1.Research progress on prevention strategies for immune platelet transfusion refractoriness
Peizhe ZHAO ; Yi XU ; Yajun LIANG ; Qing LI ; Yuan ZHOU ; Xianguo XU
Chinese Journal of Blood Transfusion 2025;38(3):448-454
Platelet transfusion refractoriness (PTR) is a common issue among patients with hematological diseases and tumors. This article reviews the diagnostic criteria, influencing factors, and recent prevention and management strategies for immune PTR. The diagnostic criteria typically involve post-transfusion platelet increment (PI), platelet recovery rate (PPR), and corrected count increment (CCI). Both immune and non-immune factors can lead to PTR, with immune factors mainly including HLA and HPA antibodies. Prevention and management strategies include the use of leukocyte-reduced platelets, HLA and HPA antigen-matched platelets, intravenous immunoglobulin therapy, and immunosuppressive strategies. Although various strategies have been proposed and applied in clinical practice, the prevention and management of immune PTR remain challenging. Future research needs to explore more effective individualized treatment strategies, while also considering the potential application of emerging technologies such as nanotechnology in the field of transfusion.
2.Construction of an evaluation index system for community visual health services in Shanghai
Chengyuan ZHANG ; Yuting WU ; Yajun PENG ; Tao YU ; Yi XU ; Senlin LIN ; Haidong ZOU ; Lina LU
Shanghai Journal of Preventive Medicine 2025;37(3):282-287
ObjectiveTo improve the quality and service performance of community visual health services in Shanghai, and to establish a set of reasonable and effective evaluation index system for community visual health services. MethodsCentered on the national and Shanghai-based visual health policies and based on the current status and development trends of community visual health service program in Shanghai, the candidate indicators were formed through literature review and expert interviews, firstly. The framework of an evaluation index system was formulated through qualitative research successively, which was further revised and perfected using the Delphi method. Coefficient weights were calculated using the analytic hierarchy process (AHP), culminating in the establishment of the community visual health evaluation index system, lastly. ResultsA total of 22 visual health experts from district-level center for disease control, hospital ophthalmology and leaders in charging of visual health service in community health centers participated in the Delphi questionnaire survey, with a questionnaire recovery rate of 100% and an expert authority coefficient of 0.86, indicating high credibility. After a round of correspondence to experts’ importance ratings and discussions, a comprehensive evaluation index system comprising 3 primary indicators, 12 secondary indicators, and 47 tertiary indicators, along with 5 additional indicators, was finalized. ConclusionAn index system tailored to effective evaluation for community visual health initiatives was drawn up in this study, which can promote the capacity building in community eye health services, facilitating the high-quality development of visual health courses, and enhancing residents’ eye health.
3.Effect of Huangqin Qingre Chubi Capsules-containing Serum on CircRNA_0001543/NF-κB Expression in Co-cultured PBMCs and Human FLSs from Patients with Ankylosing Spondylitis
Yajun QI ; Jian LIU ; Qiao ZHOU ; Yuedi HU ; Xiang DING ; Chengzhi CONG ; Xu LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):87-95
