1.Kaempferide inhibited progression of osteoarthritis by targeting the HIF-1 signaling pathway.
Xianjie WEI ; Hesuyuan HUANG ; Ping YUAN ; Peisen XIE ; Keshi ZHANG ; Zhenpeng GUAN
Chinese Medical Journal 2025;138(21):2813-2823
BACKGROUND:
Osteoarthritis (OA) is a prevalent joint disorder that significantly impairs quality of life among elderly individuals because of chronic pain and physical disability. As the global burden of OA continues to rise, novel therapeutic strategies are urgently needed. Kaempferide (KA), a flavonoid derived from traditional Chinese herbal medicine, is known for its anti-inflammatory properties. However, the effect of KA on the progression of OA has not been well investigated. This study aimed to explore the therapeutic potential of KA in an OA model and investigate the underlying mechanisms via transcriptomic sequencing.
METHODS:
An in vitro OA model was established using SW1353 cells treated with interleukin-1 beta (IL-1β) and different concentrations of KA (30, 60, or 90 μmol/L) for 24 h. The anti-inflammatory effects of KA were assessed using quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blotting. In vivo , a papain-induced OA rat model was used to evaluate the therapeutic effects of KA through histological and behavioral analyses. Transcriptomic sequencing was performed to explore the differentially expressed genes (DEGs) and related signaling pathways. Statistical analysis was conducted using one-way analysis of variance.
RESULTS:
KA significantly increased cell viability in the OA chondrocyte model and downregulated the expression of inflammatory cytokines and cartilage degradation markers, with the greatest reduction observed at 90 μmol/L. In vivo , KA treatment mitigated cartilage degradation and improved gait behavior in OA rats. Transcriptomic analysis revealed substantial modulation of DEGs, implicating the hypoxia-inducible factor-1 (HIF-1) signaling pathway as a key mechanism. Further blocking and rescue experiments revealed that KA regulated key molecules within the HIF-1 pathway, specifically interferon-gamma (IFN-γ) and hypoxia-inducible factor 1-alpha (HIF-1α), confirming their critical roles in mediating the therapeutic effects of KA.
CONCLUSION
KA inhibited the progression of OA by targeting the HIF-1 signaling pathway, reducing inflammation, and cartilage degradation.
Animals
;
Osteoarthritis/metabolism*
;
Signal Transduction/drug effects*
;
Rats
;
Rats, Sprague-Dawley
;
Humans
;
Male
;
Hypoxia-Inducible Factor 1/metabolism*
;
Interleukin-1beta
2.Total alkaloids from Thesium chinense inhibit lipopolysaccharide-induced respiratory inflammation by modulating Nrf2/NF-κB/NLRP3 signaling pathway.
Guohui LI ; Yueqin GUAN ; Lintao XU ; Guangcheng PENG ; Qingtong HAN ; Tian WANG ; Zhenpeng XU ; Xuesen WEN ; Hongxiang LOU ; Tao SHEN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(4):421-430
Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of T. chinense (BC-Alk) are potent active substances underlying the traditional and clinical applications of T. chinense and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice in vivo. Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-κB phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-κB, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of T. chinense and Bairui Granules.
Animals
;
Lipopolysaccharides/adverse effects*
;
Alkaloids/pharmacology*
;
NF-kappa B/metabolism*
;
NF-E2-Related Factor 2/metabolism*
;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
;
Mice
;
Signal Transduction/drug effects*
;
Anti-Inflammatory Agents/pharmacology*
;
Male
;
Mice, Inbred C57BL
;
Humans
;
Drugs, Chinese Herbal/administration & dosage*
;
Pneumonia/genetics*
3.Onco-metabolic surgery: the bridge between curative resection of gastric cancer and the remission of type 2 diabetes mellitus
Lyujia CHENG ; Zhenpeng WU ; Yuhan QIAO ; Yunsong JIANG ; Lin XIANG ; Lina WU ; Bingsheng GUAN ; Hanlin TANG ; Shifang HUANG ; Jingge YANG
Chinese Journal of Gastrointestinal Surgery 2024;27(11):1178-1185
The close relationship between gastric cancer (GC) and type 2 diabetes mellitus (T2DM) has garnered significant attention. On one hand, T2DM may play a role in the development and progression of GC, correlating with poor patient outcomes. On the other hand, after radical surgery for GC, T2DM can be effectively managed, potentially improving tumor prognosis. In recent years, bariatric and metabolic surgery (BMS) has revolutionized T2DM treatment for obese and overweight patients. Comparative analyses reveal similarities between surgical approaches for gastric cancer and BMS, leading to the emergence of the onco-metabolic surgery (OMS) concept, which suggests that radical tumor resection and T2DM remission in GC patients can be potentially achieved through a single procedure. However, there are notable differences between OMS and BMS, including target populations, surgical details, and perioperative management. Therefore, optimizing the application of the OMS concept in GC patients holds significant clinical importance. This article provides a review to facilitate the better implementation of this concept in practice.
