1.Analysis of Toxicity Characteristics and Rational Drug Use of Polygoni Multiflori Radix
Qiongyi FU ; Yupu QI ; Yu HUAN ; Yagang SONG ; Xiangxiang WU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):222-231
ObjectivePolygoni Multiflori Radix is a commonly used tonic traditional Chinese medicine (TCM) in clinical practice, but liver injury has often been reported in recent years. Some related preparations containing Polygoni Multiflori Radix have been reported by the National Medical Products Administration many times for the risk of liver injury. This has caused extensive discussion on the potential toxicity of TCM in China and abroad, which has limited the clinical use of Polygoni Multiflori Radix to some extent. To understand the adverse reactions of Polygoni Multiflori Radix, the safe and rational use of Polygoni Multiflori Radix in clinical practice was discussed. MethodsThe pharmacovigilance thought of modern Chinese medicine and the TCM pharmacovigilance system framework of ''identification of poison, use of poison, anti-poison, and detoxification'' were employed to mine the relevant toxicity records, usage and dosage, processing compatibility, and contraindication of taking Polygoni Multiflori Radix in ancient books. The drug safety information of Polygoni Multiflori Radix was summarized by comparing with modern reports. ResultsA total of 74 ancient books related to Polygoni Multiflori Radix were included, suggesting that the toxicity of Polygoni Multiflori Radix was recognized in ancient times. The main chemical components of Polygoni Multiflori Radix had both efficacy and toxicity, and the adverse reactions may be related to long-term use, excessive use, and individual differences. The results showed that the toxic components of Polygoni Multiflori Radix could be reduced by peeling, steaming with black beans, and processing without iron tools. The toxic effects of Polygoni Multiflori Radix could be reduced by the compatibility of Polygoni Multiflori Radix with Poria, Psoraleae Fructus, and Cistanches Herba. ConclusionReasonable dosage, standard processing, correct compatibility, and syndrome differentiation are the key points to standardize the use of Polygoni Multiflori Radix and reduce the incidence of adverse reactions. Clinically, the toxicity classification of TCM should be strengthened, and the susceptible population should be prioritized. The detection indicators and early warning mechanisms should be improved, and precise drug dosage and course of treatment should be guaranteed. These measures can ensure the safe use of Polygoni Multiflori Radix.
2.Analysis of Toxicity Characteristics and Rational Drug Use of Polygoni Multiflori Radix
Qiongyi FU ; Yupu QI ; Yu HUAN ; Yagang SONG ; Xiangxiang WU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):222-231
ObjectivePolygoni Multiflori Radix is a commonly used tonic traditional Chinese medicine (TCM) in clinical practice, but liver injury has often been reported in recent years. Some related preparations containing Polygoni Multiflori Radix have been reported by the National Medical Products Administration many times for the risk of liver injury. This has caused extensive discussion on the potential toxicity of TCM in China and abroad, which has limited the clinical use of Polygoni Multiflori Radix to some extent. To understand the adverse reactions of Polygoni Multiflori Radix, the safe and rational use of Polygoni Multiflori Radix in clinical practice was discussed. MethodsThe pharmacovigilance thought of modern Chinese medicine and the TCM pharmacovigilance system framework of ''identification of poison, use of poison, anti-poison, and detoxification'' were employed to mine the relevant toxicity records, usage and dosage, processing compatibility, and contraindication of taking Polygoni Multiflori Radix in ancient books. The drug safety information of Polygoni Multiflori Radix was summarized by comparing with modern reports. ResultsA total of 74 ancient books related to Polygoni Multiflori Radix were included, suggesting that the toxicity of Polygoni Multiflori Radix was recognized in ancient times. The main chemical components of Polygoni Multiflori Radix had both efficacy and toxicity, and the adverse reactions may be related to long-term use, excessive use, and individual differences. The results showed that the toxic components of Polygoni Multiflori Radix could be reduced by peeling, steaming with black beans, and processing without iron tools. The toxic effects of Polygoni Multiflori Radix could be reduced by the compatibility of Polygoni Multiflori Radix with Poria, Psoraleae Fructus, and Cistanches Herba. ConclusionReasonable dosage, standard processing, correct compatibility, and syndrome differentiation are the key points to standardize the use of Polygoni Multiflori Radix and reduce the incidence of adverse reactions. Clinically, the toxicity classification of TCM should be strengthened, and the susceptible population should be prioritized. The detection indicators and early warning mechanisms should be improved, and precise drug dosage and course of treatment should be guaranteed. These measures can ensure the safe use of Polygoni Multiflori Radix.
