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.Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine.
Xin-Ran DU ; Meng-Yi WU ; Mao-Can TAO ; Ying LIN ; Chao-Ying GU ; Min-Feng WU ; Yi CAO ; Da-Can CHEN ; Wei LI ; Hong-Wei WANG ; Ying WANG ; Yi WANG ; Han-Zhi LU ; Xin LIU ; Xiang-Fei SU ; Fu-Lun LI
Journal of Integrative Medicine 2025;23(6):641-653
Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy*
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Humans
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Medicine, Chinese Traditional/methods*
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Integrative Medicine
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Drugs, Chinese Herbal/therapeutic use*
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Practice Guidelines as Topic
3.Separate and Combained Associations of PM 2.5 Exposure and Smoking with Dementia and Cognitive Impairment.
Lu CUI ; Zhi Hui WANG ; Yu Hong LIU ; Lin Lin MA ; Shi Ge QI ; Ran AN ; Xi CHEN ; Hao Yan GUO ; Yu Xiang YAN
Biomedical and Environmental Sciences 2025;38(2):194-205
OBJECTIVE:
The results of limited studies on the relationship between environmental pollution and dementia have been contradictory. We analyzed the combined effects of PM 2.5 and smoking on the prevalence of dementia and cognitive impairment in an elderly community-dwelling Chinese population.
METHODS:
We assessed 24,117 individuals along with the annual average PM 2.5 concentrations from 2012 to 2016. Dementia was confirmed in the baseline survey at a qualified clinical facility, and newly suspected dementia was assessed in 2017, after excluding cases of suspected dementia in 2015. National census data were used to weight the sample data to reflect the entire population in China, with multiple logistic regression performed to analyze the combined effects of PM 2.5 and smoking frequency on dementia and cognitive impairment.
RESULTS:
Individuals exposed to the highest PM 2.5 concentration and smoked daily were at higher risk of dementia than those in the lowest PM 2.5 concentration group ( OR, 1.603; 95% CI [1.626-1.635], P < 0.0001) and in the nonsmoking group ( OR, 1.248; 95% CI [1.244-1.252]; P < 0.0001). Moderate PM 2.5 exposure and occasional smoking together increased the short-term risk of cognitive impairment. High-level PM 2.5 exposure and smoking were associated with an increased risk of dementia, so more efforts are needed to reduce this risk through environmental protection and antismoking campaigns.
CONCLUSION
High-level PM 2.5 exposure and smoking were associated with an increased risk of dementia. Lowering the ambient PM 2.5, and smoking cessation are recommended to promote health.
Humans
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Dementia/etiology*
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Male
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Aged
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Female
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Cognitive Dysfunction/etiology*
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China/epidemiology*
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Particulate Matter/analysis*
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Smoking/epidemiology*
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Air Pollutants/analysis*
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Aged, 80 and over
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Environmental Exposure/adverse effects*
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Prevalence
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Middle Aged
4.Comparative Transcriptomic and Metabolomic Analyses Reveal the Mechanism by Which Foam Macrophages Restrict Survival of Intracellular Mycobacterium Tuberculosis.
Xiao PENG ; Yuan Yuan LIU ; Li Yao CHEN ; Hui YANG ; Yan CHANG ; Ye Ran YANG ; Xuan ZHANG ; An Na JIA ; Yong Bo YU ; Yong Li GUO ; Jie LU
Biomedical and Environmental Sciences 2025;38(7):781-791
OBJECTIVES:
This study aimed to investigate the impact of foam macrophages (FMs) on the intracellular survival of Mycobacterium tuberculosis (MTB) and identify the molecular mechanisms influencing MTB survival.
METHODS:
An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival.
RESULTS:
Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate (cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival.
