1.Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury.
Yao HE ; Xue YANG ; Chenyu ZHANG ; Min DENG ; Bin TU ; Qian LIU ; Jiaying CAI ; Ying ZHANG ; Li SU ; Zhiwen YANG ; Hongfeng XU ; Zhongyuan ZHENG ; Qun MA ; Xi WANG ; Xuejun LI ; Linlin LI ; Long ZHANG ; Yongzhuo HUANG ; Lu TIE
Acta Pharmaceutica Sinica B 2025;15(6):3107-3124
Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.
2.Expression and significance of α7 nicotinic acetylcholine receptor on thymic T follicular helper cells in myasthenia gravis
Meng WANG ; Menghao YANG ; Xinzheng CUI ; Zirui SUN ; Chenshuo SHI ; Zhiwen ZHANG ; Lixiang ZHENG ; Qingyong ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(12):1771-1776
Objective To investigate the expression of α7 nicotinic acetylcholine receptor (α7nAChR) in thymic T follicular helper cells (TFH) and its significance in patients with myasthenia gravis (MG). Methods Fifteen MG patients who underwent surgical treatment at the Myasthenia Gravis Comprehensive Diagnosis and Treatment Center of Henan Provincial People’s Hospital from June 2022 to June 2023 were selected as a MG group, including 7 males and 8 females, aged 12-30 years. Twelve patients who underwent partial thymectomy to optimize surgical field exposure during cardiac surgery at Fuwai Central China Cardiovascular Hospital from June 2022 to June 2023 were selected as a control group, including 5 males and 7 females aged 20-35 years. Thymus single cell suspension was obtained by grinding the thymus tissue, and flow cytometry was used to detect the expression of α7nAChR in TFH cells. The thymus cell suspension was purified using density gradient centrifugation, followed by immunomagnetic bead separation to obtain CD4+T cells. CXCR5 antibody and coupled magnetic beads were added to isolate TFH cells. Real-time fluorescent polymerase chain reaction and Western blotting were performed to further investigate the expression of α7nAChR in TFH cells. Results Compared with the control group, the proportion of thymic TFH cells in the MG group was significantly increased (P<0.05), along with significantly decreased mRNA and protein expression levels of α7nAChR within these cells (P<0.01). Conclusion The findings suggest that there is a reduced expression of α7nAChR within thymic TFH cells in MG patients, leading to weakened immunosuppressive function which may indirectly contribute to disease onset and progression.
3.The current status and its related factors of vascular access team building in hemodialysis centers in China
Yao LIU ; Jing LI ; Liyun CAO ; Qizhuang JIN ; Xizi ZHENG ; Xiufang DUAN ; Chun LI ; Jing XIANG ; Mo SU ; Zhiwen WANG
Chinese Journal of Nephrology 2025;41(2):90-98
Objective:To investigate the current status of vascular access team building and analysis its related factors in hemodialysis centers in China.Methods:The study was a cross-sectional survey. Using a convenience sampling method, a questionnaire was designed to investigate the clinical practice of vascular access teams in 527 hemodialysis centers in China from March to April 2022. The related factors of the formation of vascular access teams and the setting up of vascular access coordinators (VAC) were analyzed by multivariate logistic regression method.Results:A total of 506 valid questionnaires were recovered, with a recovery rate of 96.02%. There were 247 (48.81%) and 193 (38.14%) hemodialysis centers respectively across China that had built vascular access teams and set up VAC. Hemodialysis centers with more than 10 years of practice had higher rate of implementation than those in hemodialysis centers with practice years less or equal than 10 years in developing standardized procedures for vascular access management ( χ 2=8.288, P=0.004), holding continuous quality improvement meetings on vascular access ( χ 2=8.210, P=0.004), establishing vascular access teams ( χ 2=33.805, P<0.001) and setting up vascular access coordinators ( χ 2=16.038, P<0.001), and the difference was statistically significant. The results of multivariate logistic regression analysis showed that the number of dialysis machines ( OR=2.221, 95% CI 1.118-4.415, P=0.023), the number of patients on dialysis( OR=2.946, 95% CI 1.375-6.310, P=0.005), and the establishment of VAC positions ( OR=9.463, 95% CI 5.307-16.874, P<0.001), and the standardized vascular access management process ( OR=3.383, 95% CI 2.012-5.687, P<0.001) were the related factors of vascular access team building. The related factors of setting up a VAC position in hemodialysis center were opening vascular access clinic ( OR=2.704,95% CI 1.382-5.290, P=0.004), the formation of a vascular access team ( OR=9.464, 95% CI 5.312-16.860, P<0.001), and constructing standardized procedures for vascular access management ( OR=3.663, 95% CI 2.243-5.982, P<0.001). Conclusion:The implementation rates of vascular access team and VAC position in hemodialysis centers were 48.81% and 38.14%, respectively. The number of dialysis machines, the number of patients on dialysis, the standardized procedures for vascular access management, the vascular access clinic, the vascular access team, and the VAC position were the relevant factors of the team building for vascular access.