ObjectiveThis study aims to explore the effects of Huangqin Qingre Chubi capsules-containing serum on the expression of CircRNA_0001543/nuclear factor-kappa B (NF-κB) in co-cultured peripheral blood mononuclear cells (PBMCs) and human fibroblast-like synoviocytes (FLSs) from patients with ankylosing spondylitis (AS). MethodsVenous blood was collected from patients with AS to isolate PBMCs. FLSs were co-cultured with AS patients' PBMCs, and FLSs were harvested after co-culture for subsequent experiments. The normal control group consisted of normal FLSs, while the model group comprised co-cultured AS PBMCs and FLSs to simulate AS pathology. The Huangqin Qingre Chubi capsules group involved adding Huangqin Qingre Chubi capsules-containing serum to the co-cultured cells(6.48 g·kg-1). To investigate the effect of HQC-containing serum on the viability of co-cultured cells, and the experiment was divided into the following groups based on the dilution concentration: blank group, 10% HQC group, 20% HQC group, and 30% HQC group.To study the influence of the optimal concentration of HQC-containing serum on cytokine and pathway indicators in each group, the experiment was divided into three groups: normal group, model group, and optimal concentration HQC-containing serum group.For the validation of the transfection efficiency of the CircRNA_0001543 interference plasmid, the experiment was divided into the following groups: blank group, si-NC group (with transfection reagent), si-circ_0001543-1 group (with transfection reagent and interference plasmid No. 1 targeting circ_0001543), si-circ_0001543-2 group (with transfection reagent and interference plasmid No. 2 targeting circ_0001543), and si-circ_0001543-3 group (with transfection reagent and interference plasmid No. 3 targeting circ_0001543).For the validation of the transfection efficiency of the CircRNA_0001543 overexpression plasmid, the experiment was divided into the following groups: blank group, OE-NC group (with transfection reagent), and OE-circ_0001543 group (with transfection reagent and overexpression plasmid targeting circ_0001543).To study the effects of CircRNA_0001543 interference/overexpression on cytokine and pathway indicators in each group, the experiment was divided into the following groups: si-NC group, si-CircRNA_0001543 group, OE-NC group, and OE-CircRNA_0001543 group. Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of interleukin-1β (IL-1β), IL-10, IL-37, and tumor necrosis factor-α (TNF-α). Real-time quantitative polymerase chain reaction (Real-time PCR) was utilized to measure the expression of CircRNA_0001543, IκBα, and NF-κB p65. ResultsAfter 48 hours, 30% Huangqin Qingre Chubi Capsules-containing serum significantly inhibited the proliferation of co-cultured PBMCs and FLSs, which was determined to be the optimal experimental drug-containing serum concentration. Compared with those in the normal group, the expressions of NF-κB p65 mRNA, IκBα mRNA, IL-1β, and TNF-α in the model group were significantly increased (P<0.01), while the expressions of CircRNA_0001543 mRNA, IL-10, and IL-37 were significantly decreased (P<0.01). Compared with those in the model group, the expressions of NF-κB p65 mRNA, IκBα mRNA, IL-1β, and TNF-α in the Huangqin Qingre Chubi Capsules-containing serum group were significantly decreased (P<0.05), and the expressions of CircRNA_0001543 mRNA, IL-10, and IL-37 were significantly increased (P<0.05), with the most prominent changes in the 30% drug-containing serum group (P<0.01). Compared with that in the si-NC group, the expression of CircRNA_0001543 was significantly reduced in the si-CircRNA_0001543 group (P<0.01). Compared with that in the OE-NC group, the expression of CircRNA_0001543 was significantly increased in the OE-CircRNA_0001543 group (P<0.01), indicating that the si-CircRNA_0001543 and OE-CircRNA_0001543 plasmids were successfully transfected. Based on the optimal drug-containing serum of Huangqin Qingre Chubi Capsules, si-CircRNA_0001543 transfection led to significantly increased expressions of NF-κB p65 mRNA, IκBα mRNA, IL-1β, and TNF-α and decreased the expressions of IL-10 and IL-37 (P<0.01). In contrast, OE-CircRNA_0001543 transfection significantly decreased the expressions of NF-κB p65 mRNA, IκBα mRNA, IL-1β, and TNF-α (P<0.01) and increased the expressions of IL-10 and IL-37 (P<0.01). ConclusionHuangqin Qingre Chubi capsules-containing serum can improve immune inflammation in AS by increasing the expression of CircRNA_0001543, regulating the NF-κB pathway, suppressing pro-inflammatory cytokines, and enhancing anti-inflammatory cytokine expression.