CONCLUSIONS
FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
Mycobacterium tuberculosis/physiology*
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Transcriptome
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Metabolomics
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Foam Cells/microbiology*
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Humans
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Metabolome
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Tuberculosis/microbiology*
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Gene Expression Profiling
5.Sertraline hydrochloride combined with compound chamomile lidocaine gel for the treatment of premature ejaculation
Shu-Gen LI ; Shang GAO ; Zhen-Wei GU ; Dao-Hua ZHAO ; Jie JIANG ; Xiao-Ting LU ; Lan-Xiang LIU ; Hao-Ran LIU ; Ze CHEN
National Journal of Andrology 2024;30(9):809-812
Objective:To investigate the effect of sertraline hydrochloride combined with compound chamomile lidocaine gel in the treatment of premature ejaculation(PE).Methods:We selected 80 cases of PE treated in our hospital from June 2021 to May 2023 and equally randomized them into a control and an observation group,the former medicated with compound chamomile lidocaine gel while the latter with sertraline hydrochloride in addition,both for 6 weeks.We recorded and compared the intravaginal ejaculation latency time(IELT),the number of successful sexual intercourses per week,the Premature Ejaculation Diagnostic Tool(PEDT)scores,and the incidence of adverse reactions between the two groups of patients.Results:After the treatment,the IELT was signif-icantly longer([5.39±1.17]vs[2.49±0.73]min,P<0.05),the weekly number of successful sexual intercourses remarkably higher(1.82±0.45 vs 0.93±0.19,P<0.05)and the PEDT scores markedly lower(7.42±2.04 vs 9.85±2.36,P<0.05)in the observation than in the control group,but no statistically significant differences were observed in the baseline PEDT scores or the incidence of adverse reactions between the two groups(P>0.05).Conclusion:Sertraline hydrochloride combined with com-pound chamomile lidocaine gel is definitely effective in the treatment of PE,which can significantly improve the patients'quality of sexual life,with a high safety and low incidence of adverse reactions.
6.Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics
Yu-long CHEN ; You ZHAI ; Xiao-yan WANG ; Wei-xia LI ; Hui ZHANG ; Ya-li WU ; Liu-qing YANG ; Xiao-fei CHEN ; Shu-qi ZHANG ; Lu NIU ; Ke-ran FENG ; Kun LI ; Jin-fa TANG ; Ming-liang ZHANG
Acta Pharmaceutica Sinica 2024;59(2):382-394
Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and
7.The application value of imaging in the diagnosis and treatment of external auditory canal cholesteatoma in children
Shuochun WU ; Xuefeng SUN ; Yingxia LU ; Chang LIU ; Xiaoli YI ; Ran TAO
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(2):97-100
OBJECTIVE To investigate the HRCT and MRI characteristic of external auditory canal cholesteatoma(EACC)in children.METHODS A total of 40 patients(45 lesions)with EACC confirmed by pathology were retrospectively analyzed with HRCT and MRI characteristics and clinical therapeutic value.Imaging findings of 40 patients(45 lesions)with EACC were retrospectively analyzed.RESULTS Soft tissues were found in all the external auditory canal(EAC).Of the forty-five soft tissues,7 manifested as inhomogeneous strip soft tissues and 38 as lesions solid soft tissues;30 located in medial part of the EAC and covered the tympanic membrane,while the other 15 presented as tympanic membrane perforation and involved the tympanic cavity.The MRI of the 3 ears showed high signal on T2/T1 iso-intensity,high signal on DWI,and low signal on ADC.Normal whole bony EAC was observed in 17 cases and enlarged medial EAC in 28 cases.Seven cases only involved in the superior wall,but 38 cases displayed as multiple bone wall involved,of which 6 involved in circumferential walls.Thirty-three cases displayed atactic ear bone margin,11 displayed blunted or disappeared drum shield plate.Destroy of long crus of incus and manubrium mallei occurred in 15 cases,of short crus of incus in 8 cases,of stapes in 2 cases,and mastoiditis in 5 cases.According to the pneumatization degree of mastoid air cell,37 cases were classified into pneumatic type,7 cases into mixed type,and the last one into diploic type.CONCLUSION The children EACC tends to be limited and rarely involved in middle ear and mastoid process.No patient with peri-ear infection was found.Application of HRCT and MRI help accurate location and determination of cholesteatoma.According to the extent of the lesion,selecting the appropriate surgical method is an effective method to remove cholesteatoma,improve hearing and reduce recurrence.
