1.Cordycepin Inhibits Fat Infiltration after Rotator Cuff Tear Injury by Regulating Wnt/β-catenin Signaling Pathway
Qiu'en XIE ; Dengwen LIANG ; Shao WU ; Xuhui HAO ; Liguang LIANG ; Bangxiang JIAN ; Junhong DONG ; Lei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):98-106
ObjectiveTo investigate the effect and mechanism of cordycepin in inhibiting fat infiltration after rotator cuff injuries in rats by regulating the Wnt/β-catenin signaling pathway, providing a theoretical basis for clinical treatment of rotator cuff injuries. MethodsFifty SPF-grade female SD rats were used in this study, with 10 randomly selected as the blank group. A rotator cuff injury repair model was established by supraspinatus tendon and suprascapular nerve compression. The successfully modeled rats were randomized into model and low-dose (20 mg·kg-1), medium-dose (40 mg·kg-1), and high-dose (80 mg·kg-1) cordycepin groups. After 6 weeks of treatment, the gait analysis was performed to assess the limb function in rats. Oil red O staining and Masson staining were employed to observe pathological changes in the muscle tissue. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the serum. Immunohistochemistry (IHC) was employed to detect the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), which are markers of adipogenesis. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of Wnt3a, Wnt10b, and β-catenin. ResultsCompared with the blank group, the model group showed decreases in stride length and paw print area (P<0.01), an increase in ratio of wet muscle mass reduction and a decrease in muscle fiber cross-sectional area (P<0.05), and decreased ratios of fat infiltration area and collagen fiber area (P<0.01). Additionally, the model group showed elevated levels of IL-1β, IL-6, and TNF-α (P<0.05), up-regulated protein levels of PPARγ and C/EBPα (P<0.01), and down-regulated mRNA and protein levels of Wnt3a, Wnt10b, and β-catenin (P<0.05, P<0.01). Compared with the model group, the low-, medium-, and high-dose cordycepin groups showed increases in stride length and paw print area (P<0.01), a decrease in ratio of wet muscle mass reduction and an increase in muscle fiber cross-sectional area (P<0.05), and increases in ratios of fat infiltration area and collagen fiber area (P<0.05, P<0.01). In addition, cordycepin lowered the serum levels of IL-1β, IL-6, and TNF-α (P<0.05, P<0.01), down-regulated the protein levels of PPARγ and C/EBPα (P<0.01), and up-regulated the mRNA and protein levels of Wnt3a, Wnt10b, and β-catenin (P<0.05, P<0.01). ConclusionCordycepin can improve the limb function, alleviate rotator cuff muscle atrophy, fat infiltration, and fibrosis, and inhibit inflammation in rats by regulating the Wnt/β-catenin signaling pathway.
2.Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis
Jian LIU ; Hongchun ZHANG ; Chengxiang WANG ; Hongsheng CUI ; Xia CUI ; Shunan ZHANG ; Daowen YANG ; Cuiling FENG ; Yubo GUO ; Zengtao SUN ; Huiyong ZHANG ; Guangxi LI ; Qing MIAO ; Sumei WANG ; Liqing SHI ; Hongjun YANG ; Ting LIU ; Fangbo ZHANG ; Sheng CHEN ; Wei CHEN ; Hai WANG ; Lin LIN ; Nini QU ; Lei WU ; Dengshan WU ; Yafeng LIU ; Wenyan ZHANG ; Yueying ZHANG ; Yongfen FAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):182-188
The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis (GS/CACM 337-2023) was released by the China Association of Chinese Medicine on December 13th, 2023. This expert consensus was developed by experts in methodology, pharmacy, and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine (CACM) and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine (pulmonary diseases) and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung, acute bronchitis, and acute attack of chronic bronchitis from the aspects of applicable populations, efficacy evaluation, usage, dosage, drug combination, and safety. It is expected to guide the rational drug use in medical and health institutions, give full play to the unique value of Qinbaohong Zhike oral liquid, and vigorously promote the inheritance and innovation of Chinese patent medicines.
