1.Role of Macrophage Activation and Polarization in Myocardial Fibrosis and Intervention of Traditional Chinese Medicine
Kunpeng YAO ; Huzhi CAI ; Xiang ZHAO ; Ke GONG ; Chuning TIAN ; Yuntao LUO ; Liqi PENG ; Guangyang OU ; Qingyang CHEN ; Xinyu CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):272-282
Myocardial fibrosis (MF) is a common pathological manifestation of various heart diseases. Due to the non-renewable nature of myocardial cells, the occurrence of MF represents irreversible damage to the myocardium. Previous studies have suggested that fibroblast-mediated collagen deposition is the main mechanism of MF. Recent studies have found that there is an immune regulation mechanism in the heart itself, and macrophage activation/polarization plays an important role in MF. With the deepening of traditional Chinese medicine research, scholars have found that traditional Chinese medicine can interfere with MF by regulating the renin-angiotensin-aldosterone system (RAAS) system and the inflammatory process, repairing the extracellular matrix, managing oxidative stress, and maintaining the balance of autophagy. This process is closely related to the activation and M1/M2 polarization of macrophages. Throughout the MF process, macrophage activation is beneficial, but excessive activation will be harmful. In the early stage of MF, appropriate M1 macrophage polarization is conducive to activating immunity and removing harmful substances. In the middle and late stages of MF, appropriate M2 macrophage polarization is conducive to remodeling the damaged myocardium. If macrophage activation is excessive/insufficient, or the balance of M1/M2 macrophage polarization is broken, the effect changes from improvement to destruction. Traditional Chinese medicines that regulate the activation/polarization of macrophages have the effects of replenishing Qi and nourishing Yin, as well as regulating Qi and activating blood, but there are also some heat-clearing, dampness-drying, and detoxification products. Therefore, the occurrence of MF may be caused by Qi and Yin deficiency, damp heat accumulation, and Qi stagnation and blood stasis. By summarizing the biological processes involved in macrophage activation/polarization in MF, this paper expounded on the research progress of traditional Chinese medicine in regulating macrophage activation and M1/M2 polarization from different angles to improve MF, so as to provide a reference for the treatment of MF with traditional Chinese medicine.
2.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.
3.Exploring Effect of Concentration on Quantitative Accuracy of QAMS by Taking Ginsenosides as an Example
Xi CHEN ; Shasha KONG ; Yuntao DAI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):184-191
ObjectiveTo investigate the influence of concentration ratio(CR) between the internal reference and target components on the quantitative accuracy of quantitative analysis of multi-components by single marker(QAMS) by taking ginsenosides as an example. MethodUltra performance liquid chromatography(UPLC) was employed, the contents of nine components in Ginseng Radix et Rhizoma(ginsenosides Rg1, Re, Rf, Rh1, Rb1, Rc, Rb2, Rb3, Rd) were determined by external standard method(ES). Using ginsenoside Rg1 as the internal reference, the contents of the remaining 8 ginsenosides were determined by QAMS, and the quantitative results were compared with those of ES to evaluate the quantitative accuracy of the established QAMS. According to the contents of these 9 ginsenosides, the simulated sample solutions with different CRs of ginsenoside Rg1 to ginsenosides Rf, Rb2, Rd were prepared with the reference substance(CR=100∶1, 10∶1, 5∶1, 2∶1, 1∶1, 0.5∶1, 0.25∶1), in order to validate the effect of the CRs between the internal reference and other components on the quantitative accuracy of the QAMS. ResultThe results of ginsenosides Re, Rf, Rb1, Rc, Rb2 calculated by the two methods were the same with the relative standard deviation(RSD)<3%, however, the results of ginsenosides Rh1, Rb3 and Rd calculated by the two methods were different with RSDs of 7.06%-9.61%. According to the result of the simulated sample solution, the difference between the calculated results of ES and QAMS was large when the CR between the internal reference(ginsenoside Rg1) and other components was 5 or 10 or even higher. ConclusionThe quantitative error of QAMS will increase when the CR between the quantitative component and the internal reference is too large, so it is suggested that when establishing the QAMS, the components with close concentration to the internal reference should be selected for quantification.
4.Clinical Significance of FOXP3 Expression in BRCA1/2-Mutant Breast Cancer
Linxi CHEN ; Li HU ; Jiuan CHEN ; Lu YAO ; Juan ZHANG ; Ye XU ; Yuntao XIE
Cancer Research on Prevention and Treatment 2024;51(7):561-566
Objective To investigate the potential significance of FOXP3 expression in BRCA1/2-mutant breast cancer.Methods A total of 48 BRCA mutation carriers(16 with BRCA1 and 32 with BRCA2)and 78 age-matched non-carriers were included in this study.Immunohistochemistry was used to detect the expression of FOXP3 in breast cancer tissues.The FOXP3 RNA expression in 39 BRCA1,36 BRCA2,and 948 non-carrier breast cancer patients from TCGA-BRCA and the correlation with homologous recombin-ation deficiency scores were evaluated to validate the immunohistochemistry results.Results The FOXP3 positive rate was 43.8%(7/16)in BRCA1 mutation carriers,59.4%(19/32)in BRCA2 mutation carriers,and 9.0%(7/78)in non-carriers.The FOXP3 positive rates in patients with BRCA1/2 mutant breast cancer were significantly higher than those in non-carriers(P=0.002;P<0.001).TCGA-BRCA results showed that the FOXP3 RNA level in BRCA1/2 mutant breast cancer was significantly higher than that in non-carriers(P=0.02,P=0.004).The FOXP3 RNA level was positively correlated with the homologous recombination deficiency score(Spearman R=0.30,P<2.2e-16).Conclusion Patients with BRCA1/2 mutant breast cancers have higher FOXP3expression than non-carriers,and may be more sensitive to immunotherapy.
