1.Exercise-induced Mitohormesis in Counteracting Age-related Sarcopenia
Zi-Yi ZHANG ; Mei MA ; Hai BO ; Tao LIU ; Yong ZHANG
Progress in Biochemistry and Biophysics 2025;52(6):1349-1361
Sarcopenia, an age-related degenerative skeletal muscle disorder characterized by progressive loss of muscle mass, diminished strength, and impaired physical function, poses substantial challenges to global healthy aging initiatives. The pathogenesis of this condition is fundamentally rooted in mitochondrial dysfunction, manifested through defective energy metabolism, disrupted redox equilibrium, imbalanced dynamics, and compromised organelle quality control. This comprehensive review elucidates the central role of exercise-induced mitochondrial hormesis as a critical adaptive mechanism counteracting sarcopenia. Mitohormesis represents an evolutionarily conserved stress response wherein sublethal mitochondrial perturbations, particularly transient low-dose reactive oxygen species (ROS) generated during muscle contraction, activate cytoprotective signaling cascades rather than inflicting macromolecular damage. The mechanistic foundation of this process involves ROS functioning as essential signaling molecules that activate the Keap1 nuclear factor erythroid 2 related factor 2 (Nrf2) antioxidant response element pathway. This activation drives transcriptional upregulation of phase II detoxifying enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GPx), thereby enhancing cellular redox buffering capacity. Crucially, Nrf2 engages in bidirectional molecular crosstalk with peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1α), the principal regulator orchestrating mitochondrial biogenesis through coordinated induction of nuclear respiratory factors 1 and 2 (NRF1/2) along with mitochondrial transcription factor A (Tfam), collectively facilitating mitochondrial DNA replication and respiratory complex assembly. Concurrently, exercise-induced alterations in cellular energy status, specifically diminished ATP to AMP ratios, potently activate AMP activated protein kinase (AMPK). This energy-sensing kinase phosphorylates PGC-1α while concomitantly stimulating NAD dependent deacetylase sirtuin 1 (SIRT1) activity, which further potentiates PGC-1α function through post-translational deacetylation. The integrated AMPK/PGC-1α/SIRT1 axis coordinates mitochondrial biogenesis, optimizes network architecture through regulation of fusion proteins mitofusin 1 (Mfn1), mitofusin 2 (Mfn2) and optic atrophy protein 1 (OPA1), and enhances clearance of damaged organelles via selective activation of mitophagy receptors BCL2 interacting protein 3 (Bnip1) and FUN14 domain containing 1 (FNDC1). Exercise further stimulates the mitochondrial unfolded protein response (UPRmt), increasing molecular chaperones such as heat shock protein 60 (HSP60) and HSP10 to preserve proteostasis. Within the mitochondrial matrix, SIRT3 fine-tunes metabolic flux through deacetylation of electron transport chain components, improving phosphorylation efficiency while attenuating pathological ROS emission. Distinct exercise modalities differentially engage these pathways. Aerobic endurance training primarily activates AMPK/PGC-1α signaling and UPRmt to expand mitochondrial volume and oxidative capacity. Resistance training exploits mechanical tension to acutely stimulate mechanistic target of rapamycin complex 1 (mTORC1) mediated protein synthesis while modulating dynamin related protein 1 (Drp1) phosphorylation dynamics to support mitochondrial network reorganization. High intensity interval training generates potent metabolic oscillations that rapidly amplify AMPK/PGC-1α and Nrf2 activation, demonstrating particular efficacy in insulin-resistant phenotypes. Strategically designed concurrent training regimens synergistically integrate these adaptations. Mitochondrial-nuclear communication through tricarboxylic acid cycle metabolites and mitochondrially derived peptides such as mitochondrial open reading frame of 12s rRNA-c (MOTS-c) coordinates systemic metabolic reprogramming, with exercise-responsive myokines including fibroblast growth factor 21 (FGF-21) mediating inter-tissue signaling to reduce inflammation and enhance insulin sensitivity. This integrated framework provides the scientific foundation for precision exercise interventions targeting mitochondrial pathophysiology in sarcopenia, incorporating biomarker monitoring and exploring pharmacological potentiators including nicotinamide riboside and MOTS-c mimetics. Future investigations should delineate temporal dynamics of mitohormesis signaling and epigenetic regulation to optimize therapeutic approaches for age-related muscle decline.