4.A novel perspective on male testicular aging: Sertoli cell lysosomal dysfunction with intervention targets
Yunzhi LIN ; Yulin XIONG ; Zhiwen DENG ; Zheng LI ; Zhi ZHOU
Chinese Journal of Reproduction and Contraception 2025;45(11):1124-1130
Male reproductive aging is characterized by degenerative changes in the structure and function of the testes. Testicular aging involves alterations in various types of cells, among which lysosomal dysfunction in Sertoli cells is particularly critical. Recent studies have shown that abnormal lysosomal acidification leads to impaired phagosome degradation, which fails to maintain normal nutrient cycling and thereby exacerbates damage to the testicular microenvironment. In addition, endoplasmic reticulum stress, mitochondrial dysfunction, and epigenetic changes are also important factors contributing to reproductive aging. Therefore, molecular intervention strategies targeting lysosomal dysfunction, mitochondrial oxidative stress, and endoplasmic reticulum stress, such as the use of lysosomal activators like ML-SA1 and antioxidants, may offer new therapeutic directions for alleviating male reproductive aging. Future research should further explore the interactions between these mechanisms and potential intervention targets to improve reproductive health and quality of life in middle-aged and older men.
5.A novel perspective on male testicular aging: Sertoli cell lysosomal dysfunction with intervention targets
Yunzhi LIN ; Yulin XIONG ; Zhiwen DENG ; Zheng LI ; Zhi ZHOU
Chinese Journal of Reproduction and Contraception 2025;45(11):1124-1130
Male reproductive aging is characterized by degenerative changes in the structure and function of the testes. Testicular aging involves alterations in various types of cells, among which lysosomal dysfunction in Sertoli cells is particularly critical. Recent studies have shown that abnormal lysosomal acidification leads to impaired phagosome degradation, which fails to maintain normal nutrient cycling and thereby exacerbates damage to the testicular microenvironment. In addition, endoplasmic reticulum stress, mitochondrial dysfunction, and epigenetic changes are also important factors contributing to reproductive aging. Therefore, molecular intervention strategies targeting lysosomal dysfunction, mitochondrial oxidative stress, and endoplasmic reticulum stress, such as the use of lysosomal activators like ML-SA1 and antioxidants, may offer new therapeutic directions for alleviating male reproductive aging. Future research should further explore the interactions between these mechanisms and potential intervention targets to improve reproductive health and quality of life in middle-aged and older men.
6.The current status and its related factors of vascular access team building in hemodialysis centers in China
Yao LIU ; Jing LI ; Liyun CAO ; Qizhuang JIN ; Xizi ZHENG ; Xiufang DUAN ; Chun LI ; Jing XIANG ; Mo SU ; Zhiwen WANG
Chinese Journal of Nephrology 2025;41(2):90-98
Objective:To investigate the current status of vascular access team building and analysis its related factors in hemodialysis centers in China.Methods:The study was a cross-sectional survey. Using a convenience sampling method, a questionnaire was designed to investigate the clinical practice of vascular access teams in 527 hemodialysis centers in China from March to April 2022. The related factors of the formation of vascular access teams and the setting up of vascular access coordinators (VAC) were analyzed by multivariate logistic regression method.Results:A total of 506 valid questionnaires were recovered, with a recovery rate of 96.02%. There were 247 (48.81%) and 193 (38.14%) hemodialysis centers respectively across China that had built vascular access teams and set up VAC. Hemodialysis centers with more than 10 years of practice had higher rate of implementation than those in hemodialysis centers with practice years less or equal than 10 years in developing standardized procedures for vascular access management ( χ 2=8.288, P=0.004), holding continuous quality improvement meetings on vascular access ( χ 2=8.210, P=0.004), establishing vascular access teams ( χ 2=33.805, P<0.001) and setting up vascular access coordinators ( χ 2=16.038, P<0.001), and the difference was statistically significant. The results of multivariate logistic regression analysis showed that the number of dialysis machines ( OR=2.221, 95% CI 1.118-4.415, P=0.023), the number of patients on dialysis( OR=2.946, 95% CI 1.375-6.310, P=0.005), and the establishment of VAC positions ( OR=9.463, 95% CI 5.307-16.874, P<0.001), and the standardized vascular access management process ( OR=3.383, 95% CI 2.012-5.687, P<0.001) were the related factors of vascular access team building. The related factors of setting up a VAC position in hemodialysis center were opening vascular access clinic ( OR=2.704,95% CI 1.382-5.290, P=0.004), the formation of a vascular access team ( OR=9.464, 95% CI 5.312-16.860, P<0.001), and constructing standardized procedures for vascular access management ( OR=3.663, 95% CI 2.243-5.982, P<0.001). Conclusion:The implementation rates of vascular access team and VAC position in hemodialysis centers were 48.81% and 38.14%, respectively. The number of dialysis machines, the number of patients on dialysis, the standardized procedures for vascular access management, the vascular access clinic, the vascular access team, and the VAC position were the relevant factors of the team building for vascular access.
