1.Telpegfilgrastim for chemotherapy-induced neutropenia in breast cancer: A multicenter, randomized, phase 3 study.
Yuankai SHI ; Qingyuan ZHANG ; Junsheng WANG ; Zhong OUYANG ; Tienan YI ; Jiazhuan MEI ; Xinshuai WANG ; Zhidong PEI ; Tao SUN ; Junheng BAI ; Shundong CANG ; Yarong LI ; Guohong FU ; Tianjiang MA ; Huaqiu SHI ; Jinping LIU ; Xiaojia WANG ; Hongrui NIU ; Yanzhen GUO ; Shengyu ZHOU ; Li SUN
Chinese Medical Journal 2025;138(4):496-498
2.Recommendations for the clinical use of anti-amyloid-β monoclonal antibody for Alzheimer's disease(2025)
Nan ZHI ; Jinwen XIAO ; Rujing REN ; Binyin LI ; Jintao WANG ; Jieli GENG ; Wenwei CAO ; Yaying SONG ; Hualong WANG ; Shuguang CHU ; Guoping PENG ; Jun LIU ; Xiaoyun LIU ; Fang YUAN ; Wen WANG ; Ronghua DOU ; Xia LI ; Ling YUE ; Wenshi WEI ; Xiaoling PAN ; Xiangyang ZHU ; Dian HE ; Weinü FAN ; Jingping SHI ; Nan ZHANG ; Hui ZHAO ; Qin CHEN ; Cuibai WEI ; Xiaochun CHEN ; Gang WANG
Journal of Chongqing Medical University 2025;50(9):1133-1140
In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.
3.Screen of FDA-approved drug library identifies vitamin K as anti-ferroptotic drug for osteoarthritis therapy through Gas6.
Yifeng SHI ; Sunlong LI ; Shuhao ZHANG ; Caiyu YU ; Jiansen MIAO ; Shu YANG ; Yan CHEN ; Yuxuan ZHU ; Xiaoxiao HUANG ; Chencheng ZHOU ; Hongwei OUYANG ; Xiaolei ZHANG ; Xiangyang WANG
Journal of Pharmaceutical Analysis 2025;15(5):101092-101092
Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.
4.Study on the Prognostic Warning Value of Serum GR,SOD,Cys-C,Hcy and Lp(a)Levels in Patients with Cerebral Ischemic Stroke
Fang LI ; Xiangyang RAN ; Wei LI ; Wenjun SHI ; Liyun AN ; Lin KANG
Journal of Modern Laboratory Medicine 2025;40(2):92-97,103
Objective To explore the prognostic value of serum glutathione reductase(GR),superoxide dismutase(SOD),cystatin C(Cys-C),homocysteine(Hcy)and lipoprotein a[Lp(a)]levels in patients with cerebral ischemic stroke(CIS),and to provide a reference for improving the prognosis of CIS patients.Methods 126 patients with CIS admitted to the 980th Hospital of Joint Logistics Support Force from June 2022 to April 2023 were selected as the observation group,another 126 healthy individuals were selected as the control group at a ratio of 1:1.The expression levels of GR,SOD,Cys-C,Hcy and Lp(a)in the two groups were detected and compared after admission and during physical examination.The degree of neurological deficit in patients with CIS was classified into mild(NIHSS:2~4 points,n=35),moderate(NIHSS:5~15 points,n=47),moderate-severe(NIHSS:16~20 points,n=26)and severe(NIHSS:21~42 points,n=18)according to the National Institutes of Health Stroke Scale(NIHSS).The expression of serum GR,SOD,Cys-C,Hcy and Lp(a)in patients with different degrees of neurological deficit was compared,and the correlation between each indicator and the degree of neurological deficit was analyzed.The observation group received intravenous thrombolytic therapy after admission and was re-examined one day after thrombolysis.After treatment,follow-up visits were conducted for 28 days.According to the patient's condition(modified Rankin scale),patients were divided into good prognosis(n=94)and poor prognosis groups(n=32).The levels of each indicator in patients with different prognoses were compared,and the predictive value of GR,SOD,Cys-C,Hcy and Lp(a)expression for poor prognosis and early warning were analyzed.Results The expression levels of serum GR(48.54±3.07U/L)and SOD(157.17±25.47U/ml)in the observation group were lower than those in the control group(61.68±3.15U/L,203.63±18.31U/ml),while the expression levels of Cys-C(1.24±0.28mg/L),Hcy(15.21±1.62μmol/L)and Lp(a)(386.53±52.16mg/L)were higher than those in the control group(0.82±0.23mg/L,9.58±0.60μmol/L,257.83±45.34mg/L),with statistically significant differences(t=13.011~36.582,all P<0.05).As the disease progressed,the expression levels of GR and SOD gradually decreased,while the expression levels of Cys-C,Hcy and Lp(a)gradually increased,with statistically significant differences(F=14.685~197.041,all P<0.05).Spearman analysis,GR and SOD were negatively correlated with the degree of neurological deficit in patients with CIS(r=-0.814,-0.753,all P<0.05),while Cys-C,Hcy and Lp(a)were positively correlated with the degree of neurological deficit in patients with CIS(r=0.647,0.782,0.724,all P<0.05).The expression of GR and SOD