4.Onco-metabolic surgery: the bridge between curative resection of gastric cancer and the remission of type 2 diabetes mellitus
Lyujia CHENG ; Zhenpeng WU ; Yuhan QIAO ; Yunsong JIANG ; Lin XIANG ; Lina WU ; Bingsheng GUAN ; Hanlin TANG ; Shifang HUANG ; Jingge YANG
Chinese Journal of Gastrointestinal Surgery 2024;27(11):1178-1185
The close relationship between gastric cancer (GC) and type 2 diabetes mellitus (T2DM) has garnered significant attention. On one hand, T2DM may play a role in the development and progression of GC, correlating with poor patient outcomes. On the other hand, after radical surgery for GC, T2DM can be effectively managed, potentially improving tumor prognosis. In recent years, bariatric and metabolic surgery (BMS) has revolutionized T2DM treatment for obese and overweight patients. Comparative analyses reveal similarities between surgical approaches for gastric cancer and BMS, leading to the emergence of the onco-metabolic surgery (OMS) concept, which suggests that radical tumor resection and T2DM remission in GC patients can be potentially achieved through a single procedure. However, there are notable differences between OMS and BMS, including target populations, surgical details, and perioperative management. Therefore, optimizing the application of the OMS concept in GC patients holds significant clinical importance. This article provides a review to facilitate the better implementation of this concept in practice.
5.Efficacy and safety of flurbiprofen cataplasms versus loxoprofen sodium cataplasms in knee osteoarthritis: a randomized controlled trial.
Dong LI ; Yinchu CHENG ; Ping YUAN ; Ziyang WU ; Jiabang LIU ; Jinfu KAN ; Kun ZHANG ; Zhanguo WANG ; Hui ZHANG ; Guangwu ZHANG ; Tao XUE ; Junxiu JIA ; Suodi ZHAI ; Zhenpeng GUAN
Chinese Medical Journal 2023;136(18):2187-2194
BACKGROUND:
Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA.
METHODS:
This is an open-label, non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital. Overall, 250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio. Both medications were administered to patients for 28 days. The primary outcome was the change of pain measured by visual analog scale (VAS) score from baseline to day 28 (range, 0-10 points; higher score indicates worse pain; non-inferiority margin: 1 point; superiority margin: 0 point). There were four secondary outcomes, including the extent of pain relief, the change trends of VAS scores, joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and adverse events.
RESULTS:
Among 250 randomized patients (One patient without complete baseline record in the flurbiprofen cataplasms was excluded; age, 62.8 ± 10.5 years; 61.4% [153/249] women), 234 (93.6%) finally completed the trial. In the intention-to-treat analysis, the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior, and also superior to that in the LSC group (differences and 95% confidence interval, 0.414 (0.147-0.681); P <0.001 for non-inferiority; P = 0.001 for superiority). Similar results were observed of the VAS scores for the current pain and pain during exercise. WOMAC scores were also lower in the FPC group at week 4 (12.50 [8.00-22.50] vs . 16.00 [11.00-27.00], P = 0.010), mainly driven by the dimension of daily activity difficulty. In addition, the FPC group experienced a significantly lower incidence of adverse events (5.6% [7/124] vs . 33.6% [42/125], P <0.001), including irritation, rash and pain of the skin, and sticky hair uncovering pain.
