1.Systemic Lupus Erythematosus as a Dominant Disease in Traditional Chinese Medicine
Zihan WANG ; Yanyu CHEN ; Yong CUI ; Qingwen TAO ; Mei MO ; Ke XUE ; Xiaoxiao ZHANG ; Yuan XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):263-269
Systemic lupus erythematosus (SLE), a refractory autoimmune disease, is among the dominant diseases where traditional Chinese medicine (TCM) shows advantages in the field of rheumatology and immunology. The China-Japan Friendship Hospital hosted the "46th Youth Salon on Dominant Diseases (Systemic Lupus Erythematosus)" organized by the China Association of Chinese Medicine, which led to a consensus on "the advantages, challenges, interdisciplinary approaches, and translational achievements of integrated TCM and Western medical approaches in the diagnosis and treatment of SLE." The diagnosis and treatment of SLE currently face several challenges, such as frequent misdiagnosis and missed diagnosis in the early stages, difficulty in achieving treatment targets, multiple side effects from pharmacotherapy, and the lack of management strategies for special populations, all of which hinder the fulfillment of the clinical needs of patients. Integrated TCM and Western medical approaches can improve clinical symptoms such as skin erythema, aversion to cold and cold limbs, fatigue, dry mouth, restlessness, and heat sensation in the palms and soles, thereby improving patients' quality of life. The approaches also help consolidate the efficacy of conventional Western medicine, slow disease progression, reduce relapse rates, address multi-organ involvement, and prevent or treat complications. Additionally, they enhance efficacy and reduce toxicity, prevent the side effects of Western medications, help reduce hormone use, and offer distinct advantages in the individualized intervention of special populations, contributing to the whole-process management of the disease. However, evidence-based medical support for this integrated approach remains limited, and the quality of available evidence is generally low. Common evaluation systems and modern research methodologies should be adopted to clarify the efficacy of TCM in SLE treatment. Efforts should be made to carry out high-quality evidence-based medical research, strengthen the development of fundamental and pharmacological research, and further explain the distinct advantages of TCM in the diagnosis and treatment of SLE. Future efforts should focus on advancing the integration of TCM and modern medicine, incorporating multi-omics technologies, individualized stratification, and other precision medicine concepts, in combination with artificial intelligence. Moreover, interdisciplinary collaboration should be promoted to utilize modern technology in exploring the essence of TCM theories and screening effective formulae, thereby comprehensively improving the diagnosis and treatment of SLE through integrated TCM and Western medical approaches.
2.Salidroside inhibits osteoclast differentiation based on osteoblast-osteoclast interaction via HIF-1a pathway.
Yutong JIN ; Yao WANG ; Chuan WANG ; Lingling ZHANG ; Dandan GAO ; Haizhao LIU ; Qingwen CAO ; Chenchen TIAN ; Yuhong BIAN ; Yue WANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(5):572-584
This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals
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Osteoblasts/cytology*
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Hypoxia-Inducible Factor 1, alpha Subunit/genetics*
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Glucosides/administration & dosage*
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Cell Differentiation/drug effects*
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Phenols/administration & dosage*
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Mice
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Osteoclasts/metabolism*
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RANK Ligand/genetics*
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Rhodiola/chemistry*
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Osteogenesis/drug effects*
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Signal Transduction/drug effects*
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Interleukin-6/genetics*
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Male
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RAW 264.7 Cells
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Osteolysis/genetics*
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Humans
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Mice, Inbred C57BL
3.Clinical Characteristics and Influencing Factors of Rheumatoid Arthritis in Patients with Cold Dampness Obstruction Syndrome
Yanyu CHEN ; Yanqi LI ; Longxiao LIU ; Liubo ZHANG ; Tianyi LAN ; Nan ZHANG ; Cheng XIAO ; Yuan XU ; Qingwen TAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):140-146
