1.Analysis of plasma metabonomic characteristics of type 2 diabetes mellitus patients with turbid toxin accumulation syndrome
Ziqi ZHAO ; Pai PANG ; Yue REN ; Bin WANG ; Yuntao MA ; Qianjing YANG ; Shentao WU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):34-42
Objective:
To explore the plasma metabonomic characteristics of patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome.
Methods:
One hundred and three patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome were enrolled from November 2023 to February 2024 in the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and 54 healthy individuals were recruited. The general data of the two groups were analyzed, and the plasma metabolite content was detected using ultra-high performance liquid chromatography-Orbitrap mass spectrometry. Construct an orthogonal partial least squares discriminant analysis model to screen metabolites with significant intergroup changes. The variable importance in projection≥ 1, |log2FC|>1, and P<0.05 were used as the criteria for the screening of differential metabolites. Annotate differential metabolites using internal databases and the human metabolome database, and perform pathway analysis using MetaboAnalyst website.
Results:
There was no statistically significant difference in gender and age between the two groups.Seventeen potential differential metabolites were identified. The D-4′-phosphopantothenate, 2, 6-dichloroindophenol, 4-methylphenol, hypoxanthine, 11, 12-epoxyeicosatrienoic acids, oleamide, 3-phenyllactic acid contents were higher in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05); 3-anisic acid, 3-iodo-octadecanoic acid, mebendazole, β-alanine, citric acid, trans-aconitic acid, geranyl diphosphate, lysophosphatidylcholine(18∶2), phosphatidylethanolamine(18∶1), and caprolactam contents were lower in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05). Ten metabolic pathways were identified, including the key metabolic pantothenate and coenzyme A biosynthesis pathways.
Conclusion
Metabolic differences were observed between patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome and healthy individuals, and the underlying mechanism may involve the pantothenate and coenzyme A biosynthesis pathways, jointly mediated by D-4′-phosphopantothenate and β-alanine.
2.Mechanism of the pretreatment with electroacupuncture of "biaoben acupoint combination" for regulating cardiomyocyte mitochondrial fission in the rats of myocardial ischemia-reperfusion injury.
Yanlin ZHANG ; Song WU ; Qianru GUO ; Yuntao YU ; Sunyi WANG ; Yuqi WEI ; Xiaoman WAN ; Zhen LU ; Xiaoru HE
Chinese Acupuncture & Moxibustion 2025;45(3):335-344
OBJECTIVE:
To observe the effect of electroacupuncture (EA) pretreatment of "biaoben acupoint combination" on cardiomyocyte mitochondrial fission in the rats with myocardial ischemia-reperfusion injury (MIRI) and explore its mechanism.
METHODS:
Fifty male SD rats were randomly divided into a sham-operation group, a model group, an EA pretreatment group, an EA pretreatment + Compound C group and an EA pretreatment+ML385 group, 10 rats in each group. In the EA pretreatment, the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, EA was delivered at bilateral "Neiguan" (PC6), "Zusanli" (ST36) and "Guanyuan" (CV4) for 20 min, with continuous wave and 2 Hz of frequency, 1 mA of current, once daily for consecutive 7 days. On day 8, in the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, 30 min before model preparation, the intraperitoneal injection with Compound C (0.3 mg/kg) and ML385 (30 mg/kg) was administered respectively. Except in the sham-operation group, the ligation of the left anterior descending coronary artery was performed to prepare MIRI rat model in the rest groups. In the sham-operation group, the thread was not ligated. After modeling, the content of reactive oxygen species (ROS) in the ischemic area was measured by flow cytometry, superoxide dismutase (SOD) was detected using xanthine oxidase method, and malondialdelyde (MDA) was detected using thiobarbituric acid (TBA) chromatometry. The morphology of myocardial tissue in the ischemic area was observed with HE staining, and the mitochondria ultrastructure of cardiomyocytes observed under transmission electron microscopy. Using immunofluorescence analysis, the positive expression of mitochondrial fission factor (MFF), mitochondrial fission 1 protein antibody (Fis1) and dynamin-related protein 1 (Drp1) was detected; and with immunohistochemical method used, the protein expression of adenosine monophosphate-activated protein kinase (AMPK), nuclear factor E2-associated factor2 (Nrf2) and Drp1 in the ischemic area was detected.
