1.Itaconate derivative 4-OI inhibits M1 macrophage polarization and restores its impaired function in immune thrombocytopenia through metabolic reprogramming.
Qiang LIU ; Anli LIU ; Shaoqiu LENG ; Xiaoyu ZHANG ; Xiaolin WANG ; Zhang CHENG ; Shuwen WANG ; Jun PENG ; Qi FENG
Chinese Medical Journal 2025;138(16):2006-2015
BACKGROUND:
Macrophage polarization anomalies and dysfunction play a crucial role in the pathogenesis of immune thrombocytopenia (ITP). Itaconate is a Krebs cycle-derived immunometabolite synthesized by myeloid cells to modulate cellular metabolism and inflammatory responses. This study aimed to evaluate the immunoregulatory effects of an itaconate derivative on macrophages in patients with ITP.
METHODS:
Peripheral blood-derived macrophages from patients with ITP and healthy controls were treated with 4-octyl itaconate (4-OI), a derivative of itaconate that can penetrate the cell membrane. Macrophage polarization, antigen-presenting functions, and phagocytic capability were measured via flow cytometry and enzyme-linked immunosorbent assay (ELISA). Macrophage glycolysis in patients with ITP and the metabolic regulatory effect of 4-OI were detected using a Seahorse XFe96 Analyzer. An active murine model of ITP was used to evaluate the therapeutic effects of 4-OI in vivo .
RESULTS:
4-OI reduced the levels of CD80 and CD86 in M1 macrophages and suppressed the release of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 pro-inflammatory cytokines, suggesting that 4-OI could hinder the polarization of macrophages toward an M1 phenotype. We found that 4-OI pretreated M1 macrophages reduced the proliferation of CD4 + T cells and promoted the differentiation of regulatory T cells. In addition, after 4-OI treatment, the phagocytic capacity of M1 macrophages toward antibody-coated platelets decreased significantly in patients with ITP. In addition, the glycolytic function of M1 macrophages was elevated in individuals with ITP compared to those in healthy controls. 4-OI treatment downregulated glycolysis in M1 macrophages. The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) also inhibited the polarization of M1 macrophages and restored their functions. In vivo , 4-OI treatment significantly increased platelet counts in the active ITP murine model.
CONCLUSIONS
Itaconate derivative 4-OI inhibited M1 macrophage polarization and restored impaired functions through metabolic reprogramming. This study provides a novel therapeutic option for ITP.
Macrophages/metabolism*
;
Humans
;
Animals
;
Succinates/pharmacology*
;
Mice
;
Male
;
Female
;
Adult
;
Middle Aged
;
Flow Cytometry
;
Tumor Necrosis Factor-alpha/metabolism*
;
Enzyme-Linked Immunosorbent Assay
;
Purpura, Thrombocytopenic, Idiopathic/metabolism*
;
Glycolysis/drug effects*
;
Metabolic Reprogramming
2.Perioperative blood transfusion in hepatectomy: a decision tree analysis of influencing factors
Chengcen LUO ; Linou HONG ; Chunyu HE ; Anli PENG ; Jun YANG
Chinese Journal of Blood Transfusion 2025;38(10):1334-1339
Objective: To investigate the significant factors influencing the need for perioperative blood transfusion in patients undergoing hepatectomy. Methods: Medical records of patients who underwent elective hepatectomy in our hospital from January 2020 to December 2021 were retrospectively collected. Variables associated with transfusion were analyzed using traditional logistic regression (LR) and machine learning algorithm, the Classification and Regression Tree (CRT). The predictive values of the two methods were compared by the area under the curve (AUC) of the ROC curve. Results: Among the 402 patients, 82(20.4%) received blood transfusions. Multivariable logistic regression analysis identified several risk factors for perioperative blood transfusion, including vascular invasion, preoperative hemoglobin level, intraoperative blood loss, duration of surgery, postoperative hemoglobin level, and postoperative complications (P<0.05). In the CRT model for predicting blood transfusion, intraoperative blood loss (cutoff: 450 mL) was the parent node, with preoperative Hb, postoperative complications, and hospital stay as child nodes. The LR model demonstrated superior predictive performance compared to the CRT model, with an AUC of 0.971 (95% CI: 0.956-0.985) vs 0.937 (95% CI: 0.909-0.965). The difference in AUC between the two methods was statistically significant (P<0.05). Conclusion: Although the CRT model did not outperform logistic regression in overall predictive accuracy, it still provides a valuable tool for assisting clinicians in making decisions about blood transfusion in the perioperative period of hepatectomy, thereby facilitating more individualized guidance for preoperative blood preparation in clinical practice.