ObjectiveTo study the clinical characteristics and influencing factors of rheumatoid arthritis (RA) in the patients with cold dampness obstruction syndrome. MethodsThe RA patients treated in the Department of Traditional Chinese Medicine and Rheumatology of the China-Japan Friendship Hospital from August 2022 to June 2024 were selected. The demographic information, clinical data, laboratory test results, and traditional Chinese medicine (TCM) symptom information were collected for syndrome differentiation, on the basis of which the characteristics and influencing factors of cold dampness obstruction syndrome were analyzed. ResultsA total of 258 RA patients were selected in this study, including 88 (34.1%) patients with cold dampness obstruction syndrome, 53 (20.5%) patients with dampness and heat obstruction syndrome, 31 (12.0%) patients with wind dampness obstruction syndrome, 29 (11.2%) patients with liver-kidney deficiency syndrome, 19 (7.4%) patients with Qi-blood deficiency syndrome, 14 (5.4%) patients with phlegm-stasis obstruction syndrome, 15 (5.8%) patients with stasis obstructing collateral syndrome and 9 (3.5%) patients with Qi-Yin deficiency syndrome. The patients were assigned into two groups of cold dampness obstruction syndrome and other syndromes. The group of cold dampness obstruction syndrome had lower joint fever, 28-tender joint count (TJC28), and 28-joint disease activity score (DAS28)-C-reactive protein (CRP) and higher central sensitization, cold feeling of joints, fear of wind and cold, cold limbs, and abdominal distention than the group of other syndromes (P<0.05). The binary logistic regression analysis showed that central sensitization (OR 5.749, 95%CI 2.116-15.616, P<0.001) and DAS28-CRP (OR 0.600, 95% CI 0.418-0.862, P=0.006) were the independent factors influencing cold dampness obstruction syndrome in RA. ConclusionCold dampness obstruction syndrome is a common syndrome in RA patients. It is associated with central sensitization, cold feeling of joints, abdominal distension and may be a clinical syndrome associated with central sensitization.
4.Systemic Lupus Erythematosus as a Dominant Disease in Traditional Chinese Medicine
Zihan WANG ; Yanyu CHEN ; Yong CUI ; Qingwen TAO ; Mei MO ; Ke XUE ; Xiaoxiao ZHANG ; Yuan XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):263-269
Systemic lupus erythematosus (SLE), a refractory autoimmune disease, is among the dominant diseases where traditional Chinese medicine (TCM) shows advantages in the field of rheumatology and immunology. The China-Japan Friendship Hospital hosted the "46th Youth Salon on Dominant Diseases (Systemic Lupus Erythematosus)" organized by the China Association of Chinese Medicine, which led to a consensus on "the advantages, challenges, interdisciplinary approaches, and translational achievements of integrated TCM and Western medical approaches in the diagnosis and treatment of SLE." The diagnosis and treatment of SLE currently face several challenges, such as frequent misdiagnosis and missed diagnosis in the early stages, difficulty in achieving treatment targets, multiple side effects from pharmacotherapy, and the lack of management strategies for special populations, all of which hinder the fulfillment of the clinical needs of patients. Integrated TCM and Western medical approaches can improve clinical symptoms such as skin erythema, aversion to cold and cold limbs, fatigue, dry mouth, restlessness, and heat sensation in the palms and soles, thereby improving patients' quality of life. The approaches also help consolidate the efficacy of conventional Western medicine, slow disease progression, reduce relapse rates, address multi-organ involvement, and prevent or treat complications. Additionally, they enhance efficacy and reduce toxicity, prevent the side effects of Western medications, help reduce hormone use, and offer distinct advantages in the individualized intervention of special populations, contributing to the whole-process management of the disease. However, evidence-based medical support for this integrated approach remains limited, and the quality of available evidence is generally low. Common evaluation systems and modern research methodologies should be adopted to clarify the efficacy of TCM in SLE treatment. Efforts should be made to carry out high-quality evidence-based medical research, strengthen the development of fundamental and pharmacological research, and further explain the distinct advantages of TCM in the diagnosis and treatment of SLE. Future efforts should focus on advancing the integration of TCM and modern medicine, incorporating multi-omics technologies, individualized stratification, and other precision medicine concepts, in combination with artificial intelligence. Moreover, interdisciplinary collaboration should be promoted to utilize modern technology in exploring the essence of TCM theories and screening effective formulae, thereby comprehensively improving the diagnosis and treatment of SLE through integrated TCM and Western medical approaches.
