1.Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis
Jian LIU ; Hongchun ZHANG ; Chengxiang WANG ; Hongsheng CUI ; Xia CUI ; Shunan ZHANG ; Daowen YANG ; Cuiling FENG ; Yubo GUO ; Zengtao SUN ; Huiyong ZHANG ; Guangxi LI ; Qing MIAO ; Sumei WANG ; Liqing SHI ; Hongjun YANG ; Ting LIU ; Fangbo ZHANG ; Sheng CHEN ; Wei CHEN ; Hai WANG ; Lin LIN ; Nini QU ; Lei WU ; Dengshan WU ; Yafeng LIU ; Wenyan ZHANG ; Yueying ZHANG ; Yongfen FAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):182-188
The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis (GS/CACM 337-2023) was released by the China Association of Chinese Medicine on December 13th, 2023. This expert consensus was developed by experts in methodology, pharmacy, and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine (CACM) and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine (pulmonary diseases) and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung, acute bronchitis, and acute attack of chronic bronchitis from the aspects of applicable populations, efficacy evaluation, usage, dosage, drug combination, and safety. It is expected to guide the rational drug use in medical and health institutions, give full play to the unique value of Qinbaohong Zhike oral liquid, and vigorously promote the inheritance and innovation of Chinese patent medicines.
2.Current status of generalized pustular psoriasis: Findings from a multicenter hospital-based survey of 127 Chinese patients.
Haimeng WANG ; Jiaming XU ; Xiaoling YU ; Siyu HAO ; Xueqin CHEN ; Bin PENG ; Xiaona LI ; Ping WANG ; Chaoyang MIAO ; Jinzhu GUO ; Qingjie HU ; Zhonglan SU ; Sheng WANG ; Chen YU ; Qingmiao SUN ; Minkuo ZHANG ; Bin YANG ; Yuzhen LI ; Zhiqiang SONG ; Songmei GENG ; Aijun CHEN ; Zigang XU ; Chunlei ZHANG ; Qianjin LU ; Yan LU ; Xian JIANG ; Gang WANG ; Hong FANG ; Qing SUN ; Jie LIU ; Hongzhong JIN
Chinese Medical Journal 2025;138(8):953-961
BACKGROUND:
Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited.
METHODS:
This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed.
RESULTS:
Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P = 0.021) and transitioning to plaque psoriasis ( P = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP.
CONCLUSIONS
The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans
;
Male
;
Female
;
Psoriasis/pathology*
;
Adult
;
Cross-Sectional Studies
;
Adolescent
;
Child
;
Young Adult
;
Quality of Life
;
Middle Aged
;
China/epidemiology*
;
Recurrence
;
Risk Factors
;
Surveys and Questionnaires
;
East Asian People
3.Randomized, double-blind, parallel-controlled, multicenter, equivalence clinical trial of Jiuwei Xifeng Granules(Os Draconis replaced by Ostreae Concha) for treating tic disorder in children.
Qiu-Han CAI ; Cheng-Liang ZHONG ; Si-Yuan HU ; Xin-Min LI ; Zhi-Chun XU ; Hui CHEN ; Ying HUA ; Jun-Hong WANG ; Ji-Hong TANG ; Bing-Xiang MA ; Xiu-Xia WANG ; Ai-Zhen WANG ; Meng-Qing WANG ; Wei ZHANG ; Chun WANG ; Yi-Qun TENG ; Yi-Hui SHAN ; Sheng-Xuan GUO
China Journal of Chinese Materia Medica 2025;50(6):1699-1705
Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent
;
Child
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Child, Preschool
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Female
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Humans
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Male
;
Double-Blind Method
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Drugs, Chinese Herbal/therapeutic use*
;
Tic Disorders/drug therapy*
;
Treatment Outcome
4.Theoretical discussion and research progress on treatment of glucocorticoid- induced osteoporosis with traditional Chinese medicine.