3.Comprehensive evaluation of benign and malignant pulmonary nodules using combined biological testing and imaging assessment in 1 017 patients: A retrospective cohort study
Lei ZHANG ; Zihao LI ; Nan LI ; Jun CHENG ; Feng ZHANG ; Pinghui XIA ; Wang LÜ ; ; Jian HU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):60-66
Objective By combining biological detection and imaging evaluation, a clinical prediction model is constructed based on a large cohort to improve the accuracy of distinguishing between benign and malignant pulmonary nodules. Methods A retrospective analysis was conducted on the clinical data of the 32 627 patients with pulmonary nodules who underwent chest CT and testing for 7 types of lung cancer-related serum autoantibodies (7-AABs) at our hospital from January 2020 to April 2024. The univariate and multivariate logistic regression models were performed to screen independent risk factors for benign and malignant pulmonary nodules, based on which a nomogram model was established. The performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results A total of 1 017 patients with pulmonary nodules were included in the study. The training set consisted of 712 patients, including 291 males and 421 females, with a mean age of (58±12) years. The validation set included 305 patients, comprising 129 males and 176 females, with a mean age of (58±13) years. Univariate ROC curve analysis indicated that the combination of CT and 7-AABs testing achieved the highest area under the curve (AUC) value (0.794), surpassing the diagnostic efficacy of CT alone (AUC=0.667) or 7-AABs alone (AUC=0.514). Multivariate logistic regression analysis showed that radiological nodule diameter, nodule nature, and CT combined with 7-AABs detection were independent predictors, which were used to construct a nomogram prediction model. The AUC values for this model were 0.826 and 0.862 in the training and validation sets, respectively, demonstrating excellent performance in DCA. Conclusion The combination of 7-AABs with CT significantly enhances the accuracy of distinguishing between benign and malignant pulmonary nodules. The developed predictive model provides strong support for clinical decision-making and contributes to achieving precise diagnosis and treatment of pulmonary nodules.
4.Trends in global burden due to visceral leishmaniasis from 1990 to 2021 and projections up to 2035
Guobing YANG ; Aiwei HE ; Yongjun LI ; Shan LÜ ; Muxin CHEN ; Liguang TIAN ; Qin LIU ; Lei DUAN ; Yan LU ; Jian YANG ; Shizhu LI ; Xiaonong ZHOU ; Jichun WANG ; Shunxian ZHANG
Chinese Journal of Schistosomiasis Control 2025;37(1):35-43
Objective To investigate the global burden of visceral leishmaniasis (VL) from 1990 to 2021 and predict the trends in the burden of VL from 2022 to 2035, so as to provide insights into global VL prevention and control. Methods The global age-standardized incidence, prevalence, mortality and disability-adjusted life years (DALYs) rates of VL and their 95% uncertainty intervals (UI) were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources. The trends in the global burden of VL were evaluated with average annual percent change (AAPC) and 95% confidence interval (CI) from 1990 to 2021, and gender-, age-, country-, geographical area- and socio-demographic index (SDI)-stratified burdens of VL were analyzed. The trends in the global burden of VL were projected with a Bayesian age-period-cohort (BAPC) model from 2022 to 2035, and the associations of age-standardized incidence, prevalence, mortality, and DALYs rates of VL with SDI levels were examined with a smoothing spline model. Results The global age-standardized incidence [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)], prevalence [AAPC = -0.06%, 95% CI: (-0.06%, -0.06%)], mortality [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)] and DALYs rates of VL [AAPC = -2.38%, 95% CI: (-2.44%, -2.33%)] all appeared a tendency towards a decline from 1990 to 2021, and the highest age-standardized incidence [2.55/105, 95% UI: (1.49/105, 