4.The correlation between abnormal metabolic indexes and the severity of coronary artery lesions in patients with acute coronary syndrome
Yajun ZHAO ; Ming LIU ; Yuxiang DAI ; Xiaopan LI ; Xuelin CHENG ; Qizhe WANG ; Ru LIU ; Yaxin XU ; Sunfang JIANG
Chinese Journal of Clinical Medicine 2025;32(3):441-448
Objective To explore the influencing factors of coronary artery lesion severity in patients with acute coronary syndrome (ACS). Methods Clinical data of ACS patients admitted to Zhongshan Hospital, Fudan University from December 2017 to December 2019 were consecutively collected. The modified Gensini score was used to assess the severity of coronary artery lesions. Univariate and multivariate linear regression analyses were performed to identify independent factors associated with coronary artery lesion severity. Results A total of 1 689 ACS patients were included, with an average age of (64.04±11.45) years; 1 353 (80.11%) were male, and the mean modified Gensini score was (8.12±4.03). Multivariate linear regression analysis revealed that sex (β=0.97, P=0.001), age (β=0.03, P=0.021), estimated glomerular filtration rate (eGFR; β=-0.03, P<0.001), low-density lipoprotein cholesterol (LDL-C; β=0.58, P<0.001), apolipoprotein A1 (Apo A1; β=-1.28, P=0.012), lipoprotein(a) [Lp(a); β=0.001, P=0.033], and glycated hemoglobin A1C (HbA1C; β=0.45, P<0.001) were independent influencing factors of the modified Gensini score. Conclusions Metabolic indicators, including Apo A1, LDL-C, HbA1C, and Lp(a), may serve as risk factors for coronary artery lesion severity in ACS patients, with Apo A1 demonstrating the strongest impact.
5.Effects of a multidisciplinary integrated weight management intervention in Beilun District
XU Chunxia ; Ding Yajun ; YUAN Yunyun ; ZHOU Yachun ; PAN Xiaohua ; ZHANG Jingjing ; CHEN Lili
Journal of Preventive Medicine 2025;37(11):1103-1107,1112
Objective:
To evaluate the effects of a multidisciplinary weight management intervention, so as to provide a reference for the formulation of overweight and obesity intervention measures.
Methods:
From April to September 2025, overweight and obese residents aged 18-60 years who participated in a weight loss competition at the Health Management Center of Beilun People's Hospital in Ningbo City were selected as study subjects. They were divided into a control group and an intervention group. The control group received conventional weight management, while the intervention group received the multidisciplinary integrated weight management in addition to the conventional weight management, for a total intervention period of 8 weeks. Weight, body mass index (BMI), waist circumference, hip circumference, waist-to-hip ratio, fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and blood pressure were collected before and after the intervention through physical examinations and laboratory tests. The generalized estimating equations (GEE) method was employed to analyze the differences in indicators between the two groups before and after the intervention.
Results:
The control group comprised 241 participants, including 161 females (66.80%), with a mean age of (35.66±7.80) years. The intervention group consisted of 127 participants, including 86 females (67.72%), with a mean age of (36.80±7.05) years. No statistically significant differences were observed between the two groups at baseline in terms of age, gender, weight, BMI, or waist-to-hip ratio (all P>0.05). Results from the GEE analysis indicated significant interactions between group and time for weight, BMI, waist circumference, and hip circumference (all P<0.05) with greater reductions in these parameters observed in the intervention group compared to the control group before and after the intervention. Similarly, significant interactions between group and time were observed for FBG, TG, TC, and LDL-C (all P<0.05), with the intervention group demonstrating larger decreases in these markers compared to the control group. However, no statistically significant interactions between group and time were observed for waist-to-hip ratio, HDL-C, systolic blood pressure, and diastolic blood pressure (all P>0.05). Following the intervention, a weight loss exceeding 10% was achieved by 13 participants (5.39%) in the control group and 62 participants (48.82%) in the intervention group. The proportion of individuals with a weight loss exceeding 10% was significantly higher in the intervention group compared to the control group (P<0.05).
Conclusion
Compared to conventional weight management, multidisciplinary integrated weight management demonstrated greater efficacy in improving weight-related indicators and blood glucose, blood lipids, and enhancing weight loss outcomes among overweight and obese residents.
6.Effectiveness analysis of three internal fixation methods in treatment of avulsion fracture of tibial tubercle in adolescents.
Keyou DUAN ; Zhaodong WANG ; Yajun LIU ; Chen XU ; Zhonglian ZHU ; Jianzhong GUAN
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(1):75-82
OBJECTIVE:
To analyze the effectiveness of three internal fixation methods, namely hollow screw combined with Kirschner wire tension band, hollow screw combined with anchor nail, and modified 1/3 tubular steel plate, in the treatment of avulsion fracture of tibial tubercle (AFTT) in adolescents.
