1.Manganese porphyrin metal-organic framework nanoparticles loaded with DMXAA combined with sonodynamic therapy for the treatment of triple-negative breast cancer mouse xenografts
LIU Qianhui ; GUI Bin ; PU Huan ; LI Zhouchang ; HUANG Xin ; ZHOU Qing ; DENG Qing
Chinese Journal of Cancer Biotherapy 2026;33(3):262-269
[摘 要] 目的:构建负载STING激动剂DMXAA的锰卟啉金属有机框架纳米颗粒(DPM),探讨其对三阴性乳腺癌(TNBC)细胞4T1及其小鼠移植瘤的治疗效果。方法:通过物理吸附法制备 DPM 纳米颗粒,利用透射电镜、扫描电镜及纳米粒度电位仪表征其形貌与理化性质。常规培养4T1细胞,细胞实验分为对照组、超声辐照组(US组)、DPM治疗组(DPM组)和DPM治疗联合超声辐照组(DPM + US组),用CCK-8法检测细胞活性,免疫荧光法检测高迁移率族蛋白B1(HMGB1)和钙网蛋白(CRT)的表达,WB法检测STING通路相关蛋白的表达。构建4T1细胞移植瘤小鼠模型,分为四组,处理同细胞实验,测量肿瘤体积,免疫荧光法检测移植瘤组织中Ki-67、HMGB1、CRT和缺氧诱导因子-1ɑ(HIF-1ɑ)蛋白的表达,TUNEL法检测细胞凋亡,流式细胞术检测免疫细胞活化情况,对主要器官进行H-E染色,以评估纳米材料的体内安全性。结果:DPM呈梭形,平均粒径(268 ± 3.302)nm,电位(33.1 ± 0.87)mV。细胞实验中,DPM联合超声辐照可明显抑制4T1细胞的增殖(P < 0.001),提高4T1细胞中ROS水平(P < 0.001),诱导4T1细胞CRT表达上调(P < 0.001),HMGB1从细胞核中移至细胞质,激活STING信号通路[p-STING、p-TBK1、p-IRF3蛋白表达均显著增加(均P < 0.001)]。体内实验中,DPM联合超声辐照可显著抑制4T1细胞移植瘤生长(P < 0.001)并促进免疫细胞表型转化(P < 0.001),抑制移植瘤组织中Ki-67、HIF-1α蛋白表达(均P < 0.01),谷胱甘肽(GSH)产生(P < 0.01),促进CRT、HMGB1蛋白表达、ROS产生(P < 0.001),对主要器官结构无明显影响。结论: DPM联合超声辐照可通过激活STING通路显著抑制4T1细胞及其移植瘤的生长,诱导抗肿瘤免疫应答,且对主要器官无明显毒性。
2.Application of nanoprobe based on aggregation-induced luminescence in photothermal diagnosis and treatment of prostate cancer
Bin GUI ; Nan JIANG ; Xin HUANG ; Fanglu ZHONG ; Zhiwen WANG ; Qianhui LIU ; Yuxin GUO ; Yueying CHEN ; Huan PU ; Qing DENG
Chinese Journal of Tissue Engineering Research 2025;29(16):3400-3409
BACKGROUND:A novel aggregation induced luminescence fluorescence probe based on the mechanism of intramolecular motility restriction can be used for the detection of disease markers,tumor diagnosis,and bacterial imaging recognition.OBJECTIVE:To prepare a near-infrared Ⅱ nanoprobe called FA-DSPE-PEG-AIE@NPs based on aggregation-induced luminescence,and to explore its potential of targeted fluorescence imaging and photothermal therapy for prostate cancer.METHODS:Lecithin,polyethylene glycol phospholipids,folate polyethylene glycol phospholipids,and aggregation induced luminescent molecule 2TT-oC26B were used as raw materials.The folate-targeted nanoprobe FA-DSPE-PEG-AIE@NPs were prepared by nanoprecipitation method,and basic characterization of the nanoprobe was detected.PC3 human prostate cancer cells and human umbilical vein endothelial cells were selected as experimental objects.The cytotoxicity and phototoxicity of FA-DSPE-PEG-AIE@NPs were detected.PC3 human prostate cancer cells were selected as the experimental objects.Flow cytometry and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.PC3 human prostate cancer cells were injected subcutaneously into the abdomen of BALB/C nude mice to establish a tumor model,and nanoprobes FA-DSPE-PEG-AIE@NPs were injected into the tail vein.The mice were immediately subjected to near-infraced Ⅱ fluorescence imaging.12 hours later,the tumor was irradiated by laser for 5 minutes,and the photothermal treatment effect was observed within 14 days.RESULTS AND CONCLUSION:(1)The nanoprobes FA-DSPE-PEG-AIE@NPs with a mean diameter of(171.0±0.3)nm showed a well-defined spherical morphology.The nanoprobe had a wide absorption spectrum and tail emission extending to the near-infrared Ⅱ which emitted a bright near-infrared Ⅱ fluorescence signal under laser irradiation.(2)The nanoprobes FA-DSPE-PEG-AIE@NPs had low cytotoxicity and high phototoxicity.The results of flow cytometry and calcein/propidium iodide staining showed that nanoprobes FA-DSPE-PEG-AIE@NPs had an obvious photothermal killing effect on human prostate cancer cells.(3)The nanoprobes FA-DSPE-PEG-AIE@NPs successfully achieved near-infrared Ⅱ fluorescence imaging of mouse blood vessels and the maximum enrichment time of the tumor was 12 hours.The vessel widths of the hind leg and single blood vessels of abdomen were estimated to be 0.63 mm and 0.42 mm.The tumor volume of mice was significantly smaller after 14 days of treatment.(4)The results show that nanoprobes FA-DSPE-PEG-AIE@NPs can achieve near-infrared Ⅱ fluorescence imaging and photothermal therapy of prostate cancer effectively,which may provide a new method for early diagnosis and combined treatment of prostate cancer.
