1.Research progress on the anti-tumor effects of traditional Chinese medicine through intervention in the Nrf2/GPX4 signaling pathway
Jie HUANG ; Si LIN ; Chunjuan JIANG ; Ling WEI
China Pharmacy 2025;36(4):507-512
Nuclear factor-erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway plays a key role in the occurrence and development of tumors, and is involved in tumor cell proliferation, apoptosis, ferroptosis, invasion, migration, and drug resistance. Based on the Nrf2/GPX4 signaling pathway, this paper summarizes the research progress of the anti- tumor effects of traditional Chinese medicine. It is found that flavonoids (ginkgetin, luteolin, etc.), terpenoids (atractylenolide, cucurbitacin B, etc.), saponins (polyphyllin Ⅰ, polyphyllin Ⅶ), ester (brusatol) and other effective components, and traditional Chinese medicine extracts (total coumarins in Pileostegia tomentella and total flavonoids of Pterocarya hupehensis Skan), traditional Chinese medicine compounds (Fushao diqin fang, Xiaoai jiedu fang, etc.) can promote ferroptosis in tumor cells by inhibiting Nrf2/GPX4 signaling pathway and the expressions of its upstream and downstream factor proteins, as well as by increasing Fe2+ levels and lipid peroxidation, thereby exerting an antitumor effect.
2.Molecular Mechanisms Underlying Sleep Deprivation-induced Acceleration of Alzheimer’s Disease Pathology
Si-Ru YAN ; Ming-Yang CAI ; Ya-Xuan SUN ; Qing HUO ; Xue-Ling DAI
Progress in Biochemistry and Biophysics 2025;52(10):2474-2485
Sleep deprivation (SD) has emerged as a significant modifiable risk factor for Alzheimer’s disease (AD), with mounting evidence demonstrating its multifaceted role in accelerating AD pathogenesis through diverse molecular, cellular, and systemic mechanisms. SD is refined within the broader spectrum of sleep-wake and circadian disruption, emphasizing that both acute total sleep loss and chronic sleep restriction destabilize the homeostatic and circadian processes governing glymphatic clearance of neurotoxic proteins. During normal sleep, concentrations of interstitial Aβ and tau fall as cerebrospinal fluid oscillations flush extracellular waste; SD abolishes this rhythm, causing overnight rises in soluble Aβ and tau species in rodent hippocampus and human CSF. Orexinergic neurons sustain arousal, and become hyperactive under SD, further delaying sleep onset and amplifying Aβ production. At the molecular level, SD disrupts Aβ homeostasis through multiple converging pathways, including enhanced production via beta-site APP cleaving enzyme 1 (BACE1) upregulation, coupled with impaired clearance mechanisms involving the glymphatic system dysfunction and reduced Aβ-degrading enzymes (neprilysin and insulin-degrading enzyme). Cellular and histological analyses revealed that these proteinopathies are significantly exacerbated by SD-induced neuroinflammatory cascades characterized by microglial overactivation, astrocyte reactivity, and sustained elevation of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) through NF‑κB signaling and NLRP3 inflammasome activation, creating a self-perpetuating cycle of neurotoxicity. The synaptic and neuronal consequences of chronic SD are particularly profound and potentially irreversible, featuring reduced expression of critical synaptic markers (PSD95, synaptophysin), impaired long-term potentiation (LTP), dendritic spine loss, and diminished neurotrophic support, especially brain-derived neurotrophic factor (BDNF) depletion, which collectively contribute to progressive cognitive decline and memory deficits. Mechanistic investigations identify three core pathways through which SD exerts its neurodegenerative effects: circadian rhythm disruption via BMAL1 suppression, orexin system hyperactivity leading to sustained wakefulness and metabolic stress, and oxidative stress accumulation through mitochondrial dysfunction and reactive oxygen species overproduction. The review critically evaluates promising therapeutic interventions including pharmacological approaches (melatonin, dual orexin receptor antagonists), metabolic strategies (ketogenic diets, and Mediterranean diets rich in omega-3 fatty acids), lifestyle modifications (targeted exercise regimens, cognitive behavioral therapy for insomnia), and emerging technologies (non-invasive photobiomodulation, transcranial magnetic stimulation). Current research limitations include insufficient understanding of dose-response relationships between SD duration/intensity and AD pathology progression, lack of long-term longitudinal clinical data in genetically vulnerable populations (particularly APOE ε4 carriers and those with familial AD mutations), the absence of standardized SD protocols across experimental models that accurately mimic human chronic sleep restriction patterns, and limited investigation of sex differences in SD-induced AD risk. The accumulated evidence underscores the importance of addressing sleep disturbances as part of multimodal AD prevention strategies and highlights the urgent need for clinical trials evaluating sleep-focused interventions in at-risk populations. The review proposes future directions focused on translating mechanistic insights into precision medicine approaches, emphasizing the need for biomarkers to identify SD-vulnerable individuals, chronotherapeutic strategies aligned with circadian biology, and multi-omics integration across sleep, proteostasis and immune profiles may delineate precision-medicine strategies for at-risk populations. By systematically examining these critical connections, this analysis positions sleep quality optimization as a viable strategy for AD prevention and early intervention while providing a comprehensive roadmap for future mechanistic and interventional research in this rapidly evolving field.