METHODS:
Between January 2018 and September 2023, 19 adolescent AFTT patients who met the selection criteria were admitted. According to different internal fixation methods, patients were divided into group A (8 cases, hollow screw combined with Kirschner wire tension band), group B (6 cases, hollow screw combined with anchor nail), and group C (5 cases, modified 1/3 tubular steel plate). There was no significant difference in the baseline data of age, gender, side, cause of injury, Ogden classification, and time from injury to operation among the three groups ( P>0.05). The range of motion (ROM), weight-bearing time, normal activity time of knee joint, and the hospital for special surgery (HSS) score at last follow-up were recorded and compared among the three groups. Recorded whether the fracture was displaced, whether the fracture line was blurred at 1 month after operation, whether there was epiphyseal dysplasia, and whether there was incision infection and other complications.
RESULTS:
There was no significant difference in hospital stay between the groups ( P>0.05). All patients were followed up 10-24 months, with an average of 14.3 months; there was no significant difference between the groups ( P>0.05). All the incisions healed well without soft tissue irritation or fracture nonunion, and no limb shortening deformity or epiphyseal dysplasia was found during follow-up. At 1 month after operation, the knee joint ROM and hospitalization expenses in group A were better than those in groups B and C, the fracture healing time, knee joint weight-bearing time, and normal activity time of knee joint were better than those in group C, and the hospitalization expenses in group C were better than those in group B, with significant differences ( P<0.05); there was no significant difference in the other indicators between the groups ( P>0.05). In group A, the fracture line was blurred 1 month postoperatively, the fracture ends were in close contact, and there was no fracture displacement; in groups B and C, the fracture line was clear in 2 cases, and 1 case in group C had slight fracture displacement; except for 1 case in group B, there was no fracture split in the other two groups. There was no significant difference in the incidences of blur of fracture line, fracture displacement, and intraoperative bone split between the groups at 1 month after operation ( P>0.05). At last follow-up, the HSS scores of knee joints in the three groups were excellent and good, and there was no significant difference between the groups ( P>0.05).
CONCLUSION
Hollow screw combined with Kirschner wire tension band technique is effective in treating adolescent AFTT, which has the advantages of stabilizing fracture, accelerating fracture healing and rehabilitation, early feasible knee joint functional exercise, and reducing hospitalization expenses.
Humans
;
Tibial Fractures/surgery*
;
Adolescent
;
Male
;
Fracture Fixation, Internal/instrumentation*
;
Female
;
Fractures, Avulsion/surgery*
;
Bone Wires
;
Bone Screws
;
Bone Plates
;
Treatment Outcome
;
Range of Motion, Articular
;
Bone Nails
;
Weight-Bearing
;
Fracture Healing
7.Application of intermediate screw assisted reduction and fixation technique in treatment of Schatzker type Ⅴ and Ⅵ tibial plateau fractures.
Zhaodong WANG ; Keyou DUAN ; Yajun LIU ; Chen XU ; Zhonglian ZHU ; Pinghui ZHOU ; Jianzhong GUAN
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(5):529-535
OBJECTIVE:
To explore effectiveness of intermediate screw assisted reduction and fixation technique in the treatment of Schatzker type Ⅴ and Ⅵ tibial plateau fractures.
METHODS:
A clinical data of 22 patients with Schatzker type Ⅴ and Ⅵ tibial plateau fractures, who were admitted between June 2022 and December 2023 and met the selection criteria, was retrospectively analyzed. During operation, the intermediate screw assisted reduction and fixation technique was used. There were 14 males and 8 females with an average age of 46.3 years (range, 17-65 years). The fractures were caused by traffic accident in 13 cases, by falls in 5 cases, and by falling from height in 4 cases. According to Schatzker classification criteria, 9 cases were type Ⅴ and 13 cases were type Ⅵ. The interval between injury and operation was 5-12 days (mean, 7.9 days). The operation time, intraoperative fluoroscopy times, and length of hospital stay were recorded. The range of motion of knee joint and Hospital for Special Surgery (HSS) score were recorded at last follow-up. X-ray films were taken to review the fracture healing. Rasmussen score, tibial plateau varus angle (TPVA), and posterior tibial slope (PTS) were estimated before operation, at immediate after operation, and at last follow-up in order to evaluate the fracture reduction effect and postoperative outcome.