5.Impact of Resting Heart Rate on All-cause Mortality in Ultra-high Risk Atherosclerotic Cardiovascular Disease Patients
Shihe LIU ; Xu HAN ; Qian LIU ; Hongmin LIU ; Haiyan ZHAO ; Shuohua CHEN ; Shouling WU ; Yuntao WU
Chinese Circulation Journal 2024;39(2):140-147
Objectives:To investigate the impact of resting heart rate on the risk of all-cause mortality in ultra-high risk atherosclerotic cardiovascular disease(ASCVD)patients. Methods:A total of 3 645 patients with ultra-high risk ASCVD(as defined in the 2023 Chinese Lipid Management Guidelines)were screened from the 2006 to 2020 Kailuan Study cohort,and after excluding 602 patients with missing resting heart rate,3 043 patients were included in the final analysis.Patients were divided into<68 beats/min group(n=744),68-74 beats/min group(n=786),75-80 beats/min group(n=760),and≥81 beats/min group(n=753)according to the resting heart rate.Cox proportional regression model was used to estimate the hazard ratios(HRs)and 95%CI for all-cause mortality associated with the different resting heart rate groups and every 10 beats/min increase of resting heart rate.The dose-effect relationship of resting heart rate level and all-cause mortality was assessed by a restricted cubic spline regression model.The Kaplan-Meier method was applied to calculate the cumulative all-cause mortality in different groups,and the differences were compared using log-rank test. Results:The median follow-up time was 5.81(3.46,9.64)years,there were 772(25.37%)all-cause deaths during follow up.After adjusting major confounding factors,the results showed that compared with<68 beats/min group,the risk of all-cause mortality in 75-80 beats/min group and≥81 beats/min group increased by 24%(HR=1.24,95%CI:1.01-1.52,P=0.047)and 47%(HR=1.47,95%CI:1.20-1.81,P<0.001),respectively;the risk of all-cause mortality in 68-74 beats/min group was similar(HR=1.06,95%CI:0.86-1.31,P=0.625).In addition,an increase of 10 beats/min in resting heart rate was associated with a 13%increase in the risk of all-cause mortality(HR=1.13,95%CI:1.07-1.19,P<0.001).In stratified analyses,it was found that for every 10 beats/min increase in resting heart rate,women faced a higher risk of all-cause mortality than men,and patients<65 years old faced a higher risk of all-cause mortality than patients≥65 years old.The restricted cubic spline analysis also showed that resting heart rate was linearly associated with the risk of all-cause mortality(Poverall<0.001,Pnon-linear=0.933),and the risk increased significantly with resting heart rate>70 beats/min. Conclusions:Increased resting heart rate is linearly associated with increased risk of all-cause mortality in patients with ultra-high risk ASCVD.The appropriate intervention cut-off point of resting heart rate for ultra-high risk ASCVD patients may be>75 beats/min.
6.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.
7.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.
8.Simultaneous multi-slice technique applicated in diffusion tensor imaging for evaluating brain glioma
Yakun HE ; Xiaoyu CHEN ; Siqi YI ; Yuntao HU ; Mei LAN ; Jia CHEN ; Jing REN ; Peng ZHOU ; Heping DENG
Chinese Journal of Interventional Imaging and Therapy 2024;21(8):495-498
Objective To explore the application value of simultaneous multi-slice(SMS)technique in diffusion tensor imaging(DTI)for evaluating brain glioma.Methods Thirty-four brain glioma patients were prospectively enrolled,and brain conventional DTI and SMS-DTI were acquired.The subjective scores of image quality,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were compared between SMS-DTI and conventional DTI,so were the numbers of whole brain fiber bundles,tumor relative fractional anisotropy(rFA)and relative mean diffusivity(rMD)obtained based on SMS-DTI and conventional DTI.Results Among 34 patients,there were 23 cases of high-grade glioma and 11 cases of low-grade glioma.No significant difference of subjective scores of image quality,tumor edge clarity nor magnetic susceptibility artifacts was found between SMS-DTI and conventional DTI(all P>0.05).SNR and CNR on SMS-DTI were both lower than those on conventional DTI(both P<0.05).No significant difference of the numbers of whole brain fiber bundles,rFA nor rMD of gliomas with different pathological grades was detected based on SMS-DTI compared with those on conventional DTI(all P>0.05).Conclusion SMS applicated in DTI for evaluating brain gliomas was able to shorten acquisition time under the condition of ensuring image quality and quantitative analysis accuracy.
