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.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.
3.Changes of fasting plasma glucose level before and after menopause: Research based on Kailuan health checkup cohort
Yaya ZHANG ; Qiaoyun DAI ; Shouling WU ; Shuohua CHEN ; Xueying YANG ; Yuntao WU ; Xu MA ; Jianmei WANG
Chinese Journal of Endocrinology and Metabolism 2024;40(1):22-29
Objective:To analyze the changes of fasting plasma glucose(FPG)level before and after menopause.Methods:Kailuan health checkup cohort was used to extract data of women aged≥18 years who participated in the first physical examination of Kailuan physical examination cohort and had menopausal age at the end of the seventh physical examination. A total of 3 749 women with 22 057 physical examination records were included in the analysis. Natural logarithmic transformation was applied to FPG, and a segmented linear mixed-effects model was used to analyze the changes in ln-transformed FPG before and after menopause. Additionally, an interaction analysis was performed to assess the multiplicative effect of baseline age and baseline body mass index(BMI)on ln-transformed FPG concerning pre- and post-menopausal periods.Results:The average age of the first physical examination for women in this study was (45.63±4.52)years, the median menopausal age was 51(50~53)years, and the median number of physical examinations was 6(5~7)times. The results of the piecewise linear mixed effect model showed that lnFPG increased from 1 year before menopause, with an average annual increase of 0.021 mmol/L, and continued to increase from menopause to 5 years after menopause, with an average annual increase of 0.007 mmol/L. LnFPG tended to be stable after 5 years of menopause. Baseline age could affect the changes of lnFPG before and after menopause, and there was a negative multiplicative interaction between baseline age ≥45 years and the time period from 6 years to 1 year before menopause( P=0.032). Women with baseline age ≥45 years had a higher average annual increase in lnFPG from 1 year before menopause to 5 years after menopause than women with baseline age <45 years( P<0.05). On lnFPG, there was a positive multiplicative interaction between baseline BMI and time segments around menopause. Compared to women with BMI <24.0 kg/m 2, obese women displayed more annual increase in lnFPG from 6 years to 1 year before menopause as well as from menopause to 5 years after menopause( P<0.05). Conclusions:Menopause has an adverse impact on FPG, with the most significant changes occurring within the period of one year before menopause and up to five years after menopause. Age and BMI significantly influence the changes in FPG before and after menopause.
4.Comparison of occupational exposure limits in China with threshold limit values announced by American Conference of Governmental Industrial Hygienists
Qiangzhi GUO ; Yazhen WANG ; Yuntao MU ; Jinling LIU ; Xue JIANG ; Di LIU ; Chen SHEN ; Lingling LI ; Yi LIU
Journal of Environmental and Occupational Medicine 2024;41(11):1290-1296
Background The threshold limit values (TLVs) established and regularly updated by the American Conference of Governmental Industrial Hygienists (ACGIH) are widely adopted and referenced globally, serving as a crucial reference for China's occupational exposure limits (OELs). It is necessary to track it regularly and compare it with China's OELs. Objective To compare the OELs stipulated in Occupational exposure limits for hazardous agents in the workplace—Part 1: Chemical hazardous agents (GBZ 2.1—2019) and the ACGIH TLVs (2024) and to provide references for subsequent formulation and revision of OELs in China. Methods The OELs specified in GBZ 2.1—2019 and the TLVs issued by ACGIH were used to establish a database using Microsoft Excel 2019 software. Cross verification was conducted through matching Chemical Abstracts Service Registry Numbers (CAS Rn) and both Chinese and English names to ensure accuracy. Then, comparisons and analyses were carried out based on the type of limit values, which were matched as follows: permissible concentration-time weighted average (PC-TWA) with threshold limit value-time weighted average (TLV-TWA), permissible concentration-short term exposure limit (PC-STEL) with threshold limit value-short term exposure limit (TLV-STEL), and maximum allowable concentration (MAC) with threshold limit value-ceiling (TLV-C). Comparisons included types, quantities, and sizes of limits. Results The GBZ 2.1—2019 OELs and the ACGIH TLVs (2024) were generally consistent in terms of types and definitions, but there were differences in the number and size of the limits. In terms of the number of limits, GBZ 2.1—2019 specified 365 OELs for 358 chemical hazardous agents, while ACGIH TLVs (2024) included 316 corresponding limits. Among these, 148 (46.9%) limits were consistent, 38 (12.0%) were basically consistent, and 130 (41.1%) were inconsistent. In terms of the size of the limits, out of the 130 inconsistent limits, 51 OELs were lower than the corresponding TLVs, 67 OELs were higher than the corresponding TLVs, and 12 were under different limit types. For some chemical hazardous agents, their OELs were significantly lower or higher than their TLVs. Conclusion Some of the OELs for chemical hazardous agents specified in GBZ 2.1—2019 are significantly lower or higher than the TLVs. For these chemical hazardous factors, it is recommended to prioritize their inclusion in research projects and to complete the revisions as soon as possible based on the latest scientific evidence.
