1.Mechanism of Taishan Panshisan in Inhibiting Oxidative Stress Injury of Trophoblast Cells by Regulating KEAP1/Nrf2/FoxO3 Signaling Pathway
Yangyang DUAN ; Xianglun JI ; Jiahong CHEN ; Jinghang YANG ; Xinyu XIAO ; Shutao CHEN ; Chaorui LIN ; Fan LIN ; Shu JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):12-22
ObjectiveTo explore the effect and mechanism of Taishan Panshi powder (TSPSP) on inhibiting oxidative stress injury in human chorionic trophoblast cells (HTR-8/SVneo), and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion (SA). MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus (GEO) database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP, and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments, HTR-8/SVneo cells were divided into blank group, model group, TSPSP-containing serum 2.5%, 5%, 10% groups, and nuclear factor E2-related factor 2 (Nrf2) inhibitor group (ML385, 30 μmol·L-1). Except for the blank group, other groups were stimulated with 150 μmol·L-1 H2O2 for 3 h to establish a cell oxidative stress injury model. After successful modeling, the blank group and model group were given 10% blank serum, each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum, and the Nrf2 inhibitor group was additionally given 30 μmol·L-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h, and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde (MDA), Fe2+, and Glutathione (GSH) were detected by enzyme-linked immunosorbent assay (ELISA). Intracellular reactive oxygen species (ROS) level was detected by a fluorescent probe (DCF-DA). The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 (KEAP1), Nrf2, and forkhead box protein O3 (FoxO3) in cells were detected by immunofluorescence (IF) and real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of KEAP1, Nrf2, FoxO3, Glutathione peroxidase 4 (GPX4), and superoxide dismutase (SOD) in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1, Nrf2, and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway, nine significantly differential pathways were identified (P<0.05), among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology, and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response, FOXO and MAPK signaling pathways, etc. In in vitro experiments, compared with the blank group, the cell viability in the model group was significantly decreased (P<0.01). Compared with the model group, the cell viability in each TSPSP-containing serum group was significantly increased (P<0.01). Compared with the 10% TSPSP-containing serum group, the cell viability in the ML385 group decreased to approximately 70% (P<0.01). Compared with the blank group, the model group showed significantly increased contents of MDA, Fe2+, and ROS, decreased GSH expression (P<0.01), significantly reduced cell migration rate (P<0.01), and increased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.01), while decreased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.01). Compared with the model group, each TSPSP-containing serum group showed significantly decreased contents of MDA, Fe²⁺, and ROS, increased GSH expression (P<0.01), significantly increased migration rate (P<0.01), significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.05, P<0.01), and significantly increased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.05, P<0.01). Compared with the 10% TSPSP-containing serum group, the ML385 group showed reversed trends in all indicators (P<0.05, P<0.01). ConclusionTSPSP can inhibit H2O2-induced oxidative stress injury of trophoblast cells, and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.