5.Clinical Dominant Disease of Traditional Chinese Medicine: Rheumatoid Arthritis
Jinping WANG ; Qingwen TAO ; Mei MO ; Zihan WANG ; Nan ZHANG ; Yuan XU ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):202-210
Rheumatoid arthritis (RA) is an autoimmune disease characterized primarily by erosive arthritis, with a high prevalence and disability rate. Although significant progress has been made in the treatment of RA in recent years, challenges such as suboptimal efficacy, drug resistance, severe side effects, and high costs of long-term treatment remain, especially for patients in the early stages of RA, as well as those with RA complications, comorbidities, and severe conditions. Hosted by the China-Japan Friendship Hospital and organized by the Youth Committee of the China Association of Chinese Medicine, the 27th session of the Clinical Dominant Disease Series (Rheumatoid Arthritis) Youth Salon invited nearly 20 experts and scholars from traditional Chinese medicine (TCM), western medicine, and interdisciplinary fields to actively discuss the clinical needs of modern medicine and the advantageous stages and aspects of TCM in RA. Experts at the salon agreed that TCM has unique advantages in the treatment of RA, especially during the early stage, periods of low to moderate disease activity, remission phase, and in addressing complications and comorbidities. TCM can achieve both prevention and treatment by regulating the immune system and restoring immune homeostasis. The integrated approach of traditional Chinese and western medicine demonstrates significant advantages in active RA, refractory cases, and stages with severe complications, by rapidly controlling disease progression, alleviating symptoms, enhancing the quality of life, and facilitating recovery. Given the frequent occurrence of multiple comorbidities in RA, TCM shows potential in regulating immunity, alleviating symptoms, and improving physical constitution, which provides new insights into the comprehensive treatment of RA with comorbidities. However, high-quality clinical studies on integrated traditional Chinese and western medicine in RA are still lacking. It is necessary to establish large-scale clinical cohorts and biological databases to provide a scientific basis for the development of precision-targeted therapies and clinical treatment protocols. In the future, individualized treatment strategies integrating traditional Chinese and western medicine are expected to become an important direction for improving the quality of life in RA patients.
6.Clinical Dominant Disease of Traditional Chinese Medicine: Rheumatoid Arthritis
Jinping WANG ; Qingwen TAO ; Mei MO ; Zihan WANG ; Nan ZHANG ; Yuan XU ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):202-210
Rheumatoid arthritis (RA) is an autoimmune disease characterized primarily by erosive arthritis, with a high prevalence and disability rate. Although significant progress has been made in the treatment of RA in recent years, challenges such as suboptimal efficacy, drug resistance, severe side effects, and high costs of long-term treatment remain, especially for patients in the early stages of RA, as well as those with RA complications, comorbidities, and severe conditions. Hosted by the China-Japan Friendship Hospital and organized by the Youth Committee of the China Association of Chinese Medicine, the 27th session of the Clinical Dominant Disease Series (Rheumatoid Arthritis) Youth Salon invited nearly 20 experts and scholars from traditional Chinese medicine (TCM), western medicine, and interdisciplinary fields to actively discuss the clinical needs of modern medicine and the advantageous stages and aspects of TCM in RA. Experts at the salon agreed that TCM has unique advantages in the treatment of RA, especially during the early stage, periods of low to moderate disease activity, remission phase, and in addressing complications and comorbidities. TCM can achieve both prevention and treatment by regulating the immune system and restoring immune homeostasis. The integrated approach of traditional Chinese and western medicine demonstrates significant advantages in active RA, refractory cases, and stages with severe complications, by rapidly controlling disease progression, alleviating symptoms, enhancing the quality of life, and facilitating recovery. Given the frequent occurrence of multiple comorbidities in RA, TCM shows potential in regulating immunity, alleviating symptoms, and improving physical constitution, which provides new insights into the comprehensive treatment of RA with comorbidities. However, high-quality clinical studies on integrated traditional Chinese and western medicine in RA are still lacking. It is necessary to establish large-scale clinical cohorts and biological databases to provide a scientific basis for the development of precision-targeted therapies and clinical treatment protocols. In the future, individualized treatment strategies integrating traditional Chinese and western medicine are expected to become an important direction for improving the quality of life in RA patients.