3.Eupatilin Inhibits Proliferation, Invasion, and Metastasis of Non-small Cell Lung Cancer via EZH2/H3K27me3 Signaling Pathway
Bo XU ; Yihan YU ; Linling HU ; Bo JIANG ; Yu QI ; Shasha YUAN ; Yiling FAN ; Jixian ZHANG ; Qing MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):58-69
ObjectiveTo investigate the mechanisms by which eupatilin (Eup) inhibits proliferation, invasion, and metastasis of non-small cell lung cancer (NSCLC) through the enhancer of zeste homolog 2/histone H3 lysine 27 trimethylation (EZH2/H3K27me3) signaling pathway. MethodsIn vivo, a subcutaneous xenograft tumor model was established in nude mice using H1299 cells to evaluate the anti-NSCLC effects of Eup. Immunohistochemistry (IHC-P) was used to detect the expression of proliferation- and invasion/metastasis-related proteins, including proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor A (VEGFA). In vitro, cell counting kit-8 (CCK-8) assays were performed to determine the viability of H1299 cells treated with different concentrations of Eup (0-200 μmol·L-1) and to select appropriate concentrations. Colony formation and 5-ethynyl-2′-deoxyuridine (EdU) assays were used to evaluate cell proliferation. Wound healing and invasion assays were conducted to assess cell migration and invasion. Human umbilical vein endothelial cell (HUVEC) angiogenesis assays were used to evaluate the effects of Eup on angiogenesis. Transcriptomic analysis was performed to identify the targets of Eup in H1299 cells and to explore its major functions. Molecular docking and molecular dynamics simulations were conducted to predict the binding affinity and interaction stability between Eup and its target proteins. Western blot was used to detect the effects of Eup on the expression levels of EZH2/H3K27me3 pathway-related proteins and proliferation- and invasion/metastasis-related proteins, including PCNA, MMP-2, MMP-9, and VEGFA. ResultsIn the subcutaneous xenograft model, compared with the model group, Eup treatment dose-dependently inhibited the growth of H1299 xenograft tumors, and the tumor inhibition rate was significantly increased (P<0.05). IHC-P results showed that, compared with the model group, high-dose Eup significantly reduced the expression levels of PCNA, MMP-2, MMP-9, and VEGFA in vivo (P<0.05). In vitro, compared with the control group, Eup inhibited the proliferation, invasion, and metastasis of NSCLC cells in a concentration-dependent manner. Transcriptomic analysis further showed that, compared with the control group, Eup significantly downregulated EZH2 expression, and its functional effects were associated with inhibition of tumor metastasis. Molecular docking and molecular dynamics simulations indicated that Eup exhibited strong binding affinity with EZH2 and stable interactions. Western blot results demonstrated that, compared with the model group, Eup significantly inhibited, in a dose-dependent manner, the expression levels of EZH2, H3K27me3, and proliferation- and invasion/metastasis-related proteins (PCNA, MMP-2, MMP-9, and VEGFA) in both in vivo and in vitro experiments (P<0.05). In vitro, compared with the control group, overexpression of EZH2 via plasmid transfection partially reversed the inhibitory effects of Eup on the expression of key proteins involved in proliferation and invasion/metastasis in H1299 cells. ConclusionEup effectively inhibits the proliferation, migration, and invasion of H1299 cells both in vivo and in vitro. The underlying mechanism may be related to inhibition of the EZH2/H3K27me3 signaling pathway and downregulation of proliferation- and invasion/metastasis-related proteins, including PCNA, MMP-2, MMP-9, and VEGFA. Eup may serve as a potential therapeutic agent for suppressing proliferation and invasion/metastasis in NSCLC.