in patients with good prognosis at admission and 1 day after thrombolysis was higher than that in patients with poor prognosis(t=9.109,6.338;2.934,4.358,all P<0.05),while the expression of Cys-C,Hcy and Lp(a)was lower than that in patients with poor prognosis(t=5.246,5.118,8.561;4.636,5.298,7.461,all P<0.05).The AUC(95%CI)of combined prediction of GR,SOD,Cys-C,Hcy and Lp(a)at admission was 0.898(0.832~0.945),and the AUC(95%CI)of combined prediction of GR,SOD,Cys-C,Hcy and Lp(a)at 1 day after thrombolysis was 0.931(0.871~0.968).The RR(95%CI)values caused by the expression of GR,SOD,Cys-C,Hcy and Lp(a)at 1 day after thrombolysis were 2.868(1.594~5.161),3.194(1.807~5.645),0.155(0.082~0.291),0.150(0.071~0.319)and 0.227(0.119~0.435).Conclusion Abnormal changes in the levels of GR,SOD,Cys-C,Hcy and Lp(a)are closely related to the degree of neurological deficit and prognosis in patients with CIS.Early combined detection of GR,SOD,Cys-C,Hcy and Lp(a)levels has high predictive value and early warning for evaluating the poor prognosis of patients with CIS.
5.Textual Research on Classical Formula Mulisan
Dongsen HU ; Xiangyang ZHANG ; Canran XIE ; Jiawei SHI ; Ziyi WANG ; Zhuoyan ZHOU ; Lin ZHANG ; Yexin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):191-200
The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas (second batch) of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha, Astragali Radix, Ephedrae Radix et Rhizoma, and wheat, with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution, composition, dosage, original plants and their processing methods, decocting method, efficacy, indications, and modern clinical application of Mulisan by tracing, comparative analysis, and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition, dosage, efficacy, and indications of Mulisan were first recorded in the Treatise on Diseases, Patterns, and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods, Ostreae Concha is the shell of Ostrea rivularis, which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica, respectively, the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum, which can be used without processing, while the stir-fried fruit, being thin and deflated, demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g, Astragali Radix 8.26 g, Ephedrae Radix et Rhizoma 8.26 g, and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL, and the decoction should be taken warm. In modern clinical practice, Mulisan has a wide range of indications, including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases, neurological diseases, respiratory system diseases, and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research, development, and clinical application of Mulisan.
6.Textual Research on Classical Formula Mulisan
Dongsen HU ; Xiangyang ZHANG ; Canran XIE ; Jiawei SHI ; Ziyi WANG ; Zhuoyan ZHOU ; Lin ZHANG ; Yexin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):191-200
The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas (second batch) of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha, Astragali Radix, Ephedrae Radix et Rhizoma, and wheat, with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution, composition, dosage, original plants and their processing methods, decocting method, efficacy, indications, and modern clinical application of Mulisan by tracing, comparative analysis, and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition, dosage, efficacy, and indications of Mulisan were first recorded in the Treatise on Diseases, Patterns, and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods, Ostreae Concha is the shell of Ostrea rivularis, which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica, respectively, the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum, which can be used without processing, while the stir-fried fruit, being thin and deflated, demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g, Astragali Radix 8.26 g, Ephedrae Radix et Rhizoma 8.26 g, and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL, and the decoction should be taken warm. In modern clinical practice, Mulisan has a wide range of indications, including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases, neurological diseases, respiratory system diseases, and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research, development, and clinical application of Mulisan.