RESULTS:
Compared with the sham-operation group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 increased in the model group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 decreased (P<0.01), and the protein expression of Drp1 elevated (P<0.01). Compared with the model group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01), and the protein expression of Drp1 declined (P<0.01); and in the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the positive expression of MFF, Fis1 and Drp1, and the protein expression of Drp1 were all reduced (P<0.01). When compared with the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01, P<0.05), and the protein expression of Drp1 decreased (P<0.05). In comparison with the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the cardiac muscle fiber rupture, cell swelling and mitochondrial disorders were obviously alleviated in the EA pretreatment group. The morphological changes were similar among the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group.
CONCLUSION
Electroacupuncture pretreatment of "biaoben acupoint combination" attenuates myocardial injury in MIRI rats, probably through promoting the phosphorylation of AMPK and Nrf2, inhibiting the excessive mitochondrial fission induced by Drp1, and reducing mitochondrial dysfunction caused by mitochondrial fragmentation and vacuolation.
Animals
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Electroacupuncture
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Male
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Rats, Sprague-Dawley
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Myocardial Reperfusion Injury/physiopathology*
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Myocytes, Cardiac/cytology*
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Rats
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Acupuncture Points
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Mitochondrial Dynamics
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Humans
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Reactive Oxygen Species/metabolism*
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NF-E2-Related Factor 2/genetics*
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Superoxide Dismutase/metabolism*
3.Enhanced radiotheranostic targeting of integrin α5β1 with PEGylation-enabled peptide multidisplay platform (PEGibody): A strategy for prolonged tumor retention with fast blood clearance.
Siqi ZHANG ; Xiaohui MA ; Jiang WU ; Jieting SHEN ; Yuntao SHI ; Xingkai WANG ; Lin XIE ; Xiaona SUN ; Yuxuan WU ; Hao TIAN ; Xin GAO ; Xueyao CHEN ; Hongyi HUANG ; Lu CHEN ; Xuekai SONG ; Qichen HU ; Hailong ZHANG ; Feng WANG ; Zhao-Hui JIN ; Ming-Rong ZHANG ; Rui WANG ; Kuan HU
Acta Pharmaceutica Sinica B 2025;15(2):692-706
Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [64Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [64Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [64Cu]QM-2303 from the bloodstream. Administration of a single dose of [177Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [64Cu]/[177Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [64Cu]/[177Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.
4.Enzymatic depolymerization of polyester-cotton textiles for the recovery of terephthalic acid.
Hongzhao WANG ; Yuntao CUN ; Minxuan WANG ; Zhenwu YANG ; Hao HE ; Yushan ZHU
Chinese Journal of Biotechnology 2025;41(9):3553-3566
Polyethylene terephthalate (PET) fibers are characterized by exceptional mechanical strength, and textiles blended with cotton fibers combine both comfort and durability, showcasing widespread use in daily applications. However, improper disposal of discarded polyester-cotton textiles has resulted in severe environmental pollution, necessitating urgent and effective mitigation strategies. Enzymatic recycling of textiles offers superior environmental benefits and holds greater potential for industrial applications than alternative recycling methods. This study aims to explore a large-scale solution for the treatment of waste textiles, particularly addressing the challenge of resource recovery from polyester-cotton blended fabrics. An innovative enzymatic depolymerization process has been developed to achieve the recovery of high-purity terephthalic acid monomers. Experiments were conducted on three different textile blends with polyester-to-cotton ratios of 65/35, 70/30, and 80/20, and the influences of different colors on the process were investigated. Initially, the textiles were pretreated through mechanical grinding, which was followed by depolymerization of cotton fibers with commercial cellulase. The crystallinity of PET in the textiles was reduced through a rapid heating and cooling process. Subsequently, the PET was depolymerized by the engineered PET hydrolase. The results demonstrated that after decolorization and separation of terephthalic acid (TPA) from the reaction system, the monomer recovery rates for the three textile blends (65/35, 70/30, and 80/20) reached 90%, 91%, and 92%, respectively. Characterization analysis by nuclear magnetic resonance (NMR) confirmed that the purity of the recovered TPA was greater than 99%. In conclusion, the fully enzymatic recycling process developed in this study shows considerable promise for large-scale industrial applications and is anticipated to significantly advance the adoption and development of enzymatic recycling technologies for PET in industrial processes.
