1.Brain Aperiodic Dynamics
Zhi-Cai HU ; Zhen ZHANG ; Jiang WANG ; Gui-Ping LI ; Shan LIU ; Hai-Tao YU
Progress in Biochemistry and Biophysics 2025;52(1):99-118
Brain’s neural activities encompass both periodic rhythmic oscillations and aperiodic neural fluctuations. Rhythmic oscillations manifest as spectral peaks of neural signals, directly reflecting the synchronized activities of neural populations and closely tied to cognitive and behavioral states. In contrast, aperiodic fluctuations exhibit a power-law decaying spectral trend, revealing the multiscale dynamics of brain neural activity. In recent years, researchers have made notable progress in studying brain aperiodic dynamics. These studies demonstrate that aperiodic activity holds significant physiological relevance, correlating with various physiological states such as external stimuli, drug induction, sleep states, and aging. Aperiodic activity serves as a reflection of the brain’s sensory capacity, consciousness level, and cognitive ability. In clinical research, the aperiodic exponent has emerged as a significant potential biomarker, capable of reflecting the progression and trends of brain diseases while being intricately intertwined with the excitation-inhibition balance of neural system. The physiological mechanisms underlying aperiodic dynamics span multiple neural scales, with activities at the levels of individual neurons, neuronal ensembles, and neural networks collectively influencing the frequency, oscillatory patterns, and spatiotemporal characteristics of aperiodic signals. Aperiodic dynamics currently boasts broad application prospects. It not only provides a novel perspective for investigating brain neural dynamics but also holds immense potential as a neural marker in neuromodulation or brain-computer interface technologies. This paper summarizes methods for extracting characteristic parameters of aperiodic activity, analyzes its physiological relevance and potential as a biomarker in brain diseases, summarizes its physiological mechanisms, and based on these findings, elaborates on the research prospects of aperiodic dynamics.
2.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.
3.Application of Mitochondrial Targeting Strategy of Nano-delivery System in Tumor Diagnosis and Treatment
Jun QU ; Shuang YAN ; Long-Tian-Yang LEI ; Fei-Jun OUYANG ; Hai-Tao ZHANG ; Xu-Ping QIN
Progress in Biochemistry and Biophysics 2024;51(1):70-81
Tumor is one of the major diseases that endanger people’s health. At present, the treatments used for tumor include surgery, chemotherapy, radiotherapy and so on. Nonetheless, the traditional treatments have some disadvantages, such as insufficient treatment effect, liable to cause multidrug resistance, toxicity and side effect. Further research and exploration of tumor treatment schemes are still necessary. As the energy converter of cells, mitochondria are currently considered to be one of the most important targets for the design of new drugs for tumor, cardiovascular and neurological diseases. Nano-drug delivery carriers have the characteristics of being easily modified with active targeting groups, and it can achieve accurate targeted drug delivery to cells and organelles. This paper reviews the application of mitochondrial targeted nanoparticles in tumor diagnosis and treatment from the aspects of inhibiting tumor cell proliferation, promoting tumor cell apoptosis, inhibiting tumor recurrence and metastasis, and inducing cell autophagy.
4.Clinical trial of sindillimab combined with TN chemotherapy regimen in patients with advanced non-small cell lung cancer
Dan LIU ; Hai-Tao ZHANG ; Huan LIN ; Chun WANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):640-644
Objective To analyze the efficacy of sintilizumab combined with paclitaxel(albumin-bound)and nedaplatin(TN chemotherapy regimen)in patients with advanced non-small cell lung cancer(NSCLC)and its effects on serum tumor markers and immune cell levels.Methods The patients were divided into control group and treatment group according to random number table method.In the control group,80 mg·m-2 nedaplatin and 260 mg·m-2 paclitaxel(albumin-bound type)were injected intravenally on the 1st day for 21 days.The etreatment group was given sindilizumab 200 mg intravenously on the basis of the control group,21 days a cycle for 4 cycles.The anti-tumor efficacy,tumor markers,lung function,immune cytokines and adverse drug reactions of the two groups were compared after 4 cycles of treatment,and the 1-year survival of the two groups was statistically analyzed.Results A total of 7 cases fell off during treatment.Finally,98 patients in the treatment group and 96 patients in the control group were included in the analysis.After treatment,the objective response rate(ORR)of treatment group and control group were 43.88%(43 cases/98 cases)and 29.17%(28 cases/96 cases);the disease control rate(DCR)were 77.55%(76 cases/98 cases)and 60.42%(58 cases/96 cases),the difference was statistically significant(all P<0.05).After treatment,carbohydrate antigen 125(CA125)in treatment group and control group were(39.03±5.97)and(42.15±6.35)U·mL-1;squamous cell carcinoma antigen(SCCA)were(4.58±0.63)and(5.29±0.84)ng·mL-1;forced vital capacity(FVC)were(2.96±0.52)and(2.71±0.49)L;forced expiratory volume in the first second(FEV1)/FVC were(68.47±11.39)%and(64.92±10.43)%;Th1/Th2 were 5.01±0.63 and 5.36±0.74;Th17/Treg were 1.04±0.15 and 1.20±0.19;CD4+/CD8+were 1.36±0.19 and 1.23±0.17,respectively.The differences were statistically significant(all P<0.05).The total incidence of adverse drug reactions in treatment group and control group were 25.51%(25 cases/98 cases)and 22.92%(22 cases/96 cases),respectively,the difference was not statistically significant(P>0.05).There was no significant difference in 1-year overall survival curves between the two groups(P>0.05).Conclusion Sindilizumab combined with TN chemotherapy regimen in the treatment of advanced NSCLC can enhance the anti-tumor efficacy,reduce the level of tumor markers,improve lung function and immune function,and has good safety.
