1.The Current Issues and Thoughts on the Empowerment of Famous Doctors' Experience Inheritance by Artificial Intelligence
Xiaochen JIANG ; Fudong LIU ; Chuanlong ZHANG ; Yi LI ; Qian SHEN ; Bo PANG
Journal of Traditional Chinese Medicine 2026;67(7):710-715
In the context of the modernization of traditional Chinese medicine (TCM), the inheritance of the experiences of famous doctors faces significant challenges due to its complex nonlinear characteristics and dynamic evolution. There are still issues in the current inheritance system, such as the homogenization of talent cultivation models, lack of standardized mentoring practices, and monotonous evaluation method, which hinder the systematic inheritance and innovative development of famous doctors' experiences. Based on a systematic review of the current state of artificial intelligence (AI)-assisted inheritance of famous doctors' experiences, this study explores innovative pathways for deep integration of modern information technologies with famous doctors' experiences from key dimensions, including data authenticity assurance, interdisciplinary collaboration mechanisms, and the establishment of dynamic inheritance standards. It proposes a paradigm shift in the inheritance of TCM famous doctors' experiences in the AI era, aiming to build a new TCM inheritance system of "digital intelligence empowerment and cross-disciplinary innovation", providing theoretical support and practical pathways for the inheritance of famous doctors' experiences in TCM.
2.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.
3.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.
4.Application of Gas Chromatography Ion Mobility Spectrometry Technology Combined with Chemometric Methods in Identification of Foeniculi Fructus from Haiyuan Region
Xiurong TIAN ; Hao WANG ; Kejing PANG ; Penglong YU ; Xia LIU ; Mengyue SHEN ; Xianglin JIANG ; Yonghua LI ; Zhihong LI ; Hongqiong DING ; Qin YANG ; Xingying LI ; Qian XIONG ; Guochao WAN ; Yuexiang MA ; Zhenping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):184-192
ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan, providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas, including Minqin (Gansu), Bozhou (Anhui), Qingdao (Shandong), Dezhou (Shandong), Urumqi (Xinjiang), Nujiang (Yunnan), Gutuo (Inner Mongolia), and Haiyuan (Ningxia). Gas chromatography-ion mobility spectrometry (GC-IMS) was used to detect the volatile organic compounds (VOCs) in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology (NIST) mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform, VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted, and 97 VOCs detected via GC-IMS were subjected to principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection (VIP) values greater than 1. ResultsA total of 97 VOCs were identified, including alcohols, aldehydes, ketones, esters, organic acids, terpenoids, ethers, alkenes, and benzenes. The PLS-DA model, based on VOCs data obtained by GC-IMS, effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation, the model achieved a prediction parameter (Q2) of 0.976 and a goodness-of-fit parameter (R2) of 0.936, with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology, PLS-DA, and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.
5.Application of Gas Chromatography Ion Mobility Spectrometry Technology Combined with Chemometric Methods in Identification of Foeniculi Fructus from Haiyuan Region
Xiurong TIAN ; Hao WANG ; Kejing PANG ; Penglong YU ; Xia LIU ; Mengyue SHEN ; Xianglin JIANG ; Yonghua LI ; Zhihong LI ; Hongqiong DING ; Qin YANG ; Xingying LI ; Qian XIONG ; Guochao WAN ; Yuexiang MA ; Zhenping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):184-192
ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan, providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas, including Minqin (Gansu), Bozhou (Anhui), Qingdao (Shandong), Dezhou (Shandong), Urumqi (Xinjiang), Nujiang (Yunnan), Gutuo (Inner Mongolia), and Haiyuan (Ningxia). Gas chromatography-ion mobility spectrometry (GC-IMS) was used to detect the volatile organic compounds (VOCs) in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology (NIST) mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform, VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted, and 97 VOCs detected via GC-IMS were subjected to principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection (VIP) values greater than 1. ResultsA total of 97 VOCs were identified, including alcohols, aldehydes, ketones, esters, organic acids, terpenoids, ethers, alkenes, and benzenes. The PLS-DA model, based on VOCs data obtained by GC-IMS, effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation, the model achieved a prediction parameter (Q2) of 0.976 and a goodness-of-fit parameter (R2) of 0.936, with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology, PLS-DA, and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.
6.Long-term safety and effectiveness of roxadustat in Chinese patients with chronic kidney disease-associated anemia: The ROXSTAR registry.
Xiaoying DU ; Yaomin WANG ; Haifeng YU ; Jurong YANG ; Weiming HE ; Zunsong WANG ; Dongwen ZHENG ; Xiaowei LI ; Shuijuan SHEN ; Dong SUN ; Weimin YU ; Detian LI ; Changyun QIAN ; Yiqing WU ; Shuting PAN ; Jianghua CHEN
Chinese Medical Journal 2025;138(12):1465-1476
BACKGROUND:
Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China.
METHODS:
This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion.
RESULTS:
The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon.
CONCLUSIONS:
Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings.
REGISTRATION
Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans
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Male
;
Female
;
Anemia/etiology*
;
Middle Aged
;
Renal Insufficiency, Chronic/complications*
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Glycine/adverse effects*
;
Isoquinolines/adverse effects*
;
Aged
;
Prospective Studies
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Adult
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Hemoglobins/metabolism*
;
Treatment Outcome
;
China
;
Registries
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East Asian People
7.Studies on common irritant components in three different base sources of Polygonati Rhizoma.
