1.Visual Analysis of Literature Research on Compatibility of Bitter and Pungent Medicinals in Traditional Chinese Medicine
Wei SONG ; Lele YANG ; Zhongyi ZHANG ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):19-28
ObjectiveTo analyze the research situation, hotspots, and trend of the compatibility of bitter and pungent medicinals in traditional Chinese medicine by knowledge mapping and provide reference for the inheritance and clinical application of this theory. MethodsThe literature on the compatibility of bitter and pungent medicinals was retrieved from 6 databases, including China National Knowledge Infrastructure (CNKI), VIP, Wanfang Data, SinoMed, Web of Science, and PubMed. The literature was searched with the keywords of bitter medicinals, pungent medicinals, compatibility, Banxia Xiexin decoction, Zhuyu pills, and Zuojin pills. The search time ranged from January 1, 1984 to August 10, 2024. NoteExpress 3.7 was used for literature screening, and CiteSpace 6.1.R2 was used to visualize the number of publications, authors, institutional cooperation network, and the co-occurrence, clustering, time line, and burst of keywords. ResultsA total of 628 Chinese articles and 151 English articles related to the compatibility of bitter and pungent medicinals were included, and the annual number of publications rose with fluctuations. WEI Wei was the core author of Chinses articles and SHEN Tao and ZHAO Yanling were the core authors of English articles. China Academy of Chinese Medical Sciences formed a close cooperative network with many research institutions at home and abroad. The high-frequency keywords included pungent dispersing and bitter descending, Coptidis Rhizoma, Euodiae Fructus, Banxia Xiexin decoction, Zuojin pills, compatibility, spleen and stomach diseases, and gut microbiota, which mainly involved common prescriptions, diseases responding specifically to traditional Chinese medicine, mechanism research and so on. The keyword bursts concentrated in famous doctors' experience, network Meta-analysis, inflammatory bowel disease, diabetes mellitus, intestinal microbiota, etc. The compatibility of bitter medicinals and pungent medicinals was widely used in clinical practice. Based on pungent dispersing and bitter descending, the middle energizer was regulated for treating spleen and stomach diseases and inflammatory bowel disease. Bitter and pungent medicinals descending the turbid were used to treat diabetes mellitus and hyperlipidemia by lowering blood glucose and lipid levels. The mild bitter and slightly pungent medicinals were used as supplements to treat depression and COVID-19 by regulating Qi movement. ConclusionIn the past 40 years, the number of publications on the compatibility of bitter and pungent medicinals has been increasing, and the research team has begun to take form. Clinically, the compatibility of bitter and pungent medicinals is the main treatment for spleen and stomach diseases and glycolipid metabolic diseases. At present, the modern scientific essence of the compatibility of bitter and pungent medicinals is mainly explained based on famous doctors' experience inheritance, network meta-analysis, and intestinal flora.
2.Clinical Efficacy of Zhuyuwan in Treatment of Hyperlipidemia with Syndrome of Phlegm Turbidity and Obstruction
Lele YANG ; Danmei LUO ; Jiao CHEN ; Xiaobo ZHANG ; Wei SONG ; Wenyu ZHU ; Xin ZHOU ; Xueping LI ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):29-37
ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study, hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine (TCM) from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally, 162 valid cases were included, encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets, and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery, blood lipid levels, TCM syndrome distribution, efficacy in terms of TCM syndrome, and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery, the total response rate in the observation group was 86.36% (76/88) and that in the control group was 86.49% (64/74), with no statistically significant difference between the two groups. After treatment, both groups showed declines in levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) (P<0.05) and elevations in the level of high-density lipoprotein cholesterol (HDL-C) (P<0.05). Moreover, the observation group outperformed the control group in recovering the levels of TG, LDL-C, and HDL-C (P<0.05, P<0.01). In terms of TCM syndrome, hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% (55/63), which was higher than that (63.46%, 33/52) in the control group (χ2=9.102, P<0.01). After treatment, the scores of total TCM symptoms, primary symptoms, and secondary symptoms decreased in both groups (P<0.05), and the observation group had lower scores than the control group (P<0.01). The observation group was superior to the control group in alleviating obesity, chest tightness, and low food intake (P<0.05). In terms of safety, the level of aminotransferase was slightly elevated in the control group, and no obvious adverse reaction was observed in the observation group, with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.
