1.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.
2.Efficacy and safety of high-frequency repetitive transcranial magnetic stimulation in postherpetic neuralgia
Yu ZHAO ; Xiangyang TANG ; Zuosheng CHEN ; Fengming YAO ; Wei JIANG ; Fei XU
Chinese Journal of Neuromedicine 2025;24(8):799-805
Objective:To evaluate the efficacy and safety of high-frequency repetitive transcranial magnetic stimulation (hrTMS) in postherpetic neuralgia (PHN).Methods:A prospective randomized controlled trial was performed; 63 PHN patients treated in Department of Neurology and Department of Dermatology and Venereology of Anqing Municipal Hospital from June 2024 to March 2025 were enrolled; they were randomly assigned to 2 groups: an hrTMS group ( n=32) received hrTMS (frequency: 10 Hz; total pulses: 2,400; intensity: 90% of resting motor threshold) to the contralateral primary motor cortex (M1), and a sham stimulation group ( n=31) received sham stimulation using a sham figure-of-eight coil generating no actual magnetic field. Scores of short-form McGill pain questionnaires (pain rating index [PRI] total score, PRI sensory subscore, PRI affective subscore, visual analogue scale [VAS] score, present pain intensity [PPI] score) and N100 amplitude were collected before treatment and at 1, 2, 3, and 4 weeks after treatment. Adverse events during treatment were recorded. Results:At 2 weeks after treatment, significant difference was observed between the hrTMS group and sham stimulation group in PRI total score, VAS score, and N100 amplitude ( P<0.05). At 3 and 4 weeks after treatment, significant differences were found between the two groups in PRI total score, PRI sensory subscore, PRI affective subscore, VAS score, PPI score and N100 amplitude (3 weeks after treatment: 8.59±1.13 vs. 9.61±1.20, 5.34±0.79 vs. 5.90±0.94, 3.25±0.57 vs. 3.71±0.46, 5.78±0.66 vs. 6.42±0.92, 2.16±0.37 vs. 2.55±0.51, and [2.53±0.51] μV vs. [2.13±0.34] μV; 4 weeks after treatment: 7.53±0.92 vs. 9.68±1.35, 4.94±0.62 vs. 6.00±1.07, 2.59±0.56 vs. 3.68±0.60, 5.06±0.67 vs. 6.23±1.06, 1.97±0.17 vs. 2.52±0.51, and [2.81±0.40] μV vs. [2.16±0.52] μV, P<0.05). In the hrTMS group, PRI total score, PRI sensory subscore, PRI affective subscore, VAS score, PPI score and N100 amplitude were significantly different at 2, 3, and 4 weeks after treatment compared with those before treatment ( P<0.05). Incidence of adverse events (headache, dizziness or tinnitus) did not differ significantly between the two groups ( P>0.05). Conclusion:The hrTMS applied to the M1 region in PHN patients is effective by obviously reducing pain intensity and improving negative emotional states, with favorable safety profile.
3.Clinical guideline for diagnosis and treatment of nonunion of osteoporotic vertebral fractures (version 2025)
Haipeng SI ; Le LI ; Junjie NIU ; Wencan ZHANG ; Fuxin WEI ; Jinqiu YUAN ; Qiang YANG ; Hongli WANG ; Guangchao WANG ; Shihong CHEN ; Yunzhen CHEN ; Xiaoguang CHENG ; Jianwen DONG ; Shiqing FENG ; Rui GU ; Yong HAI ; Tianyong HOU ; Bo HUANG ; Xiaobing JIANG ; Lei ZANG ; Chunhai LI ; Nianhu LI ; Hua LIN ; Hongjian LIU ; Peng LIU ; Xinyu LIU ; Sheng LU ; Shibao LU ; Chunshan LUO ; Lvy CHAOLIANG ; Lvy WEIJIA ; Xuexiao MA ; Wei MEI ; Chunyang MENG ; Cailiang SHEN ; Chunli SONG ; Ruoxian SONG ; Jiacan SU ; Honglin TENG ; Hui SHENG ; Beiyu WANG ; Bingwu WANG ; Liang WANG ; Xiangyang WANG ; Nan WU ; Guohua XU ; Yayi XIA ; Jin XU ; Youjia XU ; Jianzhong XU ; Cao YANG ; Maowei YANG ; Zibin YANG ; Xiaojian YE ; Hailong YU ; Xijie YU ; Hua YUE ; Zhili ZENG ; Xinli ZHAN ; Hui ZHANG ; Peixun ZHANG ; Wei ZHANG ; Zhenlin ZHANG ; Jianguo ZHANG ; Tengyue ZHU ; Qiang LIU ; Huilin YANG
Chinese Journal of Trauma 2025;41(10):932-945
Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.