2.Analysis of phenotype formation mechanism of a new variety of Lonicera japonica Flos "Huajin 6" at long bud stage
Run-zhu LI ; Cong-lian LIANG ; Zhen-hua LIU ; Jia LI ; Yong-qing ZHANG ; Hai-yan LIU ; Gao-bin PU
Acta Pharmaceutica Sinica 2024;59(2):476-481
Based on the long bud stage phenotype of a new
3.Mannitol inhibits the proliferation of neural stem cell by a p38 mitogen-activated protein kinase-dependent signaling pathway
Hai-Zhen DUAN ; Xin ZHOU ; Quan HU ; Meng-Long LIU ; Shu-Hong WANG ; Ji ZHANG ; Xu-Heng JIANG ; Tian-Xi ZHANG ; An-Yong YU
Chinese Journal of Traumatology 2024;27(1):42-52
Purpose::Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.Methods::C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. Results::Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.Conclusions::Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.
4.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
5.Application status and research progress of tranexamic acid in the perioperative period of joint replacement and arthroscopic surgery
Bao-Hua YUAN ; Hai-Ping LIU ; Xing-Yong LI ; Xiao-Ting LIU ; Ji-Hai MA ; Xu-Sheng ZHANG ; Hao-Fei YANG ; Jin-Sheng LI ; Sheng-Long HAN
The Chinese Journal of Clinical Pharmacology 2024;40(7):1080-1084
Tranexamic acid is widely used in joint orthopedic surgery.At the same time,it has high safety and few adverse drug reactions.It can effectively improve intraoperative bleeding and promote early functional recovery of patients.This article reviews the mode of administration,safe dose,administration time and adverse drug reactions of tranexamic acid in the perioperative period of joint replacement and arthroscopic surgery,in order to provide reference for the clinical application of tranexamic acid.
6.Effects of hypericin on bone metabolism,biomechanics and mechanism of osteoporosis in rats with chronic obstructive pulmonary disease
Ming-Xia SHEN ; Wen-Jun DING ; Hai-Bin XIE ; Yun ZHANG ; Xing-Xing YANG ; Yong-Rui GAO
The Chinese Journal of Clinical Pharmacology 2024;40(20):3003-3007
Objective To investigate the effect and mechanism of hypericin on osteoporosis(OP)in rats with chronic obstructive pulmonary disease(COPD).Methods COPD combined with OP rat model was established by cigarette combined with bacteria.The rats were randomly divided into control group,model group(COPD combined with OP model was constructed),experimental-L group(50 mg·kg-1 hypericin was given by intragastric administration after constructing COPD combined with OP model),experimental-H group(100 mg·kg-1 hypericin was given intragastric administration after constructing COPD combined with OP model),positive group(subcutaneous injection of 16 U·kg-1 salmon calcitonin after constructing COPD combined with OP model);each group was given 12 rats for 90 days.The lung function of rats was detected by pulmonary function apparatus;bone mineral density(BMD)was detected by micro-computed tomography(CT);serum bone metabolism and inflammatory factors were detected by enzyme-linked immunosorbent assay(ELISA);Western blot assay was used to detect the relevant indicators of the pathway.Results The levels of forced vital capacity(FVC)in control group,model group,experimental-H group and positive group were(10.42±1.40),(4.10±0.60),(6.75±0.37),(4.18±0.33)mL,respectively;BMD levels were(0.31±0.04),(0.12±0.02),(0.28±0.03),(0.29±0.04)g·mm-3,respectively;bone alkaline phosphatase(BALP)levels were(200.04±20.03),(80.80±6.00),(148.16±14.23),(173.97±23.55)U·L1,respectively;interleukin-1β(IL-1β)levels were(122.60±8.70),(695.59±74.84),(422.41±44.86),(527.90±39.36)pg·mL-1,respectively;phosphorylated p38 mitogen-activated protein kinase(p-P38)protein expression levels were 0.99±0.11,0.36±0.05,0.79±0.08,0.36±0.04,respectively.Compared with the control group,the above indexes in the model group had statistical significance(all P<0.05);the above indexes in experimental-H group were significantly different from those in model group(all P<0.05).Conclusion Hypericin can inhibit inflammatory response,improve bone metabolism and biomechanics.