3.Zhuyuwan in Treatment of Hyperlipidemia Complicated with Carotid Atherosclerosis: A Randomized Controlled Trial
Wei SONG ; Lele YANG ; Zhongyi ZHANG ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):38-45
ObjectiveTo observe the efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia (syndrome of phlegm turbidity and obstruction) complicated with carotid atherosclerosis. MethodsA total of 120 patients with hyperlipidemia (syndrome of phlegm turbidity and obstruction) complicated with carotid atherosclerosis were randomly allocated into a treatment group and a control group, with 60 patients in each group. The control group orally took rosuvastatin calcium tablets, 10 mg each time, once a day. The treatment group took Zhuyuwan granules, 1 dose a day in 3 times. Both groups received diet and exercise guidance and were treated for 24 consecutive weeks. The traditional Chinese medicine (TCM) symptom scores were recorded before and after treatment. The levels of blood lipids [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)], carotid color ultrasound [carotid intima-media thickness (IMT), plaque number, maximum plaque area, and maximum plaque thickness], vascular intimal repair-related factors [nitric oxide (NO), endothelin-1 (ET-1), soluble intercellular adhesion molecule 1 (sICAM-1), and thromboxane B2 (TXB2)], and oxidative stress-related indicators [superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)] were measured before and after treatment. The occurrence of adverse reactions was observed during treatment, and the clinical efficacy of the two groups was compared after treatment. ResultsThe trial was completed and 112 patients (57 in the treatment group and 55 in the control group) were included in the statistical analysis, and the general information of the two groups was comparable. The total response rate in the treatment group was 87.72% (50/57), which was higher than that (74.55%, 41/55) in the control group (χ2=4.823, P<0.05). After treatment, the scores of main TCM symptoms such as body obesity, chest tightness, and limb numbness, the scores of secondary symptoms such as palpitation, insomnia, tastelessness in the mouth, reduced appetite, tongue and pulse manifestation scores, and the total TCM symptom score decreased in both groups (P<0.05, P<0.01). Moreover, the treatment group had lower scores of main symptoms such as body obesity, head heaviness, chest tightness, nausea, salivation, and limb numbness, scores of secondary symptoms such as tastelessness in the mouth and reduced appetite, and total TCM symptom score than the control group (P<0.05, P<0.01). After treatment, both groups showed declines in TC, TG, LDL-C, IMT, plaque number, maximum plaque area, maximum plaque thickness, ET-1, sICAM-1, and TXB2 (P<0.05, P<0.01) and elevations in levels of HDL-C, NO, and SOD (P<0.05, P<0.01). The treatment group had lower TC, TG, LDL-C, IMT, plaque number, maximum plaque area, maximum plaque thickness, ET-1, sICAM-1, and TXB2 (P<0.01) and higher levels of HDL-C, NO, SOD, and GSH-Px (P<0.05, P<0.01) than the control group. During treatment, adverse reactions occurred in 3 cases (5.26%, 1 case of dizziness, 1 case of acid reflux, and 1 case of constipation) in the treatment group and 4 cases (7.27%, 2 cases of upper respiratory tract infection, 1 case of abdominal pain, and 1 case of low back pain) in the control group. ConclusionZhuyuwan can effectively reduce blood lipid levels, inhibit the formation of carotid atherosclerotic plaque, and alleviate the syndrome of phlegm turbidity and obstruction by promoting vascular intima repair and improving the antioxidant function.