4.Anti-lung Cancer Mechanisms of Yang-warming Herbs and Formulas: A Review
Bo XU ; Yu QI ; Jixian ZHANG ; Linling HU ; Bo JIANG ; Yilong ZOU ; Cunyu FAN ; Yiling FAN ; Qing MIAO ; Yihan YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):70-79
Lung cancer, particularly non-small cell lung cancer (NSCLC), is the malignant tumor with the highest incidence and mortality in China and worldwide. In 2022, the global number of deaths reached 1.8 million, accounting for 18.7% of all cancer-related deaths, seriously threatening human health and life, and posing a severe challenge for prevention and treatment. Although treatment strategies for lung cancer have been continuously enriched in recent years, and progress has been made in targeted therapy and immunotherapy, long-term survival benefits remain limited due to primary or acquired drug resistance, low immune responsiveness, and chemotherapy-related toxicities. Therefore, there is an urgent need to explore safe and effective adjunctive therapeutic strategies. Traditional Chinese medicine (TCM), with its advantages of holistic regulation and individualized syndrome differentiation, has played an increasingly prominent role in comprehensive cancer treatment. TCM holds that "Yang deficiency leads to accumulation" is a key pathogenesis of tumors. Based on the theory that "Yang transforms Qi, while Yin forms substance", deficiency of Yang Qi results in impaired warming and transformation functions, leading to internal accumulation of Yin-cold. This is closely related to dysregulation of the immune microenvironment, "cold tumor" characteristics, and dysfunction of the neuroendocrine system in modern medicine. Accordingly, the therapeutic strategy of "warming Yang, supporting healthy Qi, and combating cancer" has gained increasing attention. In recent years, commonly used Yang-warming Chinese herbs, including Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma, Cinnamomi Cortex, Epimedii Folium, and Psoraleae Fructus, as well as their active constituents, have achieved notable progress in anti-lung cancer research by regulating multiple signaling pathways, inducing apoptosis, inhibiting metastasis, and reversing drug resistance. In addition, Yang-warming formulae such as Sini Tang and Yanghe Tang have shown promising effects in alleviating myelosuppression, improving cancer-related fatigue, managing malignant pleural effusion, and relieving cancer pain. These therapies exhibit toxicity-reducing and efficacy-enhancing effects, significantly improving patients' quality of life and survival benefits. To systematically summarize the roles and mechanisms of Yang-warming Chinese herbal medicines and compound formulae in lung cancer, this paper provides a comprehensive review of recent advances, aiming to offer insights for the clinical practice of TCM in the prevention and treatment of lung cancer.
5.Eupatilin Inhibits Proliferation, Invasion, and Metastasis of Non-small Cell Lung Cancer via EZH2/H3K27me3 Signaling Pathway
Bo XU ; Yihan YU ; Linling HU ; Bo JIANG ; Yu QI ; Shasha YUAN ; Yiling FAN ; Jixian ZHANG ; Qing MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):58-69
ObjectiveTo investigate the mechanisms by which eupatilin (Eup) inhibits proliferation, invasion, and metastasis of non-small cell lung cancer (NSCLC) through the enhancer of zeste homolog 2/histone H3 lysine 27 trimethylation (EZH2/H3K27me3) signaling pathway. MethodsIn vivo, a subcutaneous xenograft tumor model was established in nude mice using H1299 cells to evaluate the anti-NSCLC effects of Eup. Immunohistochemistry (IHC-P) was used to detect the expression of proliferation- and invasion/metastasis-related proteins, including proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor A (VEGFA). In vitro, cell counting kit-8 (CCK-8) assays were performed to determine the viability of H1299 cells treated with different concentrations of Eup (0-200 μmol·L-1) and to select appropriate concentrations. Colony formation and 5-ethynyl-2′-deoxyuridine (EdU) assays were used to evaluate cell proliferation. Wound healing and invasion assays were conducted to assess cell migration and invasion. Human umbilical vein endothelial cell (HUVEC) angiogenesis assays were used to evaluate the effects of Eup on angiogenesis. Transcriptomic analysis was performed to identify the targets of Eup in H1299 cells and to explore its major functions. Molecular docking and molecular dynamics simulations were conducted to predict the binding affinity and interaction stability between Eup and its target proteins. Western blot was used to detect the effects of Eup on the expression levels of EZH2/H3K27me3 pathway-related proteins and proliferation- and invasion/metastasis-related proteins, including PCNA, MMP-2, MMP-9, and