RESULTS:
The operation time was 85-140 minutes (mean, 103.9 minutes). Intraoperative fluoroscopy was performed 7-15 times (mean, 10.1 times). All incisions healed by first intention after operation, and no complication such as nerve or blood vessel injury occurred. The length of hospital stay ranged from 8 to 17 days (mean, 12.4 days). All patients were followed up 10-22 months (mean, 14.8 months). At last follow-up, the range of motion of knee joint was 110°-140° (mean, 125°). HSS score was rated as excellent in 16 cases, good in 5 cases, and fair in 1 case, with an excellent and good rate of 95.5%. X-ray films reexamination showed that all fractures healed with the healing time of 12-17 weeks (mean, 14.8 weeks). No internal fixation failure occurred. Rasmussen score, TPVA, and PTS at immediate after operation and at last follow-up were significantly superior to those before operation ( P<0.05). And there was no significant difference between immediately after operation and last follow-up ( P>0.05).
CONCLUSION
The treatment of Schatzker type Ⅴ and Ⅵ tibial plateau fractures with intermediate screw assisted reduction and fixation technique is reliable, which can reduce the difficulty of reduction and fixation, improve the efficiency of reduction and fixation, reduce the operation time, achieve satisfactory reduction and fixation effect and postoperative prognosis, and achieve good recovery of knee joint function.
Humans
;
Tibial Fractures/diagnostic imaging*
;
Male
;
Female
;
Adult
;
Middle Aged
;
Bone Screws
;
Fracture Fixation, Internal/instrumentation*
;
Retrospective Studies
;
Adolescent
;
Aged
;
Young Adult
;
Treatment Outcome
;
Range of Motion, Articular
;
Operative Time
;
Length of Stay
;
Tibial Plateau Fractures
8.Application of V-shaped stealth decompression technique using ultrasonic bone scalpel in anterior surgery for adjacent two-level cervical spondylosis.
Zhaodong WANG ; Keyou DUAN ; Yajun LIU ; Chen XU ; Zhonglian ZHU ; Pinghui ZHOU ; Jianzhong GUAN
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(6):741-747
OBJECTIVE:
To evaluate the effectiveness of V-shaped stealth decompression technique using ultrasonic bone scalpel in anterior surgery for adjacent two-level cervical spondylosis.
METHODS:
A clinical data of 41 patients with adjacent two-level cervical spondylosis, who admitted between January 2020 and December 2023 and met the selection criteria, was analyzed retrospectively. Among them, 22 cases were treated with anterior cervical discectomy and fusion (ACDF) assisted by V-shaped stealth decompression technique using ultrasonic bone scalpel (group A) and 19 cases with anterior cervical corpectomy and fusion (ACCF) (group B). There was no significant difference between the two groups in age, gender, disease duration, surgical segment, preoperative Japanese Orthopedic Association (JOA) score, neck dysfunction index (NDI), pain visual analogue scale (VAS) score, and the anteroposterior diameter of the spinal canal in the responsibility space of axial CT ( P>0.05). The operation time, intraoperative blood loss, postoperative drainage volume, hospital stay, complications during follow-up, JOA score, NDI, and VAS score at last follow-up, and the incidences of intervertebral fusion at 3 months after operation, and cage subsidence at last follow-up were compared between the two groups.
RESULTS:
The operations in the two groups were successfully completed. The operation time, intraoperative blood loss, postoperative drainage volume, and hospital stay in group A were significantly less than those in group B ( P<0.05). Two cases (9.1%) in group A and 4 cases (21.1%) in group B developed complications, with no significant difference in the incidence between the two groups ( P>0.05). All patients in the two groups were followed up 6-12 months (mean, 9.3 months). There was no significant difference in follow-up time between the two groups ( P>0.05). At last follow-up, the JOA score and VAS score in both groups significantly improved when compared with those before operation ( P<0.05). The change values of VAS score and the improvement rate of JOA score in group A were significantly superior to group B ( P<0.05). There was no significant difference in the change values of NDI and JOA score between the two group ( P>0.05). Imaging reexamination showed that the rate of intervertebral fusion at 3 months after operation was significantly higher in group A (81.8%) than in group B (52.6%) ( P<0.05), and all patients obtained bony intervertebral fusion at last follow-up. At last follow-up, 2 cases (9.1%) in group A and 11 cases (57.9%) in group B had cage sinking, and the difference in the incidence was significant ( P<0.05). No loosening or fracture of internal fixators occurred in all patients.