4.Visual Analysis of Literature Research on Compatibility of Bitter and Pungent Medicinals in Traditional Chinese Medicine
Wei SONG ; Lele YANG ; Zhongyi ZHANG ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):19-28
ObjectiveTo analyze the research situation, hotspots, and trend of the compatibility of bitter and pungent medicinals in traditional Chinese medicine by knowledge mapping and provide reference for the inheritance and clinical application of this theory. MethodsThe literature on the compatibility of bitter and pungent medicinals was retrieved from 6 databases, including China National Knowledge Infrastructure (CNKI), VIP, Wanfang Data, SinoMed, Web of Science, and PubMed. The literature was searched with the keywords of bitter medicinals, pungent medicinals, compatibility, Banxia Xiexin decoction, Zhuyu pills, and Zuojin pills. The search time ranged from January 1, 1984 to August 10, 2024. NoteExpress 3.7 was used for literature screening, and CiteSpace 6.1.R2 was used to visualize the number of publications, authors, institutional cooperation network, and the co-occurrence, clustering, time line, and burst of keywords. ResultsA total of 628 Chinese articles and 151 English articles related to the compatibility of bitter and pungent medicinals were included, and the annual number of publications rose with fluctuations. WEI Wei was the core author of Chinses articles and SHEN Tao and ZHAO Yanling were the core authors of English articles. China Academy of Chinese Medical Sciences formed a close cooperative network with many research institutions at home and abroad. The high-frequency keywords included pungent dispersing and bitter descending, Coptidis Rhizoma, Euodiae Fructus, Banxia Xiexin decoction, Zuojin pills, compatibility, spleen and stomach diseases, and gut microbiota, which mainly involved common prescriptions, diseases responding specifically to traditional Chinese medicine, mechanism research and so on. The keyword bursts concentrated in famous doctors' experience, network Meta-analysis, inflammatory bowel disease, diabetes mellitus, intestinal microbiota, etc. The compatibility of bitter medicinals and pungent medicinals was widely used in clinical practice. Based on pungent dispersing and bitter descending, the middle energizer was regulated for treating spleen and stomach diseases and inflammatory bowel disease. Bitter and pungent medicinals descending the turbid were used to treat diabetes mellitus and hyperlipidemia by lowering blood glucose and lipid levels. The mild bitter and slightly pungent medicinals were used as supplements to treat depression and COVID-19 by regulating Qi movement. ConclusionIn the past 40 years, the number of publications on the compatibility of bitter and pungent medicinals has been increasing, and the research team has begun to take form. Clinically, the compatibility of bitter and pungent medicinals is the main treatment for spleen and stomach diseases and glycolipid metabolic diseases. At present, the modern scientific essence of the compatibility of bitter and pungent medicinals is mainly explained based on famous doctors' experience inheritance, network meta-analysis, and intestinal flora.
5.Clinical Efficacy of Zhuyuwan in Treatment of Hyperlipidemia with Syndrome of Phlegm Turbidity and Obstruction
Lele YANG ; Danmei LUO ; Jiao CHEN ; Xiaobo ZHANG ; Wei SONG ; Wenyu ZHU ; Xin ZHOU ; Xueping LI ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):29-37
ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study, hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine (TCM) from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally, 162 valid cases were included, encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets, and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery, blood lipid levels, TCM syndrome distribution, efficacy in terms of TCM syndrome, and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery, the total response rate in the observation group was 86.36% (76/88) and that in the control group was 86.49% (64/74), with no statistically significant difference between the two groups. After treatment, both groups showed declines in levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) (P<0.05) and elevations in the level of high-density lipoprotein cholesterol (HDL-C) (P<0.05). Moreover, the observation group outperformed the control group in recovering the levels of TG, LDL-C, and HDL-C (P<0.05, P<0.01). In terms of TCM syndrome, hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% (55/63), which was higher than that (63.46%, 33/52) in the control group (χ2=9.102, P<0.01). After treatment, the scores of total TCM symptoms, primary symptoms, and secondary symptoms decreased in both groups (P<0.05), and the observation group had lower scores than the control group (P<0.01). The observation group was superior to the control group in alleviating obesity, chest tightness, and low food intake (P<0.05). In terms of safety, the level of aminotransferase was slightly elevated in the control group, and no obvious adverse reaction was observed in the observation group, with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.
