1.Molecular Mechanism of Gypenoside L Inducing Ovarian Cancer Cell Apoptosis by Regulating NUF2 and Influencing Magnesium Homeostasis
Yang HONG ; Di ZHANG ; Yuanguang DONG ; Jiaxin WANG ; Lu PAN ; Lijiang ZHOU ; Mingdian YUAN ; Qun WANG ; Nan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):155-165
ObjectiveThis paper aims to investigate the role of NDC80 kinetochore complex component (NUF2) and magnesium homeostasis in ovarian cancer cell apoptosis, as well as the regulatory mechanism of gypenoside L (Gyp-L) on NUF2 and magnesium homeostasis. MethodsOvarian cancer OVCAR3 cells were divided into a blank control group, a low-concentration Gyp-L group (50 µmol·L-1), a high-concentration Gyp-L group (100 µmol·L-1), and a cisplatin (15 µmol·L-1) group. The migration, proliferation, and apoptosis capabilities of OVCAR3 cells were evaluated through cell scratch assays, clonal experiments, and terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining. Differentially expressed genes of ovarian cancer were screened by using the Gene Expression Omnibus (GEO) database. The interaction relationships of differentially expressed genes and proteins were analyzed via the Search Tool for Recurring Instances of Neighbouring Genes (STRING) database. The prognostic survival analysis was performed by using the Tumor Immune Estimation Resource (TIMER) database, and the differential expression levels of genes were validated with the Gene Expression Profiling Interactive Analysis (GEPIA) database. The mRNA expression levels of NUF2, magnesium homeostasis-related indicators, such as magnesium transporter 1 (MAGT1), non-imprinted in Prader-Willi/Angelman syndrome 1 (NIPA1), NIPA-like domain containing 1 (NIPAL1), as well as apoptosis-related indicators B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) in OVCAR3 cells, were detected by real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of NUF2, MAGT1, NIPA1, NIPAL1, Bcl-2, and Bax in OVCAR3 cells were quantitatively analyzed by ProteinSimple WES. A model of overexpression of NUF2 was constructed, and Gyp-L intervention was performed. The molecular mechanism by which Gyp-L induces ovarian cancer cell apoptosis by regulating NUF2 and influencing magnesium homeostasis was quantitatively analyzed and detected through cell cloning, TUNEL staining, Real-time PCR, and ProteinSimple WES. Finally, the Mg2+ content and protein synthesis efficiency were detected by immunofluorescence. ResultsGyp-L significantly inhibited the migration and proliferation capabilities of OVCAR3 cells and promoted their apoptosis (P<0.05). Overexpression of NUF2 markedly increased the expression levels of MAGT1, NIPA1, NIPAL1, and Bcl-2, while reducing the expression level of Bax (P<0.05). It also significantly elevated intracellular Mg2+ content and protein synthesis efficiency and simultaneously inhibited apoptosis (P<0.05). Gyp-L could reverse the magnesium homeostasis imbalance and apoptosis inhibition caused by the overexpression of NUF2, downregulating the expression levels of NUF2, MAGT1, NIPA1, NIPAL1, and Bcl-2 (P<0.05), while upregulating the expression level of Bax (P<0.05). ConclusionGyp-L can inhibit the occurrence of ovarian cancer, and its mechanism may involve inhibiting the expression of NUF2 to maintain magnesium homeostasis and inducing apoptosis of ovarian cancer cells.