2.Mechanism of Taishan Panshisan in Inhibiting Oxidative Stress Injury of Trophoblast Cells by Regulating KEAP1/Nrf2/FoxO3 Signaling Pathway
Yangyang DUAN ; Xianglun JI ; Jiahong CHEN ; Jinghang YANG ; Xinyu XIAO ; Shutao CHEN ; Chaorui LIN ; Fan LIN ; Shu JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):12-22
ObjectiveTo explore the effect and mechanism of Taishan Panshi powder (TSPSP) on inhibiting oxidative stress injury in human chorionic trophoblast cells (HTR-8/SVneo), and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion (SA). MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus (GEO) database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP, and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments, HTR-8/SVneo cells were divided into blank group, model group, TSPSP-containing serum 2.5%, 5%, 10% groups, and nuclear factor E2-related factor 2 (Nrf2) inhibitor group (ML385, 30 μmol·L-1). Except for the blank group, other groups were stimulated with 150 μmol·L-1 H2O2 for 3 h to establish a cell oxidative stress injury model. After successful modeling, the blank group and model group were given 10% blank serum, each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum, and the Nrf2 inhibitor group was additionally given 30 μmol·L-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h, and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde (MDA), Fe2+, and Glutathione (GSH) were detected by enzyme-linked immunosorbent assay (ELISA). Intracellular reactive oxygen species (ROS) level was detected by a fluorescent probe (DCF-DA). The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 (KEAP1), Nrf2, and forkhead box protein O3 (FoxO3) in cells were detected by immunofluorescence (IF) and real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of KEAP1, Nrf2, FoxO3, Glutathione peroxidase 4 (GPX4), and superoxide dismutase (SOD) in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1, Nrf2, and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway, nine significantly differential pathways were identified (P<0.05), among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology, and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response, FOXO and MAPK signaling pathways, etc. In in vitro experiments, compared with the blank group, the cell viability in the model group was significantly decreased (P<0.01). Compared with the model group, the cell viability in each TSPSP-containing serum group was significantly increased (P<0.01). Compared with the 10% TSPSP-containing serum group, the cell viability in the ML385 group decreased to approximately 70% (P<0.01). Compared with the blank group, the model group showed significantly increased contents of MDA, Fe2+, and ROS, decreased GSH expression (P<0.01), significantly reduced cell migration rate (P<0.01), and increased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.01), while decreased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.01). Compared with the model group, each TSPSP-containing serum group showed significantly decreased contents of MDA, Fe²⁺, and ROS, increased GSH expression (P<0.01), significantly increased migration rate (P<0.01), significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.05, P<0.01), and significantly increased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.05, P<0.01). Compared with the 10% TSPSP-containing serum group, the ML385 group showed reversed trends in all indicators (P<0.05, P<0.01). ConclusionTSPSP can inhibit H2O2-induced oxidative stress injury of trophoblast cells, and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.
3.Stress Field of the Meniscus under Different Knee Brace Conditions in Jumping Motion:A Numerical Study
Jiangtao RUAN ; Yangyang MENG ; Yinguang ZHANG ; Xia XIAO
Journal of Medical Biomechanics 2024;39(1):111-117
Objective The biomechanical model for the musculoskeletal system of a human knee joint was established using a numerical simulation method.The kinematic and dynamic information captured during jumping motion simulated by the human dynamic model was used as driven data of the knee biomechanical model,followed by further analysis of the stress field distribution characteristics of the meniscus under different thermal-force coupling knee brace conditions.Methods Based on computed tomography and magnetic resonance imaging of the subject,a realistic human knee model,including bone,articular cartilage,meniscus,ligaments and peripheral soft tissues of the knee joint,was constructed.Furthermore,two gaits,namely taking-off and landing-on,of jumping motion with an increased risk of meniscus injuries were selected according to mechanical features in full-cycle jumping motion.Subsequently,the stress field characteristics of the knee meniscus under four different thermal-force coupling knee braces were analyzed,the changes of the peak stress of the meniscus and its stress concentration area were discussed,and the protective efficacy and mechanical basis of meniscal injuries and wearing knee braces were explored.Results The anterior part of the medial knee meniscus was a vulnerable area under concentrated stress.Under the knee brace thermal-force coupling condition,the stress concentration area of the medial meniscus was transferred from its narrow and weak anterior part to its wide and thick middle part,and the peak stress was also significantly reduced.The peak stress on the medial meniscus and that on the lateral meniscus were similar,indicating that the two parts of the meniscus bore the external load evenly,and the meniscus stress concentration area decreased.Conclusions Thermal-force coupling knee braces have good protective effects against knee meniscus injury.The numerical simulation provides theoretical support and technical guidance for the design of multifunctional thermal knee braces.