Ting-Ting XU ; Ying DING ; Xia ZHANG ; Long WANG ; Shan-Shan XU ; Chun-Dong SONG ; Wen-Sheng ZHAI ; Xian-Qing REN
China Journal of Chinese Materia Medica 2025;50(16):4437-4450
Glucocorticoid-induced osteoporosis(GIOP) is a serious metabolic bone disease caused by long-term application of glucocorticoids(GCs). Traditional Chinese medicine(TCM) has unique advantages in improving bone microstructure and antagonizing hormone toxicity. This paper systematically reviews the theoretical research, clinical application, and basic research progress of TCM intervention in GIOP. In terms of theoretical research, the theory of "kidney governing bone and generating marrow" indicates that the kidney is closely related to bone development, revealing that core pathogenesis of GIOP is Yin-Yang disharmony, which can be discussed using the theories of "Yin fire", "ministerial fire", and "Yang pathogen damaging Yin". Thus, regulating Yin and Yang is the basic principle to treat GIOP. In terms of clinical application, effective empirical prescriptions(such as Bushen Zhuanggu Decoction, Bushen Jiangu Decoction, and Zibu Ganshen Formula) and Chinese patent medicines(Gushukang Capsules, Hugu Capsules, Xianling Gubao Capsules, etc.) can effectively increase bone mineral density(BMD) and improve calcium and phosphorus metabolism. The combination of traditional Chinese and western medicine can reduce the risk of fracture and play an anti-GIOP role. In terms of basic research, it has been clarified that active ingredients of TCM(such as fraxetin, ginsenoside Rg_1, and salidroside) reduce bone loss and promote bone formation by inhibiting oxidative stress, ferroptosis, and other pathways, effectively improving bone homeostasis. Additionally, classical prescriptions(Modified Yiguan Decoction, Modified Qing'e Pills, Zuogui Pills, etc.) and Chinese patent medicines(Gushukang Granules, Lurong Jiangu Dropping Pills, Gubao Capsules, etc.) can improve bone marrow microcirculation, promote osteoblast differentiation, and inhibit bone cell apoptosis through multiple pathways, multiple targets, and multiple mechanisms. Through the above three aspects, the TCM research status on GIOP is elucidated in the expectation of providing reference for its diagnosis and treatment using traditional Chinese and western medicine treatment programs.
Osteoporosis/physiopathology*
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Humans
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Glucocorticoids/adverse effects*
;
Drugs, Chinese Herbal/administration & dosage*
;
Animals
;
Medicine, Chinese Traditional
;
Bone Density/drug effects*
5.Early clinical observation of the efficacy of a three-stage traditional Chinese medicine external treatment plan for talus Bone bruises caused by acute ankle sprain.
Mei-Qi YU ; Lei ZHANG ; Tian-Xin CHEN ; Ting-Ting DONG ; Yan LI ; Jun-Ying WU ; Bo JIANG ; Sheng ZHANG ; Xiao-Hua LIU ; Jin SUN ; Qing-Lin WANG
China Journal of Orthopaedics and Traumatology 2025;38(8):835-841
OBJECTIVE:
To explore the early clinical efficacy of a three-stage external treatment with traditional Chinese medicine (TCM) in the treatment of talar bone contusion caused by acute ankle sprain.
METHODS:
A retrospective analysis was performed on 360 patients with primary lateral ankle sprain admitted from September 2021 to July 2024. Patients with talar bone contusion were selected based on MRI examination, and 73 cases were finally included. According to different treatment methods, they were divided into the observation group and the control group. The observation group consisted of 35 cases, including 16 males and 19 females, aged 24 to 37 years old with an average of (30.34±2.68) years old, and received the three-stage external TCM treatment combined with the "POLICE" protocol. The control group included 38 cases, including 18 males and 20 females, aged 24 to 35 years old with an average of (29.87±2.57) years old, and was treated with the "POLICE" protocol alone. The volume of bone marrow edema (BME) area shown by MRI before treatment and 6 weeks after treatment was measured using 3D Slicer software, and the BME improvement rate was calculated. The "Figure of 8" measurement method was used to assess ankle swelling before treatment and at 1 and 3 weeks after treatment. The visual analogue scale (VAS) was used to evaluate ankle pain before treatment and at 1 and 6 weeks after treatment. At 6 weeks after treatment, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Karlsson ankle function score system were used to evaluate the improvement of ankle function.