3.Construction and clinical practice of vector management strategy for preventing ventilator-associated pneumonia by blocking etiological characteristics
Xinhua XIA ; Ying WANG ; Pengbo YAN ; Yanling SUN ; Meimei SI ; Lie QIN ; Yuxia WANG ; Yanan LI ; Ling CHEN ; Zijun ZHANG
Chinese Journal of Practical Nursing 2024;40(4):283-288
Objective:To establish an environmental management strategy for the prevention of ventilator-associated pneumonia from the perspective of etiological characteristics and to verify its application effect.Methods:Based on a sampling survey, this study constructed preventive management strategies for ventilator-associated pneumonia by blocking pathogen characteristics from the perspective of both colonization and infection management in patients. From July 2021 to June 2023, a non-synchronous randomized controlled study was conducted, including a control group of 59 cases and an experimental group of 57 cases from ICU of Tianjin Teda Hospital, all of them were mechanically ventilated patients. The effectiveness of the strategy was confirmed.Results:In the control group, there were 35 males and 24 females, with an average age of (46.97 ± 18.84) years. In the experimental group, there were 39 males and 18 females, with an average age of (47.49 ± 13.85) years. During the study period, there were 9 cases of ventilator-associated pneumonia (VAP) in the control group and 2 cases in the experimental group, the difference between the two groups was statistically significant (exact odds ratio=0.031). The duration of mechanical ventilation in the experimental group (122.41 ± 18.36) h, which was shorter than that in the control group (187.62 ± 18.05) h, and the difference was statistically significant ( t=19.28, P<0.05). The length of ICU stay in the experimental group was (8.38 ± 0.79) d, in the control group was (10.99 ± 1.10) d, the difference between them was statistically significant ( t=14.66, P<0.05). On the 7th day, there were 7 cases of positive pathogenic bacteria in sputum culture in the experimental group, which was significantly different from the 29 cases in the control group ( χ2=16.73, P<0.05). Conclusions:The vector management strategy for preventing ventilator-associated pneumonia by blocking etiological characteristics can reduce the incidence of VAP, shorten the duration of mechanical ventilation and ICU stay, and reduce the pathogen load in the sputum of mechanically ventilated patients on the 7th day.