VEGFA. ResultsIn the subcutaneous xenograft model, compared with the model group, Eup treatment dose-dependently inhibited the growth of H1299 xenograft tumors, and the tumor inhibition rate was significantly increased (P<0.05). IHC-P results showed that, compared with the model group, high-dose Eup significantly reduced the expression levels of PCNA, MMP-2, MMP-9, and VEGFA in vivo (P<0.05). In vitro, compared with the control group, Eup inhibited the proliferation, invasion, and metastasis of NSCLC cells in a concentration-dependent manner. Transcriptomic analysis further showed that, compared with the control group, Eup significantly downregulated EZH2 expression, and its functional effects were associated with inhibition of tumor metastasis. Molecular docking and molecular dynamics simulations indicated that Eup exhibited strong binding affinity with EZH2 and stable interactions. Western blot results demonstrated that, compared with the model group, Eup significantly inhibited, in a dose-dependent manner, the expression levels of EZH2, H3K27me3, and proliferation- and invasion/metastasis-related proteins (PCNA, MMP-2, MMP-9, and VEGFA) in both in vivo and in vitro experiments (P<0.05). In vitro, compared with the control group, overexpression of EZH2 via plasmid transfection partially reversed the inhibitory effects of Eup on the expression of key proteins involved in proliferation and invasion/metastasis in H1299 cells. ConclusionEup effectively inhibits the proliferation, migration, and invasion of H1299 cells both in vivo and in vitro. The underlying mechanism may be related to inhibition of the EZH2/H3K27me3 signaling pathway and downregulation of proliferation- and invasion/metastasis-related proteins, including PCNA, MMP-2, MMP-9, and VEGFA. Eup may serve as a potential therapeutic agent for suppressing proliferation and invasion/metastasis in NSCLC.
6.Anti-lung Cancer Mechanisms of Yang-warming Herbs and Formulas: A Review
Bo XU ; Yu QI ; Jixian ZHANG ; Linling HU ; Bo JIANG ; Yilong ZOU ; Cunyu FAN ; Yiling FAN ; Qing MIAO ; Yihan YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):70-79
Lung cancer, particularly non-small cell lung cancer (NSCLC), is the malignant tumor with the highest incidence and mortality in China and worldwide. In 2022, the global number of deaths reached 1.8 million, accounting for 18.7% of all cancer-related deaths, seriously threatening human health and life, and posing a severe challenge for prevention and treatment. Although treatment strategies for lung cancer have been continuously enriched in recent years, and progress has been made in targeted therapy and immunotherapy, long-term survival benefits remain limited due to primary or acquired drug resistance, low immune responsiveness, and chemotherapy-related toxicities. Therefore, there is an urgent need to explore safe and effective adjunctive therapeutic strategies. Traditional Chinese medicine (TCM), with its advantages of holistic regulation and individualized syndrome differentiation, has played an increasingly prominent role in comprehensive cancer treatment. TCM holds that "Yang deficiency leads to accumulation" is a key pathogenesis of tumors. Based on the theory that "Yang transforms Qi, while Yin forms substance", deficiency of Yang Qi results in impaired warming and transformation functions, leading to internal accumulation of Yin-cold. This is closely related to dysregulation of the immune microenvironment, "cold tumor" characteristics, and dysfunction of the neuroendocrine system in modern medicine. Accordingly, the therapeutic strategy of "warming Yang, supporting healthy Qi, and combating cancer" has gained increasing attention. In recent years, commonly used Yang-warming Chinese herbs, including Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma, Cinnamomi Cortex, Epimedii Folium, and Psoraleae Fructus, as well as their active constituents, have achieved notable progress in anti-lung cancer research by regulating multiple signaling pathways, inducing apoptosis, inhibiting metastasis, and reversing drug resistance. In addition, Yang-warming formulae such as Sini Tang and Yanghe Tang have shown promising effects in alleviating myelosuppression, improving cancer-related fatigue, managing malignant pleural effusion, and relieving cancer pain. These therapies exhibit toxicity-reducing and efficacy-enhancing effects, significantly improving patients' quality of life and survival benefits. To systematically summarize the roles and mechanisms of Yang-warming Chinese herbal medicines and compound formulae in lung cancer, this paper provides a comprehensive review of recent advances, aiming to offer insights for the clinical practice of TCM in the prevention and treatment of lung cancer.