RESULTS:
A total of 73 patients with talar bone contusion caused by ankle sprain completed the 6-week follow-up. At 6 weeks after treatment, the BME improvement rate in the observation group was (39.18±0.06)%, which was higher than (26.75±0.03)% in the control group, with a statistically significant difference (P<0.05). After 1 week of treatment, the VAS score in the observation group was (2.89±0.72) points, lower than (3.37±0.79) points in the control group, and the difference was statistically significant (P<0.05). The ankle swelling degree in the observation group was (50.20±3.19) cm, lower than (52.00±3.60) cm in the control group, with a statistically significant difference (P<0.05). After 3 weeks of treatment, there was no statistically significant difference in ankle swelling between the two groups. At 6 weeks after treatment, there was no statistically significant difference in VAS scores between the two groups. At 6 weeks after treatment, the AOFAS ankle-hindfoot score and Karlsson score in the observation group were (87.43±4.18) and (82.77±5.93) points, respectively, which were higher than (82.92±4.87) and (76.45±6.85) points in the control group, with statistically significant differences (P<0.05). According to the AOFAS ankle-hindfoot score, 8 cases were excellent and 27 cases were good in the observation group;2 cases were excellent, 33 cases were good, and 3 cases were fair in the control group. The difference between the two groups was statistically significant (χ2=7.089, P=0.029).
CONCLUSION
The three-stage external TCM treatment combined with the "POLICE" protocol has a significant early clinical efficacy. It can significantly reduce ankle pain and swelling in patients with bone contusion caused by acute lateral ankle sprain, promote the absorption of bone marrow edema, and accelerate the recovery of ankle function.
Ankle Injuries/drug therapy*
;
Drugs, Chinese Herbal/administration & dosage*
;
Talus/injuries*
;
Retrospective Studies
;
Administration, Cutaneous
;
Magnetic Resonance Imaging
;
Humans
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Male
;
Female
;
Young Adult
;
Adult
;
Contusions/etiology*
;
Visual Analog Scale
;
Musculoskeletal Pain/etiology*
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Recovery of Function/drug effects*
;
Treatment Outcome
;
Follow-Up Studies
6.Clinical characteristics and prognosis of acute erythroleukemia in children.
Ping ZHU ; Wen-Jing QI ; Ye-Qing TAO ; Ding-Ding CUI ; Guang-Yao SHENG ; Chun-Mei WANG
Chinese Journal of Contemporary Pediatrics 2025;27(1):88-93
OBJECTIVES:
To investigate the clinical characteristics and prognosis of acute erythroleukemia (AEL) in children.
METHODS:
A retrospective analysis was conducted on the clinical data, treatment, and prognosis of 8 children with AEL treated at the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023.
RESULTS:
Among the 7 patients with complete bone marrow morphological analysis, 4 exhibited trilineage dysplasia, with a 100% incidence of erythroid dysplasia (7/7), a 71% incidence of myeloid dysplasia (5/7), and a 57% incidence of megakaryocytic dysplasia (4/7). Immunophenotyping revealed that myeloid antigens were primarily expressed as CD13, CD33, CD117, CD38, and CD123, with 4 cases expressing erythroid antigens CD71 and 2 cases expressing CD235a. Chromosomal analysis indicated that 2 cases presented with abnormal karyotypes, including +8 in one case and +4 accompanied by +6 in another; no complex karyotypes were observed. Genetic abnormalities were detected in 4 cases, with fusion genes including one case each of dup MLL positive and EVI1 positive, as well as mutations involving KRAS, NRAS, WT1, and UBTF. Seven patients received chemotherapy, with 6 achieving remission after one course of treatment; 2 underwent hematopoietic stem cell transplantation, and all had disease-free survival. Follow-up (median follow-up time of 6 months) showed that only 3 patients survived (2 cases after hematopoietic stem cell transplantation and 1 case during treatment).
CONCLUSIONS
Children with AEL have unique clinical and biological characteristics, exhibit poor treatment response, and have a poor prognosis; however, hematopoietic stem cell transplantation may improve overall survival rates.
Humans
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Male
;
Female
;
Prognosis
;
Child, Preschool
;
Retrospective Studies
;
Child
;
Leukemia, Erythroblastic, Acute/diagnosis*
;
Infant
;
Adolescent
7.Non-Down-syndrome-related acute megakaryoblastic leukemia in children: a clinical analysis of 17 cases.
