1.Exploring Pathogenesis and Treatment of Primary Osteoporosis from Theory of Qi Deficiency and Stagnation and Mitochondrial Autophagy
Jiali ZHANG ; Yubin ZHANG ; Ruoying SONG ; Jianqiang LI ; Feng LI ; Jiayi GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):230-241
Primary osteoporosis (POP) is a metabolic bone disease characterized by reduced bone mass, degenerated bone microstructure, and increased bone fragility. Its pathogenesis involves the interaction of multiple factors such as genetics, aging, endocrine, and environment, which remain incompletely elucidated. Mitochondrial dysfunction can lead to insufficient adenosine triphosphate (ATP) production and abnormal accumulation of reactive oxygen species (ROS), activating oxidative stress and inflammation pathways, thereby inhibiting osteoblast differentiation and promoting osteoclast activation, exacerbating the negative bone metabolism balance in POP. Mitochondrial autophagy, as the core mechanism of mitochondrial quality control, selectively identifies and clears damaged mitochondria to effectively reduce ROS accumulation and energy metabolism disorders, thus maintaining the balance between osteoblast and osteoclast differentiation. It plays a critical role in maintaining bone homeostasis and the prevention and treatment of POP. The traditional Chinese medicine (TCM) theory of Qi transformation shares similarities with the functions of mitochondria in energy generation and substance conversion. The pathological state of Qi deficiency and stagnation may be associated with mitochondrial autophagy dysfunction, and the pathogenic characteristics of combined phlegm and stasis align with the metabolic waste accumulation induced by obstructed autophagy flow. This article explores the correlation of the theory of Qi deficiency and stagnation with mitochondrial autophagy and elucidates its potential role in the pathogenesis of POP. Additionally, considering the pathogenesis features of POP, which involve deficiency causing stagnation and a mixture of deficiency and excess, this article proposes a novel therapeutic approach: tonifying Qi to support the body and unblocking collaterals to resolve stagnation from the perspective of mitochondrial autophagy. This article aims to provide theoretical support and research insights for further exploration of TCM in the prevention and treatment of POP.
2.Exploring Pathogenesis and Treatment of Primary Osteoporosis from Theory of Qi Deficiency and Stagnation and Mitochondrial Autophagy
Jiali ZHANG ; Yubin ZHANG ; Ruoying SONG ; Jianqiang LI ; Feng LI ; Jiayi GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):230-241
Primary osteoporosis (POP) is a metabolic bone disease characterized by reduced bone mass, degenerated bone microstructure, and increased bone fragility. Its pathogenesis involves the interaction of multiple factors such as genetics, aging, endocrine, and environment, which remain incompletely elucidated. Mitochondrial dysfunction can lead to insufficient adenosine triphosphate (ATP) production and abnormal accumulation of reactive oxygen species (ROS), activating oxidative stress and inflammation pathways, thereby inhibiting osteoblast differentiation and promoting osteoclast activation, exacerbating the negative bone metabolism balance in POP. Mitochondrial autophagy, as the core mechanism of mitochondrial quality control, selectively identifies and clears damaged mitochondria to effectively reduce ROS accumulation and energy metabolism disorders, thus maintaining the balance between osteoblast and osteoclast differentiation. It plays a critical role in maintaining bone homeostasis and the prevention and treatment of POP. The traditional Chinese medicine (TCM) theory of Qi transformation shares similarities with the functions of mitochondria in energy generation and substance conversion. The pathological state of Qi deficiency and stagnation may be associated with mitochondrial autophagy dysfunction, and the pathogenic characteristics of combined phlegm and stasis align with the metabolic waste accumulation induced by obstructed autophagy flow. This article explores the correlation of the theory of Qi deficiency and stagnation with mitochondrial autophagy and elucidates its potential role in the pathogenesis of POP. Additionally, considering the pathogenesis features of POP, which involve deficiency causing stagnation and a mixture of deficiency and excess, this article proposes a novel therapeutic approach: tonifying Qi to support the body and unblocking collaterals to resolve stagnation from the perspective of mitochondrial autophagy. This article aims to provide theoretical support and research insights for further exploration of TCM in the prevention and treatment of POP.