Phthalic Acids/chemistry*
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Polyesters/chemistry*
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Textiles
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Cotton Fiber
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Polyethylene Terephthalates/chemistry*
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Cellulase/chemistry*
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Recycling/methods*
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Polymerization
5.Research progress in online monitoring technologies for workplace dust concentration
Qiangzhi GUO ; Yuntao MU ; Jinning YU ; Chuntao GE ; Chen WANG ; Zhiguo ZHOU ; Xue JIANG ; Yazhen WANG ; Jinling LIU ; Di LIU ; Shibiao SU
China Occupational Medicine 2025;52(4):472-476
Occupational pneumoconiosis remains the most common occupational disease in China, with occupational mineral dust exposure being its primary causative factor. Although national standards for online monitoring and early warning systems of coal mine dust concentrations have been established, national occupational health standards for rapid and online monitoring of dust concentration and particle size distribution in other industries are still limited. Among dust concentration sensor technologies, the light scattering method is the preferred choice for online dust monitoring owing to its wide measurement range and low cost. The beta-ray absorption method is mature but highly sensitive to humidity. The electrostatic induction method offers high sensitivity, simple structure, and low maintenance costs but exhibits high errors in low-concentration dust monitoring. The tapered element oscillating microbalance method is highly sensitive but costly. Multi-sensor data fusion technology can improve monitoring reliability, however, mature domestic products are not yet available. For monitoring dust particle size distribution, sieving and sedimentation methods are cumbersome. The aerodynamic method shows broad prospects in the online monitoring of respirable dust but has obvious measurement errors for larger dust particles. The use of optical measurement method is limited by dust morphology and is not suitable for monitoring coal dust particle size distribution. The electrical mobility method is primarily applicable to submicron dust. Future research should focus on promoting the application of monitoring technology for respirable dust particle size distribution in online monitoring of industrial dust. By integrating Internet of Things, data mining, and artificial intelligence technologies, along with multi-sensor data fusion and numerical simulation, dust concentration prediction models can be established to achieve accurate dust concentration monitoring and early warning of exceedances. The advancements of technologies will provide scientific support for the assessment of industrial dust hazards and the prevention and control of occupational pneumoconiosis.
6.Application and advancement of digital teaching materials in teaching epidemiology
Xinyu YANG ; Ziqi DONG ; Xiaoqun WANG ; Yuntao LIU ; Siyan ZHAN ; Shengfeng WANG
Chinese Journal of Epidemiology 2024;45(4):597-601
This study aims at examining the application and development of digital teaching materials in the field of epidemiology, encompassing both China and international contexts. The research involved conducting search on websites and literature databases to assess the status of digital teaching materials in epidemiology, nationally and internationally. At present, in China, digital teaching materials used in epidemiology are primarily presented in the form of printed books with added QR codes, providing teaching resources such as videos and exercises. However, issues with the level of interactivity have been identified. In foreign countries, with stronger emphasis placed on personalization, interactivity, and the use of rich media technologies in the digital teaching materials, epidemiologically. Enhanced digitization regarding materials and learning outcomes is achieved through features such as real-time notes, interactive animations, and quizzes. These approaches are considered worth considering for adoption. This study provides valuable insights for the digital transformation of epidemiology education.
7.Interpretation of guidelines for the diagnosis and treatment of diabetes mellitus with hyperlipidemia combined with disease and syndrome
Ziqi ZHAO ; Yuntao MA ; Pai PANG ; Shentao WU ; Qing NI ; Bin WANG
International Journal of Traditional Chinese Medicine 2024;46(4):409-414
Along with the change in lifestyle and diet, diabetes mellitus with hyperlipidemia has been a major risk and death factor for cardiovascular disease with the increasing incidence of diabetes mellitus with hyperlipidemia year by year. In order to promote and make full use of unique characteristics and advantages of TCM, the guidance writing group adopted the pattern of combination with disease and syndrome to make a standardized approach to diagnosis and treatment based on emphasis on diagnosis and treatment. Guidelines for the Diagnosis and Treatment of Diabetes Mellitus with Hyperlipidemia Combined with Disease and Syndrome (hereinafter referred to as " the Guideline") was published in the World Chinese Medicine in August, 2021. Based on the pattern of combination with disease and syndrome, the Guideline highlights the significant characteristics, such as: precise diagnosis and treatment by combined with disease and syndrome, updating criteria, rehabilitation diet therapy and exercise and following the principles which include but not limited to evidence-based medicine. According to the evidence of evidence-based medicine and expert consensus, the Guideline gives recommendations for diagnosis, treatment and rehabilitation of diabetes mellitus with hyperlipidemia. In the article, the main contents and characteristics of the new guideline were interpreted in order to provide concise and practical guidance for clinicians and promote the clinical popularization and application of the Guideline.