5.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.
6.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.
7.Relationship between plasma mtDNA,tissue MIP1α,MCP-1 and recovery of hip function in patients with hip fractures
Zhonglei SU ; Yuntao GUO ; Jinfeng LIU ; Wenjuan WANG ; Yuantao DUAN ; Xin'an GUO
Journal of Clinical Surgery 2024;32(11):1200-1204
Objective To analyze the relationship between plasma mitochondrial DNA(mtDNA),macrophage inflammatory protein-1α(MIP1α)and monocyte chemotactic protein 1(MCP-1)in vastus lateralis tissues and postoperative muscle atrophy,recovery of hip function in patients with hip fractures.Methods A total of 86 patients with hip fractures and 43 patients with coxitis in Jinan Eighth People's Hospital were enrolled as hip fracture group and coxitis group between October 2020 and October 2022,respectively.The lateral muscle tissues were collected as samples during surgery.The level of plasma mtDNA was detected by real-time fluorescence quantitative polymerase chain reaction.Before surgery,levels of serum interleukin-6(IL-6)and tumor necrosis factor α(TNF-α)were detected by enzyme-linked immunosorbent assay.Before surgery,cross-sectional areas of types Ⅰ and Ⅱ vastus lateralis fibers were detected by immunofluorescence method.Before surgery,expression levels of MIP1α and MCP-1 proteins in lateral muscle tissues were detected by Western blot.All patients with hip fracture were effectively followed up for 6 months after surgery.At 3 and 6 months after surgery,total lean mass(TLM)and unaffected limb lean mass(ULLM)were detected by DXA.Results The level of plasma mtDNA in hip fracture group was higher than that in coxitis group before surgery[(4.12±0.53)vs(2.37±0.36),P<0.05],levels of serum IL-6 and TNF-α were higher than those in coxitis group[(34.68±6.14)pg/ml,(21.54±4.12)pg/ml vs(12.74±3.06)pg/ml,(10.81±2.71)pg/ml,P<0.05],cross-sectional areas of types Ⅰ and Ⅱ vastus lateralis fibers were smaller than those in coxitis group[(4321.45±441.36)μm2,(2384.38±247.11)μm2 vs(5417.63±553.27)μm2,(3569.24±368.22)μm2,P<0.05],and expression levels of MIP1α and MCP-1 proteins were higher than those in coxitis group[(2.34±0.25),(2.47±0.28)vs(1.18±0.15),(1.95±0.23),P<0.05].In patients with hip fracture after 6 months of follow-up,there were 53 cases with good prognosis and 33 cases with poor prognosis.The level of plasma mtDNA in poor prognosis group was higher than that in good prognosis group before surgery[(4.53±0.52)vs(3.87±0.44),P<0.05],levels of serum IL-6 and TNF-α were higher than those in good prognosis group[(35.97±5.32)pg/ml,(20.74±4.27)pg/ml vs(33.51±5.16)pg/ml,(22.83±4.33)pg/ml,P<0.05],cross-sectional areas of types Ⅰ and Ⅱ vastus lateralis fibers were smaller than those in good prognosis group[(4174.26±434.60)μm2,(2309.56±246.18)μm2 vs(4394.42±450.12)μm2,(2430.97±250.72)μm2,P<0.05],and expression levels of MIP1α and MCP-1 proteins were higher than those in good prognosis group[(2.47±0.28),(1.95±0.23)vs(2.26±0.24),(1.82±0.21),P<0.05].TLM and ULLM at 6 months after surgery were lower than those at 3 months after surgery in good prognosis group and poor prognosis group(P<0.05).At 3 and 6 months after surgery,there was no significant different in TLM or ULLM between good prognosis group and poor prognosis group(P>0.05).Conclusion Traumatic stress injury will increase level of plasma mtDNA in patients with hip fracture,which will induce the increase of systemic inflammatory indexes(serum IL-6,TNF-α)and inflammatory factors(MCP-1,MIP1α)levels,aggravate muscle atrophy and cause postoperative decline of hip function.