7.Safety and efficacy of domestically produced novel bioabsorbable vascular scaff old in the treatment of complex coronary artery lesions for 3 years
Deng-Shuang ZHOU ; Qiong YOU ; Hai-Liang MO ; Zi-Jun WU ; Yu-Biao LIN ; Lu-Jun CHEN ; Jun-Yu FAN ; Yong-Jian LIN ; Rui-Sheng ZHANG ; Pei-Shan WAN ; Wei-Guo ZHOU ; Keng WU
Chinese Journal of Interventional Cardiology 2024;32(9):509-515
Objective To investigate the safety and efficacy of novel bioabsorbable vascular scaffold(BVS)in the treatment of patients with complex coronary artery disease.Methods This was a retrospective,matched,single-center observational study.45 patients with coronary atherosclerotic cardiopathy received BVS treatment in the cardiovascular medicine department Department of the Affiliated Hospital of Guangdong Medical University from June 2020 to June 2021(BVS),and 45 patients treated with drug-eluting stents(DES)group were selected according to matching study requirements during the same period.Baseline,surgical,and follow-up data were compared between the two groups to evaluate safety and efficacy.The main measures of safety were:surgical time,intraoperative adverse events,etc.,and the end point of efficacy was target lesion failure(TLF),including cardiac death,target vessel myocardial infarction,and ischa-driven target lesion revascularization.Results A total of 90 patients were enrolled in this study,all of whom were followed up for at least 3 years.There were 20 cases of bifurcation lesions and 25 cases of diffuse long lesions in the two groups,and 50 cases of imaging were reviewed among the 90 patients.The proportion of stable coronary heart disease,history of diabetes,history of hypertension,history of smoking,pre-dilated balloon pressure and postoperative diastolic blood pressure in BVS group was higher than that in DES group,and the proportion of family history was lower than that in DES group(all P<0.05).There were no statistically significant differences in the rates of cardiac death,target vessel myocardial infarction,and ischemia-driven revascularization of target lesions between the two groups(all P>0.05).Binary Logistic regression model analysis showed that the diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis(OR 2.786,95%CI 1.096-7.081,P=0.031).Conclusions Compared with traditional DES,BVS implantation has consistent safety and efficacy in the treatment of complex coronary artery disease within 3 years.The diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis.
8.Clinical study of lumbar stability after unilateral biportal endoscopy in the treatment of degenerative lumbar diseases
Dongyue LI ; Qingjun SU ; Xinuo ZHANG ; Luming TAO ; Yong HAI
Chinese Journal of Surgery 2024;62(3):187-193
Objectives:To investigate the clinical efficacy of unilateral biportal endoscopy (UBE) in the treatment of degenerative lumbar disease (DLD) and its impact on postoperative lumbar stability.Methods:This is a retrospective case series study. A total of 109 cases of DLD treated with UBE in the Department of Orthopaedic, Beijing Chaoyang Hospital Affiliated to Capital Medical University from July 2020 to June 2022 were analyzed retrospectively. There were 47 males and 62 females, aged (53.3±8.2) years (range: 21 to 80 years). The surgical segments were single segment in 80 cases, two segments in 25 cases, and three segments in 4 cases. The low back pain and leg pain of visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) score and Oswestry disability index (ODI) were evaluated before and after operation. The modified MacNab criteria were used for evaluation of the clinical consequences. Postoperative three-dimensional lumbar CT was performed to observe the preservation of the facet joints and the angle of the medial surface of the facetectomy(β angle). At 12 months after surgery, X ray of the flexion and extension lumbar spine were reviewed. The comparison and analysis of the data were conducted using paired sample t tests or generalized estimation equations. Results:All 109 patients underwent operative procedures successfully. The operation time was (94.5±37.1) minutes (range:56 to 245 minutes), the times of X ray was 6.8±4.0 (range:4 to 16 times), and the days of hospitalization was (5.3±3.7) days (range:4 to 14 days). Complications included dural tears in 4 cases, transient lower limb numbness in 4 cases, epidural hematoma in 2 case. The follow-up time was (19.6±7.2) months (range:12 to 36 months). The postoperative low back pain VAS, leg pain VAS, JOA score and ODI were significantly improved(all P<0.05). According to the modified MacNab criteria, the excellent and good rate was 88.99%(97/109) at 12 months after surgery. One case underwent revision surgery because of recurrent lumbar disc herniation. In term of radiographic evaluation, the area of the surgical side facet joints after UBE surgery was reserved more than 60%. The β angle was less than 90° in all patients. After 12 months of surgery, there was no surgical segment instability or spondylolisthesis by the X-ray of the flexion and extension lumbar spine. Conclusion:UBE can achieve satisfactory clinical efficacy in the treatment of DLD, and maintain the stability of the lumbar spine.