3.Early Nutrition, Growth Parameters and DNA Methylation Differences of Preterm Monochorionic Diamniotic Twins Combined with Selective Intrauterine Growth Restriction
Jiali FENG ; Peisong CHEN ; Muxue YU
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(2):328-335
ObjectiveTo investigate early nutrition and growth of preterm monochorionic diamniotic(MCDA) twins combined with selective intrauterine growth restriction(sIUGR) and explore the potential role of DNA methylation in regulating extrauterine growth. MethodsTwenty-four pairs of preterm MCDA twins combined with sIUGR hospitalized in the Department of Neonatology of The First Affiliated Hospital of Sun Yat-sen University from March 2019 to February 2022 were enrolled, divided into larger twins group(n=24) and smaller twins group (n=24) according to birth weight. The comparison of daily nutritional intakes, the incidence of neonatal complications and physical growth from birth to 24 months of corrected age between two groups was performed using t-test, analysis of ANOVA, Chi-square test or Fisher's exact test. Differential DNA methylation analysis was performed using the methylation microarrays and differentially methylated site was validated using pyrosequencing method. ResultsThere were no significant differences in the daily intake of carbohydrate, protein, fat and energy between two groups (all P>0.05). There were no significant differences in the incidence of asphyxia, neonatal respiratory distress syndrome, bronchopulmonary dysplasia, retinopathy of prematurity and necrotizing enterocolitis between two groups (all P>0.05). Z-scores for weight, length and head circumference were significantly lower in the smaller twins group compared with the larger twins group from birth to 24 months of corrected age(all P =0.000). Difference in Z-scores for weight and length at term, 6 months, 12 months of corrected age did not differ significantly from that at birth(all P>0.05) while difference in Z-scores for weight and length between the twins at 18 months and 24 months of corrected age were significantly lower than that at birth (P = 0.009, P = 0.032, P = 0.026, P = 0.004). Difference in Z-scores for head circumference at 6 months, 12 months, 18 months, 24 months of corrected age were significantly lower than at birth (P = 0.001, others P = 0.000) except at term(P>0.05). The differences in weight, length and head circumference between the twins at term, 6 months, 12 months, 18 months and 24 months of corrected age significantly reduced (P = 0.001, P = 0.007, P = 0.001, others P = 0.000). Eighteen differentially methylated sites were identified and the methylation level of NFATC1 gene in the smaller twins group was significantly higher than that in the larger twins group(P = 0.043). ConclusionMCDA twins combined with sIUGR shares similar early nutrition and neonatal complications, while smaller twins at 24 months of corrected age grow faster than larger twins, which might be related to a higher methylation level of NFATC1 gene in smaller twins.
4.Exploring Clinical Application and Mechanism of Huangqi Guizhi Wuwutang Based on Theory of Treating Different Diseases with Same Method
Jiali ZHANG ; Yubin ZHANG ; Chuang GUO ; Ruoying SONG ; Zhipeng LI ; Yongbing WEN ; Feng LI ; Jiayi GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(22):224-235
Huangqi Guizhi Wuwutang was first documented in ZHANG Zhongjing's Synopsis of the Golden Chamber in the Eastern Han Dynasty as the principal formula for treating blood obstruction syndrome. It is composed of Astragali Radix, Cinnamomi Ramulus, Paeoniae Radix Alba, Zingiberis Rhizoma Recens, and Jujubae Fructus. This formula exhibits the effects of replenishing Qi, warming meridians, harmonizing blood, and relieving obstruction, being primarily indicated for blood obstruction syndrome characterized by diminished Yin and Yang functions with external manifestations of bodily numbness. Traditional Chinese medicine (TCM) emphasizes strict adherence to pathogenesis while applying tailored therapies, employing consistent treatment approaches for conditions with diverse clinical presentations but shared pathogenesis, which embodies the principle of treating different diseases with the same method. In modern clinical practice, Huangqi Guizhi Wuwutang is widely applied in multisystem disorders presenting with symptoms such as cutaneous numbness, cold-induced pain and stiffness, and soreness and weakness, including diabetic peripheral neuropathy, cervical radiculopathy, rheumatoid arthritis, coronary heart disease, pediatric spastic cerebral palsy, and recovery phases of cerebral infarction, demonstrating proven efficacy. Modern pharmacological studies confirm its anti-inflammatory, antioxidant-stress, hemorheological-improving, immunomodulatory, and neuroprotective effects by regulating multiple signaling pathways such as nuclear factor (NF)-κB/NOD-like receptor protein 3 (NLRP3) and nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE), thereby addressing common pathological processes including inflammation, hypercoagulability, oxidative stress, immune dysregulation, and neural injury, highlighting the integrated regulatory advantages of TCM formulas with multi-target, multi-level, multi-component, and multi-pathway mechanisms. According to the theory of treating different diseases with the same method and focusing on three core syndromes of blood obstruction, this article systematically reviews and elucidates the clinical extensions and shared mechanisms of this formula, aiming to provide evidence-based insights for the modern adaptation and precise application of this classical formula in orthopedic and related disciplines for chronic musculoskeletal disorders.