Ding-Ding CUI ; Ye-Qing TAO ; Xiao-Pei JIA ; An-Na LIAN ; Qiu-Xia FAN ; Dao WANG ; Xue-Ju XU ; Guang-Yao SHENG ; Chun-Mei WANG
Chinese Journal of Contemporary Pediatrics 2025;27(9):1113-1118
OBJECTIVES:
To investigate the clinical features and prognosis of children with non-Down-syndrome-related acute megakaryoblastic leukemia (non-DS-AMKL).
METHODS:
A retrospective analysis was conducted on the medical data of 17 children with non-DS-AMKL who were admitted to Children's Hospital of The First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023, and their clinical features, treatment, and prognosis were summarized.
RESULTS:
Among the 17 children with non-DS-AMKL, there were 8 boys and 9 girls. Fourteen patients had an onset age of less than 36 months, with a median age of 21 months (range:13-145 months). Immunophenotyping results showed that 16 children were positive for CD61 and 13 were positive for CD41. The karyotype analysis was performed on 16 children, with normal karyotype in 6 children and abnormal karyotype in 9 children, among whom 5 had complex karyotype and 1 had no mitotic figure. Detected fusion genes included EVI1, NUP98-KDM5A, KDM5A-MIS18BP1, C22orf34-BRD1, WT1, and MLL-AF9. Genetic alterations included TET2, D7S486 deletion (suggesting 7q-), CSF1R deletion, and PIM1. All 17 children received chemotherapy, among whom 16 (94%) achieved complete remission after one course of induction therapy, and 1 child underwent hematopoietic stem cell transplantation (HSCT) and remained alive and disease-free. Of all children, 7 experienced recurrence, among whom 1 child received HSCT and died of graft-versus-host disease. At the last follow-up, six patients remained alive and disease-free.
CONCLUSIONS
Non-DS-AMKL primarily occurs in children between 1 and 3 years of age. The patients with this disorder have a high incidence rate of chromosomal abnormalities, with complex karyotypes in most patients. Some patients harbor fusion genes or gene mutations. Although the initial remission rate is high, the long-term survival rate remains low.
Humans
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Male
;
Female
;
Leukemia, Megakaryoblastic, Acute/etiology*
;
Child, Preschool
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Infant
;
Child
;
Retrospective Studies
;
Prognosis
;
Down Syndrome/complications*
8.Efficacy and Safety of DCAG Regimen in Patients with Relapsed/Refractory Acute Myeloid Leukemia.
Hui-Sheng ZHOU ; Yu-Qing LI ; Yu-Xin WANG ; Ya-Lei HU ; Kai-Li MIN ; Chun-Ji GAO ; Dai-Hong LIU ; Xiao-Ning GAO
Journal of Experimental Hematology 2025;33(1):9-19
OBJECTIVE:
To evaluate the efficacy and safety of DCAG (decitabine, cytarabine, anthracyclines, and granulocyte colony-stimulating factor) regimen in the treatment of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML).
METHODS:
The clinical data of 64 R/R AML patients received treatment at Chinese PLA General Hospital from January 1st, 2012 to December 31st, 2022 were retrospectively analyzed. Primary endpoints included efficacy measured by overall response rate (ORR) and safety. Secondary endpoints included overall survival (OS), event-free survival (EFS) and duration of response (DOR). The patients were followed from enrollment until death, or the end of last follow-up (June 1st, 2023), whichever occurred first.
RESULTS:
Sixty-four patients who failed prior therapy were enrolled and completed 1 cycle, and 26 and 5 patients completed 2 and 3 cycles, respectively. Objective response rate was 67.2% [39: complete remission (CR)/CR with incomplete hematologic recovery (CRi), 4: partial remission (PR)]. With a median follow-up of 62.0 months (1.0-120.9), the median overall survival (OS) was 23.3 and event-free survival was 10.6 months. The median OS was 51.7 months (3.4-100.0) in responders (CR/CRi/PR) while it was 8.4 months (6.1-10.7) in nonresponders ( P <0.001). Grade 3-4 hematologic toxicities were observed in all patients. Four patients died from rapid disease progression within 8 weeks after chemotherapy.
CONCLUSION
The DCAG regimen represents a feasible and effective treatment for R/R AML.