CONCLUSIONS
This study suggested that FPC is superior to LSC for treating patients with knee OA in pain relief, joint function improvement, and safety profile.
Humans
;
Female
;
Middle Aged
;
Aged
;
Osteoarthritis, Knee/drug therapy*
;
Flurbiprofen/therapeutic use*
;
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use*
;
Pain/drug therapy*
;
Treatment Outcome
;
Double-Blind Method
6.Clinical evidence-based guideline for the diagnosis and treatment of anterior cruciate ligament injury (2022 version)
Lunhao BAI ; Jiwu CHEN ; Jian CHEN ; Dongyang CHEN ; Xuesong DAI ; Zhenpeng GUAN ; Shengwei HE ; Jia JIANG ; Qing JIANG ; Hai LAN ; Ting LI ; Ning LIU ; Wei LU ; Yi QIAO ; Luning SUN ; Weiguo WANG ; Weiming WANG ; Bin XU ; Honggang XU ; Yongsheng XU ; Wenfeng XIAO ; Liang YANG ; Hongbo YOU ; Jiakuo YU ; Tengbo YU ; Xintao ZHANG ; Hui ZHANG ; Song ZHAO ; Weihong ZHU ; Jinzhong ZHAO
Chinese Journal of Trauma 2022;38(6):492-503
The anterior cruciate ligament (ACL) injury is a common sports injury that has a significant impact on knee function and patients′ mobility. With the popularity of national fitness campaign in China, the incidence of ACL injury is increasing year by year. Currently, there still lacks clinical standards or guidelines on how to choose appropriate treatment methods, surgical plans and rehabilitation protocols for ACL injury. In order to timely reflect the new treatment concept of ACL injury, standardize its diagnosis and treatment and improve the curative effect, the Sports Medicine Society of Chinese Research Hospital Association and the Editorial Board of Chinese Journal of Trauma organized domestic orthopedic and sports medicine experts to formulate the "clinical evidence-based guideline for the diagnosis and treatment of anterior cruciate ligament injury (2022 version)" based on the level of evidence-based medicine and in compliance with the principle of scientificity, practicability and advancement. The present guideline includes 12 recommendations for the diagnosis, treatment and rehabilitation of ACL injury in order to provide guidance and assistance for the clinical diagnosis and treatment of ACL injury in China.
7.Comparison of the early efficacy of unicompartmental and total knee arthroplasty in patients with medial compartmental osteoarthritis of the knee: a propensity score matching study
Zheng PEI ; Zhentao DING ; Zhao LI ; Zhenpeng GUAN
Chinese Journal of Surgery 2020;58(6):452-456
Objective:To compare the short-term efficacy of unicompartmental knee arthroplasty (UKA) and total knee arthroplasty(TKA) in the treatment of medial compartmental knee osteoarthritis.Methods:A retrospective analysis was performed on 197 patients with medial compartment osteoarthritis of the knee treated by the same group of doctors from January 2015 to December 2018.There were 86 males and 111 females, aged (67.7±10.5) years (range: 46 to 92 years), among which 101 cases received UKA and 96 cases received TKA.The UKA and TKA patients were matched by the propensity score matching method, and a total of 41 pairs of patients were successfully matched.The difference of short-term outcomes between the two groups were compared by t test, χ 2 test or Fisher exact probability methods. Results:Compared with TKA group, the postoperative reduction of hemogloblin in the UKA group was lower ((15.3±6.4) g/L vs. (20.1±7.5) g/L, t=-3.117, P<0.01), opioid dosage was lower ((160.5±29.3) mg vs. (186.1±46.8) mg, t=-2.969, P<0.01), and the length of hospital stay was shorter ((7.0±2.0)d vs. (10.0±2.5)d, t=-6.000, P<0.01). Forgotten joint score of UKA group was higher ( (65.1±7.6) vs. (58.3±13.9) , t=2.732, P<0.01), the incidence of knee clunk or crepitus was lower ( P=0.03) . There was no significant difference in the time of surgical tourniquet, range of motion, American knee society clinical score and incidence of deep vein thrombosis in lower extremities between the two groups.No complications such as surgical site infection, prosthesis loosening and dislocation occurred in the two groups. Conclusion:The early effect of UKA is similar to that of TKA, and it is better than TKA in the aspects of knee clunk or crepitus, forgotten joint score, blood loss, opioid dosage and postoperative hospital stay.