5.Study on mechanism of immunogenic cell death induced by ginsenoside octanoate through induction of autophagy in hepatocellular carcinoma cells
Fuxiang SONG ; Zhenzhen DAI ; Jingjing SHENG ; Jiali CHEN ; Hui ZHANG ; Hua FENG ; Yao PAN ; Zeyuan DENG ; Fang CHEN
Chinese Journal of Immunology 2025;41(6):1427-1432
Objective:To investigate the effect of ginsenoside octanoate(Rh2-O)on inducing immunogenic cell death in hepa-tocellular carcinoma cells and its molecular mechanism.Methods:Effects of ginsenoside caprylate(Rh2-O)and autophagy inhibitor 3-MA on the activity of hepatocellular carcinoma cells were detected by CCK-8 assay.The effect of Rh2-O on CRT membrane eversion in Hepa1-6 cells were detected by immunofluorescence assay.Rh2-O treated mouse hepatocellular carcinoma cells were used to pre-pare a tumor vaccine for in vivo vaccination experiments in mice.Extracellular ATP levels were detected in real-time.The expression of autophagy-related genes and proteins were measured by real-time fluorescence PCR and Western blot,and the mitochondrial morphol-ogy and co-localization with autophagy proteins were observed by laser confocal microscopy.Results:Rh2-O showed strong cytotoxicity to Hepa1-6 cells[cell viability:(58.54±3.56)%]at a concentration of 150 μmol/L,and a large amount of CRT was observed on the surface of the cell membrane.The tumor emergence rate was 36.36%in the vaccinated group and 100%in the control group.The tumor vaccine prepared by Rh2-O effectively protected mice from the same type of tumor attack;Rh2-O induced an increase in the level of cellular secreted ATP(P<0.05),the mRNA of autophagy-related genes ATG3,p62,LC3 expression levels and autophagy-associated proteins LC3A and LC3B expression levels were increased(P<0.05),and co-localization of mitochondria with autophagy proteins was significantly increased(P<0.05).In addition,Rh2-O action on 3-MA pretreated hepatocellular carcinoma cells resulted in a signifi-cant decrease in extracellular ATP levels(P<0.001).Conclusion:Rh2-O may induce immunogenic cell death by inducing autophagy in hepatocellular carcinoma cells.
6.CD34 + selected donor hematopoietic stem cell infusion for poor graft function after allogeneic hematopoietic stem cell transplantation: a retrospective cohort study
Shuo LIU ; Qiang LI ; Zhenyun LIU ; Ruihui DU ; Bin LIU ; Zhaoyong MA ; Erlie JIANG ; Sizhou FENG ; Jiali SUN
Chinese Journal of Hematology 2025;46(10):921-928
Objective:To evaluate the efficacy of purified donor CD34 positive hematopoietic stem cell (CD34 + cell) infusion in patients with poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods:The clinical data of 25 patients with PGF who underwent donor CD34 + cell sorting and infusion at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between September 2019 and March 2023, were retrospectively analyzed. The cohort included 19 haploidentical and 6 HLA-matched cases. CD34 + cells were purified using immunomagnetic beads for therapeutic infusion. The purification efficiency was evaluated based on the purity and recovery rate of CD34 + cells. Clinical outcomes were assessed by hematopoietic recovery, overall survival (OS) rate, and the incidence of graft-versus-host disease (GVHD) . Results:The median total number of CD34 + cells was 2.64 (0.82-6.53) × 10 8 before purification and 2.22 (0.48-5.68) ×10 8 after purification, with a median recovery rate of 78.37% (58.48%-115.72%) . After infusion of purified CD34 + cells, 8 of 10 patients (80.0%) with poor neutrophil engraftment achieved recovery (absolute neutrophil count ≥ 0.5×10 9/L) , with a median time to recovery of 21 (10-40) days. And 15 of 21 patients (71.4%) with poor platelet engraftment achieved recovery (platelet count ≥ 20×10 9/L) , with a median time to recovery of 15 (13-38) days. Only 3 patients (12.0%) developed GVHD after the infusion of purified CD34 + cells, including 2 cases of grade I acute GVHD and 1 case of limited chronic GVHD. With a median follow-up of 14.47 (0.23-41.63) months, the overall OS rate after CD34 + cell infusion was (65.63± 8.28) %. Seventeen patients survived, with a median survival time of 19.07 (0.23-41.63) months. Conclusion:Purification of CD34 + cells using immunomagnetic beads is effective, and the infusion of these purified donor CD34 + cells can safely and effectively improve PGF after allo-HSCT.