2.Modified Guizhi Fulingwan Regulates miR-34a-5p/DLL1/Notch Signaling Pathway to Promote Apoptosis and Inhibit Prostate Cancer
Yuanguang DONG ; Ying YANG ; Penghao SUN ; Yang HONG ; Lu PAN ; Jiapeng LI ; Lijiang ZHOU ; Di ZHANG ; Mingdian YUAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(18):122-133
ObjectiveTo explore the molecular mechanism through which modified Guizhi Fulingwan (MGZFLW) promotes apoptosis and inhibits prostate cancer through the miR-34a-5p/δ-like protein 1 (DLL1)/Notch signaling pathway based on the traditional Chinese medicine theory of Yang transforming Qi while Yin constituting form. MethodsThe optimal intervention conditions of MGZFLW-containing serum and docetaxel (DXT) were screened by the cell counting kit-8 (CCK-8) method. Human prostate cancer cells (PC-3) were allocated into blank, MGZFLW (10%), and DXT (30 nmol·L-1) groups. The effects of MGZFLW-containing serum on the migration and proliferation of PC-3 cells were evaluated by cell scratch and colony formation assays, and the apoptosis of PC-3 cells was detected by terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. The cells were transfected with miR-34a-5p mimics and miR-34a-5p inhibitor. The mRNA levels of miR-34a-5p, DLL1, Notch1 and its downstream effector factors Notch1 intracellular domain (NICD1), Hes family basic helix-loop-helix transcription factor 1 (Hes1), and hairy/enhancer-of-split related with YRPW motif 1 (Hey1) were determined by Real-time PCR. The protein levels of DLL1, Notch1, NICD1, Hes1, and Hey1 were determined by a WES fully automatic protein system. The effect of miR-34a-5p on the DLL1-mediated Notch pathway was evaluated based on the results. Further, after MGZFLW-containing serum intervention, the expression of DLL1 and Notch1 was detected by the immunofluorescence (IF) assay, and the mRNA and protein levels of miR-34a-5p/DLL1/Notch pathway-related molecules were quantified by Real-time PCR and the WES fully automatic protein system, respectively, to explore the regulatory effect of MGZFLW-containing serum on the miR-34a-5p/DLL1/Notch pathway. ResultsMGZFLW-containing serum inhibited the viability, migration, and proliferation and promote the apoptosis of PC-3 cells (P<0.01). The overexpression of miR-34a-5p down-regulated the mRNA and protein levels of key molecules in the DLL1/Notch signaling pathway and promoted cell apoptosis (P<0.01), while inhibition of miR-34a-5p had the opposite effects. MGZFLW-containing serum reversed the activation of the DLL1/Notch pathway and the inhibition of apoptosis caused by miR-34a-5p inhibition, up-regulated the expression of miR-34a-5p, and down-regulated the expression of related molecules in this pathway (P<0.01). ConclusionMGZFLW can up-regulate the expression of miR-34a-5p to inhibit the DLL1/Notch signaling pathway and promote the apoptosis of prostate cancer cells, thereby inhibiting prostate cancer. This study provides experimental evidence for clarifying the molecular mechanism of the anti-prostate cancer effect of this formula.
3.Cost-effectiveness of Fractional Flow Reserve Versus Intravascular Ultrasound to Guide Percutaneous Coronary Intervention: Results From the FLAVOUR Study
Doyeon HWANG ; Hea-Lim KIM ; Jane KO ; HyunJin CHOI ; Hanna JEONG ; Sun-ae JANG ; Xinyang HU ; Jeehoon KANG ; Jinlong ZHANG ; Jun JIANG ; Joo-Yong HAHN ; Chang-Wook NAM ; Joon-Hyung DOH ; Bong-Ki LEE ; Weon KIM ; Jinyu HUANG ; Fan JIANG ; Hao ZHOU ; Peng CHEN ; Lijiang TANG ; Wenbing JIANG ; Xiaomin CHEN ; Wenming HE ; Sung Gyun AHN ; Ung KIM ; You-Jeong KI ; Eun-Seok SHIN ; Hyo-Soo KIM ; Seung-Jea TAHK ; JianAn WANG ; Tae-Jin LEE ; Bon-Kwon KOO ;
Korean Circulation Journal 2025;55(1):34-46
Background and Objectives:
The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea.
Methods:
A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D.
Results:
From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis.
Conclusions
Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.
4.Cost-effectiveness of Fractional Flow Reserve Versus Intravascular Ultrasound to Guide Percutaneous Coronary Intervention: Results From the FLAVOUR Study
Doyeon HWANG ; Hea-Lim KIM ; Jane KO ; HyunJin CHOI ; Hanna JEONG ; Sun-ae JANG ; Xinyang HU ; Jeehoon KANG ; Jinlong ZHANG ; Jun JIANG ; Joo-Yong HAHN ; Chang-Wook NAM ; Joon-Hyung DOH ; Bong-Ki LEE ; Weon KIM ; Jinyu HUANG ; Fan JIANG ; Hao ZHOU ; Peng CHEN ; Lijiang TANG ; Wenbing JIANG ; Xiaomin CHEN ; Wenming HE ; Sung Gyun AHN ; Ung KIM ; You-Jeong KI ; Eun-Seok SHIN ; Hyo-Soo KIM ; Seung-Jea TAHK ; JianAn WANG ; Tae-Jin LEE ; Bon-Kwon KOO ;
Korean Circulation Journal 2025;55(1):34-46
Background and Objectives:
The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea.
Methods:
A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D.
Results:
From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis.
Conclusions
Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.