7.Efficacy and influencing factors of thymectomy for bulbar myasthenia gravis
Zhiwen ZHANG ; Xinzheng CUI ; Lixiang ZHENG ; Chenshuo SHI ; Meng WANG ; Menghao YANG ; Qingyong ZHANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(9):531-535
Objective:To determine the efficacy and influencing factors of thymectomy for bulbar myasthenia gravis.Methods:The clinical data of 120 patients with bulbar myasthenia gravis admitted to the Myasthenia Gravis Comprehensive Diagnosis and Treatment Center of Henan Provincial People's Hospital from March 2018 to June 2023 were collected, with 61 males and 59 females. There were 66 patients with thymoma and 54 patients with non-thymoma. The duration of bulbar muscle involvement before operation ranged from 11 days to 108 months. Preoperative AChR-Ab was positive in 105 cases and negative in 15 cases. There were 28 cases with bulbar muscle involvement as the initial symptom and 92 cases as the non-initial symptom. There were 7 cases with crisis and 113 cases without crisis in the past. The postoperative efficacy was evaluated according to the Myasthenia Gravis post-treatment status evaluation program of the American Myasthenia Gravis Society. Univariate analysis and logistic regression analysis were used to analyze the factors that may affect the surgical efficacy. Results:All 120 patients successfully underwent extended thymectomy, there was no perioperative death. The follow-up time was 3-57 months, with a median of 24 months. Twenty-two patients (18.33%) achieved complete durable remission, 1 patient (0.83%) maintained remission, 65 patients (54.17%) had minimal symptoms, and 20 patients (16.70%) improved. No change in 8 cases (6.67%), no aggravation cases (0), deterioration in 2 cases (1.67%), and death in 2 cases (1.67%). 23 cases(19.17%) achieved clinical remission and 85 cases (70.83%) achieved partial remission. Univariate analysis showed that positive AChR-Ab before operation and duration of bulbar muscle involvement before operation were the influencing factors of surgical efficacy in patients with bulbar MG, and the difference was statistically significant ( P<0.05). Logistic regression analysis showed that positive AChR-Ab before operation and the duration of bulbar muscle involvement before operation were independent influencing factors of surgical efficacy. Conclusion:Thymectomy can effectively relieve the symptoms of bulbar myasthenia gravis. Patients with positive AChR-Ab before surgery and shorter duration of bulbar muscle involvement may benefit more from thymectomy.
