex pathological mechanisms and the presence of the blood-brain barrier(BBB), which significantly limits the effectiveness of drug therapy. Traditional drug delivery modes include oral administration, intravenous injection and transdermal delivery, which have certain advantages, but it is difficult for the drugs to effectively cross the BBB. Therefore, it is crucial to find drug delivery modes that can efficiently traverse the BBB. Nasal drug delivery, as a non-invasive method, can realize the targeted delivery of drugs to the CNS via three pathways, including olfactory neurons, trigeminal neurons and blood circulation, and shows a broad application prospect in the treatment of CNS diseases. Numerous studies have further confirmed that nasal drug delivery combined with novel drug delivery systems such as lipid nanocarriers, nanoparticles, nanoemulsions and composite in situ gels can effectively load the active components of traditional Chinese medicine(TCM), and significantly increase drug concentration in the brain, which provides new strategies for the treatment of CNS diseases. In this paper, the current status of drug delivery for CNS diseases was systematically sorted out, the characteristics of nasal drug delivery were discussed in depth, and the research progress of passive targeting, active targeting, and "guiding the meridian" drug delivery strategies for the nasal-to-brain transport of TCM active components was summarized and analyzed, which was aimed to provide references and insights for the development of drugs for CNS diseases and the application of TCM in nasal-to-brain delivery.
6.Investigation of latent tuberculosis infection among the elderly in rural areas of Changxing County, Zhejiang Province
Jian ZHANG ; Yufang SONG ; Feilin REN ; Xuejing LI ; Jiasheng QIN ; Bin SHAO
Shanghai Journal of Preventive Medicine 2025;37(6):503-506
ObjectiveTo investigate the current status of latent tuberculosis infection (LTBI) among the elderly population in rural areas of Changxing County, Zhejiang Province, and to provide an evidence for the development of LTBI prevention and control measures. MethodsBetween January and May 2024, elderly individuals participating in urban and rural residents’ health checkups were screened for Mycobacterium tuberculosis infection using a domestically produced interferon-γ release assay (IGRA) kit. Individuals tested positive by IGRA but without active tuberculosis were classified as LTBI cases. The prevalence of LTBI among the participants was subsequently analyzed. ResultsAmong the 6 765 subjects, 637 tested positive by IGRA, including one identified active tuberculosis patient, resulting in a LTBI prevalence rate of 9.40%. There was a statistically significant difference in positivity rates across different IGRA methodologies (χ2=35.530, P<0.001). Higher LTBI rate was observed in males, individuals with a history of diabetes mellitus, and those with a history of pulmonary tuberculosis, exhibiting statistically significant differences (χ2=32.401, P<0.001; χ2=5.789, P=0.020; χ2=39.248, P<0.001, respectively.) No statistically significant difference in LTBI rate was found across different age groups (χ2=0.238, P=0.971). ConclusionThe prevalence of LTBI among the elderly rural residents in Changxing County is relatively low. Male, individuals with a history of diabetes mellitus, and those with a history of pulmonary tuberculosis have an increased risk of LTBI, warranting targeted risk monitoring and timely interventions.
7.Clinical significance of determining the level of biliary calprotectin in patients with cholangiocarcinoma or choledocholithiasis
Tingting JI ; Bingqing BAI ; Yufang CUI ; Shaofei WANG ; Jianglong HONG ; Yang LI ; Junjun BAO ; Qiao MEI
Journal of Clinical Hepatology 2024;40(3):568-572
ObjectiveTo investigate the difference in the level of biliary calprotectin between patients with cholangiocarcinoma and those with choledocholithiasis. MethodsClinical data and bile samples were collected from 34 patients with cholangiocarcinoma and 78 patients with choledocholithiasis who were diagnosed and treated with endoscopic retrograde cholangiopancreatography in The First Affiliated Hospital of Anhui Medical University from May 2021 to September 2022. Fluorescence lateral flow immunoassay was used to measure the levels of calprotectin, hemoglobin, and lactoferrin in bile. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; the Spearman correlation test was used for correlation analysis; the DeLong test was used for comparison of the area under the ROC curve (AUC). ResultsCompared with the choledocholithiasis group, the cholangiocarcinoma group had significant increases in the levels of calprotectin [4 795.50 (2 286.79 — 20 179.73) ng/mL vs 411.16 (67.03 — 1 991.88) ng/mL, Z=5.572, P<0.001] and fluoride [115.70 (109.10 — 125.50) mmol/L vs 106.60 (98.60 — 114.40) mmol/L, Z=2.702, P=0.007]. The patients with cholangiocarcinoma were further divided into high cholangiocarcinoma group and low cholangiocarcinoma group, and there was no significant difference between the two groups in the level of calprotectin [3 867.71 (2 235.66 — 26 407.40) ng/mL vs 4 795.50 (2 361.15 — 13 070.53) ng/mL, Z=0.129, P>0.05]. Biliary calprotectin level was correlated with white blood cell count, hemoglobin concentration, and lactoferrin concentration in bile (r=0.316, 0.353, and 0.464, all P<0.05). The ROC curve analysis showed that biliary calprotectin (with a sensitivity of 79.4% and a specificity of 75.6%), blood CA19-9 (with a sensitivity of 82.4% and a specificity of 78.2%), and their combination (with a sensitivity of 88.2% and a specificity of 73.1%) had good sensitivity and specificity in the diagnosis of cholangiocarcinoma. ConclusionThere is an increase in the level of biliary calprotectin in patients with cholangiocarcinoma, and therefore, it might become a biomarker for the diagnosis of cholangiocarcinoma.