9.Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fracture with kyphotic deformity in the elderly (version 2024)
Jian CHEN ; Qingqing LI ; Jun GU ; Zhiyi HU ; Shujie ZHAO ; Zhenfei HUANG ; Tao JIANG ; Wei ZHOU ; Xiaojian CAO ; Yongxin REN ; Weihua CAI ; Lipeng YU ; Tao SUI ; Qian WANG ; Pengyu TANG ; Mengyuan WU ; Weihu MA ; Xuhua LU ; Hongjian LIU ; Zhongmin ZHANG ; Xiaozhong ZHOU ; Baorong HE ; Kainan LI ; Tengbo YU ; Xiaodong GUO ; Yongxiang WANG ; Yong HAI ; Jiangang SHI ; Baoshan XU ; Weishi LI ; Jinglong YAN ; Guangzhi NING ; Yongfei GUO ; Zhijun QIAO ; Feng ZHANG ; Fubing WANG ; Fuyang CHEN ; Yan JIA ; Xiaohua ZHOU ; Yuhui PENG ; Jin FAN ; Guoyong YIN
Chinese Journal of Trauma 2024;40(11):961-973
The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.
10.Correlation study of transcranial sonography combined with serum biomarkers and cognitive status in patients with Parkinson′s disease
Hai WANG ; Yingchun ZHANG ; Changwei DING ; Caishan WANG ; Yujing SHENG ; Xiaofang CHEN ; Ying ZHANG ; Min YANG ; Pan MAO ; Yong YANG ; Ping FENG ; Chengjie MAO ; Jing CHEN ; Chunfeng LIU
Chinese Journal of Ultrasonography 2024;33(6):512-518
Objective:To explore the correlation between transcranial sonography (TCS) combined with serum homocysteine (Hcy), blood glucose, blood lipids, the cognitive status of Parkinson′s disease (PD) patients, and to analyze the clinical application value of these parameters in assessing the cognitive status of PD patients.Methods:A total of 152 PD patients admitted to the Second Affiliated Hospital of Soochow University from January 2020 to June 2023 were retrospectively collected as the PD group, and 101 healthy examinees matched for age and gender during the same period were selected as control group. Clinical data [age, gender, duration of illness, Montreal Cognitive Assessment (MoCA) score, Mini-Mental State Examination (MMSE) score, Unified Parkinson′s Disease Rating Scale Part Ⅲ (UPDRS-Ⅲ) score, Hoehn-Yahr (H-Y) stage, etc.], serum tests (Hcy, blood glucose, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein concentration), and TCS examination results (third ventricular width, midbrain area, peak systolic velocity of bilateral middle cerebral arteries, bilateral middle cerebral artery resistance index, bilateral substantia nigra hyperechoic area) were collected. The two groups were divided into pure PD group and PD group with elevated Hcy, pure control group and control group with elevated Hcy, based on an Hcy concentration threshold of ≥15 μmol/L. The differences in the above parameters among the four groups were compared. The correlation between Hcy and cognitive status (MoCA score, MMSE score) of PD patients and the above parameters were analyzed.Results:The MoCA score and MMSE score of the PD group with elevated Hcy were lower than those of the pure PD group, and the UPDRS-Ⅲ score and H-Y stage were higher than those of the pure PD group (all P<0.001). The order of Hcy concentration from high to low was PD group with elevated Hcy, pure Hcy elevation group, pure PD group, and pure control group. The differences in serum data and TCS data among the four groups were statistically significant (all P<0.001). Spearman correlation analysis showed: ①In the PD group, the concentration of Hcy was positively correlated with glucose concentration, H-Y stage, low-density lipoprotein concentration, right middle cerebral artery resistance index, UPDRS-Ⅲ score, total cholesterol concentration, triglyceride concentration, left middle cerebral artery resistance index, third ventricular width, and age ( rs=0.422, 0.350, 0.348, 0.334, 0.325, 0.300, 0.293, 0.283, 0.221, 0.164, all P<0.05); Hcy concentration was negatively correlated with midbrain area, MMSE score, MoCA score, peak systolic velocity of right middle cerebral artery, peak systolic velocity of left middle cerebral artery, and high-density lipoprotein concentration ( rs=-0.328, -0.282, -0.245, -0.229, -0.224, -0.192, all P<0.05). ②Clinical data, serum data, and TCS data of PD patients were all correlated with MoCA score and MMSE score, with midbrain area showing the largest positive correlation ( rs=0.524, 0.516; both P<0.05) and H-Y stage showing the largest negative correlation( rs=-0.490, -0.468; both P<0.05). Conclusions:PD patients with elevated Hcy have lower cognitive scores than pure PD patients. The correlation between Hcy concentration and blood glucose concentration is the highest in PD patients, followed by H-Y stage. The cognitive scores of PD patients are most correlated with midbrain area and unrelated to substantia nigra hyperechoic area. Lowering serum Hcy concentration in PD patients may be one of the ways to delay cognitive impairment.

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