7.Human Gravity Line Research and its Application in the Field of Spinal Medicine
Yifeng SHI ; Haibo LIANG ; Xiangyang WANG
Journal of Medical Biomechanics 2025;40(2):470-476
The human gravity line(GL)is a virtual vertical line that passes through the centre of gravity(COG)of the human body and holds significant importance in assessing human biomechanics.Due to the inability to directly determine GL through imaging method,its application in past research and clinical practice has been somewhat limited.However,with the advancement of technology,the measurement and application of GL have made remarkable progress,becoming an essential supplement to traditional radiographic measurements and demonstrating an increasingly broad application prospect in the field of spinal health.This review summarizes the GL's anatomical basis,measurement method,and its relationship with other commonly used vertical lines.Furthermore,the current status of GL's clinical application in the field of spinal health is also summmrzied,and its potential role in the diagnosis and treatment of spinal diseases is discussed.It is hoped that the findings will offer new perspectives for the diagnosis and treatment of spinal diseases,and promote further research and application of GL in the field of spinal medicine.
8.The role of STAT3 phosphorylation in regulating ferroptosis and its impact on cisplatin resistance in human osteosarcoma cells
Xinping Wang ; Linkuan Wang ; Pengchao Hu ; Yihua Shi
Acta Universitatis Medicinalis Anhui 2025;60(9):1670-1681
Objective:
To investigate the role of STAT3 phosphorylation in ferroptosis regulation and its impact on cisplatin resistance mechanisms in human osteosarcoma cells.
Methods:
Human osteosarcoma HOS cells and cispl- atin-resistant HOS / DDP cells were treated with cisplatin ( 0. 5,1,2,4,8,16,32 mg / L) ,the ferroptosis inducer Erastin ( Era) ( 2 μmol / L) ,and / or the ferroptosis inhibitor Ferrostatin-1 ( Fer1) ( 10 μmol / L) .Cell viability and proliferation were assessed using the Cell Counting Kit-8 ( CCK-8) and colony formation assays,and cell migration was evaluated via a scratch assay.Reactive oxygen species ( ROS) ,intracellular ferrous iron levels,mitochondrial membrane potential,mitochondrial function,malondialdehyde ( MDA) levels,and the reduced glutathione / oxi- dized glutathione ( GSH / GSSG) ratio were measured using commercial kits.The mRNA expression of ferroptosis- related genes was analyzed by quantitative reverse transcription polymerase chain reaction ( RT-qPCR) .The protein levels of glutathione peroxidase 4 ( GPX4) ,solute carrier family 7 member 11 ( SLC7A11) ,phosphorylated STAT3 ( p-STAT3) ,and total STAT3 were determined by Western blot.
Results:
With cisplatin treatment,HOS cells ex- hibited decreased cell viability,mitochondrial membrane potential,and GSH / GSSG ratio ( P<0. 01) ,along with elevated levels of ROS,ferrous ion,and MDA content ( P <0. 01) . The protein levels of GPX4 ( P <0. 01) , SLC7A11,and p-STAT3 also decreased ( P <0. 05) .Coadministration with the ferroptosis inhibitor Ferrostatin-1 ( Fer-1) reversed these aforementioned effects ( P <0. 05) .In HOS / DDP cells,the mRNA levels of ferroptosis- suppressive genes ( GPX4,FTH1,SLC7A11,and AIFM2) were significantly higher than those in HOS cells ( P < 0. 05) ,whereas the expression of ferroptosis-promoting genes ( ACSL4 and PTGS2) was significantly lower ( P < 0. 05) .The cisplatin-induced reductions in cell viability and mitochondrial membrane potential,as well as the in- creases in ROS,ferrous ion,and MDA levels,were less pronounced in HOS / DDP cells than in HOS cells.The SLC7A11 protein level showed no significant change. However,combined treatment with the ferroptosis inducer Erastin ( Era) resulted in significant decreases in viability,mitochondrial membrane potential,and the GSH / GSSG ratio in HOS / DDP cells ( P<0. 05) .Furthermore,the protein levels of p-STAT3,GPX4,and SLC7A11 were also markedly reduced ( P<0. 05) .
Conclusion
The activation of ferroptosis mediated by p-STAT3 enhances cisplatin sensitivity in HOS / DDP cells.
9.Screen of FDA-approved drug library identifies vitamin K as anti-ferroptotic drug for osteoarthritis therapy through Gas6
Yifeng SHI ; Sunlong LI ; Shuhao ZHANG ; Caiyu YU ; Jiansen MIAO ; Shu YANG ; Yan CHEN ; Yuxuan ZHU ; Xiaoxiao HUANG ; Chencheng ZHOU ; Hongwei OUYANG ; Xiaolei ZHANG ; Xiangyang WANG
Journal of Pharmaceutical Analysis 2025;15(5):1033-1047
Ferroptosis of chondrocytes is a significant contributor to osteoarthritis(OA),for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis.Here,we screen for anti-ferroptotic drugs in Food and Drug Administration(FDA)-approved drug library via a high-throughput manner in chondrocytes.We identified a group of FDA-approved anti-ferroptotic drugs,among which vitamin K showed the most powerful protective effect.Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix(ECM)degradation in chondrocytes.Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus(DMM)mouse model.Mechanistically,transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6(Gas6).Furthermore,exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase(AXL)/phosphatidylinositol 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)axis.Together,we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis,indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.