8.Network meta-analysis for efficacy and safety of TACE combined with anti-angiogenic drugs in the treatment of unresectable primary liver cancer
Fenping LU ; Guangyan XING ; Bowen LIU ; Xiaobin LI ; Kai ZHAO ; Yun RAN ; Fenfang WU ; Shiping HU
China Pharmacy 2024;35(20):2533-2540
OBJECTIVE To systematically evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with anti-angiogenic drugs for the treatment of unresectable primary liver cancer (PLC). METHODS Retrieved from Chinese and English databases such as CNKI, the Cochrane Library, Google, and Baidu Academic, randomized controlled trial (RCT) about TACE combined with anti-angiogenic drugs for the treatment of unresectable PLC were collected from the inception to May 27, 2024. After screening the literature, extracting data, and evaluating the quality of the literature, network meta-analysis was performed using R 4.2.2 and Stata 17.0. RESULTS A total of 44 RCT were included, involving 5 607 patients and 8 interventions. The network meta-analysis results showed that for prolonging median overall survival (mOS) and median progression- free survival (mPFS), TACE+apatinib had the best efficacy, with TACE+apatinib and TACE+sorafenib ranking as the top two. For improving objective response rate (ORR) and disease control rate (DCR), TACE+donafenib had the best efficacy, with TACE+ donafenib and TACE+ lenvatinib ranking as the top two. In terms of safety, TACE+donafenib was the best, with TACE+donafenib and TACE+apatinib ranking as the top two. CONCLUSIONS TACE+apatinib and TACE+donafenib have good efficacy for patients with unresectable PLC, and TACE+donafenib has the best safety profile.
9.Exploring the risk "time interval window" of sequential medication of Reduning injection and penicillin G injection based on the correlation between biochemical indexes and metabolomics characteristics
Ming-liang ZHANG ; Yu-long CHEN ; Xiao-yan WANG ; Xiao-fei CHEN ; Hui ZHANG ; Ya-li WU ; Liu-qing YANG ; Shu-qi ZHANG ; Lu NIU ; Ke-ran FENG ; Wei-xia LI ; Jin-fa TANG
Acta Pharmaceutica Sinica 2024;59(7):2098-2107
Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.
10.Expression of CD226 in the small intestinal group 3 innate lymphoid cells (ILC3) in mice.
Lu YANG ; Jingchang MA ; Yitian LIU ; Tingting WANG ; Yuling WANG ; Ran ZHUANG ; Zhengxiang ZHANG
Chinese Journal of Cellular and Molecular Immunology 2024;40(1):1-6
Objective To observe the expression of adhesion molecule CD226 on the small intestinal group 3 innate lymphoid cells (ILC3) in mice. Methods The bioinformatics was used to analyze the expression of CD226 on murine ILCs. Small intestinal mucosal lamina propria lymphocytes (LPL) were isolated from wild-type C57BL/6J mice, and the expression of CD226 on ILC1 and ILC3 was detected by flow cytometry. A mouse model of dextran sulfate sodium (DSS)-induced colitis was constructed to observe the changes in the expression of CD226 on ILC3. Results Both ILC1 and ILC3 in the mice small intestine expressed CD226 molecules; the proportion of ILC3 was reduced, while the expression level of CD226 on ILC3 was increased in the colitis model. Conclusion CD226 is expressed on the small intestines of mice, and although the proportion of ILC3 decreases in the DSS-induced colitis, the expression of CD226 on ILC3 increases.
Animals
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Mice
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Colitis/chemically induced*
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Immunity, Innate
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Intestine, Small
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Lymphocytes
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Mice, Inbred C57BL

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