8.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.
9.The impact of non-HDL-C level on major adverse cardiovascular and cerebrovascular events and all-cause mortality after revascularization
Xuewen WANG ; Shihe LIU ; Xu HAN ; Qian LIU ; Shuohua CHEN ; Xiujuan ZHAO ; Lu LI ; Shouling WU ; Yuntao WU
Chinese Journal of Cardiology 2024;52(6):667-675
Objective:To investigate the impact of non-high-density lipoprotein cholesterol (non-HDL-C) level on major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause mortality in the Kailuan Study cohort undergoing revascularization.Methods:This is a prospective cohort study, with participants from the Kailuan Study cohort who participated in physical examinations from 2006 to 2020 and received revascularization therapy for the first time. According to the level of non-HDL-C, the study subjects were divided into 3 groups:<2.6 mmol/L group, 2.6-<3.4 mmol/L group, and≥3.4 mmol/L group. Annual follow-up was performed, and the endpoint events were MACCE and all-cause mortality. Cox proportional regression model was implemented to estimate the impact on MACCE and all-cause mortality associated with the different non-HDL-C groups. The partial distributed risk model was used to analyze the impact of different non-HDL-C levels on MACCE event subtypes, and death was regarded as a competitive event. The restricted cubic spline regression model was used to explore the dose-response relationship between non-HDL-C level and all-cause mortality, MACCE and its subtypes.Results:A total of 2 252 subjects were enrolled in the study, including 2 019 males (89.65%), aged (62.8±8.3) years, the follow-up time was 5.72 (3.18, 8.46) years. There were 384 cases(17.05%) of MACCE and 157 cases(6.97%) of all-cause mortality. Compared with patients with non-HDL-C≥3.4 mmol/L, patients with non-HDL-C<2.6 mmol/L were associated with a 38% reduced risk of MACCE after revascularization [ HR=0.62(95% CI: 0.48-0.80)]. Every 1 mmol/L decrease in non-HDL-C was associated with a 20% reduction in the risk of MACCE [ HR=0.80(95% CI: 0.73-0.88)]. The results of restricted cubic spline also showed that non-HDL-C levels after revascularization therapy were positively correlated with MACCE events (overall association P<0.001, non-linear association P=0.808). For all-cause mortality, compared to the non-HDL-C≥3.4 mmol/L group, the HR for all-cause mortality after revascularization in non-HDL-C<2.6 mmol/L group was 0.67(95% CI: 0.46-1.01). Every 1 mmol/L decrease in non-HDL-C was associated with a 15% reduction in the risk of all-cause mortality [ HR=0.85(95% CI: 0.73-0.99)]. The restricted cubic spline results showed a linear association between non-HDL-C levels after revascularization therapy and the risk of all-cause mortality (overall association P=0.039, non-linear association P=0.174). Conclusion:The decrease in non-HDL-C levels after revascularization were significantly associated with a reduced risk of MACCE and all-cause mortality.
10.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.


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