4.07/105)], prevalence [0.64/105, 95% UI: (0.37/105, 1.02/105)], mortality [0.51/105, 95% UI: (0, 1.80/105)] and DALYs rates of VL [33.81/105, 95% UI: (0.06/105, 124.09/105)] were seen in tropical Latin America in 2021. The global age-standardized incidence and prevalence of VL were both higher among men [0.57/105, 95% UI: (0.45/105, 0.72/105); 0.14/105, 95% UI: (0.11/105, 0.18/105)] than among women [0.27/105, 95% UI: (0.21/105, 0.33/105); 0.06/105, 95% UI: (0.05/105, 0.08/105)], and the highest mortality of VL was found among children under 5 years of age [0.24/105, 95% UI: (0.08/105, 0.66/105)]. The age-standardized incidence (r = -0.483, P < 0.001), prevalence (r = -0.483, P < 0.001), mortality (r = -0.511, P < 0.001) and DALYs rates of VL (r = -0.514, P < 0.001) correlated negatively with SDI levels from 1990 to 2021. In addition, the global burden of VL was projected with the BAPC model to appear a tendency towards a decline from 2022 to 2035, and the age-standardized incidence, prevalence, mortality and DALYs rates were projected to be reduced to 0.11/105, 0.03/105, 0.02/105 and 1.44/105 in 2035, respectively. Conclusions Although the global burden of VL appeared an overall tendency towards a decline from 1990 to 2021, the burden of VL showed a tendency towards a rise in Central Asia and western sub-Saharan African areas. The age-standardized incidence and prevalence rates of VL were relatively higher among men, and the age-standardized mortality of VL was relatively higher among children under 5 years of age. The global burden of VL was projected to continue to decline from 2022 to 2035.
5.Analysis of Treatment of Diabetic Kidney Disease with Modified Buyang Huanwutang Based on 5hmC-Seal Sequencing Technology
Baixin ZHEN ; Haoyu CHEN ; Duolikun MAIMAITIYASEN ; Xuehui LI ; Hong XIAO ; Xiaxuan LI ; Kuerban SUBINUER ; Lei ZHANG ; Hangyu CHEN ; Jian LIN ; Linlin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):208-217
ObjectiveTo improve the therapeutic effect of Buyang Huanwutang(BYHW) on diabetic kidney disease (DKD) and explore new methods for developing new Chinese medicine decoctions,we utilized 5-hydroxymethylcytosine (5hmC)-Seal sequencing technology and network pharmacology to modify BYHW. MethodsWe selected 14 diabetes mellitus (DM) patients and 15 DKD patients hospitalized in the Department of Endocrinology of Peking University Third Hospital in 2021. Circulating free DNA (cfDNA) in the patients’ plasma was sequenced. After data processing and screening, we performed temporal clustering analysis to select a DKD 5hmC gene set, which was then cross-validated with a DKD database gene set to obtain the DKD gene set. We retrieved target genes of the seven herbal components of BYHW from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Encyclopedia of Traditional Chinese Medicine (ETCM), and performed cross-analysis with the DKD gene set to identify common genes shared by the disease and the Chinese medicines. A protein-protein interaction (PPI) network was constructed for the common genes to screen out the key genes. Chinese medicines targeting these key genes were searched against ETCM to identify removable Chinese medicines. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed on non-common DKD genes, and key genes in DKD-related pathways were selected based on machine learning. The GSE30529 dataset was used to verify the expression trends of 5hmC-modified genes and the feasibility of target genes as drug targets. TCMBank was used to search for target genes and obtain compounds targeting these genes and the corresponding Chinese medicines to construct a "key target-compound-Chinese medicine" network. Molecular docking was employed to verify the binding affinity of compounds with key targets. TCMSP and ETCM were used to search and count the candidate Chinese medicines targeting DKD-related genes, and a new decoction was formed by adding the selected Chinese medicines. A mouse model of DKD was established to examine the efficacy of the new decoction based on the mouse body mass, random