1.Oxidative Stress-related Signaling Pathways and Antioxidant Therapy in Alzheimer’s Disease
Li TANG ; Yun-Long SHEN ; De-Jian PENG ; Tian-Lu RAN ; Zi-Heng PAN ; Xin-Yi ZENG ; Hui LIU
Progress in Biochemistry and Biophysics 2025;52(10):2486-2498
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, functional impairment, and neuropsychiatric symptoms. It represents the most prevalent form of dementia among the elderly population. Accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of AD. Notably, elevated levels of oxidative stress have been observed in the brains of AD patients, where excessive reactive oxygen species (ROS) can cause extensive damage to lipids, proteins, and DNA, ultimately compromising neuronal structure and function. Amyloid β‑protein (Aβ) has been shown to induce mitochondrial dysfunction and calcium overload, thereby promoting the generation of ROS. This, in turn, exacerbates Aβ aggregation and enhances tau phosphorylation, leading to the formation of two pathological features of AD: extracellular Aβ plaque deposition and intracellular neurofibrillary tangles (NFTs). These events ultimately culminate in neuronal death, forming a vicious cycle. The interplay between oxidative stress and these pathological processes constitutes a core link in the pathogenesis of AD. The signaling pathways mediating oxidative stress in AD include Nrf2, RCAN1, PP2A, CREB, Notch1, NF‑κB, ApoE, and ferroptosis. Nrf2 signaling pathway serves as a key regulator of cellular redox homeostasis, exerts important antioxidant capacity and protective effects in AD. RCAN1 signaling pathway, as a calcineurin inhibitor, and modulates AD progression through multiple mechanisms. PP2A signaling pathway is involved in regulating tau phosphorylation and neuroinflammation processes. CREB signaling pathway contributes to neuroplasticity and memory formation; activation of CREB improves cognitive function and reduce oxidative stress. Notch1 signaling pathway regulates neuronal development and memory, participates in modulation of Aβ production, and interacts with Nrf2 toco-regulate antioxidant activity. NF‑κB signaling pathway governs immune and inflammatory responses; sustained activation of this pathway forms “inflammatory memory”, thereby exacerbating AD pathology. ApoE signaling pathway is associated with lipid metabolism; among its isoforms, ApoE-ε4 significantly increases the risk of AD, leading to elevated oxidative stress, abnormal lipid metabolism, and neuroinflammation. The ferroptosis signaling pathway is driven by iron-dependent lipid peroxidation, and the subsequent release of lipid peroxidation products and ROS exacerbate oxidative stress and neuronal damage. These interconnected pathways form a complex regulatory network that regulates the progression of AD through oxidative stress and related pathological cascades. In terms of therapeutic strategies targeting oxidative stress, among the drugs currently used in clinical practice for AD treatment, memantine and donepezil demonstrate significant therapeutic efficacy and can improve the level of oxidative stress in AD patients. Some compounds with antioxidant effects (such asα-lipoic acid and melatonin) have shown certain potential in AD treatment research and can be used as dietary supplements to ameliorate AD symptoms. In addition, non-drug interventions such as calorie restriction and exercise have been proven to exerted neuroprotective effects and have a positive effect on the treatment of AD. By comprehensively utilizing the therapeutic characteristics of different signaling pathways, it is expected that more comprehensive multi-target combination therapy regimens and combined nanomolecular delivery systems will be developed in the future to bypass the blood-brain barrier, providing more effective therapeutic strategies for AD.
2.Research progress on dihydrochalcones from Lithocarpus litseifolius extracts in treatment of type 2 diabetes mellitus and its complications.
Yun-Qin WEI ; Yu-Lan CAI ; Yan YANG ; Shang-Heng FAN ; Lin-Li WU ; Gui-Lan NIE
China Journal of Chinese Materia Medica 2025;50(3):658-671
Type 2 diabetes mellitus(T2DM) is a prevalent metabolic and endocrine disorder. Long-term hyperglycemia can lead to severe chronic complications, imposing substantial economic burdens on both society and patients. Despite the availability of various hypoglycemic agents for clinical use, these agents often fail to meet the therapeutic needs of T2DM and its complications. Consequently, there is an urgent need for novel therapeutic strategies and drugs. Lithocarpus litseifolius(L. litseifolius), commonly referred to as "cordyceps on trees", has a long history of use in traditional medicine and can be applied in tea, sugar, and medicine. Research indicates that L. litseifolius extracts are rich in dihydrochalcones, including trilobatin, phloridzin, and phloretin, which exhibit a range of pharmacological activities, such as anti-inflammatory, antioxidant, hypoglycemic, hypolipidemic, hepatoprotective, and cardioprotective effects. These properties suggest potential applications in the treatment of T2DM and its complications. This review systematically compiled and organized the relevant literature from the past decade on dihydrochalcones(trilobatin, phloridzin, and phloretin) from L. litseifolius extracts. It highlighted recent research progress regarding their role in treating T2DM and its complications through mechanisms such as reducing insulin resistance, regulating glucose transport, improving glucose and lipid metabolism, modulating enzyme activity, regulating gut microbiota, and alleviating inflammation and oxidative damage. The purpose of this review is to provide a reference and basis for future research on the prevention and treatment of T2DM and its complications using dihydrochalcones(trilobatin, phloridzin, and phloretin) from L. litseifolius extracts.
