1.Effects of long-term endurance exercise on kl/FGF23 axis and calcium-phosphorus metabolism in naturally aging mice
Tuanhui PENG ; Hongming SONG ; Ling YANG ; Xiaoge DING ; Pengjun MENG
Chinese Journal of Tissue Engineering Research 2026;30(5):1089-1095
BACKGROUND:Studies have shown that disorders of mineral metabolism may be responsible for premature aging and that the kl/FGF23 axis plays an important role in mineral metabolism.OBJECTIVE:To explore the effect of long-term endurance exercise on the kl/FGF23 axis in naturally aging mice,and to observe the impact of long-term endurance exercise on calcium and phosphorus metabolism,so as to provide a reference for the influence of long-term endurance exercise on natural aging.METHODS:Twenty-two 5-week-old SPF male balb/c mice were randomly divided into three groups:young and quiet control group,natural aging quiet group and natural aging exercise group.Mice in the young and quiet control group were then killed immediately.Mice in the natural aging quiet group were raised normally until 60 weeks of age.Mice in the natural aging exercise group were subjected to adaptive exercise for 1 week,followed by the maximum running speed test.The official exercise speed was set at 70%of the maximum running speed,and exercise was performed on Mondays,Wednesdays,and Fridays for 50 minutes each.Maximum running speed was retested at 8-week intervals to adjust the official exercise speed until the age of 60 weeks.(3)Enzyme-linked immunoassay was used to measure the levels of femoral fibroblast growth factor 23,renal fibroblast growth factor receptor 1,1α-hydroxylase,and serum 1,25(OH)2D3.RESULTS AND CONCLUSION:(1)Compared with the young and quiet control group,serum calcium and phosphorus levels in natural aging quiet group had no significant changes(P>0.05),but bone calcium and phosphorus levels were significantly reduced(P<0.01).Compared with the natural aging quiet group,the serum phosphorus level was significantly reduced(P<0.05),the serum calcium level did not change(P>0.05),and bone calcium and phosphorus levels were significantly increased in the natural aging exercise group(P<0.05).(2)Compared with the young and quiet control group,the level of fibroblast growth factor 23 in the femur of the natural aging quiet group was significantly increased(P<0.05).Compared with the natural aging quiet group,the level of fibroblast growth factor 23 in the femur of the natural aging exercise group was reduced,but it was not statistically significant(P>0.05).(3)Compared with the young and quiet control group,the renal Klotho protein expression,the renal fibroblast growth factor receptor 1,1α-hydroxylase,and serum 1,25(OH)2 D3 levels in the natural aging quiet group were significantly decreased(P<0.05,P<0.01).Compared with the natural aging quiet group,the levels of the above-mentioned indicators were significantly increased in the natural aging exercise group(P<0.05,P<0.01).To conclude,long-term endurance exercise can regulate Klotho protein and fibroblast growth factor 23 through the kl/FGF23 axis,thereby affecting the expression of 1α-hydroxylase and the level of 1,25(OH)2D3,and further regulating the body's calcium and phosphorus metabolism,especially phosphate metabolism.This indicates that long-term endurance exercise can delay the natural aging of the body through the kl/FGF23 axis.
2.In vitro biocompatibility of graded glass infiltrated ultra-translucent zirconia
Qiya ZHANG ; Yixiang TONG ; Shijiao YANG ; Yumeng ZHANG ; Ling DENG ; Wei WU ; Yao XIE ; Jian LIAO ; Ling MAO
Chinese Journal of Tissue Engineering Research 2026;30(2):443-450
BACKGROUND:In previous studies,glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by a double sintering method to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials that can maintain high transparency and high flexural strength.OBJECTIVE:To evaluate the in vitro biocompatibility of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials.METHODS:(1)Glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by double sintering to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia(or 5Y-PSZ ultra-translucent zirconia,3Y-TZP transparent zirconia)was placed in DMEM culture medium containing 10%fetal bovine serum for 12,24 and 72 hours,and the surface area ratio of culture medium to sample was 3 mL/cm2,and the 12-,24-and 72-hour material extracts were obtained.(2)After culturing mouse fibroblast L929 for 24 hours,the original culture medium was discarded and divided into 7 groups for culture:the control group was replaced with DMEM culture medium containing 10%fetal bovine serum by volume,and the other 6 groups were replaced with 24-hour extract of 3Y-TZP transparent zirconia,24-hour extract of 5Y-PSZ ultra-translucent zirconia,24-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,72-hour extract of 3Y-TZP transparent zirconia,72-hour extract of 5Y-PSZ ultra-translucent zirconia,and 72-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.After 1,3,and 5 days of culture,cell growth was observed under a microscope,and the cell proliferation rate was obtained by CCK-8 assay to determine cytotoxicity.(3)Human anticoagulated blood was mixed with 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,5Y-PSZ ultra-translucent zirconia,and 3Y-TZP transparent zirconia,and the hemolysis rate was detected after 0.5 hours.Human anticoagulated blood was mixed with 12-hour extract of 3Y-TZP transparent zirconia,12-hour extract of 5Y-PSZ ultra-translucent zirconia,and 12-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,and the hemolysis rate was detected after 0.5 hours.RESULTS AND CONCLUSION:(1)Under the microscope,it could be seen that the number of cells in each group increased with the extension of culture time,and the cell morphology of each experimental group was basically the same as that of the control group.The cytotoxicity grade of the 24-hour extract of 3Y-TZP transparent zirconia group on the first day of culture was grade 0,and the cytotoxicity grade of the other experimental groups at each time period was grade 1.(2)Neither the material nor the material extract caused obvious hemolytic reaction,and the hemolytic rate was less than 5%.(3)The results showed that 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia had no significant effect on the growth and proliferation of mouse fibroblasts L929,and did not cause hemolytic reaction with human blood,and had good in vitro biocompatibility.