blood glucose, urinary microalbumin (mALB), serum creatinine (Scr), and blood urea nitrogen (BUN) and by hematoxylin-eosin staining, periodic acid-Schiff staining, Masson staining, immunofluorescence assay, and Real-time PCR. ResultsThe cross-analysis results showed that the DKD gene set included 507 genes, of which 30 were target genes of BYHW. The PPI analysis indicated that the top 15% target genes regarding the degree were interleukin-6 (IL-6), Toll-like receptor 4 (TLR4), lactotransferrin (LTF), lipoprotein lipase (LPL), and sterol regulatory element-binding transcription factor 1 (SREBF1). Persicae Semen and Pheretima in BYHW were unrelated to key genes and removed. Machine learning identified 10 potential target genes, among which TBC1 domain family member 5 (TBC1D5), RAD51 paralog B (RAD51B), and proteasome 20S subunit alpha 6 (PSMA6) had expression trends consistent with the GSE30529 dataset and could serve as drug targets. The "key target-compound-Chinese medicine" network and molecular docking results indicated that the compounds with good binding affinity to target proteins were arginine, glycine, myristicin, serine, and tyrosine, corresponding to 121 Chinese medicines. The top 10 Chinese medicines targeting DKD-related genes were Lycii Fructus, Ginseng Radix et Rhizoma, Dioscoreae Rhizoma, Rehmanniae Radix Praeparata, Isatidis Radix, Glehniae Radix, Ophiopogonis Radix, Allii Sativi Bulbus, Isatidis Folium, and Bolbostemmatis Rhizoma. Based on traditional Chinese medicine theory, the new decoction was obtained after removal of Persicae Semen and Pheretima and addition of Rehmanniae Radix Praeparata and Dioscoreae Rhizoma. Animal experiment results indicated that the modified BYHW improved the kidney function and inhibited renal fibrosis in DKD mice, with better effects than the original decoction. ConclusionThe BYHW modified based on 5hmC-Seal sequencing demonstrates better performance in inhibiting fibrosis and ameliorating DKD than the original decoction. This elucidates the biomedical theory behind the epigenetic modification of traditional Chinese medicine prescriptions, potentially offering new perspectives for the exploration of these prescriptions
6.Analysis of Treatment of Diabetic Kidney Disease with Modified Buyang Huanwutang Based on 5hmC-Seal Sequencing Technology
Baixin ZHEN ; Haoyu CHEN ; Duolikun MAIMAITIYASEN ; Xuehui LI ; Hong XIAO ; Xiaxuan LI ; Kuerban SUBINUER ; Lei ZHANG ; Hangyu CHEN ; Jian LIN ; Linlin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):208-217
ObjectiveTo improve the therapeutic effect of Buyang Huanwutang(BYHW) on diabetic kidney disease (DKD) and explore new methods for developing new Chinese medicine decoctions,we utilized 5-hydroxymethylcytosine (5hmC)-Seal sequencing technology and network pharmacology to modify BYHW. MethodsWe selected 14 diabetes mellitus (DM) patients and 15 DKD patients hospitalized in the Department of Endocrinology of Peking University Third Hospital in 2021. Circulating free DNA (cfDNA) in the patients’ plasma was sequenced. After data processing and screening, we performed temporal clustering analysis to select a DKD 5hmC gene set, which was then cross-validated with a DKD database gene set to obtain the DKD gene set. We retrieved target genes of the seven herbal components of BYHW from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Encyclopedia of Traditional Chinese Medicine (ETCM), and performed cross-analysis with the DKD gene set to identify common genes shared by the disease and the Chinese medicines. A protein-protein interaction (PPI) network was constructed for the common genes to screen out the key genes. Chinese medicines targeting these key genes were searched against ETCM to identify removable Chinese medicines. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed on non-common DKD genes, and key genes in DKD-related pathways were selected based on machine learning. The GSE30529 dataset was used to verify the expression trends of 5hmC-modified genes and the feasibility of target genes as drug targets. TCMBank was used to search for target genes and obtain compounds targeting these genes and the corresponding Chinese medicines to construct a "key target-compound-Chinese medicine" network. Molecular docking was employed to verify the binding affinity of compounds with key targets. TCMSP and ETCM were used to search and count the candidate Chinese medicines targeting DKD-related genes, and a new decoction was formed by adding the selected Chinese medicines. A mouse model of DKD was established to examine the efficacy of the new decoction based on the mouse body mass, random blood glucose, urinary microalbumin (mALB), serum creatinine (Scr), and blood urea nitrogen (BUN) and by hematoxylin-eosin staining, periodic acid-Schiff staining, Masson staining, immunofluorescence assay, and Real-time PCR. ResultsThe cross-analysis results showed that the DKD gene set included 507 genes, of which 30 were target genes of BYHW. The PPI analysis indicated that the top 15% target genes regarding the degree were interleukin-6 (IL-6), Toll-like receptor 4 (TLR4), lactotransferrin (LTF), lipoprotein lipase (LPL), and sterol regulatory element-binding transcription factor 1 (SREBF1). Persicae Semen and Pheretima in BYHW were unrelated to key genes and removed. Machine learning identified 10 potential target genes, among which TBC1 domain family member 5 (TBC1D5), RAD51 paralog B (RAD51B), and proteasome 20S subunit alpha 6 (PSMA6) had expression trends consistent with the GSE30529 dataset and could serve as drug targets. The "key target-compound-Chinese medicine" network and molecular docking results indicated that the compounds with good binding affinity to target proteins were arginine, glycine, myristicin, serine, and tyrosine, corresponding to 121 Chinese medicines. The top 10 Chinese medicines targeting DKD-related genes were Lycii Fructus, Ginseng Radix et Rhizoma, Dioscoreae Rhizoma, Rehmanniae Radix Praeparata, Isatidis Radix, Glehniae Radix, Ophiopogonis Radix, Allii Sativi Bulbus, Isatidis Folium, and Bolbostemmatis Rhizoma. Based on traditional Chinese medicine theory, the new decoction was obtained after removal of Persicae Semen and Pheretima and addition of Rehmanniae Radix Praeparata and Dioscoreae Rhizoma. Animal experiment results indicated that the modified BYHW improved the kidney function and inhibited renal fibrosis in DKD mice, with better effects than the original decoction. ConclusionThe BYHW modified based on 5hmC-Seal sequencing demonstrates better performance in inhibiting fibrosis and ameliorating DKD than the original decoction. This elucidates the biomedical theory behind the epigenetic modification of traditional Chinese medicine prescriptions, potentially offering new perspectives for the exploration of these prescriptions
7.Analysis of the nutritional status and influencing factors of Tibetan and Mongolian children and adolescents in Golmud City, Qinghai Province in 2022
Chinese Journal of School Health 2025;46(5):651-656
Objective:
To investigate the nutritional status and influencing factors among Tibetan and Mongolian children and adolescents aged 7-18 years in high-altitude regions, so as to provide evidence for early prevention and control of malnutrition in this population.
Methods:
From May to June 2022, a cluster sampling method was employed to recruit 1 019 Tibetan and Mongolian children and adolescents aged 7-18 years from two primary and secondary schools in Golmud City. Physical examinations, dietary frequency questionnaires, and physical activity assessments were conducted. Nutritional status was classified as obesity, combined overweight/obesity, underweight, or central obesity according to national standards including Screening for Overweight and Obesity among School-age Children and Adolescents, Screening Standard for Malnutrition of School-age Children and Adolescents, Blue Book on Obesity Prevention and Control in China. Chi-square tests, t-test and Logistic regression analyses were performed to identify factors associated with different nutritional statuses.