8.Prevention and treatment of bearing dislocation of mobile-bearing unicompartmental knee arthroplasty
Chinese Journal of Surgery 2020;58(6):416-419
Bearing dislocation is a special complication of mobile-bearing unicompartmental arthroplasty, caused by many factors, such as imbalance of the flexion and extension gap, malposition of components, impingement by the remaining osteophytes and cement, damage or delayed chronic laxity of medial collateral ligament, traumatic accident and habitual high knee flexion. It can be reduced by strictly controlling the operation indications before operation, osteotomy and implanting the prosthesis accurately while protecting the medial collateral ligament during operation, actively guiding the appropriate rehabilitation actions and activity intensity of patients after operation. Treatment should be individualized according to the causes and individual conditions of patients.
9.Comparison of the early efficacy of unicompartmental and total knee arthroplasty in patients with medial compartmental osteoarthritis of the knee: a propensity score matching study
Zheng PEI ; Zhentao DING ; Zhao LI ; Zhenpeng GUAN
Chinese Journal of Surgery 2020;58(6):452-456
Objective:To compare the short-term efficacy of unicompartmental knee arthroplasty (UKA) and total knee arthroplasty(TKA) in the treatment of medial compartmental knee osteoarthritis.Methods:A retrospective analysis was performed on 197 patients with medial compartment osteoarthritis of the knee treated by the same group of doctors from January 2015 to December 2018.There were 86 males and 111 females, aged (67.7±10.5) years (range: 46 to 92 years), among which 101 cases received UKA and 96 cases received TKA.The UKA and TKA patients were matched by the propensity score matching method, and a total of 41 pairs of patients were successfully matched.The difference of short-term outcomes between the two groups were compared by t test, χ 2 test or Fisher exact probability methods. Results:Compared with TKA group, the postoperative reduction of hemogloblin in the UKA group was lower ((15.3±6.4) g/L vs. (20.1±7.5) g/L, t=-3.117, P<0.01), opioid dosage was lower ((160.5±29.3) mg vs. (186.1±46.8) mg, t=-2.969, P<0.01), and the length of hospital stay was shorter ((7.0±2.0)d vs. (10.0±2.5)d, t=-6.000, P<0.01). Forgotten joint score of UKA group was higher ( (65.1±7.6) vs. (58.3±13.9) , t=2.732, P<0.01), the incidence of knee clunk or crepitus was lower ( P=0.03) . There was no significant difference in the time of surgical tourniquet, range of motion, American knee society clinical score and incidence of deep vein thrombosis in lower extremities between the two groups.No complications such as surgical site infection, prosthesis loosening and dislocation occurred in the two groups. Conclusion:The early effect of UKA is similar to that of TKA, and it is better than TKA in the aspects of knee clunk or crepitus, forgotten joint score, blood loss, opioid dosage and postoperative hospital stay.
10.Prevention and treatment of bearing dislocation of mobile-bearing unicompartmental knee arthroplasty
Chinese Journal of Surgery 2020;58(6):416-419
Bearing dislocation is a special complication of mobile-bearing unicompartmental arthroplasty, caused by many factors, such as imbalance of the flexion and extension gap, malposition of components, impingement by the remaining osteophytes and cement, damage or delayed chronic laxity of medial collateral ligament, traumatic accident and habitual high knee flexion. It can be reduced by strictly controlling the operation indications before operation, osteotomy and implanting the prosthesis accurately while protecting the medial collateral ligament during operation, actively guiding the appropriate rehabilitation actions and activity intensity of patients after operation. Treatment should be individualized according to the causes and individual conditions of patients.

Result Analysis
Print
Save
E-mail