8.Research on the Role and Clinical Application Value of the Histone H2A Deubiquitinase BAP1 in the Occurrence and Progression of Malignant Glioma Cells
Yufang LI ; Zhifeng LIN ; Ying XIANG ; Fei QI ; Feizhou HAN ; Zhongli QIAN ; Tao WANG ; Xu CHEN
Journal of Modern Laboratory Medicine 2024;39(2):7-11,33
Objective To explore the role of breast/ovarian cancer susceptibility gene 1 associated protein 1(BAP1)in the occurrence and progression of human malignant glioma and the feasibility of BAP1 as a clinical diagnostic marker for malignant glioma.Methods The differential expression of BAP1 in normal and glioma tissue was analyzed based on the GSE4290 and GSE90598 sub-datasets from the gene expression omnibus(GEO)database.Receiver operating characteristic(ROC)curve analysis was conducted to assess the early diagnostic value of BAP1 for malignant glioma.Primary lesion tissues from 28 nonpaired malignant glioma patients and non-tumor brain tissues removed by internal decompression surgery in 5 patients with traumatic brain injury collected independently were collected,and the expression levels of BAP1 were measured using quantitative real-time polymerase chain reaction(qRT-PCR).Specific small interfering RNAs(siRNAs)targeting BAP1 were transiently transfected into U251 cells to further evaluate their interference efficiency.Flow cytometry was employed to analyze changes in the cell cycle and apoptosis of U251 cells with BAP1 knockdown.Results The results of bioinformatics showed that the expression of BAP1 in malignant glioma tissues was lower than that in normal brain tissues(GSE 4290:1 209±18.49 vs 1 476±53.90,GSE 90598:5.19±0.10 vs 5.65±0.21),and the differences were significant(t=5.115,2.267,all P<0.05).ROC curve showed that BAP1 could efficiently differentiate malignant glioma tissue from normal brain tissue(GSE4290:AUC=0.78,GSE90598:AUC=0.75,all P<0.05).The expression level of BAP1 in primary malignant glioma tissue was lower than that in normal brain tissue(0.27±0.04 vs 1.06±0.07),and the difference was significant(t=10.22,P<0.001).After down-regulating the expression of BAP1 in U251 cells,the proportion of S phase cells increased from 17.59%to 27.21%(siBAP1-1)and 25.79%(siBAP1-2),respectively,and the differences were significant(t=6.576,6.642,all P<0.01).However,the apoptosis levels decreased from 10.17%to 2.70%(siBAP-1)and 3.00%(siBAP-2),respectively,and the differences were significant(t=10.31,9.428,all P<0.01).Conclusion Histone H2A deubiquitinase BAP1 could exert the function of tumor suppressor genes by inhibiting rapid cell cycle progression and promoting apoptosis in malignant glioma,and could serve as a potential clinical diagnostic biomarker for malignant glioma.