7.Effect of hip abductor muscle exercise on three-dimensional gait and collapse rate in patients with non-traumatic femoral head necrosis
Yingjia YUAN ; Yanzi YI ; Jin LI ; Ke WANG ; Yu WANG ; Tianye LIN ; Qingwen ZHANG ; Wei HE ; Qiushi WEI
Chinese Journal of Tissue Engineering Research 2025;29(33):7211-7216
BACKGROUND:Non-traumatic necrosis of the femoral head is a difficult joint disease,and preserving one's own femoral head is of great significance for young patients.Currently,there is a lack of regular and unified functional exercise plans.OBJECTIVE:To investigate the effect of hip abductor muscle exercise on the three-dimensional gait and collapse rate of patients with non-traumatic femoral head necrosis,and to provide theoretical basis for effective rehabilitation of patients with non-traumatic femoral head necrosis.METHODS:Totally 81 non-traumatic and non-surgical patients with femoral head necrosis(81 hips)admitted to the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from June 2020 to June 2022 were included.Patients were randomly divided into a control group(n=40)and a hip abductor muscle exercise group(n=41).The control group received routine physical therapy and medication treatment.The hip abductor muscle exercise group underwent hip abductor muscle exercise on the basis of the control group.The gait status(hip joint range of motion,step length difference,and ground contact time difference)of two groups of patients was evaluated using the Tecnobody balance assessment system before and 12 weeks after treatment.The BIODEX-S4 isokinetic muscle strength testing system was used to test the peak force distance of hip abduction isokinetic muscle strength.Gluteus medius width ratio was compared between two groups.The collapse rate was compared between two groups of patients 1 year after treatment.RESULTS AND CONCLUSION:(1)There was no statistically significant difference between the hip abductor muscle exercise group and the control group in terms of age,gender,side profile,body mass index,and etiology(P>0.05).(2)Before treatment,there was no significant statistical difference in the range of motion of the affected hip joint between the two groups(P>0.05).After treatment,the range of motion of the affected hip joint in both groups improved compared to before treatment(P<0.05),and the range of motion of the affected hip joint in the hip abductor muscle exercise group was significantly higher than that in the control group(P<0.05).(3)Before treatment,there was no significant statistical difference in the step length and touchdown time between the two groups(P>0.05).12 weeks after treatment,the difference in step length and touchdown time between the two groups decreased compared to before treatment(P<0.05),and the difference in step length and touchdown time between the hip abductor muscle exercise group after treatment was significantly greater than that of the control group(P<0.05).(4)Before treatment,there was no significant statistical difference in gluteus medius width ratio between the two groups(P>0.05).12 weeks after treatment,the gluteus medius width ratio of both groups increased compared to that before treatment(P<0.05),and the gluteus medius width ratio of the hip abductor muscle exercise group was significantly higher than that of the control group(P<0.05).(5)At 1 year after treatment,the comparison of femoral head collapse rates between the two groups showed significant statistical significance(P<0.05),and that in the hip abductor muscle exercise group(22%)was significantly lower than that in the control group(45%).(6)It is concluded that exercise of the hip abductor muscle effectively enhances hip joint function,improves gait,and reduces the rate of femoral head collapse in patients with non-traumatic femoral head necrosis.It is recommended to use hip abductor muscle exercise as one of the basic methods for hip preservation in non-traumatic femoral head necrosis.