4.Treatment of Asthenospermia and Infertility with Liver Constraint and Kidney Deficiency in 45 Cases by Shugan Bushen Yulin Decoction (疏肝补肾毓麟汤) and Vitamin E Soft Capsules: A Multicenter Randomized Controlled Trial
Wang WANG ; Jigang CAO ; Min XIAO ; Yangyang ZHU ; Mengjie GAO ; Qikai WANG ; Xiaocui JIANG ; Heng HAO ; Siyi CHEN
Journal of Traditional Chinese Medicine 2024;65(18):1909-1914
ObjectiveTo observe the clinical efficacy and safety of Shugan Bushen Yulin Decoction (疏肝补肾毓麟汤, SBYD) in the treatment of asthenospermia and infertility with liver constraint and kidney deficiency. MethodsA multicenter, randomized, controlled clinical study was conducted in three hospitals in central China. Totally 95 patients with asthenospermia and infertility were controlled. According to random number table, the patients were divided into treatment group (47 cases) and control group (48 cases). The control group was given vitamin E soft capsules (100 mg per time, twice daily) orally, and the treatment group was given SBYD (one dose daily, 30 min after breakfast and dinner, about 200 ml each time) orally. The course of treatment was 12 weeks in both groups. After the treatment, the sperm concentration, percentage of forward motile sperm (PR), and percentage of total sperm activity, that is PR + percentage of non-progressively motile sperm (NP) were compared between groups, and the clinical efficacy was judged. Traditional Chinese medicine (TCM) syndrome score (inlcuding 6 single symptom scores and total symptoms score) and 21-item depression, anxiety, and stress scale (DASS-21) scores (including depression, anxiety and stress scores) were compared between the two groups before and after treatment. The patients were followed up for 6 months, and the pregnancy status of spouse between groups was compared. The occurrence of adverse events and vital signs during the trial were recorded for safety assessment. ResultsTwo cases in the treatment group and three cases in the control group dropped out. Finally, 45 cases in each group were included in the statistical analysis. The total effective rate was 86.67% (39/45) in the treatment group, significantly higher than 73.74% (33/45) in the control group (P<0.05). After treatment, PR and PR + NP significantly increased in both groups, and were much higher in the treatment group than in the control group (P<0.05). The scores of lumbar and knee soreness, emotional disturbance, cold sperm, chest and rib-side and lesser abdomen distension and pain, frequent sighing, and the total TCM syndrome score in the treatment group decreased after treatment (P<0.05); and except for cold sperm, the scores of other symptoms mentioned above as well as the total TCM syndrome score in the treatment group were lower than those in the control group (P<0.05). The scores of depression, anxiety and stress of DASS-21 in the treatment group decreased after treatment, and were lower than those in the control group (P<0.05). After 6 months of follow-up, the spouses of 5 patients in the treatment group and 3 patients in the control group got pregnant (P>0.05). No adverse events occurred in both groups during the treatment, and their vital signs were stable. ConclusionSBYD can obviously improve sperm vitality and effectively improve the clinical symptoms, anxiety and depression, and is safe in treating asthenospermia and infertility with liver constraint and kidney deficiency.
5.Treatment of Gastric Ulcer in Active Stage with Carbuncle Theory in Toxicity-heat Theory Based on "State-target Medicine"
Liming CHEN ; Guozheng LIU ; Shuo YANG ; Yan LI ; Yangyang SUN ; Yuening BIAN ; Yilin ZHAO ; Jingdong XIAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):217-227
"State-target medicine" is a traditional Chinese medicine (TCM) diagnosis and treatment theoretical system proposed by Academician Tong Xiaolin based on the current development of modern medicine. The active stage of gastric ulcer, as a precancerous state of gastric cancer, has a great impact on people's health. Prof. ZHOU Xuewen, a master of TCM, innovatively put forward the theory of "toxicity-heat" etiology for the active stage of gastric ulcer, which plays an important guiding role in clinical diagnosis and treatment. The article took the theoretical system of "state-target medicine" as the framework to explain the rationale, method, formula, and medicine of Prof. ZHOU Xuewen, who applied the Xiaoyong Kuidekang based on the "toxicity-heat" theory to treat the gastric ulcer in the active stage. The Chinese medical name of gastric ulcer, "gastric carbuncle", was established, and it was believed that gastric ulcer is born due to "toxicity" and is based on "toxicity and heat". In the course of the disease, "toxicity", "heat", "deficiency", and "stasis" coexisted, and its pathogenesis was divided into three phases, namely, toxicity-heat accumulation phase, toxicity-heat affecting the health phase, and weakened body resistance and strengthened toxicity phase. According to the positioning of gastric ulcer as an "internal carbuncle", Prof. ZHOU Xuewen proposed the treatment of gastric ulcer in the active stage with "carbuncle theory" and introduced the surgical methods of "elimination", "support", and "tonifying" into the treatment of gastric ulcer in the active stage. Prof. ZHOU Xuewen took "clearing heat and removing toxins, eliminating carbuncle and generating muscle" as the basic treatment of the disease. For different stages of the disease, Prof. ZHOU Xuewen emphasized the use of the methods of clearing heat and removing toxins, supporting rot and muscle growth, and strengthening the spleen and harmonizing the stomach and created the representative formula for the treatment of gastric ulcer in the active stage with "carbuncle theory", namely "Xiaoyong Kuidekang", which could regulate state and targets.