4.Characteristics of abnormal coronary aorta origin in adults and cause analysis of missed diagnosis by transthoracic echocardiography
Si-Yang ZUO ; Sen LI ; You-Xiang KANG ; Xiao-Ling ZHAO ; Li-Xing WANG ; Rui CHEN ; Zhi-Yu FENG
Chinese Medical Equipment Journal 2024;45(1):71-75
Objective To analyze the characteristics of adult anomalous aortic origin of coronary artery(AAOCA)and the causes of missed diagnosis by transthoracic echocardiography(TTE)so as to facilitate TTE in diagnosing adult AAOCA.Methods A total of 37 adult patients with AAOCA diagnosed by non-invasive coronary CT angiography(CCTA)and/or invasive coronary angiography(ICA)were selected as research samples at some hospital from January 2019 to December 2022,and their clinical symptoms and the findings of 12-lead electrocardiogram,cardiac enzymes and TTE were summarized;the patients were typed according to the site of origin of coronary artery anomalies,and the causes for the missed diagnosis of TTE were eplored.Chi-square test was used to compare the differences in TTE missed diagnoses.Results Of the 37 patients,31 ones had no or only mild symptoms;most ones had negative results in terms of 12-lead electrocardiography,cardiac enzymes,changes in the size of the cardiac chambers,segmental ventricular wall motion abnormalities and left ventricular systolic function.The patients with anomalous origin of the right coronary artery from left sinus(ARCA-L)gained the largest proportion of 59.45%(22/37);21 patients were diagnosed with anomalous origin of coronary artery arising from the opposite sinus(ACAOS)in the two examinations of TTE,of whom there were 19 cases of ARCA-L,and the detection rate of ACAOS by TTE was 87.5%;all the 13 patients origins in branches and high-grade openings were missed by TTE.The detection rate of ACAOS by TTE was significantly higher than that of coronary artery anomalies originating in branches and in high openings,and the difference was statistically significant(21/24 vs 0/13,P<0.001).Conclusion Most adult AAOCA patients lack specificity in symptoms and related examination results.TTE has a high detection rate of ACAOS,while it is easy to miss the diagnosis of coronary artery anomalies originating from branches and high openings.Ultrasonographers have to identify false negative AAOCA by multi-section and multi-angle scanning and color Doppler flow imaging in order to reduce the rate of missed diagnosis.[Chinese Medical Equipment Journal,2024,45(1):71-75]
5.Exploration on the Biological Implications of"Earth Deficiency and Wood Depression"Pathogenesis of Hypertension from Intestinal Flora-bile Acid Axis
Meilong SI ; Hua JIN ; Minke LIU ; Yu WANG ; Qiuju ZHANG ; Shuangfang LIU ; Bishi LING ; Shangwen QI
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(3):13-18
There is a bidirectional relationship between intestinal flora and bile acids,and the imbalance of intestinal flora-bile acid axis metabolism is closely related to hypertension.Based on classical TCM literature and clinical practice,this article found that"earth deficiency"is the important pathological basis of hypertension,"wood depression"is the initiating factor of hypertension,and"earth deficiency and wood depression"is the key pathogenesis of hypertension.Combined with the research results of modern medicine and molecular biology,it is considered that the imbalance of intestinal flora and abnormal bile acid metabolism are closely related to the"earth deficiency"and"wood depression"of TCM respectively,and the imbalance of intestinal flora-bile acid axis coincides with the"earth deficiency and wood depression"of TCM in the process of hypertension.It is of great theoretical and practical significance to explore the biological connotation of hypertension"earth deficiency and wood depression"from the perspective of intestinal flora-bile acid axis for guiding TCM to prevent and treat hypertension.
6.In vitro effect of immediate and delayed post-space preparation on apical leakage following 2 root canal ob-turation techniques respectively
Ling SI ; Long JIANG ; Yaqin ZHU
Journal of Practical Stomatology 2024;40(6):793-798
Objective:To compare the effect of immediate and delayed post-space preparation on apical sealing ability between 2 root canal obturation techniques.Methods:60 freshly extracted single-rooted human premolars were collected and instrumented by M3-Pro instruments.The specimens were randomly divided into 6 groups and respectively treated by AH-Plus sealer with warm vertical compac-tion(WVC)followed by delayed post-space preparation(PSP)(A1);AH-Plus sealer with WVC followed by immediate PSP(A2);AH-Plus sealer with WVC,control group(A3);iRoot SP sealer with single cone(SC)followed by delayed PSP(B1);iRoot SP sealer with SC followed by immediate PSP(B2);iRoot SP sealer with SC,control group(B3).In group A1,A2,B1 and B2,gutta percha was removed by 1# starter drill and post-space was prepared by 2# finishing drill leaving 5 mm of apical filling.In control groups(A3 and B3),only apical 5 mm of the specimens was obturated.Dye leakage was measured as the linear penetration(LP)of the stain.The SPSS one-way analysis of variance test was used for statistical analysis.Results:The LP(mm)of group A1,A2,A3,B1,B2 and B3 was 3.986±0.500,3.382±0.806,2.178±0.554,3.844±0.877,3.416±0.579 and 1.897±0.217 respectively.Among A1,A2 and A3 groups,P<0.05.The LP of group A1 was higher than that of group A2(P<0.05).Among group B1,B2 and B3,P<0.05,but be-tween group B1 and B2,P>0.05.Between group A1 and B1,P>0.05.Between A2 and B2,P>0.05.Conclusion:Apical sealing is affected by PSP with the 2 root obturation techniques.Delayed PSP may have negative effect on apical sealing compared with immediate PSP,especially in the specimens compacted by AH-Plus sealer with WVC.