8.Epidemiological survey of out-of-hospital sudden cardiac death in Hangzhou from 2016 to 2019
Mingwei WANG ; Qingwen YU ; Ting TANG ; Xuhan TONG ; Siqi HU ; Yao YOU ; Chen CHEN ; Jiake TANG ; Shenghui ZHANG ; Xinyan FU ; Xingwei ZHANG ; Liansheng WANG
Journal of Chinese Physician 2025;27(8):1185-1190
Objective:To evaluate the epidemiological characteristics and influencing factors of out-of-hospital sudden cardiac death (SCD) in Hangzhou from 2016 to 2019.Methods:SCD events recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019 were reviewed. Demographic and mortality data were recorded, and the distribution patterns of SCD events in terms of date, time, and population with different characteristics were observed. Time series analysis method and a distributed lag nonlinear model based on quasi-Poisson distribution were used to explore the possible nonlinear association between ambient temperature and SCD incidence.Results:A total of 4 744 out-of-hospital sudden death events were recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019. After excluding non-SCD events and observed events with missing items, 3 743 SCD events were finally included in the study. The survey results showed that the incidence of out-of-hospital SCD in Hangzhou was 96.5 cases per 100 000 person-years. Most of the people who experienced SCD were aged ≥60 years. The incidence in males (2 462 cases, 66%) was significantly higher than that in females (1 281 cases, 34%), and the proportion of events occurring during the day (2 737 cases, 73%) was significantly higher than that at night (1 006 cases, 27%), mainly occurring between 7: 00 and 9: 00. High temperature was associated with an increased risk of SCD. When the average daily temperature was higher than 25.5 ℃, the risk of SCD increased with the further increase of average daily temperature.Conclusions:SCD events mainly occur in the elderly population aged ≥60 years, with a significantly higher incidence in males than in females, and more frequently during the day than at night, mainly between 7: 00 and 9: 00 in the morning. High temperature is closely related to the risk of SCD. It is particularly important to carry out targeted SCD screening and prevention for different populations and implement appropriate prevention strategies for high-risk groups of SCD in high-temperature weather.
9.Correlation analysis between serum prostaglandin E2, heat-shock protein 70 and the severity of bleeding in peptic ulcers
Yu ZHANG ; Qingwen ZHOU ; Xiaofeng ZHANG ; Qingni CHENG
Chinese Journal of Postgraduates of Medicine 2025;48(12):1131-1136
Objective:To investigate the correlation between serum prostaglandin E2 (PGE2), heat-shock protein 70 (HSP-70) and the severity of bleeding in patients with peptic ulcer bleeding (PUB).Methods:A total of 122 patients with peptic ulcer (PU) admitted to Chang'an Hospital from March 2021 to March 2024 were retrospectively collected and divided into simple PU group (50 cases) and PUB group (72 cases) according to whether PUB occurred. Serum levels of PGE2 and HSP-70 were determined by enzyme-linked immunosorbent assay (ELISA). Spearman test was used to analyze the correlation between serum PGE2, HSP-70 levels and bleeding severity in PUB patients. Logistic regression was used to analyze the risk factors of PUB, and receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum PGE2 and HSP-70 levels on the bleeding degree of PUB patients.Results:The proportion of non-steroidal anti-inflammatory drugsnon-ster (NSAID) used and Helicobacter pylori (Hp) infection, thromboplastin time (APTT) and prothrombin time (PT) in the PUB group were higher than those in the PU group: 42.00%(21/50) vs. 25.00%(18/72), 36.00%(18/50) vs. 58.33%(42/72), (28.78 ± 3.24) s vs. (26.72 ± 3.89) s, (13.14 ± 2.56) s vs. (11.26 ± 2.15) s, and the serum levels of PGE2 and HSP-70 were lower than those