6.Research progress on intestinal microecological in chronic kidney disease
Lin ZHU ; Jie NIU ; Lan XIAO ; Lingyun YIN ; Yangyang YU ; Yuqing WANG ; Ping ZHOU
Chinese Pediatric Emergency Medicine 2024;31(8):632-636
Chronic kidney disease(CKD)has a significant impact on global public health and is one of the important factors leading to the rise of incidence rate and mortality of non communicable diseases.Intestinal microecology is involved in many pathophysiological activities,such as immunity and nutrient absorption.With proposal of the concept of intestine-kidney axis in 2002,researchers found that the decline of glomerular filtration rate led to accumulation of uremic toxins in intestine,destroyed the intestinal mucosal barrier,led to the translocation of toxins,activated the systemic oxidative stress response,further promoted the progress of CKD.This article reviewed the function of gut microbiota,intestine-gut kidney axis,and the application of microbial preparations in CKD.
7.Development and validation of a prognostic model based on metabolic risk score to predict overall survival of endometrial cancer in Chinese patients
Xingchen LI ; Xiao YANG ; Yuan CHENG ; Yangyang DONG ; Jingyuan WANG ; Jianliu WANG
Journal of Gynecologic Oncology 2023;34(6):e69-
Objective:
Metabolic syndrome (MetS) is closely related to the increased risk and poor prognosis of endometrial cancer (EC). The purpose of this study was to analyze the relationship between metabolic risk score (MRS) and EC, and establish a predictive model to predict the prognosis of EC.
Methods:
A retrospective study was designed of 834 patients admitted between January 2004 to December 2019. Univariate and multivariate Cox analysis were performed to screen independent prognostic factors for overall survival (OS). A predictive nomogram is built based on independent risk factors for OS. Consistency index (C-index), calibration plots and receiver operating characteristic curve were used to evaluate the predictive accuracy of the nomogram.
Results:
The patients were randomly divided into training cohort (n=556) and validation cohort (n=278). The MRS of EC patients, ranging from −8 to 15, was calculated. Univariate and multivariate Cox analysis indicated that age, MRS, FIGO stage, and tumor grade were independent risk factors for OS (p<0.05). The Kaplan–Meier analysis demonstrated that EC patients with low score showed a better prognosis in OS. Then, a nomogram was established and validated based on the above four variables. The C-index of nomogram were 0.819 and 0.829 in the training and validation cohorts, respectively. Patients with high-risk score had a worse OS according to the nomogram.
Conclusion
We constructed and validated a prognostic model based on MRS and clinical prognostic factors to predict the OS of EC patients accurately, which may help clinicians personalize prognostic assessments and effective clinical decisions.
8.Research progress on standardized clinical outcome of peritoneal dialysis
Chinese Journal of Nephrology 2023;39(8):630-634
As a home treatment and economical and practical treatment mode, peritoneal dialysis (PD) is an effective renal replacement therapy for end-stage kidney disease. The number of PD patients in the world is increasing, and prognosis has been significantly improved. However, compared with the general population, the quality of life of PD patients is not satisfactory, and the disease burden is still very high. There is significant heterogeneity in the reports of clinical outcomes of PD in different countries and regions. The heterogeneity seriously affects the validity of clinical research evidence and the continuous improvement of the quality of PD centers. New progress has been made in the study of standardized clinical outcome of PD in recent years. The article reviews the heterogeneity of PD clinical outcome report, standardized clinical outcome classification and core outcome to standardize the report of PD clinical outcome, improve the clinical research quality and management level of PD, and finally improve the prognosis of patients.