CONCLUSION
Using ultrasonic bone scalpel can transform single vertebral ACCF into two-segment ACDF in anterior cervical spondylosis surgery. The V-shaped stealth decompression technique is safe and efficient, with the advantages of minimal trauma, fewer postoperative complications, and rapid recovery of patients.
Humans
;
Spondylosis/surgery*
;
Male
;
Female
;
Middle Aged
;
Decompression, Surgical/instrumentation*
;
Retrospective Studies
;
Cervical Vertebrae/surgery*
;
Spinal Fusion/instrumentation*
;
Diskectomy/instrumentation*
;
Adult
;
Treatment Outcome
;
Aged
;
Ultrasonic Surgical Procedures/methods*
;
Operative Time
9.LIM and calponin homology domains 1 may function as promising biological markers to aid in the prognostic prediction of oral squamous cell carcinoma.
Li XU ; Wen SHI ; Yuehua LI ; Yajun SHEN ; Shang XIE ; Xiaofeng SHAN ; Zhigang CAI
Journal of Peking University(Health Sciences) 2025;57(1):19-25
OBJECTIVE:
To explore the function of LIM and calponin homology domains 1 (LIMCH1) in the development and progression of oral squamous cell carcinoma (OSCC), along with their potential clinical applications.
METHODS:
By utilizing transcriptome sequencing data from two groups of oral squamous cell carcinoma patients, along with bioinformatics analytical techniques such as Gene Ontology (GO) and gene co-expression networks, we identified genes that might play a pivotal role in the pathogenesis of oral squamous cell carcinoma. We employed real-time quantitative PCR and Western blotting to validate the expression patterns of these genes across twelve patient tissue samples. Furthermore, we conducted CCK-8 assays, flow cytometry analyses, and scratch wound healing assays to assess the impact of key genes on the biological behaviors of both the Cal27 oral squamous cell carcinoma cell line and the potentially malignant DOK oral lesion cell line. Additionally, we examined correlations between these key genes and clinical disease parameters in 214 oral squamous cell carcinoma patients using The Cancer Genome Atlas (TCGA) data; gene set enrichment analysis (GSEA) analysis results were also incorporated to enhance our findings from real-time quantitative PCR and Western blotting regarding potential mechanisms underlying the action of these key genes.
RESULTS:
The integrated analysis of sequencing data and bioinformatics revealed that LIMCH1 exhibited significantly reduced mRNA (P < 0.001) and protein levels (P < 0.01) in the oral squamous cell carcinoma tissues compared with normal control tissues. In the Cal27 cells, the low LIMCH1 level group demonstrated a larger wound healing area within 24 hours than the control group (P < 0.01), enhanced proliferation capacity over 72 hours relative to the control group (P < 0.01), and an increased apoptosis rate within 24 hours compared with the high expression group (P < 0.05). However, no significant differences were observed between the low and high level groups in DOK cells. Furthermore, it was determined that low LIMCH1 level correlated with poor prognosis in the patients (P=0.013) and a higher lymph node metastasis rate (P < 0.05). Investigations into the potential mechanisms of action indicated that LIMCH1 did not influence the onset or progression of oral squamous cell carcinoma via the epithelial-mesenchymal transition pathway.
CONCLUSION
LIMCH1 level may function as a promising biomarker to aid in the prognostic assessment of oral squamous cell carcinoma; however, its precise mechanistic role requires further investigation.
Humans
;
Mouth Neoplasms/metabolism*
;
Prognosis
;
Carcinoma, Squamous Cell/metabolism*
;
Biomarkers, Tumor/metabolism*
;
LIM Domain Proteins/metabolism*
;
Cell Line, Tumor
;
Cell Proliferation
;
Male
;
Female
10.IMM-H007 promotes hepatic cholesterol and triglyceride metabolism by activating AMPKα to attenuate hypercholesterolemia.
Jiaqi LI ; Mingchao WANG ; Kai QU ; Yuyao SUN ; Zequn YIN ; Na DONG ; Xin SUN ; Yitong XU ; Liang CHEN ; Shuang ZHANG ; Xunde XIAN ; Suowen XU ; Likun MA ; Yajun DUAN ; Haibo ZHU
Acta Pharmaceutica Sinica B 2025;15(8):4047-4063
Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N 6-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe -/- and Ldlr -/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.


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