7.Patient guideline for non-pharmacological management of core symptom clusters in lung cancer patients undergoing chemotherapy
Ruiqi XI ; Lil ZHANG ; Lin XIAO ; Benxiang ZHU ; Qi QIAN ; Yuanyuan LUO ; Jingxia MIAO ; Peijuan CHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(10):1515-1526
Objective Patients with lung cancer often experience interrelated symptoms such as fatigue, pain, and sleep disturbances during chemotherapy, forming a core symptom cluster that significantly impacts daily functioning, treatment experience, and quality of life. Currently, evidence on non-pharmacological management of this core symptom cluster is scattered, and there is a lack of standardized, patient- and caregiver-friendly guidance tools that are easy to understand and implement. This patient guideline aims to provide decision support for self-management of the core symptom cluster in patients undergoing chemotherapy for lung cancer. Methods Guided by evidence-based methodology, qualitative interviews and on-site questionnaire surveys were conducted to identify the health-related needs of stakeholders. Domestic and international guideline websites, relevant professional association websites, and comprehensive databases were systematically searched according to the inclusion and exclusion criteria. The included literature was evaluated for quality, and recommendations were extracted, integrated, and graded to form a summary of the best evidence. Based on the identified health issues and evidence summary, preliminary recommendations for the patient guideline were developed. The recommendations were then revised through two rounds of Delphi expert consultation, and consensus was reached on the strength of recommendations, forming the final version of the patient guideline. Results The patient guideline covered four major sections: screening and assessment of core symptom clusters, daily management, intervention measures, and timing of referral. The core content included nine aspects: screening of core symptom clusters, assessment, lifestyle habits, dietary interventions, sleep environment, exercise interventions, psychological interventions, Traditional Chinese Medicine interventions, and referral indications. In total, the guidelines addressed 16 health issues and provided 25 recommendations. Conclusion The development process of this patient guideline is rigorous and fully considered the needs of patients. Expert review concludes that the recommendations are highly feasible and appropriate.
8.Textual Research and Application of Famous Classical Formula Huopo Xialingtang
Miao YU ; Huikang ZHANG ; Xiaofan QI ; Fuping LI ; Jichun ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):192-200
Huopo Xialingtang is a famous classical formula for treating dampness and warmth, which is included in the Catalogue of Ancient Famous Classical Formulas(The First Batch). In this paper, bibliometric methods was used to collect the literature related to Huopo Xialingtang, and 16 items of related literature were retrieved, involving five medical books, which were used to textual research on the origin, name, composition, drug dosage, preparation method, processing and main treatment symptoms of this formula. The results indicated that Huopo Xialingtang was originated from Yiyuan written by Shi Funan in the Qing dynasty, and and was later named and extended by He Lianchen. The composition of the proposed formula was consistent with the record of Yiyuan, and the origin of each Chinese materia medica was basically clear. Houpo was the dried bark and root bark of Magnolia officinalis, Zexie was the dried tubers of Alisma orientale, Kuxingren was the dried mature seeds of Prunus armeniaca, Doukou was the dried mature fruits of Amomum kravanh, the origin of Tuhuoxiang was consistent with the 2018 edition of Shanghai Standards of Processing Chinese Crud Drugs, and the origins of the remaining Chinese medicines were consistent with the 2020 edition of Chinese Pharmacopoeia. The converted dose of each Chinese medicine was 7.46 g for Agastache rugosa, 3.73 g for Magnoliae Officinalis Cortex, 8.39 g for Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine, 11.19 g for Poria, 11.19 g for Armeniacae Semen Amarum, 14.92 g for Coicis Semen, 2.61 g for Amomi Fructus Rotundus, 5.60 g for Polyporus, 5.60 g for Alismatis Rhizoma, 14.92 g for Tetrapanacis Medulla. Huopo Xialingtang was initially used for the treatment of dampness and warmth at the beginning of the disease, and was later expanded to treat dampness obstruction, dampness-warming dysentery and so on, but always with the dampness-heat in the lungs and spleen as the pathogenesis. In modern times, the clinical application is more extensive, used in digestive, respiratory, endocrine, nervous system and other types of diseases, especially for chronic gastritis, stomach pain and fever. By combing the ancient literature of Huopo Xialingtang, we verified the origin of the formula and determined the key information of the prescription, which can provide literature reference for the clinical application and drug development of this formula.