Chalcones/chemistry*
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Diabetes Mellitus, Type 2/metabolism*
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Humans
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Animals
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Elaeocarpaceae/chemistry*
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Drugs, Chinese Herbal/therapeutic use*
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Hypoglycemic Agents/chemistry*
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Plant Extracts/chemistry*
3.Relationship between glycolysis mediated by HIF-1α/BNIP3 pathway and oxygen-induced retinal angiogenesis in neonatal mice
Yan Yi ; Feifei Chen ; Yun Tan ; Heng Du
Acta Universitatis Medicinalis Anhui 2025;60(2):226-233
Objective :
Based on glycolysis of hypoxia inducible factor-1α(HIF-1α)/Bcl2/adenovirus E1B interacting protein 3(BNIP3) pathway, to study the mechanism of oxygen-induced retinal angiogenesis in neonatal mice.
Methods :
Human umbilical vein endothelial cells(HUVECs) were divided into normoxic group, hypoxia+si-NC group, hypoxia +si-HIF-1α group and hypoxia+si-HIF-1α+BNIP group. In normoxic group, HUVECs were exposed to normoxic(21% O2) and cultured. Hypoxia +si-NC group, hypoxia +si-HIF-1α group and hypoxia +si-HIF-1α+BNIP3 group were treated with si-NC, si-HIF-1α or si-HIF-1α combined with BNIP3 plasmid for 36 h, and then exposed to hypoxia(1% O2) for culture. The autophagy, glycolysis, proliferation, migration and tube formation of mitochondria were investigated by immunofluorescence, metabolic measurement, cell viability, scratch experiment and tube formation experiment. On the 7th day after birth, C57BL/6J mice were randomly assigned to different treatment groups: control group, oxygen-induced retinopathy(OIR) group, OIR+si-HIF-1α group and OIR+si-BNIP group. The neovascularization and vascular occlusion were measured.
Results:
Compared with normoxic group, the rate of LC3+MitoTracker+ spots, glucose uptake and lactic acid release in HUVECs in hypoxia +si-NC group increased significantly(P<0.001). Compared with hypoxia +si-NC group, the rate of LC3+MitoTracker+ spots, glucose uptake and lactic acid release in HUVECs in hypoxia +si-HIF-1α group decreased significantly(P<0.01). Compared with normoxic group, the proliferation activity of HUVECs in hypoxia +si-NC group decreased significantly(P<0.05), and the wound healing area and the number of tubes formed increased significantly(P<0.01). Compared with hypoxia+si-NC group, the proliferation activity of HUVECs in hypoxia +si-HIF-1α group decreased significantly at the 24th, 48th and 72th hours of culture(P<0.05), and the wound healing area and the number of tubes formed decreased significantly(P<0.001). Overexpression of BNIP3 reversed the effects of HIF-1α knock-down on mitochondrial autophagy, glycolysis and biological function. Compared with OIR group, the neovascularization and vascular occlusion areas in retina of mice in OIR+si-HIF-1α group and OIR+si-BNIP3 group reduced significantly(P<0.05).
Conclusion
HIF-1α/BNIP3 signaling pathway promotes mitochondrial autophagy activation in HUVECs under hypoxia, which plays an important role in controlling endothelial function and angiogenesis.