Results:
The detection rates of obesity, combined overweight/obesity, underweight, and central obesity were 8.0%, 18.1%, 5.2%, and 19.7%, respectively. The height of children and adolescents across all age groups was generally lower than the national standard values. Tibetan participants exhibited significantly lower height-for-age Z-scores (HAZ)(9-10, 13-17 years, Z =2.01, 2.78, 4.16, 3.38, 4.12, 3.63, 3.00) and BMI-for-age Z-scores (BAZ) compared to Mongolian participants ( Z =-2.95, -2.47, -2.31, -2.89, -2.14, -2.17)( P < 0.05 ). Multivariate Logistic regression revealed that Mongolian children and adolescents had higher risks of obesity ( OR =2.20) and combined overweight/obesity ( OR = 2.18 ) ( P <0.05). Additionally, insufficient moderate-to-vigorous physical activity (MVPA) was associated with an increased risk of central obesity ( OR =1.48, P <0.05), compared with children and adolescents who meet the standard of MVPA.
Conclusions
The rates of overweight and obesity among Tibetan and Mongolian children and adolescents in Golmud City are higher, influenced by multiple factors. Nutrition interventions and physical activity strategies tailored to ethnic characteristics should be implemented, with emphasis on promoting MVPA to improve nutritional outcomes in this population.
8.Plasma miRNA testing in the differential diagnosis of very early-stage hepatocellular carcinoma: a multicenter real-world study
Jie HU ; Ying XU ; Ao HUANG ; Lei YU ; Zheng WANG ; Xiaoying WANG ; Xinrong YANG ; Zhenbin DING ; Qinghai YE ; Yinghong SHI ; Shuangjian QIU ; Huichuan SUN ; Qiang GAO ; Jia FAN ; Jian ZHOU
Chinese Journal of Clinical Medicine 2025;32(3):350-354
Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP<20 ng/mL, DCP<40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P<0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P<0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.
9.Correlation of serum IL-35, IgG4/IgG, TSI levels with the activity and severity of thyroid associated ophthalmopathy
Yu YAN ; Qin ZHONG ; Lei YANG ; Jian ZHANG ; Shuangle LI
International Eye Science 2025;25(10):1662-1666
AIM: To investigate the correlation of serum interleukin-35(IL-35), immunoglobulin 4/immunoglobulin(IgG4/IgG), thyroid stimulating immunoglobulin(TSI)levels with the activity and severity of thyroid associated ophthalmopathy(TAO).METHODS:Prospective study. A total of 148 TAO patients admitted to our hospital from January 2023 to July 2024 were selected as the observation group. They were assigned into an active group(75 cases)and an inactive group(73 cases)based on their activity level, and were assigned into a severe group(95 cases)and a mild group(53 cases)based on the severity of their condition; another 148 healthy patients who underwent physical examinations were regarded as the control group. The levels of IL-35, IgG4/IgG, and TSI in serum were compared between the two groups. The correlation between serum IL-35, IgG4/IgG, and TSI levels and TAO activity and severity of illness were analyzed. A multivariate Logistic regression was performed to analyze the influencing factors of TAO patients developing severe symptoms. ROC curve was applied to analyze the diagnostic value of serum IL-35, IgG4/IgG, and TSI levels for the development of severe TAO in patients.RESULTS: Compared with the control group, the serum IL-35 level in the observation group was significantly lower, while IgG4/IgG and TSI levels were significantly higher(all P<0.01). Compared with non-active TAO patients, active TAO patients had significantly lower serum IL-35 level and significantly higher IgG4/IgG and TSI levels(all P<0.01). Compared with the mild TAO patients, severe TAO patients had significantly lower serum IL-35 level and significantly higher disease duration, IgG4/IgG, and TSI levels(all P<0.01). The serum IL-35 level was negatively correlated with TAO activity and disease severity(r=-0.529, -0.554, both P<0.01), while serum IgG4/IgG level was positively correlated with TAO activity and disease severity(r=0.625, 0.663, both P<0.01). Serum TSI levels were positively correlated with TAO activity and disease severity(r=0.594, 0.607, both P<0.01). Multivariate Logistic regression analysis showed that serum IL-35, IgG4/IgG, and TSI levels were all factors influencing the progression of TAO patients to severe disease(all P<0.01). The areas under the curve(AUC)for diagnosing the progression of TAO patients to severe disease using serum IL-35, IgG4/IgG, and TSI levels were 0.868, 0.859, and 0.830, respectively. The combined AUC for the three markers was 0.955, significantly higher than that of each individual marker(Zthree factors combination-IL-35=2.893, Zthree factors combination-IL-35=3.510, Zthree factors combination-IL-35=4.157, P=0.004, <0.01, <0.01).CONCLUSION: Serum IL-35 level is significantly downregulated in TAO patients, while IgG4/IgG and TSI levels are significantly upregulated. The levels of IL-35, IgG4/IgG, and TSI are correlated with the activity and severity of TAO, and their combination has high diagnostic value for TAO developing into severe.