6.Zhuyuwan in Treatment of Hyperlipidemia Complicated with Carotid Atherosclerosis: A Randomized Controlled Trial
Wei SONG ; Lele YANG ; Zhongyi ZHANG ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):38-45
ObjectiveTo observe the efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia (syndrome of phlegm turbidity and obstruction) complicated with carotid atherosclerosis. MethodsA total of 120 patients with hyperlipidemia (syndrome of phlegm turbidity and obstruction) complicated with carotid atherosclerosis were randomly allocated into a treatment group and a control group, with 60 patients in each group. The control group orally took rosuvastatin calcium tablets, 10 mg each time, once a day. The treatment group took Zhuyuwan granules, 1 dose a day in 3 times. Both groups received diet and exercise guidance and were treated for 24 consecutive weeks. The traditional Chinese medicine (TCM) symptom scores were recorded before and after treatment. The levels of blood lipids [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)], carotid color ultrasound [carotid intima-media thickness (IMT), plaque number, maximum plaque area, and maximum plaque thickness], vascular intimal repair-related factors [nitric oxide (NO), endothelin-1 (ET-1), soluble intercellular adhesion molecule 1 (sICAM-1), and thromboxane B2 (TXB2)], and oxidative stress-related indicators [superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)] were measured before and after treatment. The occurrence of adverse reactions was observed during treatment, and the clinical efficacy of the two groups was compared after treatment. ResultsThe trial was completed and 112 patients (57 in the treatment group and 55 in the control group) were included in the statistical analysis, and the general information of the two groups was comparable. The total response rate in the treatment group was 87.72% (50/57), which was higher than that (74.55%, 41/55) in the control group (χ2=4.823, P<0.05). After treatment, the scores of main TCM symptoms such as body obesity, chest tightness, and limb numbness, the scores of secondary symptoms such as palpitation, insomnia, tastelessness in the mouth, reduced appetite, tongue and pulse manifestation scores, and the total TCM symptom score decreased in both groups (P<0.05, P<0.01). Moreover, the treatment group had lower scores of main symptoms such as body obesity, head heaviness, chest tightness, nausea, salivation, and limb numbness, scores of secondary symptoms such as tastelessness in the mouth and reduced appetite, and total TCM symptom score than the control group (P<0.05, P<0.01). After treatment, both groups showed declines in TC, TG, LDL-C, IMT, plaque number, maximum plaque area, maximum plaque thickness, ET-1, sICAM-1, and TXB2 (P<0.05, P<0.01) and elevations in levels of HDL-C, NO, and SOD (P<0.05, P<0.01). The treatment group had lower TC, TG, LDL-C, IMT, plaque number, maximum plaque area, maximum plaque thickness, ET-1, sICAM-1, and TXB2 (P<0.01) and higher levels of HDL-C, NO, SOD, and GSH-Px (P<0.05, P<0.01) than the control group. During treatment, adverse reactions occurred in 3 cases (5.26%, 1 case of dizziness, 1 case of acid reflux, and 1 case of constipation) in the treatment group and 4 cases (7.27%, 2 cases of upper respiratory tract infection, 1 case of abdominal pain, and 1 case of low back pain) in the control group. ConclusionZhuyuwan can effectively reduce blood lipid levels, inhibit the formation of carotid atherosclerotic plaque, and alleviate the syndrome of phlegm turbidity and obstruction by promoting vascular intima repair and improving the antioxidant function.