9.Expert consensus on non-surgical treatment for acute lateral ankle sprain (version 2025)
Hui CHE ; Wenge DING ; Shiming FENG ; Xueping GU ; Qinwei GUO ; Jianchao GUI ; Yinghui HUA ; Yuefeng HAO ; Qinglin HAN ; Bo HU ; Xiaojun LIANG ; Guoping LI ; Yunxia LI ; Qi LI ; Yanlin LI ; Xin MA ; Jun MA ; Xudong MIAO ; Jianzhong QIN ; Xiaodong QIN ; Xu SUN ; Kefu SUN ; Weidong SONG ; Dai SHI ; Zhongmin SHI ; Youlun TAO ; Xu WANG ; Youhua WANG ; Liheng WANG ; Anli WANG ; Aiguo WANG ; Weidong WU ; Yajun XU ; Weidong XU ; Renjie XU ; Yongsheng XU ; Tengbo YU ; Lianqi YAN ; Xiaodong YUAN ; Yuan ZHU ; Mingzhu ZHANG ; Hongtao ZHANG ; Xintao ZHANG ; Xiaofei ZHENG
Chinese Journal of Trauma 2025;41(6):517-529
Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.
10.Dehydrated hereditary stomatocytosis in 23 cases: a single-center retrospective cohort study from Peking Union Medical College Hospital (2018–2024)
Qi WANG ; Hao CAI ; Liling LIN ; Jian LI ; Bing HAN ; Miao CHEN
Chinese Journal of Hematology 2025;46(11):1014-1019
Objective:Dehydrated hereditary stomatocytosis (DHS), a rare condition caused by pathogenic PIEZO1 or KCNN4 mutations, remains under-recognized. This study aimed to improve the diagnosis and management of DHS in China by retrospectively analyzing clinical and genetic characteristics.Methods:Patients diagnosed with DHS at Peking Union Medical College Hospital between 2018 and 2024 were included. All had suspected congenital hemolytic anemia and were confirmed by next-generation sequencing to harbor pathogenic PIEZO1 or KCNN4 mutations. Clinical features, genotypes, iron overload, and treatment outcomes were collected and analyzed.Results:Twenty-three DHS patients were identified, including 21 with PIEZO1 and 2 with KCNN4 mutations. Common manifestations were splenomegaly, jaundice, cholelithiasis, and secondary iron overload. Mild and moderate anemia occurred in 8.7% and 17.4% of patients, respectively, and stomatocytes were present in only 17.4%. The median time from symptom onset to diagnosis was 11 years. The predominant PIEZO1 variants were c.7367G > A and c.6328C > T, with nine novel mutations identified. Both KCNN4 mutations involved c.1055G > A. No clear genotype–phenotype correlation was observed. Secondary hepatic iron overload was found in 21.7% of patients.Conclusion:DHS is often underdiagnosed or misdiagnosed. Genetic testing enables accurate identification, and regular monitoring for secondary hepatic iron overload is crucial for long-term management.

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