1.Design and application effect of continuing education case library combined with case-based learning for rehabilitation therapists
Liguo QIAN ; Tongxuan WU ; Qiaoyun ZHANG ; Jian XING ; Yanyan YANG
Chinese Journal of Rehabilitation Theory and Practice 2026;32(3):249-257
ObjectiveTo investigate the demand and the application outcomes of case-based learning (CBL) combined with teaching case library in continuing education courses for rehabilitation therapists. MethodsA convergent mixed-methods research design was adopted, involving 51 rehabilitation therapists and 31 instructors who participated in the advanced training program at the Department of Rehabilitation Medicine, Peking University Third Hospital between October, 2022 and October, 2024. Self-developed questionnaires were used to collect data on the perceived needs of teachers and students regarding CBL and teaching case library. Differences between CBL + teaching case library and traditional lecturing in student evaluations, classroom participation and interaction were compared using Student Evaluation of Teaching in Medical Lectures, Classroom Participation Scale and Flanders Interaction Analysis System. Semi-structured interviews were conducted to obtain evaluations and attitudes towards this method from both instructors and students' perspectives. ResultsThe survey showed that 91.4% of participating teachers and students supported the use of CBL in the courses, and 82.7% advocated that the teaching case library should include typical cases. Significant differences were observed in teaching preference between teachers and students (χ² = 17.597, P < 0.01). Application effects demonstrated that CBL+teaching library significantly outperformed traditional teaching methods in student previewing behaviors, classroom interaction and learning outcomes (|Z| ≥ 2.646, P < 0.01). Flanders Interaction Analysis indicated that CBL+teaching library was superior to traditional teaching in terms of students' motivation to speak and autonomous learning. Qualitative Research generated four positive themes including cultivating clinical reasoning, being close to clinical practice, deepening knowledge understanding and improving teaching quality; and three negative themes including increasing teaching burden, high software and hardware requirements and posing great challenges to students were generated. ConclusionCompared with traditional teaching methods, CBL combined with teaching case library is closely linked to clinical practice, facilitating students' clinical reasoning, enhancing teaching effectiveness and satisfaction, and therefore aligning with the goals and needs of continuing education for rehabilitation therapists, which is highly recognized by both instructors and students.
2.Design and application effect of continuing education case library combined with case-based learning for rehabilitation therapists
Liguo QIAN ; Tongxuan WU ; Qiaoyun ZHANG ; Jian XING ; Yanyan YANG
Chinese Journal of Rehabilitation Theory and Practice 2026;32(3):249-257
ObjectiveTo investigate the demand and the application outcomes of case-based learning (CBL) combined with teaching case library in continuing education courses for rehabilitation therapists. MethodsA convergent mixed-methods research design was adopted, involving 51 rehabilitation therapists and 31 instructors who participated in the advanced training program at the Department of Rehabilitation Medicine, Peking University Third Hospital between October, 2022 and October, 2024. Self-developed questionnaires were used to collect data on the perceived needs of teachers and students regarding CBL and teaching case library. Differences between CBL + teaching case library and traditional lecturing in student evaluations, classroom participation and interaction were compared using Student Evaluation of Teaching in Medical Lectures, Classroom Participation Scale and Flanders Interaction Analysis System. Semi-structured interviews were conducted to obtain evaluations and attitudes towards this method from both instructors and students' perspectives. ResultsThe survey showed that 91.4% of participating teachers and students supported the use of CBL in the courses, and 82.7% advocated that the teaching case library should include typical cases. Significant differences were observed in teaching preference between teachers and students (χ² = 17.597, P < 0.01). Application effects demonstrated that CBL+teaching library significantly outperformed traditional teaching methods in student previewing behaviors, classroom interaction and learning outcomes (|Z| ≥ 2.646, P < 0.01). Flanders Interaction Analysis indicated that CBL+teaching library was superior to traditional teaching in terms of students' motivation to speak and autonomous learning. Qualitative Research generated four positive themes including cultivating clinical reasoning, being close to clinical practice, deepening knowledge understanding and improving teaching quality; and three negative themes including increasing teaching burden, high software and hardware requirements and posing great challenges to students were generated. ConclusionCompared with traditional teaching methods, CBL combined with teaching case library is closely linked to clinical practice, facilitating students' clinical reasoning, enhancing teaching effectiveness and satisfaction, and therefore aligning with the goals and needs of continuing education for rehabilitation therapists, which is highly recognized by both instructors and students.