3.Combined therapy of super-pulsed CO2 laser and traditional Chinese medicine for prevention and treatment of post-traumatic hypertrophic scar
Dan YAN ; Zechun HUANG ; Hui LI ; Han YU ; Anli ZHANG ; Zhiwei LIANG ; Hongmei WANG ; Li PENG ; Xiaxia LI
Chinese Journal of Medical Aesthetics and Cosmetology 2010;16(5):317-319
Objective To analyse the clinical efficacy of combined therapy of super-pulsed CO2 laser and traditional Chinese medicine on the prevention and treatment of post-traumatic hypertrophic scar, and to discuss effective comprehensive therapy for hypertrophic scars. Methods 108 cases of early post-traumatic hypertrophic scar were divided randomly into three groups with 36 cases each: combined treatment group of super-pulsed CO2 laser and traditional Chinese medicine (combined group), Chinese medicine treatment group (Chinese medicine group) and simple laser-treated group (laser group). They were regularly treated for 6 months and followed up for longer than 1 year. Clinical effects were evaluated according to scar property and subjective symptoms in patients. Results The total effective rate was 97.2 % and 86.1% in combined group and Chinese medicine group that were higher than 61.1 % in laser group. Obviously effective rate of the three methods were 55. 6 %, 27.8 % and 11. 1 %, respectively, and the difference of obviously effective rate between combined group and other two groups was significally different. Conclusion The method combined with super-pulsed CO2 laser and traditional Chinese medicine for prevention and treatment of post-traumatic hypertrophic scar has advantages of high obviously effective rate, long-term and stable effects, less complication, and it can achieve satisfactory cosmetic effects.
4.Modified round block technique in removal of huge breast tumor and mammoplasty
Zechun HUANG ; Zhiwei LIANG ; Zhangmei TAN ; Anli ZHANG ; Dan YAN ; Shuaihua LI ; Hongmei WANG ; Li PENG ; Xiaxia LI
Chinese Journal of Medical Aesthetics and Cosmetology 2010;16(3):148-151
Objective To explore a surgical method which can not only remove the enormous breast tumor entirely, but also maintain the breast function and obtain satisfactory shape.Methods On the basis of traditional round block technique, we designed different form's outer ring and breast lateral Sshaped incision line according to the size of breast tumor and the degree of the papillae ptosis, trimmed away the epidermis between the two circles, a S-shape skin incision along lateral border of breast was made; after reaching to the capsule of tumor, we stripped off the tumor entirely along capsule surface, a large breast cavus subdermalis remained, and then made full use of the dermal-fat flap or dermal-fat breast flap to fill the cavity after tumor removal so that the shape of breast was reconstructed. Results All of the 5 cases maintained the breast function and satisfactory shape after surgery, no sensory obstacle and necrosis occurred in the papillae and areola, and the wound reached good healing. Up to 2 years of follow-up there was no recurrence of tumor was found. Conclusions The modified round block' technique is an i-deal method for removal of a huge breast tumor. The design is nimble and simple, and postoperative breast shape is satisfactory with light scar formation.
5.Correction of epicanthus by transverse-one's procedure
Zechun HUANG ; Zhiwei LIANG ; Zhangmei TAN ; Anli ZHANG ; Li PENG ; Hongmei WANG
Chinese Journal of Medical Aesthetics and Cosmetology 2009;15(5):313-315
Objective To explore a simple and effective epicanthoplasty.Methods A total of 65 cases were corrected by incising the epicanthus levelly,extending the incision along the lower palpebral margin,separating the skin about 1 cm×1 cm scope below incision,cutting off part of the orbicularis and epicanthus ligament,fixing epicanthus angle to nasal aponeurosis,and suturing the incision without tension.Results All the cases corrected by the transverse-one's procedure were followup one month to one year,and satisfactory results obtained.Conclusion This method is a simple and effective epicanthoplasty with less tissue damage and good appearance.

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