Yu-Xin GU ; Hong-Li YU ; Min SHEN ; Xin-Zhi WANG ; Kui-Long WANG ; Jie CAO ; Qian-Lin CHEN ; Yan-Qing XU ; Chang-Li SHEN ; Hao WU
China Journal of Chinese Materia Medica 2025;50(12):3223-3231
To explore the common irritant components in different base sources of Polygonati Rhizoma(PR). A rabbit eye irritation experiment was conducted to compare the irritant effects of raw products of Polygonatum kingianum, P. officinale, and P. multiflorum. The irritant effects of different solvent extraction parts and needle crystals of PR were compared, and the irritant components were screened. The morphology and structure of the purified needle crystal of PR were observed by microscope and scanning electron microscope and characterized by X-ray diffraction. Rabbit eye irritation and mouse abdominal inflammation model were used to evaluate rabbit eye irritation scores, inflammatory mediators, inflammatory factors levels in the peritoneal exudate of mice, with the peritoneal pathological section used as indicators. The inflammatory effect of needle crystals of PR was studied, and the content of calcium oxalate in three kinds of PR was determined by HPLC. The common protein in three kinds of PR was screened and compared by double enzymatic hydrolysis in solution combined with mass spectrometry. The results showed that three kinds of PR raw products had certain irritant effects on rabbit eyes, among which P. kingianum had the strongest irritant effect. There were no obvious irritant effects in the different solvent extraction parts of P. kingianum. Compared with the blank group, the needle crystal of PR had a significant irritant effect on rabbit eyes, and the inflammatory mediators and inflammatory factors in the peritoneal exudate were significantly increased(P<0.05) in a dose-dependent manner. Meanwhile, the peritoneal tissue of mice was damaged with significant inflammatory cell infiltration after intraperitoneal injection of needle crystal, indicating that needle crystal had an inflammatory effect. Microscope and scanning electron microscope observations showed that the needle crystals of PR were slender, with a length of about 100-200 μm and sharp ends. X-ray diffraction analysis showed that the needle crystals of PR were calcium oxalate monohydrate crystals. The results of HPLC showed that the content of calcium oxalate in P. kingianum was the highest among the three kinds of PR. It was speculated that the content of needle crystal in P. kingianum was higher than that in P. officinale and P. multiflorum, which was consistent with the results of the rabbit eye irritation experiment. The results of mass spectrometry showed that ribosome inactivating protein and mannose/sialic acid binding lectin were related to inflammation and cell metabolism in all three kinds of PR. There was no obvious irritant effect in different solvent extracts of PR. The calcium oxalate needle crystal contained was the main irritant component of PR, and three kinds of PR contained common ribosome inactivating protein and mannose/sialic acid binding lectin, which may be related to the inflammatory irritant effect of PR.
Animals
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Rabbits
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Mice
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Polygonatum/chemistry*
;
Drugs, Chinese Herbal/toxicity*
;
Rhizome/chemistry*
;
Male
;
Eye/drug effects*
;
Female
;
Humans
8.Predictive value of bpMRI for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L.
Lai DONG ; Rong-Jie SHI ; Jin-Wei SHANG ; Zhi-Yi SHEN ; Kai-Yu ZHANG ; Cheng-Long ZHANG ; Bin YANG ; Tian-Bao HUANG ; Ya-Min WANG ; Rui-Zhe ZHAO ; Wei XIA ; Shang-Qian WANG ; Gong CHENG ; Li-Xin HUA
National Journal of Andrology 2025;31(5):426-431
Objective: The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods: The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results: Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62-24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16-17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12-3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion: For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans
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Male
;
Prostatic Neoplasms/diagnostic imaging*
;
Lymphatic Metastasis
;
Retrospective Studies
;
Nomograms
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Prostate-Specific Antigen/blood*
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Lymph Nodes/pathology*
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Pelvis
;
Predictive Value of Tests
;
Prostatectomy
;
Lymph Node Excision
;
Risk Factors
;
Magnetic Resonance Imaging
;
Logistic Models
;
Middle Aged
;
Aged
9.Enzyme-independent functions of HDAC3 in the adult heart.
Sichong QIAN ; Chen ZHANG ; Wenbo LI ; Shiyang SONG ; Guanqiao LIN ; Zixiu CHENG ; Wenjun ZHOU ; Huiqi YIN ; Yueli WANG ; Haiyang LI ; Ying H SHEN ; Zheng SUN
Acta Pharmaceutica Sinica B 2025;15(7):3561-3574
The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.
10.Inhibition of WAC alleviates the chondrocyte proinflammatory secretory phenotype and cartilage degradation via H2BK120ub1 and H3K27me3 coregulation.
Peitao XU ; Guiwen YE ; Xiaojun XU ; Zhidong LIU ; Wenhui YU ; Guan ZHENG ; Zepeng SU ; Jiajie LIN ; Yunshu CHE ; Yipeng ZENG ; Zhikun LI ; Pei FENG ; Qian CAO ; Zhongyu XIE ; Yanfeng WU ; Huiyong SHEN ; Jinteng LI
Acta Pharmaceutica Sinica B 2025;15(8):4064-4077
Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

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