3.Effects of long-term endurance exercise on kl/FGF23 axis and calcium-phosphorus metabolism in naturally aging mice
Tuanhui PENG ; Hongming SONG ; Ling YANG ; Xiaoge DING ; Pengjun MENG
Chinese Journal of Tissue Engineering Research 2026;30(5):1089-1095
BACKGROUND:Studies have shown that disorders of mineral metabolism may be responsible for premature aging and that the kl/FGF23 axis plays an important role in mineral metabolism.OBJECTIVE:To explore the effect of long-term endurance exercise on the kl/FGF23 axis in naturally aging mice,and to observe the impact of long-term endurance exercise on calcium and phosphorus metabolism,so as to provide a reference for the influence of long-term endurance exercise on natural aging.METHODS:Twenty-two 5-week-old SPF male balb/c mice were randomly divided into three groups:young and quiet control group,natural aging quiet group and natural aging exercise group.Mice in the young and quiet control group were then killed immediately.Mice in the natural aging quiet group were raised normally until 60 weeks of age.Mice in the natural aging exercise group were subjected to adaptive exercise for 1 week,followed by the maximum running speed test.The official exercise speed was set at 70%of the maximum running speed,and exercise was performed on Mondays,Wednesdays,and Fridays for 50 minutes each.Maximum running speed was retested at 8-week intervals to adjust the official exercise speed until the age of 60 weeks.(3)Enzyme-linked immunoassay was used to measure the levels of femoral fibroblast growth factor 23,renal fibroblast growth factor receptor 1,1α-hydroxylase,and serum 1,25(OH)2D3.RESULTS AND CONCLUSION:(1)Compared with the young and quiet control group,serum calcium and phosphorus levels in natural aging quiet group had no significant changes(P>0.05),but bone calcium and phosphorus levels were significantly reduced(P<0.01).Compared with the natural aging quiet group,the serum phosphorus level was significantly reduced(P<0.05),the serum calcium level did not change(P>0.05),and bone calcium and phosphorus levels were significantly increased in the natural aging exercise group(P<0.05).(2)Compared with the young and quiet control group,the level of fibroblast growth factor 23 in the femur of the natural aging quiet group was significantly increased(P<0.05).Compared with the natural aging quiet group,the level of fibroblast growth factor 23 in the femur of the natural aging exercise group was reduced,but it was not statistically significant(P>0.05).(3)Compared with the young and quiet control group,the renal Klotho protein expression,the renal fibroblast growth factor receptor 1,1α-hydroxylase,and serum 1,25(OH)2 D3 levels in the natural aging quiet group were significantly decreased(P<0.05,P<0.01).Compared with the natural aging quiet group,the levels of the above-mentioned indicators were significantly increased in the natural aging exercise group(P<0.05,P<0.01).To conclude,long-term endurance exercise can regulate Klotho protein and fibroblast growth factor 23 through the kl/FGF23 axis,thereby affecting the expression of 1α-hydroxylase and the level of 1,25(OH)2D3,and further regulating the body's calcium and phosphorus metabolism,especially phosphate metabolism.This indicates that long-term endurance exercise can delay the natural aging of the body through the kl/FGF23 axis.