Humans
;
Leukemia, Myeloid, Acute/drug therapy*
;
Cytarabine/administration & dosage*
;
Granulocyte Colony-Stimulating Factor/administration & dosage*
;
Retrospective Studies
;
Male
;
Female
;
Decitabine
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Anthracyclines/administration & dosage*
;
Middle Aged
;
Adult
;
Treatment Outcome
;
Aged
;
Recurrence
9.Protective effect of achyranthes bidentata against doxorubicin-induced spermatogenic disorder in mice: An investigation based on the glycolytic metabolic pathway.
Man-Yu WANG ; Yang FU ; Pei-Pei YUAN ; Li-Rui ZHAO ; Yan ZHANG ; Qing-Yun MA ; Yan-Jun SUN ; Wei-Sheng FENG ; Xiao-Ke ZHENG
National Journal of Andrology 2025;31(2):99-107
OBJECTIVE:
To investigate the protective effect of achyranthes bidentata (AB) on sperm quality in mice with spermatogenic disorder through the glycolytic metabolic pathway and its action mechanism.
METHODS:
We equally randomized 40 Kunming mice into a normal control, a model control, a low-dose AB (3.5 g/kg) and a high-dose AB group (7.0 g/kg), and established the model of spermatogenic disorder in the latter three groups of mice by intraperitoneal injection of doxorubicin (30 mg/kg). Two days after modeling, we collected the testis and kidney tissues and blood samples from the mice for observation of the pathological changes in the testis tissue by HE staining, detection of perm motility with the sperm quality analyzer, examination of the apoptosis of testis cells by flow cytometry, measurement of the levels of testosterone (T), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in the serum and testis tissue by ELISA, and determination of expressions of the key enzymes of glycolysis hexokinase Ⅱ (HK2), pyruvate kinase M2 (PKM2), platelet phosphofructokinase (PFKP), lactate dehydrogenase A (LDHA) and the meiosis proteins REC8 and SCP3 by Western blot, and the mRNA expressions of glycolytic phosphofructokinase 1 (PFK1), phosphoglycerate kinase 1 (PGK1), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) by fluorescence quantitative PCR (FQ-PCR).
RESULTS:
Compared with the model controls, the mice in the AB groups showed significant increases in the testis coefficient, kidney index, sperm concentration, sperm motility, spermatogonia, primary spermatocytes, spermatids, sperm count and the serum T level (P<0.05 or P<0.01), but dramatic decreases in the apoptosis of testis cells and percentage of morphologically abnormal sperm (P<0.01). Achyranthes bidentata also significantly elevated the levels of SOD and CAT, and down-regulated the mRNA expressions of MDA, TNF-α and IL-1β (P<0.05 or P<0.01), and up-regulated the protein expressions of HK2, PKM2, PFKP, LDHA, REC8 and SCP3, and expressions of the glycolysis key genes Pfk1 and Pgk1 (P<0.05 or P<0.01).
CONCLUSION
Achyranthes bidentata ameliorates doxorubicin-induced spermatogenic disorder in mice by regulating the glycolytic pathway and reducing oxidative stress and the expressions of inflammatory factors.
Glycolysis/drug effects*
;
Doxorubicin/toxicity*
;
Spermatogenesis/drug effects*
;
Random Allocation
;
Male
;
Animals
;
Mice
;
Disease Models, Animal
;
Achyranthes/chemistry*
;
Spermatozoa/pathology*
;
Oxidative Stress/drug effects*
;
Primary Cell Culture
;
Apoptosis/drug effects*
;
Sperm Motility/drug effects*
;
Testis/pathology*
;
Infertility, Male/prevention & control*
;
Medicine, Chinese Traditional/methods*
;
Animals, Outbred Strains
10.Extracellular vesicles deliver thioredoxin to rescue stem cells from senescence and intervertebral disc degeneration via a feed-forward circuit of the NRF2/AP-1 composite pathway.
Xuanzuo CHEN ; Sheng LIU ; Huiwen WANG ; Yiran LIU ; Yan XIAO ; Kanglu LI ; Feifei NI ; Wei WU ; Hui LIN ; Xiangcheng QING ; Feifei PU ; Baichuan WANG ; Zengwu SHAO ; Yizhong PENG
Acta Pharmaceutica Sinica B 2025;15(2):1007-1022
Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.

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