3.Design and application effect of continuing education case library combined with case-based learning for rehabilitation therapists
Liguo QIAN ; Tongxuan WU ; Qiaoyun ZHANG ; Jian XING ; Yanyan YANG
Chinese Journal of Rehabilitation Theory and Practice 2026;32(3):249-257
ObjectiveTo investigate the demand and the application outcomes of case-based learning (CBL) combined with teaching case library in continuing education courses for rehabilitation therapists. MethodsA convergent mixed-methods research design was adopted, involving 51 rehabilitation therapists and 31 instructors who participated in the advanced training program at the Department of Rehabilitation Medicine, Peking University Third Hospital between October, 2022 and October, 2024. Self-developed questionnaires were used to collect data on the perceived needs of teachers and students regarding CBL and teaching case library. Differences between CBL + teaching case library and traditional lecturing in student evaluations, classroom participation and interaction were compared using Student Evaluation of Teaching in Medical Lectures, Classroom Participation Scale and Flanders Interaction Analysis System. Semi-structured interviews were conducted to obtain evaluations and attitudes towards this method from both instructors and students' perspectives. ResultsThe survey showed that 91.4% of participating teachers and students supported the use of CBL in the courses, and 82.7% advocated that the teaching case library should include typical cases. Significant differences were observed in teaching preference between teachers and students (χ² = 17.597, P < 0.01). Application effects demonstrated that CBL+teaching library significantly outperformed traditional teaching methods in student previewing behaviors, classroom interaction and learning outcomes (|Z| ≥ 2.646, P < 0.01). Flanders Interaction Analysis indicated that CBL+teaching library was superior to traditional teaching in terms of students' motivation to speak and autonomous learning. Qualitative Research generated four positive themes including cultivating clinical reasoning, being close to clinical practice, deepening knowledge understanding and improving teaching quality; and three negative themes including increasing teaching burden, high software and hardware requirements and posing great challenges to students were generated. ConclusionCompared with traditional teaching methods, CBL combined with teaching case library is closely linked to clinical practice, facilitating students' clinical reasoning, enhancing teaching effectiveness and satisfaction, and therefore aligning with the goals and needs of continuing education for rehabilitation therapists, which is highly recognized by both instructors and students.
4.Application of optimized combination prediction model in the prediction of hand, foot and mouth disease
Weijie TIAN ; Qian GAO ; Kun YANG ; Zhirong ZHAO ; Jian CHEN
Journal of Public Health and Preventive Medicine 2026;37(1):58-62
Objective To explore scientific and accurate prediction methods for the incidence of hand, foot, and mouth disease in the post-pandemic era, and to address modeling challenges caused by abnormal fluctuations in case numbers from 2020 to 2023. Methods The seasonal index was used to pre-process the data. The traditional seasonal autoregressive integrated moving average (SARIMA) model, singular spectrum analysis (SSA)-ARIMA model, ARIMA-Long short-term memory (LSTM) model, and SSA-ARIMA-LSTM model were used to fit the incidence from 2013 to 2023, and the incidence of hand, foot and mouth disease in 2024 was predicted. The real data collected in 2024 were used as the test set to compare the prediction performance of the models. Results The fitting performance of the constructed models was as follows: the ARIMA model had MAE=107.50 and RMSE=144.53, the SSA-ARIMA model showed MAE=2.84 and RMSE=4.33, the ARIMA-LSTM model achieved MAE=99.46 and RMSE=131.59, and the SSA-ARIMA-LSTM model had MAE=96.35 and RMSE=132.13. In terms of prediction performance, the ARIMA model resulted in MAE=151.64 and RMSE=146.70, the SSA-ARIMA model demonstrated MAE=41.22 and RMSE=57.01, the ARIMA-LSTM model yielded MAE=220.75 and RMSE=257.89, and the SSA-ARIMA-LSTM model recorded MAE=58.83 and RMSE=72.06. Conclusion The SSA-ARIMA model has the best fitting degree and the highest prediction accuracy, and is suitable for predicting the incidence trend of hand, foot and mouth disease.