4.Expert Consensus on Clinical Application of Qidong Yixin Oral Liquid
Changkuan FU ; Xiaochang MA ; Mingjun ZHU ; Yue DENG ; Hongxu LIU ; Mingxue ZHANG ; Ying CHEN ; Yan ZHOU ; Ling ZHANG ; Jianhua FU ; Wei YANG ; Yu'er HU ; Ming CHEN ; Yanming XIE ; Yuanyuan LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):147-158
The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis (VMC). It has the functions of tonifying Qi, nourishing the heart,calming the mind, and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However,the understanding of its efficacy evidence, advantageous aspects, dosage and administration, and medication safety remains insufficient in clinical practice. Therefore,the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid (hereinafter referred to as consensus) was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine,successively completing multiple tasks such as the consensus project initiation,determination of clinical problems,evidence search and evaluation,formation of recommendation opinions and consensus suggestions,solicitation of opinions,peer review, submission for review and release, and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions,clarifying the clinical positioning,efficacy advantages,syndrome differentiation,dosage and administration,combination therapy,timing of medication,adverse reactions,contraindications, and precautions of Qidong Yixin oral liquid,indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease,providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23, 2024. Standard number:GSCACM-376-2024.
5.Perioperative immune dynamics and clinical outcomes in patients undergoing on-pump cardiac surgery
Zhiyuan CHENG ; Xinyi LIAO ; Juan WU ; Ping YANG ; Tingting WANG ; Qinjuan WU ; Wentong MENG ; Zongcheng TANG ; Jiayi SUN ; Jia TAN ; Jing LIN ; Dan LUO ; Hao WANG ; Chaonan LIU ; Jiyue XIONG ; Liqin LING ; Jing ZHOU ; Lei DU
Chinese Journal of Blood Transfusion 2026;39(1):31-43
Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10
/L vs preoperative 3.07×10
/L, P<0.001), with significant upregulation of CD11b (7.30×10
/L vs preoperative 3.05×10
/L, P<0.001) and CD54 (7.15×10
/L vs preoperative 2.99×10
/L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10
/L vs preoperative 1.12×10
/L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10
/L vs preoperative 1.12×10
/L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.
6.Epidemic trends and prevention and control effectiveness of notifiable infectious diseases in Yichang City based on interrupted time series
Qian WU ; Hao ZHANG ; Zhongcheng YANG ; Ling ZHOU ; Yi LIANG ; Yajun CAO
Journal of Public Health and Preventive Medicine 2026;37(1):88-92
Objective To analyze the epidemiological characteristics of statutory infectious diseases in Yichang City from 2015 to 2023 and evaluate the effectiveness of non-pharmaceutical interventions (NPIs) in infectious disease prevention and control, and to provide a basis for formulating prevention and control strategies. Methods Descriptive epidemiological methods were used to analyze annual incidence rates. SARIMA and SARIMA intervention models were constructed to predict the incidence rates of infectious diseases. Interrupted time series analysis (ITS) was applied to assess the control effectiveness. Results The average annual incidence rate from 2015 to 2023 was 787.47/100 000, with the top five diseases being influenza, hand-foot-and-mouth disease, hepatitis B, tuberculosis, and diarrheal diseases. The average incidence rate from 2015 to 2019 (654.31/100 000) was significantly higher than that from 2020 to 2022 (489.01/100 000) (χ2= 3 499.6, P < 0.05). The total incidence rate in 2023 (2 396.51/100 000) was significantly higher than the average annual incidence rates from 2015-2019 (χ2= 108 186.1, P < 0.05) and 2020-2022 (χ2= 112 869.4, P < 0.05). SARIMA model results indicated that the actual incidence rate from 2020 to 2022 decreased by 73.49% compared to the predicted rate without intervention, with the highest decline observed in respiratory infectious diseases (79.57%). The SARIMA-intervention model showed a 55.48% relative decrease in the total incidence rate for 2023, with the largest reduction in respiratory infectious diseases (63.28%) and a slight increase in intestinal infectious diseases (5.48%). Conclusion NPIs effectively reduce the incidence of statutory infectious diseases in the short term, especially for acute respiratory and intestinal infectious diseases. However, long-term effectiveness faces challenges, necessitating the development of differentiated prevention and control strategies.