10.Development of an Analytical Software for Forensic Proteomic SAP Typing
Feng HU ; Meng-Jiao WANG ; Jia-Lei WU ; Dong-Sheng DING ; Zhi-Yuan YANG ; An-Quan JI ; Lei FENG ; Jian YE
Progress in Biochemistry and Biophysics 2025;52(9):2406-2416
ObjectiveThe proteome of biological evidence contains rich genetic information, namely single amino acid polymorphisms (SAPs) in protein sequences. However, due to the lack of efficient and convenient analysis tools, the application of SAP in public security still faces many challenges. This paper aims to meet the application requirements of SAP analysis for forensic biological evidence’s proteome data. MethodsThe software is divided into three modules. First, based on a built-in database of common non-synonymous single nucleotide polymorphisms (nsSNPs) and SAPs in East Asian populations, the software integrates and annotates newly identified exonic nsSNPs as SAPs, thereby constructing a customized SAP protein sequence database. It then utilizes a pre-installed search engine—either pFind or MaxQuant—to perform analysis and output SAP typing results, identifying both reference and variant types, along with their corresponding imputed nsSNPs. Finally, SAPTyper compares the proteome-based typing results with the individual’s exome-derived nsSNP profile and outputs the comparison report. ResultsSAPTyper accepts proteomic DDA mass spectrometry raw data (DDA acquisition mode) and exome sequencing results of nsSNPs as input and outputs the report of SAPs result. The pFind and Maxquant search engines were used to test the proteome data of 2 hair shafts of2 individuals, and both obtained SAP results. It was found that the results of the Maxquant search engine were slightly less than those of pFind. This result shows that SAPTyper can achieve SAP fingding function. Moreover, the pFind search engine was used to test the proteome data of 3 hair shafts from 1 European person and 1 African person in the literature. Among the sites fully matched by the literature method, sites detected by SAPTyper are also included; for semi-matching sites, that is, nsSNPs are heterozygous, both literature method and SAPTyper method had the risk of missing detection for one type of the allele. Comparing the analysis results of SAPTyper with the SAP test results reported in the literature, it was found that some imputed nsSNP sites identified by the literature method but not detected by SAPTyper had a MAF of less than 0.1% in East Asian populations, and therefore they were not included in the common nsSNP database of East Asian populations constructed by this software. Since the database construction of this software is based on the genetic variation information of East Asian populations, it is currently unable to effectively identify representative unique common variation sites in European or African populations, but it can still identify SAP sites shared by these populations and East Asian populations. ConclusionAn automated SAP analysis algorithm was developed for East Asian populations, and the software named SAPTyper was developed. This software provides a convenient and efficient analysis tool for the research and application of forensic proteomic SAP and has important application prospects in individual identification and phenotypic inference based on SAP.


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