8.Correlation between neutrophil-to-lymphocyte ratio and disease activity in Behcet's disease
Changfen YUAN ; Ying XU ; Yunfan GUO ; Yuntao WU ; Xiuyan WANG ; Jingyi ZHANG
Tianjin Medical Journal 2024;52(3):311-314
Objective To explore the correlation between neutrophil-to-lymphocyte ratio(NLR)and Behcet's disease(BD)activity.Methods A total of 103 BD patients were divided into the low activity group(0-4,61 cases)and the high activity group(5-11,42 cases)according to electronic medical record-based disease activity index(EMRAI)score.The white blood cell(WBC),neutrophil(NEU),lymphocyte(LY),platelet(PLT),red blood cell(RBC),hemoglobin(Hb),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),IgG,IgA,IgM,complement C3 and C4 were detected.NLR and platelet-to-lymphocyte ratio(PLR)were calculated.The correlation between NLR,PLR and ESR,CRP,EMRAI were analyzed.Logistic regression was used to analyze the influencing factors of BD disease activity.Receiver operating characteristic(ROC)curve was drawn to evaluate the effectiveness of NLR in judging BD disease activity.Results WBC,NEU,PLT,ESR,CRP,NLR,PLR,complement C3 and C4 in patients were higher in the high activity group than those in the low activity group(P<0.05),and there were no significant differences in other indexes(P>0.05).NLR was positively correlated with ESR,CRP and EMRAI in the whole group,while PLR was positively correlated with ESR,CRP and EMRAI in the whole group(P<0.05).Logistic regression analysis showed that high NLR was a risk factor for BD disease activity(OR=1.511,95%CI:1.080-2.113,P<0.05).ROC curve analysis showed that the area under the curve(AUC)of NLR in evaluating BD disease activity was 0.706(95%CI:0.603-0.809).Conclusion NLR is effective in judging the disease activity of BD patients,and can be used as a biological index to evaluate the disease activity of BD.
9.Development and Verification of a Traditional Chinese Medicine Diagnostic Scale for Type 2 Diabetes Mellitus with Turbid-Toxin Accumulation Syndrome
Pai PANG ; Bin WANG ; Shentao WU ; Yuntao MA ; Cuijuan SHI ; Meizhen ZHANG
Journal of Traditional Chinese Medicine 2024;65(2):159-166
To develop a traditional Chinese medicine (TCM) diagnostic scale for type 2 diabetes mellitus with turbid-toxin accumulation syndrome and to validate the performance of the scale. A candidate pool was established through literature review and expert consultation, and a clinical case information collection form was developed accordingly. Patients with type 2 diabetes mellitus admitted to the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from July 2021 to January 2022 were investigated, and 312 valid clinical case information collection forms were obtained, which were randomly divided into 235 cases in the study group and 77 cases in the validation group. Four statistical methods, namely, differentiation analysis, Cronbach's coefficient, correlation coefficient, and stepwise regression, were used to screen out the candidate items, and Logistic regression analysis and factor analysis were used to assign weights to the items, and the final diagnostic model was determined by the receiver operating characteristic (ROC) curve, and the diagnostic thresholds were calculated for the Yoden index. The final TCM diagnostic scale for type 2 diabetes mellitus was composed of 8 items: turbid dirt coating (with a weight value of 23, the same below), sticky stools (16), fullness in the epigastrium and abdomen (12), dark complexion (12), irritability (11), brown spots on the skin (11), heaviness of head (10), and chest stuffiness (5), and the degree score was 0, 0.5, 1.0, and 1.5 points corresponding to no, mild, moderate and severe symptoms, respectively. The total score was the sum of the degree score multiplied by the weighted value of each item, and when the total score reached 33 points, it is diagnosed as the turbid-toxin accumulation syndrome. The established scale was tested and evaluated in the study group and the validation group, and the results showed that the sensitivity of the study group and the validation group was 89.38% and 89.47%, with the specificity of 95.90% and 89.74%, the Yoden index of 0.85 and 0.79, the positive predictive value of 95.28% and 89.47%, the negative predictive value of 90.70% and 89.74%, the diagnostic advantage ratios of 198.18 and 72.67, and the Kappa values of 0.86 and 0.79, which indicated that the TCM diagnostic scale for turbid-toxin accumulation syndrome of type 2 diabetes mellitus showed good diagnostic ability.