7.Differentiation and Treatment of Lipid Turbidity Disease Based on Theory of "Spleen Ascending and Stomach Descending"
Yun HUANG ; Wenyu ZHU ; Wei SONG ; Xiaobo ZHANG ; Xin ZHOU ; Lele YANG ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):244-252
Lipid turbidity disease is a metabolic disease featuring lipid metabolism disorders caused by many factors such as social environment, diet, and lifestyle, which is closely related to many diseases in modern medicine, such as hyperlipidemia, obesity, fatty liver, atherosclerosis, metabolic syndrome, and cardiovascular and cerebrovascular diseases, with a wide range of influence and far-reaching harm. According to the Huangdi Neijing, lipid turbidity disease reflects the pathological change of the body's physiologic grease. Grease is the thick part of body fluids, which has the function of nourishing, and it is the initial state and source of important substances in the human body such as brain, marrow, essence, and blood. Once the grease of the human body is abnormal, it can lead to lipid turbidity disease. The Huangdi Neijing also points out the physiological relationship between the transportation and transformation of body fluids and the rise and fall of the spleen and stomach, which can deduce the pathological relationship between the occurrence of lipid turbidity disease and the abnormal rise and fall of the spleen and stomach functions. Lipid turbidity disease is caused by overconsumption of fatty and sweet foods or insufficient spleen and stomach endowments, leading to disorders of the function of promoting clear and reducing turbidity in the spleen and stomach. This leads to the transformation of thick grease in body fluids into lipid turbidity, which accumulates in the body's meridians, blood vessels, skin pores, and organs, forming various forms of metabolic diseases. The research team believed that the pathological basis of lipid turbidity disease was the abnormal rise and fall of the spleen and stomach and the obstruction of the transfer of grease. According to the different locations where lipid turbidity stays, it was divided into four common pathogenesis types: ''inability to distinguish between the clear and turbid, turbid stagnation in the Ying blood'', ''spleen not rising clear, turbid accumulation in the vessels'', ''spleen dysfunction, lipid retention in the pores'', ''spleen failure to transportation and transformation, and grease accumulation in the liver''. According to the pathogenesis, it could be divided into four common syndromes, namely, turbid stagnation in the Ying blood, turbid accumulation in the vessels, lipid retention in the pores, and grease accumulation in the liver, and the corresponding prescriptions were given for syndrome differentiation and treatment, so as to guide clinical differentiation and treatment of the lipid turbidity disease.
8.Association Between Surrogate Markers of Insulin Resistance and Incident Cardiovascular Disease in a Population With Stages 0-3 Cardiovascular-Kidney-Metabolic Syndrome:A Prospective Cohort Study
Yajie ZHAO ; Lele WANG ; Jiawei LI ; Bing GUO ; Juying ZHANG ; Xiaolin GUO ; Yuying LUO ; Gonghua WU ; Xing ZHAO
Journal of Sichuan University (Medical Sciences) 2025;56(2):495-505
Objective To investigate the association between 8 insulin resistance(IR)surrogate markers and incident atherosclerotic cardiovascular disease(ASCVD)in population with cardiovascular-kidney-metabolic syndrome(CKM)of stages 0-3,and to identify the surrogate marker with the best predictive performance.Methods A study was conducted on 20121 community residents classified as CKM stages 0-3 from the Chengdu cohort of the China Multi-Ethic Cohort.A Cox proportional hazards model was used to calculate hazard ratios(HRs)between each IR surrogate marker and incident ASCVD.Cubic spline regression was employed to explore the dose-response relationships between these markers and incident ASCVD.The relative relationships between different markers and incident ASCVD were examined through the ratio of HRs(RHRs).Time-dependent area under the receiver operating characteristic curve(TDAUC)and Uno's C-statistic were calculated to compare the predictive performance of each marker for incident ASCVD.Based on the PREVENT equation components and the 8 surrogate markers under analysis,random forest feature selection was used to determine the contribution of each marker to accurate prediction.Results During a follow-up period of82 741.93 person-years,1447 incident cases of ASCVD were recorded,with an incidence density of 17.49 per 1000 person-years.Association analyses indicated that the triglyceride to high-density lipoprotein cholesterol ratio(TG/HDL)and the TyG/(TG/HDL)index were not associated with incident ASCVD(P>0.05).The TyG index combined with obesity measurement parameters emerged as a reliable predictor of ASCVD incidence.The most promising indicator,TyG index with waist-to-height ratio(TyG_WHtR),exhibited an inverted J-shaped association with incident ASCVD(P for nonlinearity=0.045;TDAUC=0.640;C=0.634),while the TyG index with body mass index(TyG_BMI),waist circumference(TyG_WC),and waist-to-hip ratio(TyG_WHR)showed positive linear associations(all P for trend<0.05),with relatively lower predictive performance(C=0.564,0.588,and 0.598,respectively).Although both the TyG index and the metabolic score for insulin resistance(METS-IR)were associated with increased ASCVD risk(TyG:Q2 vs.Q1,HR=1.23 and Q4 vs.Q1,HR=1.24;METS-IR:P for non-linearity=0.045),they exhibited poor predictive performance for incident ASCVD.Conclusion The TyG index combined with obesity measurement parameters is an ideal IR surrogate marker for predicting incident ASCVD in populations with stages 0-3 CKM.Monitoring these markers will facilitate the prevention and control of cardiovascular diseases in CKM populations.