7.Study on mechanism of immunogenic cell death induced by ginsenoside octanoate through induction of autophagy in hepatocellular carcinoma cells
Fuxiang SONG ; Zhenzhen DAI ; Jingjing SHENG ; Jiali CHEN ; Hui ZHANG ; Hua FENG ; Yao PAN ; Zeyuan DENG ; Fang CHEN
Chinese Journal of Immunology 2025;41(6):1427-1432
Objective:To investigate the effect of ginsenoside octanoate(Rh2-O)on inducing immunogenic cell death in hepa-tocellular carcinoma cells and its molecular mechanism.Methods:Effects of ginsenoside caprylate(Rh2-O)and autophagy inhibitor 3-MA on the activity of hepatocellular carcinoma cells were detected by CCK-8 assay.The effect of Rh2-O on CRT membrane eversion in Hepa1-6 cells were detected by immunofluorescence assay.Rh2-O treated mouse hepatocellular carcinoma cells were used to pre-pare a tumor vaccine for in vivo vaccination experiments in mice.Extracellular ATP levels were detected in real-time.The expression of autophagy-related genes and proteins were measured by real-time fluorescence PCR and Western blot,and the mitochondrial morphol-ogy and co-localization with autophagy proteins were observed by laser confocal microscopy.Results:Rh2-O showed strong cytotoxicity to Hepa1-6 cells[cell viability:(58.54±3.56)%]at a concentration of 150 μmol/L,and a large amount of CRT was observed on the surface of the cell membrane.The tumor emergence rate was 36.36%in the vaccinated group and 100%in the control group.The tumor vaccine prepared by Rh2-O effectively protected mice from the same type of tumor attack;Rh2-O induced an increase in the level of cellular secreted ATP(P<0.05),the mRNA of autophagy-related genes ATG3,p62,LC3 expression levels and autophagy-associated proteins LC3A and LC3B expression levels were increased(P<0.05),and co-localization of mitochondria with autophagy proteins was significantly increased(P<0.05).In addition,Rh2-O action on 3-MA pretreated hepatocellular carcinoma cells resulted in a signifi-cant decrease in extracellular ATP levels(P<0.001).Conclusion:Rh2-O may induce immunogenic cell death by inducing autophagy in hepatocellular carcinoma cells.
8.Lichong Xiaozheng Granules enhances cisplatin sensitivity of ovarian cancer xenografts in rats by regulating adenine nucleotide translocator 3-mediated mitochondrial apoptosis
Yiliu CHEN ; Min MA ; Ran SU ; Yinbin ZHU ; Qing FENG ; Jiali LUO ; Weifeng FENG ; Xianxin YAN
Journal of Southern Medical University 2025;45(11):2309-2319
Objective To investigate the molecular mechanism by which Lichong Xiaozheng Granules(LCXZ)sensitize ovarian cancer to cisplatin(DDP)treatment.Methods LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage.In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts,the effects of daily gavage of distilled water(control group),intraperitoneal injection of DDP(5 mg/kg)once a week,or both DDP injection and daily LCXZK gavage(15 g/kg)on tumor growth were evaluated.Histopathological changes in the xenografts and kidneys were assessed with HE staining.RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis.The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting.Results A total of 218 blood-borne components of LCXZ were detected by LC-MS.In the tumor-bearing mice,treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3%and 72.6%compared with that in the control group,respectively.Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups.Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3(ANT3)with binding energies below-6 kcal/mol.Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice,and these changes were more pronounced in the combined treatment group.The expression levels of BAX,ANT3,cleaved caspase-3 and cleaved caspase-9 were increased,whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups.Conclusion LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.