5.Cost-effectiveness of Fractional Flow Reserve Versus Intravascular Ultrasound to Guide Percutaneous Coronary Intervention: Results From the FLAVOUR Study
Doyeon HWANG ; Hea-Lim KIM ; Jane KO ; HyunJin CHOI ; Hanna JEONG ; Sun-ae JANG ; Xinyang HU ; Jeehoon KANG ; Jinlong ZHANG ; Jun JIANG ; Joo-Yong HAHN ; Chang-Wook NAM ; Joon-Hyung DOH ; Bong-Ki LEE ; Weon KIM ; Jinyu HUANG ; Fan JIANG ; Hao ZHOU ; Peng CHEN ; Lijiang TANG ; Wenbing JIANG ; Xiaomin CHEN ; Wenming HE ; Sung Gyun AHN ; Ung KIM ; You-Jeong KI ; Eun-Seok SHIN ; Hyo-Soo KIM ; Seung-Jea TAHK ; JianAn WANG ; Tae-Jin LEE ; Bon-Kwon KOO ;
Korean Circulation Journal 2025;55(1):34-46
Background and Objectives:
The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea.
Methods:
A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D.
Results:
From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis.
Conclusions
Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.
6.Early effectiveness of navigation-free robot-assisted total knee arthroplasty in treating knee osteoarthritis with extra-articular deformities.
Chen MENG ; Yongqing XU ; Rongmao SHI ; Luqiao PU ; Jian'an JI ; Xingyou YAO ; Xizong ZHOU ; Chuan LI
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(1):5-12
OBJECTIVE:
To evaluate the early effectiveness of navigation-free robot-assisted total knee arthroplasty (TKA) compared to traditional TKA in the treatment of knee osteoarthritis combined with extra-articular deformities.
METHODS:
The clinical data of 30 patients with knee osteoarthritis combined with extra-articular deformities who met the selection criteria between June 2019 and January 2024 were retrospectively analyzed. Fifteen patients underwent CORI navigation-free robot-assisted TKA and intra-articular osteotomy (robot group) and 15 patients underwent traditional TKA and intra-articular osteotomy (traditional group). There was no significant difference in age, gender, body mass index, affected knee side, extra-articular deformity angle, deformity position, deformity type, and preoperative knee range of motion, American Knee Society (KSS) knee score and KSS function score, and lower limb alignment deviation between the two groups ( P>0.05). The operation time, intraoperative blood loss, and complications of the two groups were recorded and compared. The knee range of motion and lower limb alignment deviation were recorded before operation and at 6 months after operation, and the knee joint function was evaluated by KSS knee score and function score.
RESULTS:
There was no significant difference in operation time between the two groups ( P>0.05); the intraoperative blood loss in the robot group was significantly less than that in the traditional group ( P<0.05). Patients in both groups were followed up 6-12 months, with an average of 8.7 months. The incisions of all patients healed well, and there was no postoperative complication such as thrombosis or infection. At 6 months after operation, X-ray examination showed that the position of the prosthesis was good in both groups, and there was no loosening or dislocation of the prosthesis. The knee joint range of motion, the lower limb alignment deviation, and the KSS knee score and KSS function score significantly improved in both groups ( P<0.05) compared to preoperative ones. The changes of lower limb alignment deviation and KSS function score between pre- and post-operation in the robot group were significantly better than those in the traditional group ( P<0.05), while the changes of other indicators between pre- and post-operation in the two groups were not significant ( P>0.05).
CONCLUSION
Compared to traditional TKA, navigation-free robot-assisted TKA for knee osteoarthritis with extra-articular deformities results in less intraoperative blood loss, more precise reconstruction of lower limb alignment, and better early effectiveness. However, long-term effectiveness require further investigation.
Humans
;
Arthroplasty, Replacement, Knee/methods*
;
Osteoarthritis, Knee/surgery*
;
Robotic Surgical Procedures/methods*
;
Male
;
Female
;
Retrospective Studies
;
Range of Motion, Articular
;
Middle Aged
;
Aged
;
Treatment Outcome
;
Osteotomy/methods*
;
Knee Joint/physiopathology*
;
Operative Time
7.Biomechanical Effects of Lumbar Manipulation on Lumbar Structure under Transient Load
Longhao CHEN ; Xingchen ZHOU ; Yu TIAN ; Qiong XIA ; Zhizhen LÜ ; Lijiang LÜ
Journal of Medical Biomechanics 2025;40(3):776-783
Lumbar manipulation plays an important role in the non-surgical treatment of lumbar degenerative diseases.Lumbar manipulation is a compound technique that contains many mechanical elements and motion characteristics at the moment of operation.Quantifying and objectifying parameters of the manipulation,summarizing technical characteristics of the operation,and discussing biomechanical mechanism of the manipulation in-depth,can contribute to teaching assessment and clinical diagnosis and treatment standards of the manipulation,making the manipulation safer and efficient,and further promoting inheritance and development of the traditional Chinese medicine manipulation.This article reviews and synthesizes domestic and foreign biomechanical research papers on lumbar manipulation for the treatment of lumbar degenerative diseases in recent years.The biomechanical effects on the lumbar spine and its accessory structures under manual transient loading,the measurement of technical parameters,and the characteristics of manual operation are summarized.