10.Determination and Mechanism Prediction of Potential Active Ingredients in Erdongtang Based on UHPLC-QqQ-MS and Network Pharmacology
Xueyuan WANG ; Baoxin LI ; Shougang SHI ; Zhengjun HUANG ; Yuntao DAI ; Xuemei QIN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):28-34
ObjectiveTo establish an ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry(UHPLC-QqQ-MS) for determination of the active ingredients in Erdongtang, and to predict the targets and pathways of anti-insulin resistance action of this formula. MethodThe analysis was performed on an ACQUITY UPLC BEH C18 column(2.1 mm×100 mm, 1.7 μm) with the mobile phase of 0.1% formic acid aqueous solution(A)-acetonitrile(B) for gradient elution(0-3 min, 90%-87%A; 3-6 min, 87%-86%A; 6-9 min, 86%-83%A; 9-11 min, 83%-75%A; 11-18 min, 75%-70%A; 18-19 min, 70%-52%A; 19-22 min, 52%A; 22-25 min, 52%-5%A; 25-27 min, 5%-90%A; 27-30 min, 90%A). The contents of active ingredients in Erdongtang was detected by electrospray ionization(ESI) and multiple reaction monitoring(MRM) mode under positive and negative ion modes. On this basis, network pharmacology was applied to predict the targets and pathways of Erdongtang exerting anti-insulin resistance effect. ResultThe 20 active ingredients in Erdongtang showed good linear relationships within a certain mass concentration range, and the precision, stability, repeatability and recovery rate were good. The results of determination showed that the ingredients with high content in 15 batches of samples were baicalein(1 259.39-1 635.78 mg·L-1), baicalin(1 078.37-1 411.52 mg·L-1), the ingredients with medium content were mangiferin(148.59-217.04 mg·L-1), timosaponin BⅡ(245.10-604.89 mg·L-1), quercetin-3-O-glucuronide(89.30-423.26 mg·L-1), rutin(46.91-1 553.61 mg·L-1), glycyrrhizic acid(55.97-391.47 mg·L-1), neomangiferin(37.45-127.03 mg·L-1), nuciferine(0.89-63.48 mg·L-1), hyperoside(6.96-136.78 mg·L-1), liquiritin(30.89-122.78 mg·L-1), liquiritigenin(26.64-110.67 mg·L-1), protodioscin(58.57-284.26 mg·L-1), the ingredients with low content were wogonin(7.16-20.74 mg·L-1), pseudoprotodioscin(5.49-22.96 mg·L-1), ginsenoside Rb1(7.31-23.87 mg·L-1), ginsenoside Rg1(10.78-28.33 mg·L-1), ginsenoside Re(7.78-24.76 mg·L-1), ophiopogonin D(2.08-4.29 mg·L-1), methylophiopogonanone A(0.74-1.67 mg·L-1). The results of network pharmacology indicated that the mechanism of anti-insulin resistance exerted by Erdongtang might be related to the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway. ConclusionThe established UHPLC-QqQ-MS has the advantages of simple sample processing, strong exclusivity and high sensitivity, and can simultaneously determine the contents of the main ingredients from seven herbs in Erdongtang, which can lay the foundation for the development of Erdongtang compound preparations. The results of the network pharmacology can provide a reference for the mechanism study of Erdongtang in the treatment of type 2 diabetes mellitus.


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