4.Clinical guideline for diagnosis and treatment of nonunion of osteoporotic vertebral fractures (version 2025)
Haipeng SI ; Le LI ; Junjie NIU ; Wencan ZHANG ; Fuxin WEI ; Jinqiu YUAN ; Qiang YANG ; Hongli WANG ; Guangchao WANG ; Shihong CHEN ; Yunzhen CHEN ; Xiaoguang CHENG ; Jianwen DONG ; Shiqing FENG ; Rui GU ; Yong HAI ; Tianyong HOU ; Bo HUANG ; Xiaobing JIANG ; Lei ZANG ; Chunhai LI ; Nianhu LI ; Hua LIN ; Hongjian LIU ; Peng LIU ; Xinyu LIU ; Sheng LU ; Shibao LU ; Chunshan LUO ; Lvy CHAOLIANG ; Lvy WEIJIA ; Xuexiao MA ; Wei MEI ; Chunyang MENG ; Cailiang SHEN ; Chunli SONG ; Ruoxian SONG ; Jiacan SU ; Honglin TENG ; Hui SHENG ; Beiyu WANG ; Bingwu WANG ; Liang WANG ; Xiangyang WANG ; Nan WU ; Guohua XU ; Yayi XIA ; Jin XU ; Youjia XU ; Jianzhong XU ; Cao YANG ; Maowei YANG ; Zibin YANG ; Xiaojian YE ; Hailong YU ; Xijie YU ; Hua YUE ; Zhili ZENG ; Xinli ZHAN ; Hui ZHANG ; Peixun ZHANG ; Wei ZHANG ; Zhenlin ZHANG ; Jianguo ZHANG ; Tengyue ZHU ; Qiang LIU ; Huilin YANG
Chinese Journal of Trauma 2025;41(10):932-945
Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.
5.Efficacy and safety of high-frequency repetitive transcranial magnetic stimulation in postherpetic neuralgia
Yu ZHAO ; Xiangyang TANG ; Zuosheng CHEN ; Fengming YAO ; Wei JIANG ; Fei XU
Chinese Journal of Neuromedicine 2025;24(8):799-805
Objective:To evaluate the efficacy and safety of high-frequency repetitive transcranial magnetic stimulation (hrTMS) in postherpetic neuralgia (PHN).Methods:A prospective randomized controlled trial was performed; 63 PHN patients treated in Department of Neurology and Department of Dermatology and Venereology of Anqing Municipal Hospital from June 2024 to March 2025 were enrolled; they were randomly assigned to 2 groups: an hrTMS group ( n=32) received hrTMS (frequency: 10 Hz; total pulses: 2,400; intensity: 90% of resting motor threshold) to the contralateral primary motor cortex (M1), and a sham stimulation group ( n=31) received sham stimulation using a sham figure-of-eight coil generating no actual magnetic field. Scores of short-form McGill pain questionnaires (pain rating index [PRI] total score, PRI sensory subscore, PRI affective subscore, visual analogue scale [VAS] score, present pain intensity [PPI] score) and N100 amplitude were collected before treatment and at 1, 2, 3, and 4 weeks after treatment. Adverse events during treatment were recorded. Results:At 2 weeks after treatment, significant difference was observed between the hrTMS group and sham stimulation group in PRI total score, VAS score, and N100 amplitude ( P<0.05). At 3 and 4 weeks after treatment, significant differences were found between the two groups in PRI total score, PRI sensory subscore, PRI affective subscore, VAS score, PPI score and N100 amplitude (3 weeks after treatment: 8.59±1.13 vs. 9.61±1.20, 5.34±0.79 vs. 5.90±0.94, 3.25±0.57 vs. 3.71±0.46, 5.78±0.66 vs. 6.42±0.92, 2.16±0.37 vs. 2.55±0.51, and [2.53±0.51] μV vs. [2.13±0.34] μV; 4 weeks after treatment: 7.53±0.92 vs. 9.68±1.35, 4.94±0.62 vs. 6.00±1.07, 2.59±0.56 vs. 3.68±0.60, 5.06±0.67 vs. 6.23±1.06, 1.97±0.17 vs. 2.52±0.51, and [2.81±0.40] μV vs. [2.16±0.52] μV, P<0.05). In the hrTMS group, PRI total score, PRI sensory subscore, PRI affective subscore, VAS score, PPI score and N100 amplitude were significantly different at 2, 3, and 4 weeks after treatment compared with those before treatment ( P<0.05). Incidence of adverse events (headache, dizziness or tinnitus) did not differ significantly between the two groups ( P>0.05). Conclusion:The hrTMS applied to the M1 region in PHN patients is effective by obviously reducing pain intensity and improving negative emotional states, with favorable safety profile.