5.Effects of resistance training on quadriceps mass and knee joint function in patients with osteoporosis and sarcopenia
Jian ZHOU ; Tao ZHANG ; Weili ZHOU ; Xingcheng ZHAO ; Jun WANG ; Jie SHEN ; Li QIAN ; Ming LU
Chinese Journal of Tissue Engineering Research 2026;30(5):1081-1088
BACKGROUND:The quadriceps strength of patients with osteoporosis and sarcopenia is significantly reduced,which can further reduce the function of the knee joint,affect the function of the lower limbs and even lead to a decrease in whole-body coordination.It is speculated that a reasonable quadriceps training program and personalized guidance are beneficial to the recovery of knee joint function in patients with osteoporosis and sarcopenia.OBJECTIVE:To observe the effect of short-term moderate-intensity resistance rehabilitation training on the mass and function of the quadriceps and knee joint function in patients with osteoporosis and sarcopenia.METHODS:Using the integrated physical examination and rehabilitation model,375 patients with osteoporosis and sarcopenia were screened at the Health Management Center of Shanghai Public Health Clinical Center.They underwent 12 weeks of combined/comprehensive exercise rehabilitation based on resistance exercise,including quadriceps resistance isotonic and isometric contraction training twice a week(3-5 sets each time,10-15 minutes per set)and aerobic exercise/balance exercise two or three times a week(30 minutes each time).Assessments and data collection were performed before rehabilitation training,12 weeks after rehabilitation training,and at follow-up 12 weeks after stopping rehabilitation training,mainly including knee joint range of motion and proprioception,quadriceps muscle strength,and cross-sectional area(magnetic resonance imaging results),pain,knee joint function(Hospital for Special Surgery score)and walking function("up-and-go"time and 6 m pace test results)as well as the patient's psychological status assessment.RESULTS AND CONCLUSION:All 375 patients completed 12 weeks of rehabilitation training and 12 weeks of follow-up without any adverse events.(1)Compared with before training,the patients' gait speed and knee range of motion increased significantly after 12 weeks of rehabilitation training(P<0.01),the time of"stand-to-walk"decreased(P<0.01),and the proprioception of the knee joint and the strength of the quadriceps femoris were significantly improved(P<0.01);and at the follow-up visit 12 weeks after stopping training,the above indicators and functions of the patients were well maintained(P>0.05).(2)Magnetic resonance imaging results showed that the effective cross-sectional area of the quadriceps femoris did not improve significantly after 12 weeks of rehabilitation training(P>0.05);but the Hospital for Special Surgery score of knee joint function increased significantly(P<0.01),and the visual analog pain scale score decreased significantly(P<0.01),suggesting that this may be related to the improvement of quadriceps femoris quality by resistance rehabilitation training.(3)The results of the Hospital Anxiety and Depression Scale score showed that the anxiety and depression scores of the patients continued to decrease,both at 12 weeks of rehabilitation training and at 12 weeks after stopping training(P<0.01).It is suggested that resistance rehabilitation training of the quadriceps can help patients with osteoporosis and sarcopenia to restore quadriceps muscle strength,increase range of motion,improve proprioception and joint stability,thereby enhancing knee joint function,reducing pain,improving depression and anxiety,and to a certain extent promoting the coordinated recovery of the musculoskeletal system.