4.Prediction of Shared Target Genes in Cardiac Complications Induced by IAV and SARS-CoV-2 Using Machine Learning and Validation in H1N1 Infection Models
Yuansheng LIAO ; Heng LI ; Yun LIAO ; Yunguang HU ; Anguo YIN ; Meijun KONG ; Longding LIU ; Ying ZHANG
Journal of Kunming Medical University 2025;46(5):75-88
Objective To predict and preliminarily validate potential shared key genes involved in cardiac complications caused by influenza A virus(IAV)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections.Methods Differentially expressed genes(DEGs)associated with cardiac complications were obtained from the Gene Expression Omnibus(GEO)database.A hierarchical intersection strategy was applied.First,cardiac complication related DEGs were overlapped with 2 independent virus related gene sets:3 454 human genes linked to IAV infection in GeneCards and 333 human protein-coding genes interacting with SARS-CoV-2 in the Human Protein Atlas.The 2 overlap results were then intersected to yield 22 hub genes.Lasso regression,random forest(RF)and support vector machine algorithms(SVM)were employed to refine this list.Predicted genes were validated in vitro in H1N1-infected human cardiomyocyte AC16 cells and in vivo in IFITM3 knockout mice challenged with H1N1,assessing transcriptional changes.Results A total of 22 hub genes were identified through integrative bioinformatics analysis.Application of the 3 machine learning algorithms resulted in 5 common key genes:ACE2,TBK1,NUP210,PUSL1,and MEPCE.In vitro infection of AC16 cells with H1N1 revealed dynamic transcriptional changes in all 5 genes post-infection(P<0.05).In vivo experiments using H1N1-infected IFITM3 knockout mice confirmed the dynamic mRNA expression changes of these 5 genes,consistent with the in vitro results(P<0.05).Conclusion By combining multilayered bioinformatics analysis with 3 machine learning approaches,5 common key genes are identified:ACE2,TBK1,NUP210,PUSL1 and MEPCE.Validation in H1N1 infection models confirms their relevance to IAV-induced cardiac complications.
5.Application of metagene next-generation sequencing of alveolar lavage fluid in the detection of pathogenic bacteria of pulmonary infection
He Zhang ; Xinyue Luo ; Xin Heng ; Yun Zhang ; Songping Wang ; Jun Deng
Acta Universitatis Medicinalis Anhui 2025;60(10):1917-1923,1931
Objective:
To investigate the value of metagene next⁃generation sequencing ( mNGS) in the detection of pathogens in patients with pulmonary infection.
Methods:
A retrospective analysis was performed on clinical data from 434 patients with pulmonary infections admitted over the past four years. Based on the presence of underlying comorbidities , patients were divided into underlying disease group (n = 262) and non⁃underlying disease group (n = 172) . Pathogen detection was conducted using both mNGS and conventional tests. Clinical and laboratory parameters , radiographic findings , and pathogen detection results were systematically analyzed. The diagnostic performance of the two methods in identifying causative pathogens of pulmonary infections was compared.
Results:
The positive rate of mNGS in 434 patients was higher than that of conventional tests , and the difference was statisti⁃cally significant (P < 0. 05) . The efficacy of mNGS in detecting bacteria and viruses was significantly higher than that of conventional tests , and the difference was statistically significant (P < 0. 05) . Although the fungal detection rate of mNGS was higher than that of conventional tests , the difference was not statistically significant. Among them , the detection rates of Mycobacterium tuberculosis , Mycoplasma pneumoniae , Haemophilus influenzae , Strepto⁃ coccus pneumoniae , Streptococcus constellation , Staphylococcus aureus and Aspergillus fumigatus were significantly higher than those of conventional tests , and the difference was statistically significant (P < 0. 05) . Subgroup analy- sis showed that the proportion of males , hospital stay , smoking prevalence and average age in the underlying dis- ease group were higher than those in the non-underlying disease group , and the difference was statistically signifi- cant (P < 0. 05) , while there were no significant differences in antibiotic use and endotracheal intubation rate be- tween the two groups. The most common pathogens detected by mNGS in the underlying disease group were Myco⁃ bacterium tuberculosis , Haemophilus influenzae , Streptococcus pneumoniae , Pseudomonas aeruginosa , human herpes⁃ virus type 4 and Aspergillus fumigatus , while the most common pathogens in the non-underlying disease group were Mycobacterium tuberculosis , Haemophilus influenzae , Streptococcus pneumoniae , Mycoplasma pneumoniae and Kleb⁃ siella pneumoniae. The positive rate of mNGS in the two groups was significantly higher than that of conventional tests , and the difference was statistically significant (P < 0. 05) , while the difference in the positive rate of mNGS between the two groups was not statistically significant.
Conclusion
mNGS has significant advantages over con- ventional tests of pathogen in lung infection , and is less affected by underlying diseases , which can provide an etio- logical basis for lung infection.