8.Cost-effectiveness of Fractional Flow Reserve Versus Intravascular Ultrasound to Guide Percutaneous Coronary Intervention: Results From the FLAVOUR Study
Doyeon HWANG ; Hea-Lim KIM ; Jane KO ; HyunJin CHOI ; Hanna JEONG ; Sun-ae JANG ; Xinyang HU ; Jeehoon KANG ; Jinlong ZHANG ; Jun JIANG ; Joo-Yong HAHN ; Chang-Wook NAM ; Joon-Hyung DOH ; Bong-Ki LEE ; Weon KIM ; Jinyu HUANG ; Fan JIANG ; Hao ZHOU ; Peng CHEN ; Lijiang TANG ; Wenbing JIANG ; Xiaomin CHEN ; Wenming HE ; Sung Gyun AHN ; Ung KIM ; You-Jeong KI ; Eun-Seok SHIN ; Hyo-Soo KIM ; Seung-Jea TAHK ; JianAn WANG ; Tae-Jin LEE ; Bon-Kwon KOO ;
Korean Circulation Journal 2025;55(1):34-46
Background and Objectives:
The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea.
Methods:
A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D.
Results:
From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis.
Conclusions
Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.
9.Biomechanical Effects of Lumbar Manipulation on Lumbar Structure under Transient Load
Longhao CHEN ; Xingchen ZHOU ; Yu TIAN ; Qiong XIA ; Zhizhen LÜ ; Lijiang LÜ
Journal of Medical Biomechanics 2025;40(3):776-783
Lumbar manipulation plays an important role in the non-surgical treatment of lumbar degenerative diseases.Lumbar manipulation is a compound technique that contains many mechanical elements and motion characteristics at the moment of operation.Quantifying and objectifying parameters of the manipulation,summarizing technical characteristics of the operation,and discussing biomechanical mechanism of the manipulation in-depth,can contribute to teaching assessment and clinical diagnosis and treatment standards of the manipulation,making the manipulation safer and efficient,and further promoting inheritance and development of the traditional Chinese medicine manipulation.This article reviews and synthesizes domestic and foreign biomechanical research papers on lumbar manipulation for the treatment of lumbar degenerative diseases in recent years.The biomechanical effects on the lumbar spine and its accessory structures under manual transient loading,the measurement of technical parameters,and the characteristics of manual operation are summarized.
10.Mechanism of action and clinical research progress of iguratimod in connective tissue diseases
Xiaorong YANG ; Shuhong ZHOU ; Lijiang GUO ; Ying CHEN ; Yingying JI ; Lijie XU
China Pharmacy 2024;35(5):629-634
As a new type of immunosuppressant,iguratimod can mediate the anti-inflammatory signaling pathway by inhibiting the proliferation of inflammatory cells and reducing the release of inflammatory cytokines, and play the role of anti-inflammatory. It can affect the proliferation of immune cells and the expression of immune factors,reduce the production and deposition of immune complexes in the body,and play the role of immune regulation. It can regulate bone metabolism by mediating signaling pathways such as Wnt/β-catenin,Toll-like receptor 4/nuclear factor-κB and osteoprotegerin/nuclear factor-κB receptor activating factor ligand, and play a role in bone protection. It can inhibit pulmonary fibrosis by inhibiting the expression of transforming growth factor β1/ Smad2/3 signaling pathway,tumor necrosis factor-α,interleukin-1,interleukin-6,matrix metalloproteinase-9 and other inflammatory cytokines in lung tissue,and inhibiting the expression of collagen and fibronectin. Its efficacy and safety have been confirmed in the clinical application of rheumatoid arthritis and primary Sjogren syndrome and included in the diagnosis and treatment of the disease. It has also shown good efficacy in the clinical application of other connective tissue diseases such as systemic lupus erythematosus and ankylosing spondylitis,and no obvious safety risks have been found.

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