6.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.
7.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.
8.Reappraisals of biological behaviors of PDGFRA mutant gastrointestinal stromal tumor
Wei YUAN ; Wen HUANG ; Lei REN ; Huaiyu LIANG ; Siyao DONG ; Xiangyang DU ; Chen XU ; Yong FANG ; Kuntang SHEN ; Yingyong HOU
Chinese Journal of Pathology 2024;53(1):46-51
Objective:To investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification.Methods:A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically.Results:There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant ( P=0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference ( P=0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant ( P<0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant ( P<0.001). Conclusions:GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.
9.Improvement effect and mechanism of petroleum ether extract of Saposhnikovia divaricata on rheumatoid arthritis rats by regulating neutrophil extracellular traps
Xiangyang ZHANG ; Wei WEI ; Peng XU ; Ning LI ; Wenjing GE ; Xinyi WANG ; Ruifeng LIANG ; Airong XUE
China Pharmacy 2024;35(19):2345-2351
OBJECTIVE To explore the improvement effect and mechanism of petroleum ether extract of Saposhnikovia divaricata on rheumatoid arthritis (RA) rats by regulating neutrophil extracellular traps (NETs). METHODS Establishment of rat RA model using bovine type Ⅱ collagen and Freund’s complete adjuvant. The model rats were randomly divided into model group and low-dose, middle-dose and high-dose groups (55, 110, 220 mg/kg) of petroleum ether extract of S. divaricata; the normal group without modeling was also established, with 10 rats in each group. Each group was given corresponding drugs or constant volume of 2% Tween-80 solution intragastrically, once a day, for consecutive 28 days. The toe swelling degree in rats was observed, and the arthritis index (AI) was scored. The serum levels of interleukin-1β (IL-1β), IL-10, IL-17, tumor necrosis factor-α (TNF-α), 25-hydroxyvitamin D3 [25(OH)D3], myeloperoxidase (MPO), neutrophil elastase (NE) and NETs in rats were detected. The histopathological changes in ankle joint were observed. The expression of citrullinated histone H3 (CitH3) in ankle joint as well as the expressions of cytochrome P450 24A1 (CYP24A1), cytochrome P450 27B1 (CYP27B1),vitamin D receptor (VDR) and peptidyl arginine deiminase 4 疾病。E-mail:zhongyao626@126.com (PAD4) in synovium were all determined. RESULTS Compared with the model group, the toe swelling degree and AI score in the middle-dose and high-dose groups of petroleum ether extract of S. divaricata decreased significantly from day 14 to day 28 after administration (P<0.05 or P<0.01). The serum levels of IL-1β, IL-17, TNF-α, MPO, NE and NETs decreased significantly, while the levels of IL-10 and 25(OH)D3 increased significantly (P<0.05 or P<0.01). The widened ankle joint space and the improved structure were found; the expression of CitH3 in ankle joint, and the expressions of CYP24A1 and PAD4 in synovium were down-regulated significantly, while the expressions of CYP27B1 and VDR were up-regulated significantly in synovium (P<0.05 or P<0.01). CONCLUSIONS The petroleum ether extract of S. divaricata may inhibit the production of NETs and improve the symptoms of RA by regulating the vitamin D system.
10.MiRNA320a Inhibitor-Loaded PLGA-PLL-PEG Nanoparticles Contribute to Bone Regeneration in Trauma-Induced Osteonecrosis Model of the Femoral Head
Ying ZHANG ; Chuan LI ; Qiushi WEI ; Qiang YUAN ; Wei HE ; Ning ZHANG ; Yiping DONG ; Zhenhao JING ; Leilei ZHANG ; Haibin WANG ; Xiangyang CAO
Tissue Engineering and Regenerative Medicine 2024;21(1):185-197
BACKGROUND:
This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH).
METHODS:
The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo. Hematoxylin–eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay.
RESULTS:
High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model.
CONCLUSION
The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH.

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