6.Comparison of interoperability among the standard systems of Chinese,the United States,European,and Japanese Pharmacopoeias and other standard systems
Xinyi XU ; Zhen LIU ; Leran TAO ; Haoyun SONG ; Dan LI ; Wenli YU ; Guannan WANG ; Heng LI ; Yun WANG ; Zhaopeng YANG
China Pharmacist 2024;27(2):233-241
Objective To provide reference for the optimization and improvement of interoperability between the standard system of the Chinese Pharmacopoeia and other standards.Methods The interoperability of various pharmacopoeia standard systems was compared by searching for citations from the Chinese Pharmacopoeia,the United States Pharmacopoeia-National Formulary,the European Pharmacopoeia,the Japanese Pharmacopoeia,and other standards,including references to domestic regulations and guidelines,standards of the International Organization for Standardization,guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use,documents of the World Health Organization,and standards from other countries and international organizations.Results In recent years,pharmacopoeias in the world had continuously increased the citation of non pharmacopoeial standards.The types,quantities,and fields of the United States Pharmacopoeia-National Formulary referencing other standards far exceed those of other pharmacopoeias.The Chinese Pharmacopoeia cites the least number of other standards.Conclusion It is suggested that the Chinese Pharmacopoeia should enhance the interoperability with other standard systems in the standards of various professional fields,enhance the openness,harmonization and advantages,and form a more complete standard system.
7.Long non-coding RNA MALAT1 in hematological malignancies and its clinical applications
Chunlan ZHANG ; Yun QIN ; Yu WU ; Heng XU ; Yang SHU
Chinese Medical Journal 2024;137(10):1151-1159
Metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1) is a well-established oncogenic long non-coding RNA, the higher expression of which is strongly correlated with cancer events such as tumorigenesis, progression, metastasis, drug resistance, and treatment outcome in solid cancers. Recently, a series of studies has highlighted its potential role in hematological malignancies in terms of these events. Similar to solid cancers, MALAT1 can regulate various target genes via sponging and epigenetic mechanisms, but the miRNAs sponged by MALAT1 differ from those identified in solid cancers. In this review, we systematically describe the role and underlying mechanisms of MALAT1 in multiple types of hematological malignancies, including regulation of cell proliferation, metastasis, stress response, and glycolysis. Clinically, MALAT1 expression is related to poor treatment outcome and drug resistance, therefore exhibiting potential prognostic value in multiple myeloma, lymphoma, and leukemia. Finally, we discuss the evaluation of MALAT1 as a novel therapeutic target against cancer in preclinical studies.
8.Anatomical principal variations of the human pelvic ring using statistic shape model
Xiu-Yun SU ; Jie HE ; Wei ZHAO ; De-Shun SUN ; Heng LI ; Yi-Yi OU ; Guo-Xian PEI
Acta Anatomica Sinica 2024;55(6):715-720
Objective To construct a three-dimensional statistical shape model of the pelvis and analyze the individual variation and gender differences of the three-dimensional shape of the pelvis.Methods We collected CT data from 201 Chinese individuals and used deep learning to automatically reconstruct three-dimensional models of the pelvis.Through three-dimensional model registration,dense correspondence mesh mapping,and the use of statistical shape modelling(SSM)and principal component(PC)analysis method,we extracted models of variations(MoV)of pelvic shape changes and statistically compared the shape MoV between males and females.Results We analysed the top 10 principal components of shape variations,which accounted for 86.1%of the total variability.Among them,PC01,PC02,and PC04 showed significant differences between genders(P<0.001),accounting for a total variability of 60.1%.PC08 and PC 10 demonstrated pelvic asymmetry,accounting for a total variability of 3.8%.Conclusion We constructed a three-dimensional statistical shape model of the pelvis in Chinese individuals,revealing the morphological variation and sex differences of Chinese pelvis.
9.Clinical phenotyping of severe Mycoplasma pneumoniae pneumonia in children
Heng WANG ; Weihan XU ; Jinrong LIU ; Yun PENG ; Xiaoxia PENG ; Xiaohui WEN ; Xiaolei TANG ; Hui XU ; Hui LIU ; Yuelin SHEN ; Xiaoyan ZHANG ; Haiming YANG ; Yaguang PENG ; Huimin LI ; Shunying ZHAO
Chinese Journal of Pediatrics 2024;62(7):669-675
Objective:To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods:This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children′s Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t-test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results:Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U=334.00, P<0.001). They were regarded as subtype "lung consolidation-atelectasis-necrosis". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype "lung consolidation-atelectasis". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions:Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as "lung consolidation-atelectasis-necrosis" and "lung consolidation-atelectasis". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.
10.Development status and countermeasures of medical device industry in Jilin Province
Yu-Heng YANG ; Wen-Yuan JIA ; Yun LIU ; Yong-Zheng YAN ; Yun-Gang LUO ; Guo-Min LIU
Chinese Medical Equipment Journal 2024;45(7):67-71
The development status of medical device industry in Jilin Province was described,and the main problems during the development of medical device industry in Jilin Province was analyzed.Some countermeasures were put forward including enlarging the industrial scale,constructing business incubators in the field of medical device,guaranteeing the market access of the products,accelerating the registration and approval,strengthening the cross-discipline construction and forming medical-industrial institutes.References were provided for the development of medical device industry in Jilin Province.[Chinese Medical Equipment Journal,2024,45(7):67-71]


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