8.Core decompression combined with BMP activity inducing rod implantation for early femoral head necrosis
Liming ZHENG ; Feng WEN ; Wei WANG ; Zhiwen ZHANG
The Journal of Practical Medicine 2024;40(9):1280-1285
Objective To investigate the effect of core decompression combined with bone-morphogenetic proteins(BMP)activity inducing rod implantation in the treatment of early-stage femoral head necrosis.Methods Retrospective analysis of 116 patients with early-stage femoral head necrosis from June 2018 to June 2022 were divided into core decompression combined with BMP activity inducing rod group(BMP group)and allograft bone group.Sixty cases in the BMP group were treated with core decompression combined with implantation of BMP-activated induced rods,and 56 cases in the allograft group were treated with core decompression combined with bone grafting of the allograft bone by punching and compression.The differences in hip Harris scores and visual analogue scores(VAS)of pain between the two groups at preoperative,6 months postoperative and 1 year postop-erative,and the patient treatment response and femoral head survival rate at 1 year postoperative were compared.Results All patients were followed-up,and the difference between the preoperative VAS score and Harris score of the two groups was not statistically significant(P>0.05),and the VAS score and Harris score of the two groups were significantly improved at 6 months and 1 year after operation,and the BMP group was better than the allograft bone group,with significant difference(P<0.05).At 1 year after surgery,the Harris hip score excellence rate of the BMP group was higher than that of the allograft bone group,and the difference was statistically significant(P<0.05);the femoral head survival rate of the BMP group was higher than that of the allograft bone group,and the difference was statistically significant(P<0.05).Conclusions Core decompression combined with BMP activity induced rod implantation was effective in the treatment of early femoral head necrosis,which accelerated the induction of new bone formation,improved the quality of new bone,provided biomechanical support for the femoral head,and effectively avoided femoral head collapse.Moreover,it has good biocompatibility and couldbe degraded and absorbed in the body,which is worthy of clinical promotion.
9.Facilitators and barriers of implementation of educational guidance intervention program for orthokeratology lens wearing: a qualitative study
Jun LIU ; Jingyu YAN ; Jinping HU ; Lili ZHENG ; Wei CHEN ; Siqi MI ; Zhiwen WANG
Chinese Journal of Modern Nursing 2024;30(33):4558-4562
Objective:To explore the facilitators and barriers in implementing the orthokeratology lens-wearing education guidance program from the perspectives of children, their families, and medical and nursing staff.Methods:Based on phenomenological research, purposive sampling was used to select five medical workers, 18 children wearing orthokeratology lenses and family members from the Optometry Center of Peking University Third Hospital as interviewees for semi-structured interviews. Colaizzi's 7-step method was used to analyze interview data.Results:Two themes (facilitators and barriers) were extracted, among which facilitators included two sub-themes (strong demand for educational guidance, trust in medical and nursing staff), and barriers consisted of two sub-themes (patient factors, external support factors) .Conclusions:In promoting the educational guidance intervention program for wearing orthokeratology lenses, medical and nursing staff need to fully play the role of facilitators, analyze and solve barriers, and ultimately promote the smooth implementation of the intervention program.
10.Study on the quality markers of Curcumae Radix standard decoction based on fingerprint and network pharmacology
Zhiwen DUAN ; Xiaoxia LIU ; Minyou HE ; Cuijie WEI ; Yongwei FENG ; Haibao QIU ; Ronghui ZHENG ; Dongmei SUN ; Xiangdong CHEN ; Zhenyu LI
International Journal of Traditional Chinese Medicine 2024;46(12):1622-1628
Objective:To establish the ultra-high performance liquid chromatography (UPLC) fingerprint and high performance liquid chromatography (HPLC) content determination method of Curcumae Radix standard decoction; To predict the quality markers of Curcumae Radix standard decoction combined with network pharmacology.Methods:UPLC method was used to establish the fingerprint of Curcumae Radix standard decoction, and the common peaks were determined. Combined with chemical pattern recognition techniques such as similarity analysis and clustering analysis, Curcumae Radix standard decoction from different producing areas was studied, and curcumol was used as an index to determine the content of 24 batches of Curcumae Radix standard decoction. At the same time, network pharmacology was used to predict potential of curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one.Results:A total of 24 batches of Curcumae Radix standard decoction from different habitats were compared and analyzed, and 10 common peaks were calibrated. The similarity of 24 batches of samples ranged from 0.982 to 0.999. Clustering analysis and principal component analysis divided them into three categories. Heat map analysis showed that peak 8 (curcumol) and peak 9 ((1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one) were the main components. The content of curcumol in 24 batches of Curcumae Radix standard decoction was 0.69-1.87 mg/g; curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β- (3-oxobutyl) bicyclo [4.1.0] heptan-3-one may regulate the neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation by regulating neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation. It was preliminarily predicted that curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one were potential quality markers of Curcumae Radix.Conclusion:Curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one are potential quality markers of Curcumae Radix standard decoction, and the established fingerprint can be used for the quality control of Curcumae Radix standard decoction.

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