7.Investigation on current situation of cognitive impairment and influencing factors in patients with Alzheimer's disease
Ling JIANG ; Yenan JI ; Guanghua YANG ; Xuan LI
Journal of Public Health and Preventive Medicine 2026;37(1):150-153
Objective To investigate the current status of cognitive impairment and its influencing factors in patients with Alzheimer's disease (AD) and to explore effective intervention strategies. Methods A total of 380 patients with AD diagnosed in the Qingdao Central Hospital were retrospectively enrolled between January 2023 and January 2025. According to scores of Montreal Cognitive Assessment (MoCA), the patients were divided into a mild cognitive impairment group (21-25 points) and a moderate to severe impairment group (<21 points). The general clinical data in the two groups were collected. The influencing factors of moderate to severe cognitive impairment were analyzed by univariate and multivariate logistic regression analysis. Results Among the 380 AD patients, 157 cases (41.32%) had mild cognitive impairment, and 223 cases (58.68%) had moderate to severe cognitive impairment. Compared with the mild cognitive impairment group, the moderate to severe cognitive impairment group had a higher proportion of patients who were aged ≥ 75 years, engaged in physical labor, had a disease course of ≥5 years, and had moderate to severe atrophy on head CT examination (P < 0.05). Age ≥75 years, disease course ≥5 years, and moderate to severe atrophy on head CT were independent risk factors of moderate to severe cognitive impairment in AD patients (P<0.05). Conclusion Cognitive impairment is closely related to age, disease course and head CT manifestations in AD patients. Interventions targeting these key factors are expected to delay cognitive decline and improve patients' quality of life.
8.Mechanism of Yangjing Zhongyutang in Regulating SIRT1/PGC-1α Signaling Pathway to Promote Mitochondrial Function and Alleviate Oxidative Stress Damage in Rats with Diminished Ovarian Reserve
Ping ZHANG ; Lijuan YANG ; Shenghui CHEN ; Wenliang YAO ; Yuliang ZHOU ; Ling MA ; Huiying WU ; Yanwen XU ; Ziyan ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):46-55
ObjectiveTo observe the effects of Yangjing Zhongyutang (YJZYT) on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) signaling pathway in cyclophosphamide (CTX)-induced rats with diminished ovarian reserve (DOR), and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group (n=7) and a model group (n=35). Rats in the model group received a single intraperitoneal injection of CTX (90 mg·kg-1) to establish the DOR model. After modeling, estrous cycles were monitored for 7 consecutive days, and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling, rats were divided into groups for intervention: estradiol valerate group (0.09 mg·kg-1), and YJZYT high-, medium-, and low-dose groups (19.98, 9.99, 5.00 g·kg-1). The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state, body weight, and ovarian wet weight of rats were observed and recorded, and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Hematoxylin-eosin (HE) staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species (ROS) expression levels. Colorimetric assays were employed to measure adenosine triphosphate (ATP) and malondialdehyde (MDA) content in ovarian tissues. Quantitative Real-time polymerase chain reaction (Real-time PCR) was used to detect mitochondrial DNA (mtDNA) copy number and the mRNA expression levels of key genes including SIRT1, PGC-1α, nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). Western blot was performed to detect the protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM. ResultsCompared with the blank group, rats in the model group exhibited disrupted estrous cycles, obviously reduced body weight, and decreased ovarian index (P<0.05). Ovarian histopathology revealed cortical thinning, loose structure, and a significant reduction in both primordial and growing follicles (P<0.01). Serum FSH and LH levels were significantly elevated (P<0.01), while E2 and AMH levels were obviously reduced (P<0.05, P<0.01). ATP content and mtDNA copy number decreased in ovarian tissue (P<0.01), ROS expression increased, MDA levels rose, while SOD and GSH-Px activities obviously decreased (P<0.05, P<0.01), mRNA and protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM were obviously downregulated (P<0.05, P<0.01). After treatment, compared with the model group, body weight and ovarian index obviously recovered in rats administered various doses of YJZYT (P<0.05), serum E2 and AMH levels increased, while FSH and LH levels obviously decreased (P<0.05, P<0.01), ovarian tissue ATP content and mtDNA copy number were up-regulated, ROS and MDA levels decreased, and antioxidant enzymes SOD and GSH-Px activity obviously increased (P<0.05, P<0.01), Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group (P<0.05, P<0.01), HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups, with a obviously increase in the number of primordial and growing follicles (P<0.05, P<0.01). Granulosa cells were neatly arranged, indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway, promoting mitochondrial biogenesis, enhancing mitochondrial function, and alleviating oxidative stress damage.