7.Detection of Haptoglobin by Surface-Enhanced Raman Scattering Based on the Shift of Characteristic Peak
Si-Qi YUE ; Zhan-Hao MO ; Jun-Qi ZHAO ; Xin QI ; Ling JIN ; Can-Can CUI ; Cheng-Yan HE ; Bing ZHAO
Chinese Journal of Analytical Chemistry 2024;52(2):231-239,中插11-中插13
Acute cerebral infarction(ACI)has the characteristics of onset nasty and high mortality,and thus the rapid determination of the occurrence and development of ACI plays a key role in the diagnosis,treatment and prognosis of ACI patients.It has shown that the serum level of human haptoglobin(Hp)is related to ACI.In this study,surface enhanced Raman scattering(SERS)combined with immune recognition was applied to establish a quantitative analysis method for serum Hp.Firstly,the SERS substrate of silver nanoparticles was prepared on silicon wafer,and 4-mercaptobenzoic Acid(MBA)was used as a Raman probe by forming Ag—S bond and connecting it on the surface of nanoparticles.The carboxyl group of MBA was linked to amino group of self-made high-affinity antibody through forming CO—NH structure thus forming a SERS self-assembled chip of Hp(Ag/MBA/anti-Hp).Hp in serum could be specifically captured by antibodies on SERS substrate,which caused the shift of SERS characteristic peak of MBA.The results showed that there was a good linear relationship between the logarithm of Hp concentration and the SERS characteristic peak shift of MBA.The detection range was 1-1000 ng/mL(R2=0.988).The Hp concentrations in serum of 90 ACI patients were determined by this method,and the results were consistent with those of ELISA method,which proved the practicability and accuracy of this method.This method was highly specific,simple and convenient,which could realize the specific recognition and quantitative analysis of serum Hp,so as to be an effective means for clinical detection of serum Hp,thus providing a reference for the treatment and prognosis of ACI.
8.Endoscopic Submucosal Dissection versus Surgical Treatment for Early Esophagogastric Junction Adenocarcinoma:Propensity Score Matching Analysis
Xue-Tong ZHANG ; Ying-Ling LIU ; Chao XU ; Si-Qing SHANG ; Kai-Guang ZHANG
Modern Interventional Diagnosis and Treatment in Gastroenterology 2024;29(4):422-428
Objective To compare the clinical efficacy and prognosis of endoscopic submucosal dissection(ESD)and surgical methods in the treatment of early esophagogastric junction adenocarcinoma(AEG),and to analyze factors influencing prognosis.Methods Hospitalized patients with early AEG who underwent ESD or surgical treatment at Anhui Provincial Hospital from January 2010 to December 2022 were collected.Among them,186 patients underwent ESD and 364 patients underwent surgical treatment.Propensity score matching was used with a ratio of 1∶1,with 164 patients in each group.Clinical outcomes,survival outcomes,and postoperative complications were compared before and after matching.Factors influencing mortality and recurrence in EGJ patients were analyzed.Results 1.Before and after matching,the ESD group had lower surgical time,hospital stay,hospital costs,intraoperative bleeding volume,and adverse events compared to the surgical group(P<0.001).2.The matched ESD group had 1-,3-,and 5-year overall survival rates of 99.5%,94.5%,and 90.2%,respectively,while the surgical group had rates of 100%,99.4%,and 97.5%for the same periods.The 1-,3-,and 5-year recurrence-free survival rates in the matched ESD group were 99.5%,96.3%,and 93.4%,respectively,compared to 100%,98.6%,and 92.5%in the surgical group.Kaplan-Meier survival analysis before and after matching showed no significant difference in overall survival and recurrence-free survival between the two groups(P>0.05).3.Age,poor differentiation,and vascular invasion were independent risk factors for OS;age and tumor size were independent risk factors for RFS.Conclusion Patients with early AEG undergoing ESD or surgical treatment have consistent clinical outcomes.ESD can be considered an effective and safe treatment for early AEG.