5.Changes in the Non-targeted Metabolomic Profile of Three-year-old Toddlers with Elevated Exposure to Polycyclic Aromatic Hydrocarbons
Yang LI ; Dan LIN ; Qin Xiu ZHANG ; Xiu Guang JU ; Ya SU ; Qian ZHANG ; Ping Hai DUAN ; Sen Wei YU ; Ling Bing WANG ; Tao Shu PANG
Biomedical and Environmental Sciences 2024;37(5):479-493
Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.
6.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.
7.Myasthenia gravis after allogeneic hematopoietic stem cell transplantation: Two case reports and literature review
Yajun SHI ; Ying HAN ; Xiaofei ZHANG ; Rui XI ; Hai BAI ; Tao WU
Chinese Journal of Hematology 2024;45(10):956-959
The onset of myasthenia gravis (MG) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) seriously threatens the survival of patients, since it is acute, and is prone to rapid progression. Two patients with acute myeloid leukemia (AML), who had undergone allo-HSCT developed shortness of breath, and gradually developed cervical weakness and dyspnea. The acetylcholine receptor (AChR) antibody and neostigmine test enabled the diagnosis of MG. The condition of the patients improved after treatment with pyridostigmine bromide, glucocorticoids and rituximab.
8.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]
9.Comparative study of minimally invasive titanium elastic nail and steel plate on the treatment of fracture of tibiofibu-lar fracture in adults
Hai-Bing ZHU ; Yong-Tao ZHANG ; He LYU ; Fu-Chang REN ; Cheng-Hong ZHOU ; Yun-Feng YING
China Journal of Orthopaedics and Traumatology 2024;37(4):352-357
Objective To compare the clinical outcomes of using elastic intramedullary nail and plate to fix fibular frac-ture.Methods The 60 patients with tibiofibular fractures admitted from January 2015 to December 2022 were divided into two groups:intramedullary nail group and plate group,30 cases each,intramedullary nail group was treated with elastic in-tramedullary nail fixation group,plate group was treated with steel plate and screw fixation group.Intramedullary nail group,there were 18 males and 12 females,aged from 22 to 75 years old with an average of(39.4±9.8)years old,including 24 cases of traffic accidents injury,6 cases of falling injury,23 cases of closed fractures,7 cases of open fractures.Steel plate group,there were 15 males and 15 females,aged from 24 to 78 years old with an average of(38.6±10.2)years old.The 22 cases were injured by traffic accident,8 cases were injured by falling.The 24 cases were closed fractures and 6 cases were open fractures.The operation time,intraoperative bleeding,American Orthopedic Foot and Ankle Society(AOFAS)ankle and hind foot scores,clinical healing time of fibula and the incidence of wound complications were compared between the two groups.Re-sults The patients in both groups were followed up for 6 to 21 months,with an average of(14.0±2.8)months.Compared with plate group,intramedullary nail group had shorter operative time,less bleeding,shorter clinical healing time of fibula,and low-er infection rate of incision,and the difference was statistically significant(P<0.05).There were 2 cases of delayed healing in intramedullary nail group,1 case of nonunion in plate group,and 2 cases of delayed healing in plate group,and there was no statistically significant difference between the two groups(P>0.05).In the last follow-up,according to the AOFAS scoring standard,the ankle function in intramedullary nail group was excellent in 17 cases,good in 12 cases,fair in 1 case,with an av-erage of(88.33±4.57)points,while in plate group,excellent in 16 cases,good in 10 cases,fair in 4 cases,with an average of(87.00±4.14)points;There was no statistical difference between the two groups(P>0.05).Conclusion Elastic intramedullary nail has the advantages of short operation time,less intraoperative bleeding,short fracture healing time and less incision com-plications in the treatment of fibular fracture,which is worthy of clinical application.
10.Analysis of risk factors for bile leakage after laparoscopic common bile duct exploration with primary closure
Wu GUO ; Jun-Jian LIU ; Hai-Tao SHANG ; De-Lin ZHANG ; Xi-Bo ZHANG ; Zhong-Lian LI
Journal of Regional Anatomy and Operative Surgery 2024;33(10):844-848
Objective To explore the risk factors for bile leakage after laparoscopic common bile duct exploration(LCBDE)with primary closure.Methods The clinical data of 560 patients with choledocholithiasis who underwent LCBDE with primary closure in Tianjin Hospital of Integrated Traditional Chinese and Western Medicine from September 2021 to September 2023 were retrospectively analyzed,and the patients were divided into the bile leak group and the non-bile leak group according to the occurrence of postoperative bile leakage.The risk factors affecting the occurrence of postoperative bile leakage were analyzed by multivariate analysis.Results A total of 64 cases(11.4% )experienced varying degrees of bile leakage,including 55 cases of grade A bile leakage,7 cases of grade B,and 2 cases of grade C.The thin common bile duct(OR=0.07,P<0.001),history of hypertension(OR=4.56,P<0.001),and high BMI(OR=1.17,P=0.002)were the risk factors for postoperative bile leakage in patients with choledocholithiasis.Conclusion Patients with thin common bile duct,hypertension and obesity are more likely to occur postoperative bile leakage.Patients with choledocholithiasis who have the above high-risk factors should be cautious in choosing LCBDE with primary closure.

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