6.Effects of resistance training on quadriceps mass and knee joint function in patients with osteoporosis and sarcopenia
Jian ZHOU ; Tao ZHANG ; Weili ZHOU ; Xingcheng ZHAO ; Jun WANG ; Jie SHEN ; Li QIAN ; Ming LU
Chinese Journal of Tissue Engineering Research 2026;30(5):1081-1088
BACKGROUND:The quadriceps strength of patients with osteoporosis and sarcopenia is significantly reduced,which can further reduce the function of the knee joint,affect the function of the lower limbs and even lead to a decrease in whole-body coordination.It is speculated that a reasonable quadriceps training program and personalized guidance are beneficial to the recovery of knee joint function in patients with osteoporosis and sarcopenia.OBJECTIVE:To observe the effect of short-term moderate-intensity resistance rehabilitation training on the mass and function of the quadriceps and knee joint function in patients with osteoporosis and sarcopenia.METHODS:Using the integrated physical examination and rehabilitation model,375 patients with osteoporosis and sarcopenia were screened at the Health Management Center of Shanghai Public Health Clinical Center.They underwent 12 weeks of combined/comprehensive exercise rehabilitation based on resistance exercise,including quadriceps resistance isotonic and isometric contraction training twice a week(3-5 sets each time,10-15 minutes per set)and aerobic exercise/balance exercise two or three times a week(30 minutes each time).Assessments and data collection were performed before rehabilitation training,12 weeks after rehabilitation training,and at follow-up 12 weeks after stopping rehabilitation training,mainly including knee joint range of motion and proprioception,quadriceps muscle strength,and cross-sectional area(magnetic resonance imaging results),pain,knee joint function(Hospital for Special Surgery score)and walking function("up-and-go"time and 6 m pace test results)as well as the patient's psychological status assessment.RESULTS AND CONCLUSION:All 375 patients completed 12 weeks of rehabilitation training and 12 weeks of follow-up without any adverse events.(1)Compared with before training,the patients' gait speed and knee range of motion increased significantly after 12 weeks of rehabilitation training(P<0.01),the time of"stand-to-walk"decreased(P<0.01),and the proprioception of the knee joint and the strength of the quadriceps femoris were significantly improved(P<0.01);and at the follow-up visit 12 weeks after stopping training,the above indicators and functions of the patients were well maintained(P>0.05).(2)Magnetic resonance imaging results showed that the effective cross-sectional area of the quadriceps femoris did not improve significantly after 12 weeks of rehabilitation training(P>0.05);but the Hospital for Special Surgery score of knee joint function increased significantly(P<0.01),and the visual analog pain scale score decreased significantly(P<0.01),suggesting that this may be related to the improvement of quadriceps femoris quality by resistance rehabilitation training.(3)The results of the Hospital Anxiety and Depression Scale score showed that the anxiety and depression scores of the patients continued to decrease,both at 12 weeks of rehabilitation training and at 12 weeks after stopping training(P<0.01).It is suggested that resistance rehabilitation training of the quadriceps can help patients with osteoporosis and sarcopenia to restore quadriceps muscle strength,increase range of motion,improve proprioception and joint stability,thereby enhancing knee joint function,reducing pain,improving depression and anxiety,and to a certain extent promoting the coordinated recovery of the musculoskeletal system.
7.Clinical features and multimodal quantitative radiological features of primary liver cancer patients with different traditional Chinese medicine syndrome types
Feng WU ; Muqing LUO ; Wantingting WEN ; Ziwei CAI ; Yinqi LIU ; Jian XIANG ; Xiaona ZHOU ; Qian GUO ; Kun ZHANG
Journal of Clinical Hepatology 2026;42(5):1093-1100
ObjectiveTo investigate the association of the traditional Chinese medicine (TCM) syndrome types of primary liver cancer (PLC) with clinical features and multimodal quantitative radiological features on computed tomography (CT) and magnetic resonance imaging (MRI), and to provide a reference for the objectification of TCM syndrome differentiation and precise diagnosis and treatment. MethodsA retrospective analysis was performed for the clinical data of 312 patients who were diagnosed with PLC in The First Affiliated Hospital of Hunan University of Chinese Medicine from March 2020 to June 2025, and according to the TCM syndrome type, they were divided into stagnation of liver Qi group with 40 patients, stagnation of liver Qi and spleen deficiency group with 109 patients, Qi stagnation and blood stasis group with 62 patients, dampness-heat toxin amassment group with 81 patients, and liver-kidney Yin deficiency group with 20 patients. Clinical features and multimodal quantitative radiological features were compared between the patients with different TCM syndrome types. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Dunn’s multiple test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups, and the Bonferroni method was used for further comparison between two groups. ResultsThere were significant differences between the patients with different TCM syndrome types in China liver cancer staging (CNLC), Child-Pugh class, alanine aminotransferase, aspartate aminotransferase, albumin, direct bilirubin, total bilirubin, prothrombin time, neutrophil, and albumin-bilirubin score (all P<0.05). In the stagnation of liver Qi group, the patients with Child-Pugh class A accounted for 75.00%; among the patients with CNLC stage I PLC, the patients with stagnation of liver Qi accounted for 60.00%, and those with Qi stagnation and blood stasis syndrome accounted for 59.68%, while among the patients with CNLC stage IV PLC, the distribution proportion of dampness-heat toxin amassment (27.16%) and liver-kidney Yin deficiency (30.00%) was significantly higher than that of stagnation of liver Qi (2.50%) (all P<0.05). Radiological examination showed that there were significant differences between the patients with different TCM syndrome types in the number of tumors, ascites, venous tumor thrombus, maximum tumor diameter, intrahepatic metastasis, and lymph node metastasis in the hepatic hilar and retroperitoneal regions (all P<0.05). Compared with the patients with stagnation of liver Qi, the patients with liver depression and spleen deficiency or liver-kidney Yin deficiency were more likely to develop intrahepatic metastasis; the patients with liver depression and spleen deficiency, dampness-heat toxin amassment, or liver-kidney Yin deficiency were more likely to develop lymph node metastasis in the hepatic hilar and retroperitoneal regions; the patients with liver-kidney Yin deficiency were more likely to experience multiple tumors; the patients with liver depression and spleen deficiency or dampness-heat toxin amassment were more likely to develop ascites (all P<0.05). Compared with the patients with Qi stagnation and blood stasis syndrome, the patients with liver depression and spleen deficiency had a significantly longer maximum tumor diameter and a significantly higher proportion of patients with venous tumor thrombus (both P<0.05). Furthermore, among the 184 patients with MRI diffusion-weighted imaging sequences, the patients with dampness-heat toxin amassment or Qi stagnation and blood stasis syndrome had significantly higher ADC values and relative ADC values than those with stagnation of liver Qi (all P<0.05). ConclusionThere are significant differences in CT/MRI radiological features and clinical features between PLC patients with different TCM syndrome types, among whom the patients with liver depression and spleen deficiency, dampness-heat toxin amassment, and liver-kidney Yin deficiency tend to exhibit progressive radiological features, and those with dampness-heat toxin amassment or Qi stagnation and blood stasis syndrome tend to have higher ADC values. These findings provide an objective basis for TCM syndrome differentiation in PLC.
8.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
9.Efficacy and Safety of Juan Bi Pill with Add-on Methotrexate in Active Rheumatoid Arthritis: A 48-Week, Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial.
Qing-Yun JIA ; Yi-Ru WANG ; Da-Wei SUN ; Jian-Chun MAO ; Luan XUE ; Xiao-Hua GU ; Xiang YU ; Xue-Mei PIAO ; Hao XU ; Qian-Qian LIANG
Chinese journal of integrative medicine 2025;31(2):99-107
OBJECTIVE:
To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA).
METHODS:
From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment.
RESULTS:
After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75).
CONCLUSION
JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597).
Humans
;
Arthritis, Rheumatoid/drug therapy*
;
Methotrexate/adverse effects*
;
Female
;
Double-Blind Method
;
Male
;
Middle Aged
;
Treatment Outcome
;
Drugs, Chinese Herbal/adverse effects*
;
Drug Therapy, Combination
;
Adult
;
Antirheumatic Agents/adverse effects*
;
Aged
10.Drofenine as a Kv2.1 inhibitor alleviated AD-like pathology in mice through Aβ/Kv2.1/microglial NLRP3/neuronal Tau axis.
Jian LU ; Qian ZHOU ; Danyang ZHU ; Hongkuan SONG ; Guojia XIE ; Xuejian ZHAO ; Yujie HUANG ; Peng CAO ; Jiaying WANG ; Xu SHEN
Acta Pharmaceutica Sinica B 2025;15(1):371-391
Alzheimer's disease (AD) is a neurodegenerative disease with clinical hallmarks of progressive cognitive impairment. Synergistic effects of the Aβ-Tau cascade reaction are tightly implicated in AD pathology, and microglial NLRP3 inflammasome activation drives neuronal tauopathy. However, the underlying mechanism of how Aβ mediates NLRP3 inflammasome remains unclear. Herein, we determined that oligomeric Aβ (o-Aβ) bound to microglial Kv2.1 and promoted Kv2.1-dependent potassium efflux to activate NLRP3 inflammasome resulting in neuronal tauopathy by using Kv2.1 inhibitor drofenine (Dfe) as a probe. The underlying mechanism has been intensively investigated by assays with Kv2.1 knockdown in vitro (si-Kv2.1) and in vivo (AAV-ePHP-si-Kv2.1). Dfe deprived o-Aβ of its capability to promote microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation by inhibiting the Kv2.1/JNK/NF-κB pathway while improving the cognitive impairment of 5×FAD-AD model mice. Our results have highly addressed that the Kv2.1 channel is required for o-Aβ-driven microglial NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Dfe as a Kv2.1 inhibitor shows potential in the treatment of AD.


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