in the PU group: (174.25 ± 18.21) ng/L vs. (236.44 ± 24.52) ng/L, (0.78 ± 0.22) μg/L vs. (1.24 ± 0.38) μg/L, there were statistical significances ( P<0.05). The serum levels of PGE2 and HSP-70 in PUB patients decreased gradually with the severity of hemorrhage ( P<0.05). Spearman test showed that serum PGE2 and HSP-70 levels were negatively correlated with the severity of bleeding in PUB patients ( r = - 0.720, - 0.586, P<0.01). Logistic regression analysis showed that serum PGE2 and HSP-70 levels were protective factors for PUB ( P<0.05), while NSAID used, Hp infection, APTT and PT were risk factors for PUB ( P<0.05). ROC curve analysis results showed that the area under the curve of serum PGE2 and HSP-70 combined to predict the severity of bleeding in PUB patients was 0.935, which was higher than that predicted by the two indexes alone. Conclusions:The expression of serum PGE2 and HSP-70 are down regulated in PUB patients, and have correlated with the severity of bleeding. The joint detection of two indicators is more conductive to predicting the degree of bleeding in PUB patients.
10.Clinical features and gene variation analysis of aminoacylase-1 deficiency patients caused by ACY1 gene mutation
Mingchao SHI ; Huihui ZHAO ; Zonghui CHEN ; Yuwei HUANG ; Renliang ZHANG ; Qingwen JIN
Chinese Journal of Neurology 2025;58(11):1198-1204
Objective:To investigate the clinical characteristics and genetic variations of patients with aminoacylase-1 deficiency (ACY1D) caused by ACY1 gene mutations, in order to enhance clinicians′ understanding of this rare disease. Methods:Clinical and genetic data of a child with ACY1D admitted to Sir Run Run Hospital, Nanjing Medical University in December 2021 were collected. Using "aminoacylase-1 deficiency" "aminoacylase-1 gene" " ACY1" and "ACY1D" as keywords, relevant cases of ACY1 gene mutations were searched in CNKI, Wanfang Data Knowledge Service Platform, OMIM, and PubMed databases until February 2025. The clinical characteristics and types of genetic variations of previously reported ACY1D patients were summarized and analyzed. Results:The patient was an 8-year and 4-month-old boy. Clinical manifestations included growth retardation, ataxia, and focal epileptic seizures. Increased excretion of various N-acetylamino acids was observed in the urine. Cranial magnetic resonance imaging showed cerebellar atrophy. Whole-exome sequencing results showed a compound heterozygous mutation in the ACY1 gene: c.1063-1G>A (IVS14-1G>A) and c.170G>A (p.G57D) (reference transcript NM_000666.2), with c.170G>A (p.G57D) being a novel mutation. Family validation results showed that the c.1063-1G>A (IVS14-1G>A) mutation originated from his mother, and the c.170G>A (p.G57D) mutation originated from his father. By literature review 11 English articles were retrieved reporting 18 ACY1D patients, along with the child in this study, totaling 19 cases, with an onset age ranging from 1 week to 4 years and 6 months. Among them, 13/19 patients showed growth retardation, 9/19 patients had language disorders, 8/19 patients had intellectual disabilities, 7/19 patients had ataxia and low muscle tone, 6/19 patients had epilepsy and febrile convulsions, and 3/19 patients had irritability, autism, and muscle weakness. Genetic testing results indicated various types of mutations in the ACY1 gene, including missense, splicing, and frameshift mutations. Conclusions:ACY1D is an autosomal recessive genetic disease caused by ACY1 gene mutations, which is relatively rare in China. The main clinical manifestations include growth retardation, intellectual and language disorders. The c.170G>A heterozygous mutation is a newly discovered variant site, expanding the mutation spectrum of the ACY1 gene. Screening for ACY1 gene variations can aid in achieving a definitive diagnosis..

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