9.In vitro biocompatibility of graded glass infiltrated ultra-translucent zirconia
Qiya ZHANG ; Yixiang TONG ; Shijiao YANG ; Yumeng ZHANG ; Ling DENG ; Wei WU ; Yao XIE ; Jian LIAO ; Ling MAO
Chinese Journal of Tissue Engineering Research 2026;30(2):443-450
BACKGROUND:In previous studies,glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by a double sintering method to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials that can maintain high transparency and high flexural strength.OBJECTIVE:To evaluate the in vitro biocompatibility of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials.METHODS:(1)Glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by double sintering to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia(or 5Y-PSZ ultra-translucent zirconia,3Y-TZP transparent zirconia)was placed in DMEM culture medium containing 10%fetal bovine serum for 12,24 and 72 hours,and the surface area ratio of culture medium to sample was 3 mL/cm2,and the 12-,24-and 72-hour material extracts were obtained.(2)After culturing mouse fibroblast L929 for 24 hours,the original culture medium was discarded and divided into 7 groups for culture:the control group was replaced with DMEM culture medium containing 10%fetal bovine serum by volume,and the other 6 groups were replaced with 24-hour extract of 3Y-TZP transparent zirconia,24-hour extract of 5Y-PSZ ultra-translucent zirconia,24-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,72-hour extract of 3Y-TZP transparent zirconia,72-hour extract of 5Y-PSZ ultra-translucent zirconia,and 72-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.After 1,3,and 5 days of culture,cell growth was observed under a microscope,and the cell proliferation rate was obtained by CCK-8 assay to determine cytotoxicity.(3)Human anticoagulated blood was mixed with 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,5Y-PSZ ultra-translucent zirconia,and 3Y-TZP transparent zirconia,and the hemolysis rate was detected after 0.5 hours.Human anticoagulated blood was mixed with 12-hour extract of 3Y-TZP transparent zirconia,12-hour extract of 5Y-PSZ ultra-translucent zirconia,and 12-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,and the hemolysis rate was detected after 0.5 hours.RESULTS AND CONCLUSION:(1)Under the microscope,it could be seen that the number of cells in each group increased with the extension of culture time,and the cell morphology of each experimental group was basically the same as that of the control group.The cytotoxicity grade of the 24-hour extract of 3Y-TZP transparent zirconia group on the first day of culture was grade 0,and the cytotoxicity grade of the other experimental groups at each time period was grade 1.(2)Neither the material nor the material extract caused obvious hemolytic reaction,and the hemolytic rate was less than 5%.(3)The results showed that 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia had no significant effect on the growth and proliferation of mouse fibroblasts L929,and did not cause hemolytic reaction with human blood,and had good in vitro biocompatibility.
10.Zuoguiwan Mitigates Oxidative Stress in Rat Model of Hyperthyroidism Due to Kidney-Yin Deficiency via DRD4/NOX4 Pathway
Ling LIN ; Qianming LIANG ; Changsheng DENG ; Li RU ; Zhiyong XU ; Chao LI ; Mingshun SHEN ; Yueming YUAN ; Muzi LI ; Lei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):43-51
ObjectiveTo decipher the mechanism by which Zuoguiwan (ZGW) treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 (DRD4)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone (0.35 mg·kg-1). After successful modeling, the rats were randomized into model, methimazole (positive control, 5 mg·kg-1), low-, medium-, and high-dose (1.85, 3.70, 7.40 g·kg-1, respectively) ZGW, and normal control groups. After 21 days of continuous gavage, the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones [triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH)], renal function indexes [serum creatine (Scr) and blood urea nitrogen (BUN)], energy metabolism markers [cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)], and oxidative stress-related factors [superoxide dismutase (SOD), malondialdehyde (MDA), and NADPH)] were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was employed to analyze the expression of DRD4, NOX4, mitochondrial respiratory chain complex proteins [NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4) and cytochrome C oxidase subunit 4 (COX4)], and inflammation-related protein [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), p38 mitogen-activated protein kinase (MAPK)] pathway in the renal tissue. ResultsCompared with the normal group, the model group showed mental malaise, body weight decreases (P<0.01), inflammatory cell infiltration in the renal tissue, a few residual parotid glands in the thyroid, elevations in serum levels of T3, T4, Scr, BUN, cAMP, cAMP/cGMP, MDA, and NADPH (P<0.01), down-regulation in protein levels of TSH, SOD, and DRD4 (P<0.05, P<0.01), and up-regulation in expression of NOX4, p-p38 MAPK/p38 MAPK, and inflammatory factors (P<0.01). Compared with the model group, ZGW increased the body weight (P<0.05, P<0.01), reduced the infiltration of renal interstitial inflammatory cells, restored the thyroid structure and follicle size, lowered the serum levels of T3, T4, Scr, BUN, cAMP, cAMP/cGMP, MDA and NADPH (P<0.05, P<0.01), up-regulated the expression of TSH, SOD and DRD4 (P<0.05, P<0.01), and down-regulated the expression of NOX4, p-p38 MAPK/p38 MAPK, and inflammatory factors (P<0.05, P<0.01). Moreover, high-dose ZGW outperformed methimazole (P<0.05). ConclusionBy activating DRD4, ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway, reduce oxidative stress and inflammatory response, thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.


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