9.Feasibility, reliability and validity of a 3D scanning volume measurement for distal upper limb volume
Xiao QIU ; Junqi LING ; Yangyang CONG ; Yulong BAI
Chinese Journal of Rehabilitation Theory and Practice 2023;29(3):364-367
ObjectiveTo clarify the feasibility of the 3D scanning volume method for distal upper limb volume measurement, and to analyze its scorer reliability and criterion-related validity. MethodsFrom January to March, 2022, a therapist (operator A) who had not been exposed to 3D scanning volume method and water displacement method was trained to use a handheld 3D laser scanner and a spilt cup to measure the volume of a PVC distal upper limb model. The operation time of 30 operations of each method was recorded. The learning curves of the two methods were plotted using cumulative sum (CUSUM) analysis. The curve was cut into the learning stage and the mastery stage by the vertex of peak. The times required to reach the mastery stage and the operation time of the mastery stage for the two methods were recorded. A total of 20 healthy subjects were recruited from Huashan Hospital of Fudan University. Two trained therapists (operator A and operator B) measured the bilateral distal upper limb volume using a handheld 3D laser scanner, and operator A measured the bilateral distal upper limb volume using a spilt cup. ResultsThe fitting learning curve of the 3D scanning volume method (R² = 0.984) reached its peak after eight times of operation; while that of the water displacement method (R² = 0.494) reached its peak after five times of operation. At mastery stage, the operator spent less time using 3D scanning volume method than using water displacement method (P < 0.05). The intraclass correlation coefficient between the two operators were both 0.979 for bilateral distal upper limb volume measure (P < 0.001). The Pearson coefficients was above 0.979 between 3D scanning volume method and water displacement method (P < 0.001). ConclusionA therapist can master the use of the 3D scanning volume method after eight times of operation, and the operation time of 3D scanning volume method is shorter than that of water displacement method at mastery stage. The 3D scanning volume method is well reliable and valid, that can be used as an alternative to the water displacement method for distal upper limb volumetric measurement.
10.Liver cell therapies: cellular sources and grafting strategies.
Wencheng ZHANG ; Yangyang CUI ; Yuan DU ; Yong YANG ; Ting FANG ; Fengfeng LU ; Weixia KONG ; Canjun XIAO ; Jun SHI ; Lola M REID ; Zhiying HE
Frontiers of Medicine 2023;17(3):432-457
The liver has a complex cellular composition and a remarkable regenerative capacity. The primary cell types in the liver are two parenchymal cell populations, hepatocytes and cholangiocytes, that perform most of the functions of the liver and that are helped through interactions with non-parenchymal cell types comprising stellate cells, endothelia and various hemopoietic cell populations. The regulation of the cells in the liver is mediated by an insoluble complex of proteins and carbohydrates, the extracellular matrix, working synergistically with soluble paracrine and systemic signals. In recent years, with the rapid development of genetic sequencing technologies, research on the liver's cellular composition and its regulatory mechanisms during various conditions has been extensively explored. Meanwhile breakthroughs in strategies for cell transplantation are enabling a future in which there can be a rescue of patients with end-stage liver diseases, offering potential solutions to the chronic shortage of livers and alternatives to liver transplantation. This review will focus on the cellular mechanisms of liver homeostasis and how to select ideal sources of cells to be transplanted to achieve liver regeneration and repair. Recent advances are summarized for promoting the treatment of end-stage liver diseases by forms of cell transplantation that now include grafting strategies.
Humans
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Liver/surgery*
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Hepatocytes/transplantation*
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Stem Cells/metabolism*
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Liver Diseases/surgery*

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