9.Effect of Zhengan Xifengtang on Blood Pressure and Fecal Microflora of Spontaneously Hypertensive Rats
Shuangfang LIU ; Hua JIN ; Bishi LING ; Shangwen QI ; Meilong SI ; Qiuju ZHANG ; Yu WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):76-85
ObjectiveTo observe the effect of Zhengan Xifengtang on blood pressure and fecal microflora of spontaneously hypertensive rats (SHRs). MethodA total of 75 male SHRs aged nine weeks were randomly divided into SHR group, Benazepril group (1.00 mg·kg-1·d-1), high-dose Zhengan Xifengtang group (34.5 g·kg-1·d-1), medium-dose Zhengan Xifengtang group (17.25 g·kg-1·d-1), and low-dose Zhengan Xifengtang group (8.625 g·kg-1·d-1). A total of 15 male Wistar-Kyoto (WKY) rats aged nine weeks were selected as the normal group. The normal group and SHR group were administrated with an equal volume of distilled water for eight weeks. During the administration, the blood pressure of the rats was measured regularly. After the intervention, fresh feces were collected with a sterile frozen storage tube, and 16S amplicon information was collected and analyzed. Plasma, hippocampus, and ileum of rats were collected for ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) detection. ResultZhengan Xifengtang decreased the systolic blood pressure and diastolic blood pressure of SHRs. Compared with the SHR group, Zhengan Xifengtang decreased the diversity of fecal microflora of SHRs. At the phylum level, Zhengan Xifengtang increased the relative abundance of SHR Verrucomicrobia and Actinobacteria and decreased the relative abundance of Synergistetes, Tenericutes, and Candidatus Saccharibacteria. Compared with the SHR group, Zhengan Xifengtang increased the relative abundance of Blautia wexlerae, Fusicatenibacter saccharivorans, and Akkermansia muciniphila and decreased the relative abundance of Clostridium lavalense, Intestinimonas butyriciproducens, Acetatifactor muris, Alloprevotella rava, and Oscillibacter valericigenes. Spearman correlation analysis showed that the systolic blood pressure of rats was negatively correlated with the relative abundance of Ethanoligenens, Aerococcus, Butyrivibrio, Olsenella, Bifidobacterium, Clostridium XIVb, Allobaculum, and Fusicatenibacter and positively correlated with the relative abundance of Alloprevotella. Zhengan Xifengtang increased the contents of plasma, hippocampal 5-hydroxy tryptamine(5-HT), and 5-hydroxyindole acetic acid(5-HIAA) in SHRs and decreased the contents of 5-HT and 5-HIAA in the ileum, and the content of 5-HT in the hippocampus was negatively correlated with that in the ileum. ConclusionZhengan Xifengtang can reduce the blood pressure of SHRs, which may be related to reducing the diversity of SHR microflora, regulating the structure of the microflora, increasing the relative abundance of 5-HT and short-chain fatty acids bacteria, and lowering the relative abundance of pathogenic bacteria related to intestinal inflammation.
10.Synthesis and activity evaluation of 6-azazindole derivatives for pancreatic cancer therapy
Yang CAO ; Qian LI ; Ya-ling WANG ; Wen-hui CUI ; Chen-liang QIAN ; Xin-xin SI
Acta Pharmaceutica Sinica 2024;59(10):2828-2835
Fragment with some anti-pancreatic cancer activity was identified by screening our internal chemical library. Eighteen compounds in 4 classes were synthesized by systematic modification and their anti-pancreatic cancer activity were evaluated. Ⅱ-1 (IC50 = 6.40 ± 0.34 μmol·L-1) and Ⅱ-2 (IC50 = 7.15 ± 0.51 μmol·L-1) exhibited outstanding activity. Subsequently, the anti-migration ability and invasion ability of Ⅱ-1 was evaluated by wound healing assay and invasion assay, Ⅱ-1 exhibited good anti-migration ability and outstanding anti-invasion ability. Using molecular docking technology and molecular dynamics simulation technology, the potential target was locked on bispecific tyrosine phosphorylation regulates kinase 1A (DYRK1A). By enzyme activity testing, the inhibitory capacity of Ⅱ-1 and Ⅱ-2 was 48% and 32%, respectively.

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