9.Association of Trajectories of Atherogenic Index of Plasma With Atherosclerotic Cardiovascular Disease
Shihe LIU ; Qian LIU ; Xu HAN ; Hongmin LIU ; Haiyan ZHAO ; Shuohua CHEN ; Shouling WU ; Yuntao WU
Chinese Circulation Journal 2024;39(7):676-681
Objectives:To investigate the association of trajectories of atherogenic index of plasma(AIP)with the risk of atherosclerotic cardiovascular disease(ASCVD). Methods:A total of 51 831 employees and retirees who participated in Kailuan Group health examination for three consecutive times from 2006 to 2010 were included in this study.AIP was calculated using the log(triglycerides[TG]/high-density lipoprotein-cholesterol[HDL-C])formula.AIP trajectory models were fitted by the SAS Proc Traj program,and according to AIP trajectory,the subjects were divided into low stability group(n=11 114),low to moderate stability group(n=21 647),medium to high stability group(n=13 659),and high stability group(n=5 411).Kaplan-Meier method was used to calculate the cumulative incidence of ASCVD in different groups and compared by log-rank test.Cox proportional risk regression model was used to analyze the effects of different AIP trajectories on ASCVD risk. Results:Finally,51 831 patients were included in the analysis.During a mean follow-up of(10.19±2.22)years,5 142(9.92%)subjects developed ASCVD,4 013(7.74%)subjects died.Cox regression analysis after adjusting for confounding factors showed:compared with the low stability group,the risk of ASCVD increased by 13%(HR=1.13,95%CI:1.04-1.23,P=0.003)and 20%(HR=1.20,95%CI:1.10-1.31,P<0.001)and 41%(HR=1.41,95%CI:1.27-1.57,P<0.001)in the low to moderate stability group,moderate to high stability group and high stability group,respectively,and the risk increased gradually(Ptrend<0.001).Stratified analysis showed that the risk of ASCVD in people aged<65 years and low-density lipoprotein cholesterol(LDL-C)<3.4 mmol/L with long-term high levels of AIP was higher than that in people aged≥65 years and LDL-C≥3.4 mmol/L(both Pinteraction<0.01). Conclusions:In Kailuan Study cohort,those with long-term high levels of AIP had a higher risk of ASCVD,and the risk gradually increased.In addition,we found that the risk of ASCVD in people with long-term high levels of AIP was higher in<65 years old than in≥65 years old,and the risk of ASCVD in people with LDL-C<3.4 mmol/L was higher than that in people with LDL-C≥3.4 mmol/L.
10.Curative effect and prognostic assessment of PKP in treating osteoporosis-caused spinal vertebral compression fractures by using imaging parameters of pelvic sagittal X-ray
Shunli ZHANG ; Rong CHEN ; Yuntao GU ; Chunzhao XU ; Chuizhi HUANG
China Medical Equipment 2024;21(6):34-39
Objective:To explore the curative effect and prognostic assessment value of percutaneous kyphoplasty(PKP)in treating osteoporosis-caused spinal vertebral compression fractures by using imaging parameters of pelvic sagittal X-ray.Methods:A total of 198 patients with osteoporosis-caused spinal vertebral compression fractures who received treatment from January 2022 to January 2023 were selected,and they were divided into effective group(171 cases)and ineffective group(27 cases)according to the treatment effect.All patients underwent PKP treatment,and the parameters of preoperative measurements included sagittal vertical axis(SVA)of cervical vertebra 7(C7),the thoracic vertebra 1 pelvic angle(T1PA),thoracic kyphosis(TK),lumbar lordosis(LL)and sacral slope(SS).The clinically curative effect and prognosis between two groups were compared.Results:After PKP treatment,49 cases of 198 patients were cured,and 69 cases appeared significant effect,and 53 cases were effective,and 27 cases were ineffective.The SVA,LL and SS levels of effective group were significantly lower than those of ineffective group,and the differences of them were statistically significant(t=6.485,3.250,2.325,P<0.05),and the T1PA and TK of the effective group were significantly higher than those of the ineffective group(t=2.387,3.245,P<0.05),respectively.In 198 patients,39 cases occurred postoperative complications(20 cases occurred bone cement leakage,and 15 cases occurred recurrent adjacent vertebral fracture,and 2 cases occurred pulmonary embolism,and 2 cases occurred others),and 159 cases did not occurred complications.The SVA,LL and SS levels in patients without complications were significantly lower than those in patients with complications(t=10.304,5.669,0.844,P<0.05),and the T1PA and TK of patients without complications were significantly higher than those of patients with complications,and the differences were significant(t=3.494,5.550,P<0.05),respectively.The results of receiver operating characteristic(ROC)curve analysis showed that SVA,T1PA,TK,LL and SS had a certain value in assessing the curative effect and prognosis of PKP in treating osteoporosis-caused spinal vertebral compression fractures.Conclusion:Preoperative detection of imaging parameters of pelvic sagittal X-ray can assess the curative effect and prognosis of osteoporosis-caused spinal vertebral compression fractures,which can provide a certain reference for clinical treatment.

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