9.Association of Rest-Activity Rhythm With the Risk of Rheumatoid Arthritis and Effect Modification by Genetic Susceptibility
Lele WANG ; Huan XU ; Gonghua WU ; Bing GUO ; Xiong XIAO ; Xing ZHAO ; Juying ZHANG
Journal of Sichuan University (Medical Sciences) 2025;56(3):785-791
Objective To investigate the association between rest-activity rhythm(RAR)and the risks of rheumatoid arthritis(RA),and to evaluate whether genetic susceptibility modifies this relationship.Methods This prospective cohort study utilized data from the UK Biobank,including 88 060 participants who did not have RA at baseline.RAR parameters(e.g.,relative amplitude)were calculated using data obtained through wrist-worn accelerometers.The participants'genetic susceptibility to RA was assessed using a polygenic risk score.Cox proportional hazards models were employed to analyze the association between RAR and RA risk,with interaction terms incorporated to evaluate the effect modification by genetic susceptibility.Results Over a median follow-up period of 7.97 years,660 incident RA cases were identified.After adjusting for age,sex,ethnicity,educational attainment,Townsend deprivation index,drinking status,smoking status,dietary score,body mass index,and polygenic risk score for incident RA,the dose-response analysis revealed a linear relationship between the RAR-related parameters,including the average amplitude during the most active 10 h(M10),interdaily stability(IS),intradaily variability(IV),and the risk of developing RA(P>0.05).In contrast,relative amplitude and the average amplitude during the least active 5 h(L5)showed a nonlinear relationship with the risk of developing RA(P<0.05).Compared to those in the the highest quartile of relative amplitude,participants in the lowest quartile had a 49%increase in the risk of developing RA(hazard ratio[HR]=1.49;95%CI,1.17-1.90).Compared to those in the lowest quartile,participants in the highest quartile of L5 had a 40%increased risk of developing RA(HR=1.40;95%CI,1.12-1.75).Every time M10 increased by one standard deviation,the risk of developing RA decreased by 12%(HR=0.88;95%CI,0.80-0.96).No evidence of effect modification by genetic susceptibility was observed in the RAR-RA association(P>0.05).Conclusion Disrupted rest-activity rhythm is associated with an increased risk of RA,which is independent of genetic susceptibility to RA.Our findings suggest that improving rest-activity rhythm may help reduce RA risks.
10.Delayed physical growth and related factors in pediatric patients with transfusion-dependent thalassemia
Zhexiang KUANG ; Jingyu ZHAO ; Xiao YU ; Jing XU ; Zhen GAO ; Yanjie LIU ; Anni WANG ; Jin DONG ; Hong PAN ; Lele ZHANG ; Liwei FANG ; Guibin WU ; Xinli LI ; Jun SHI ; Li XU ; Wenjun XIE
Chinese Journal of Hematology 2025;46(4):328-335
Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

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