9.Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury (version 2025)
Aijun XU ; Shuixia LI ; Bo CHEN ; Mengyuan YE ; Lejiao LANG ; Ning NING ; Lin ZHANG ; Changqing LIU ; Zhonglan CHEN ; Weihu MA ; Weishi LI ; Xiaoning WANG ; Dongmei BIAN ; Jiancheng ZENG ; Xin WANG ; Yuan GAO ; Yaping CHEN ; Jiali CHEN ; Yun HAN ; Xiuting LI ; Yang ZHOU ; Xiaojing SU ; Qiong ZHANG ; Tianwen HUANG ; Ping ZHANG ; Hua LIN ; Xingling XIAO ; Ruifeng XU ; Fanghui DONG ; Bing HAN ; Luo FAN ; Yanling PEI ; Suyun LI ; Xiaoju TAN ; Rongchen GUO ; Yefang ZOU ; Xiaoyun HAN ; Junqin DING ; Yi WANG ; Shuhua DENG ; Jinli GUO ; Yinhua LIANG ; Yuan CEN ; Xiaoqin LIU ; Junru CHEN ; Haiyang YU ; Lunlan LI ; Ying REN ; Yunxia LI ; Jianli LU ; Ying YING ; Lan WEI ; Yin WANG ; Qinhong XU ; Yanqin ZHANG ; Yang LYU ; Shijun ZHANG ; Sui WENJIE ; Sanlian HU ; Shuhong YANG ; Guoqing LI ; Jingjing AN ; Baorong HE ; Leling FENG
Chinese Journal of Trauma 2025;41(6):530-541
Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.
10.CD34 + selected donor hematopoietic stem cell infusion for poor graft function after allogeneic hematopoietic stem cell transplantation: a retrospective cohort study
Shuo LIU ; Qiang LI ; Zhenyun LIU ; Ruihui DU ; Bin LIU ; Zhaoyong MA ; Erlie JIANG ; Sizhou FENG ; Jiali SUN
Chinese Journal of Hematology 2025;46(10):921-928
Objective:To evaluate the efficacy of purified donor CD34 positive hematopoietic stem cell (CD34 + cell) infusion in patients with poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods:The clinical data of 25 patients with PGF who underwent donor CD34 + cell sorting and infusion at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between September 2019 and March 2023, were retrospectively analyzed. The cohort included 19 haploidentical and 6 HLA-matched cases. CD34 + cells were purified using immunomagnetic beads for therapeutic infusion. The purification efficiency was evaluated based on the purity and recovery rate of CD34 + cells. Clinical outcomes were assessed by hematopoietic recovery, overall survival (OS) rate, and the incidence of graft-versus-host disease (GVHD) . Results:The median total number of CD34 + cells was 2.64 (0.82-6.53) × 10 8 before purification and 2.22 (0.48-5.68) ×10 8 after purification, with a median recovery rate of 78.37% (58.48%-115.72%) . After infusion of purified CD34 + cells, 8 of 10 patients (80.0%) with poor neutrophil engraftment achieved recovery (absolute neutrophil count ≥ 0.5×10 9/L) , with a median time to recovery of 21 (10-40) days. And 15 of 21 patients (71.4%) with poor platelet engraftment achieved recovery (platelet count ≥ 20×10 9/L) , with a median time to recovery of 15 (13-38) days. Only 3 patients (12.0%) developed GVHD after the infusion of purified CD34 + cells, including 2 cases of grade I acute GVHD and 1 case of limited chronic GVHD. With a median follow-up of 14.47 (0.23-41.63) months, the overall OS rate after CD34 + cell infusion was (65.63± 8.28) %. Seventeen patients survived, with a median survival time of 19.07 (0.23-41.63) months. Conclusion:Purification of CD34 + cells using immunomagnetic beads is effective, and the infusion of these purified donor CD34 + cells can safely and effectively improve PGF after allo-HSCT.

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