10.Study on the Prognostic Warning Value of Serum GR,SOD,Cys-C,Hcy and Lp(a)Levels in Patients with Cerebral Ischemic Stroke
Fang LI ; Xiangyang RAN ; Wei LI ; Wenjun SHI ; Liyun AN ; Lin KANG
Journal of Modern Laboratory Medicine 2025;40(2):92-97,103
Objective To explore the prognostic value of serum glutathione reductase(GR),superoxide dismutase(SOD),cystatin C(Cys-C),homocysteine(Hcy)and lipoprotein a[Lp(a)]levels in patients with cerebral ischemic stroke(CIS),and to provide a reference for improving the prognosis of CIS patients.Methods 126 patients with CIS admitted to the 980th Hospital of Joint Logistics Support Force from June 2022 to April 2023 were selected as the observation group,another 126 healthy individuals were selected as the control group at a ratio of 1:1.The expression levels of GR,SOD,Cys-C,Hcy and Lp(a)in the two groups were detected and compared after admission and during physical examination.The degree of neurological deficit in patients with CIS was classified into mild(NIHSS:2~4 points,n=35),moderate(NIHSS:5~15 points,n=47),moderate-severe(NIHSS:16~20 points,n=26)and severe(NIHSS:21~42 points,n=18)according to the National Institutes of Health Stroke Scale(NIHSS).The expression of serum GR,SOD,Cys-C,Hcy and Lp(a)in patients with different degrees of neurological deficit was compared,and the correlation between each indicator and the degree of neurological deficit was analyzed.The observation group received intravenous thrombolytic therapy after admission and was re-examined one day after thrombolysis.After treatment,follow-up visits were conducted for 28 days.According to the patient's condition(modified Rankin scale),patients were divided into good prognosis(n=94)and poor prognosis groups(n=32).The levels of each indicator in patients with different prognoses were compared,and the predictive value of GR,SOD,Cys-C,Hcy and Lp(a)expression for poor prognosis and early warning were analyzed.Results The expression levels of serum GR(48.54±3.07U/L)and SOD(157.17±25.47U/ml)in the observation group were lower than those in the control group(61.68±3.15U/L,203.63±18.31U/ml),while the expression levels of Cys-C(1.24±0.28mg/L),Hcy(15.21±1.62μmol/L)and Lp(a)(386.53±52.16mg/L)were higher than those in the control group(0.82±0.23mg/L,9.58±0.60μmol/L,257.83±45.34mg/L),with statistically significant differences(t=13.011~36.582,all P<0.05).As the disease progressed,the expression levels of GR and SOD gradually decreased,while the expression levels of Cys-C,Hcy and Lp(a)gradually increased,with statistically significant differences(F=14.685~197.041,all P<0.05).Spearman analysis,GR and SOD were negatively correlated with the degree of neurological deficit in patients with CIS(r=-0.814,-0.753,all P<0.05),while Cys-C,Hcy and Lp(a)were positively correlated with the degree of neurological deficit in patients with CIS(r=0.647,0.782,0.724,all P<0.05).The expression of GR and SOD in patients with good prognosis at admission and 1 day after thrombolysis was higher than that in patients with poor prognosis(t=9.109,6.338;2.934,4.358,all P<0.05),while the expression of Cys-C,Hcy and Lp(a)was lower than that in patients with poor prognosis(t=5.246,5.118,8.561;4.636,5.298,7.461,all P<0.05).The AUC(95%CI)of combined prediction of GR,SOD,Cys-C,Hcy and Lp(a)at admission was 0.898(0.832~0.945),and the AUC(95%CI)of combined prediction of GR,SOD,Cys-C,Hcy and Lp(a)at 1 day after thrombolysis was 0.931(0.871~0.968).The RR(95%CI)values caused by the expression of GR,SOD,Cys-C,Hcy and Lp(a)at 1 day after thrombolysis were 2.868(1.594~5.161),3.194(1.807~5.645),0.155(0.082~0.291),0.150(0.071~0.319)and 0.227(0.119~0.435).Conclusion Abnormal changes in the levels of GR,SOD,Cys-C,Hcy and Lp(a)are closely related to the degree of neurological deficit and prognosis in patients with CIS.Early combined detection of GR,SOD,Cys-C,Hcy and Lp(a)levels has high predictive value and early warning for evaluating the poor prognosis of patients with CIS.


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