1.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.
2.Simulation research on the influence of regular porous lattice scaffolds on bone growth.
Yutao MEN ; Lele WEI ; Baibing HU ; Pujun HAO ; Chunqiu ZHANG
Journal of Biomedical Engineering 2025;42(4):808-816
To assess the implantation effectiveness of porous scaffolds, it is essential to consider not only their mechanical properties but also their biological performance. Given the high cost, long duration and low reproducibility of biological experiments, simulation studies as a virtual alternative, have become a widely adopted and efficient evaluation method. In this study, based on the secondary development environment of finite element analysis software, the strain energy density growth criterion for bone tissue was introduced to simulate and analyze the cell proliferation-promoting effects of four different lattice porous scaffolds under cyclic compressive loading. The biological performance of these scaffolds was evaluated accordingly. The computational results indicated that in the early stages of bone growth, the differences in bone tissue formation among the scaffold groups were not significant. However, as bone growth progressed, the scaffold with a porosity of 70% and a pore size of 900 μm demonstrated markedly superior bone formation compared to other porosity groups and pore size groups. These results suggested that the scaffold with a porosity of 70% and a pore size of 900 μm was most conducive to bone tissue growth and could be regarded as the optimal structural parameter for bone repair scaffold. In conclusion, this study used a visualized simulation approach to pre-evaluate the osteogenic potential of porous scaffolds, aiming to provide reliable data support for the optimized design and clinical application of implantable scaffolds.
Tissue Scaffolds/chemistry*
;
Porosity
;
Finite Element Analysis
;
Tissue Engineering/methods*
;
Computer Simulation
;
Bone Development
;
Osteogenesis
;
Humans
;
Cell Proliferation
3.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.
4.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.
5.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.
6.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.
7.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.
8.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.
9.Mediating role of accompanied childbirth experience between the dynamic adjustment after marriage and the paternal role adaptation in spouses of primipara
Lele ZHANG ; Yalan QI ; Ping LI ; Xiumei XUE
Chinese Journal of Practical Nursing 2025;41(28):2206-2212
Objective:To explore the mediating effect of accompanied childbirth experience among spouses of primipara on dynamic adjustment after marriage and paternal role adaptation, with the aim of providing reference for further improving accompanying childbirth services.Methods:Spouses of primipara who participated in accompanying childbirth at Nanjing Drum Tower Hospital Group Suqian Hospital from January 2023 to June 2024 were selected as the research subjects through convenience sampling. The general information questionnaire, the Chinese version of Dynamic Adjustment Scale, the Parents' Experiences of Childbirth and the Newborn Father's Role Adaptation Questionnaire were used to conduct a cross-sectional survey, and establish the intermediary model between the dynamic adjustment after marriage and the paternal role adaptation.Results:A total of 244 spouses of primipara were included, with an age of (28.86 ± 5.77) years. The score for dynamic adjustment in spouses of primipara was (110.82 ± 16.33) points, the score for experiences of childbirth was (124.27 ± 13.89) points, and the score for paternal role adaptation was (71.66 ± 9.22) points. The accompanied childbirth experience among spouses of primipara was positively correlated with the dynamic adjustment after marriage and the paternal role adaptation ( r=0.197, 0.511, both P<0.01). The dynamic adjustment after marriage was positively correlated with the paternal role adaptation ( r=0.403, P<0.01). The accompanied childbirth experience among spouses had a partial mediating effect between the dynamic adjustment after marriage and the parental role adaptation, which the mediating effect was 0.182, accounting for 32.79% of the total effect. Conclusions:The dynamic adjustment after marriage can directly predict the paternal role adaptation, and the experience of accompanying childbirth has a partial mediating effect between the two. The role adaptation level of the spouses of the primiparas should be improved by further improving the delivery service to meet the needs of the primiparas and their spouses.
10.Loss-of-function mutations in Chinese Han patients with familial benign chronic pemphigus are associated with an earlier age at onset
Xueying WANG ; Zhenzhen WANG ; Zhe WANG ; Zihao MI ; Lele SUN ; Hong LIU ; Furen ZHANG
Chinese Journal of Dermatology 2025;58(3):221-227
Objective:To expand the mutation spectrum of familial benign chronic pemphigus (HHD), and to deeply explore the relationship between clinical phenotypes and genotypes.Methods:HHD patients were retrospectively collected from the Department of Dermatology, Hospital for Skin Diseases, Shandong First Medical University from January 2018 to October 2023, and their clinical data and blood samples were also collected. Sanger sequencing and Whole-exome sequencing were performed on 34 HHD patients. Mutations in the ATP2C1 gene were classified into loss-of-function mutations (including frameshift mutations, nonsense mutations, and splicing mutations) and missense mutations. The relationship between clinical phenotypes and genetic mutation types was analyzed using Fisher's exact test or two-independent-sample t test, and further verified by meta-analysis. Results:The 34 HHD patients were all of Chinese Han nationality, including 20 males and 14 females, and their ages ranged from 35 to 77 years. Pathogenic mutations in the ATP2C1 gene were successfully identified in all the 34 patients, including 29 independent mutations, among which there were 9 frameshift mutations, 8 splicing mutations, 6 missense mutations, and 6 nonsense mutations. The age at onset was significantly earlier in the loss-of-function mutation group (37.62 ± 10.10 years) than in the missense mutation group (49.63 ± 14.90 years; t = 2.62, P = 0.013). However, there were no significant differences in gender, family history, disease seasonality, disease severity, or disease progression among patients with different mutation types (all P > 0.05). Meta-analysis showed that the age at onset was significantly earlier in Chinese Han patients with HHD carrying loss-of-function mutations than in those carrying missense mutations (mean difference: -4.61 years, 95% CI: -8.68 - -0.53 years, P = 0.030) . Conclusion:Chinese Han patients with HHD carrying loss-of-function mutations in the ATP2C1 gene showed significantly earlier ages at onset compared with those carrying missense mutations.

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