9.Expression of lncRNA SNHG8 in placenta accreta and its effect on trophoblast invasion and migration
Li'na GAO ; Xiaohui LIU ; Yufang ZHANG ; Xiaoling LIU ; Xiaochun HE ; Jing GAO ; Li ZHANG ; Jun SUN ; Xiujuan WANG ; Yan DONG
The Journal of Practical Medicine 2024;40(5):646-652
Objective To investigate the expression of lncRNA SNHG8 in placenta accrete(PA)and its effect on trophoblast invasion and migration.Methods qRT-PCR was used to detect the expression of lncRNA SNHG8 in placenta tissue of 30 cases in PA group and 30 cases in control group,and the correlation between lncRNA SNHG8 expression and prenatal ultrasound score of 30 cases in PA group was analyzed.Transwell and scratch assay were used to detect the effect of lncRNA SNHG8 interference on the invasion and migration of human chorionic trophoblast cells(HTR8/SVneo cells),and western blot was used to detect the expression of MMP-2 and MMP-9.The downstream targets of lncRNA SNHG8 were predicted by StarBase software,and the expression of lncRNA SNHG8 was detected in placental tissues of the two groups.Dual luciferase reporter assay was used to detect the targeting relationship between lncRNA SNHG8 and miR-542-3p.Results Compared with that of the control group,the expression of lncRNA SNHG8 was up-regulated in the placenta tissue of the PA group(P<0.05),and it was positively correlated with prenatal ultrasound score.Interference with lncRNA SNHG8 inhibited the invasion and migration of trophoblast cells(P<0.05);the protein expression of MMP-9 and MMP-2 also decreased signifi-cantly(P<0.05).Biological prediction indicates that miR-542-3p had a binding site with lncRNA SNHG8,and miR-542-3p expression was down-regulated in PA placental tissue(P<0.05).Dual luciferase reporter assay confirmed that lncRNA SNHG8 could target miR-542-3p.Compared with si-SNHG8+inhibitor-NC,co-transfection of si-SNHG8 and miR-542-3p inhibitor enhanced the invasion and migration ability of trophoblast cells(P<0.05).Conclusion lncRNA SNHG8 is highly expressed in PA and is related to the severity of PA.LncRNA SNHG8 promotes the invasion and migration of trophoblast by regulating the level of miR-542-3p.The study suggests that lncRNA SNHG8 plays an important role in the invasion and migration of PA trophoblast cells,which is expected to be a clinical diagnostic biomarker and therapeutic target.
10.Expression of immune-related genes in rheumatoid arthritis and a two-sample Mendelian randomization study of immune cells
Yidong FAN ; Gang QIN ; Kaiyi HE ; Yufang GONG ; Weicai LI ; Guangtao WU
Chinese Journal of Tissue Engineering Research 2024;28(27):4312-4318
BACKGROUND:Rheumatoid arthritis is a chronic systemic autoimmune disease.It is important to study the immunological changes involved in it for diagnosis and treatment. OBJECTIVE:To identify immune-related biomarkers associated with rheumatoid arthritis utilizing bioinformatics techniques and examine alterations in immune cell infiltration as well as the relationship between immune cells and biomarkers. METHODS:Differential expression analysis was used to identify the immune-related genes that were up-regulated in rheumatoid arthritis based on the GEO and Immport databases.Kyoto encyclopedia of genes and genomes(KEGG)and gene ontology(GO)enrichment analyses were used to investigate the possible function of these elevated genes.The immunological characteristic genes associated with rheumatoid arthritis were screened using least absolute shrinkage and selection operator(Lasso)and support vector machine recursive feature elimination(SVM-RFE).Independent datasets were used for difference validation,and the diagnostic performance was evaluated by plotting receiver operating characteristic curves for feature genes.Immune cell infiltration was used to analyze the differential profile of immune cells in rheumatoid arthritis and the correlation between the characterized genes and immune cells.In order to ascertain the causal relationship between monocytes and rheumatoid arthritis in immune cells,Mendelian randomization analysis was ultimately employed. RESULTS AND CONCLUSION:There were 39 upregulated differentially expressed genes in rheumatoid arthritis.The genes were primarily enriched in chemotaxis,cytokine activity,and immune receptor activity,according to GO enrichment analysis,while kEGG enrichment analysis revealed that the genes were considerably enriched in the tumor necrosis factor signaling pathway and peripheral leukocyte migration.Lasso and SVM-RFE identified five feature genes:CXCL13,SDC1,IGLC1,PLXNC1,and SLC29A3.Independent dataset validation of the feature genes found them to be similarly highly expressed in rheumatoid arthritis samples,with area under the curve values greater than 0.8 for all five feature genes in both datasets.Immune cell infiltration indicated that most immune cells,including natural killer cells and monocytes,exhibited increased levels of infiltration in rheumatoid arthritis samples.The correlation analysis revealed a significant positive correlation between memory B cells and immature B cells and these five feature genes.Correlation analysis showed that the five feature genes were positively correlated with memory B cells and immature B cells.The inverse variance weighting method revealed that monocytes were associated with the risk of developing rheumatoid arthritis.

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