3.Dynamic evolution of research topics in the field of physical activity and executive function
Qing DENG ; Chen QIU ; Qingjun WANG ; Gui HUANG ; Yeting ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(14):3043-3050
BACKGROUND:Research on physical activity and executive function continues to emerge,but no scholars have used visual tools to explore the dynamic evolution path of research topics in this field.OBJECTIVE:To explore the dynamic evolution process of research topics in the field of physical activity and executive function using bibliometrics methos,so as to clarify their development status and changes in knowledge structure.METHODS:The Web of Science database was searched by the search formula:TS=("Physical activity"AND"Executive function*")OR TS=(Exercise AND"Executive function*").According to the inclusion and exclusion criteria,4 386 relevant documents were selected as content,and SciMAT software was used for visual analysis.RESULTS AND CONCLUSION:The field of physical activity and executive function is booming,with more and more in-depth research and more room for future development.This field can be divided into four directions:executive function,children,the elderly,and intervention,and forms 11 main evolutionary paths.Topics such as"motor skills,""lifestyle,""aerobic exercise,"and"interventions"are likely to be the focus of future research,with the"adolescent"and"elderly"groups being the focus of research in this area.
4.Research Progress of Chinese Medicine Monomers in Treatment of Cholangiocarcinoma.
Xiang WANG ; Xiao-Qing WANG ; Kai LUO ; He BAI ; Jia-Lin QI ; Gui-Xin ZHANG
Chinese journal of integrative medicine 2025;31(2):170-182
Cholangiocarcinoma (CCA) is a malignant tumor originating from cholangiocytes. However, it remains unclear about the pathogenesis of this carcinoma, which may be related to multiple factors. Currently, CCA is mainly treated by surgery, chemotherapy, and radiotherapy. Among them, surgery is the only potentially curative option for CCA. Nevertheless, the high malignancy and asymptomatic nature of CCA may lead to poor treatment outcomes. It has been demonstrated that Chinese medicine (CM) plays a significant role in various antitumor applications. Meanwhile, CM exhibits fewer side effects and high availability. Moreover, the in vitro application of CM monomers has been explored in many domestic and foreign studies. This article mainly reviews the signaling pathways and molecular mechanisms of CM monomers in the treatment of CCA in recent years. These findings are expected to provide new insights into the treatment of CCA.
Cholangiocarcinoma/drug therapy*
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Humans
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Drugs, Chinese Herbal/pharmacology*
;
Bile Duct Neoplasms/drug therapy*
;
Medicine, Chinese Traditional
;
Animals
;
Signal Transduction/drug effects*
5.International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025).
Sheng-Sheng ZHANG ; Lu-Qing ZHAO ; Xiao-Hua HOU ; Zhao-Xiang BIAN ; Jian-Hua ZHENG ; Hai-He TIAN ; Guan-Hu YANG ; Won-Sook HONG ; Yu-Ying HE ; Li LIU ; Hong SHEN ; Yan-Ping LI ; Sheng XIE ; Jin SHU ; Bin-Fang ZENG ; Jun-Xiang LI ; Zhen LIU ; Zheng-Hua XIAO ; Jing-Dong XIAO ; Pei-Yong ZHENG ; Shao-Gang HUANG ; Sheng-Liang CHEN ; Gui-Jun FEI
Journal of Integrative Medicine 2025;23(5):502-518
Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy*
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Humans
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Medicine, Chinese Traditional/methods*
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Practice Guidelines as Topic
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Drugs, Chinese Herbal/therapeutic use*
6.Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex.
Yu-Die YANG ; Wen ZHONG ; Ming CHEN ; Qing-Chen TANG ; Yan LI ; Lu-Lu YAO ; Mei-Qi ZHOU ; Neng-Gui XU ; Shuai CUI
Journal of Integrative Medicine 2025;23(5):537-547
OBJECTIVE:
To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2).
METHODS:
The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology.
RESULTS:
Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors.
CONCLUSION
EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture
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Stress Disorders, Post-Traumatic/metabolism*
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Animals
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Lipocalin-2/metabolism*
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Prefrontal Cortex/physiopathology*
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Male
;
Mice
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Neurons/physiology*
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Disease Models, Animal
;
Fear
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Behavior, Animal
;
Mice, Inbred C57BL
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Neuroinflammatory Diseases/metabolism*
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Anxiety/therapy*
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Acupuncture Points
8.LncRNA GS1-124K5.4 targeting regulation of PRDX6 on proliferation,migration and Invasion of lung squamous carcinoma cells
Yu-ning HU ; Yan-lei GE ; Ye JIN ; Jun-qing GAN ; Wei-nan YAO ; Ya-nan WU ; Xuan ZHENG ; Zi-qing LIU ; Xin SU ; Guo-gui SUN
Chinese Pharmacological Bulletin 2025;41(8):1531-1541
Aim To investigate the effect of long-chain non-coding RNA(lncRNA)GS1-124K5.4 targeting regulation of PRDX6 on proliferation,migration and in-vasion of lung squamous carcinoma(LUSC)cells and the underlying mechanism.Methods The expression level of lncRNA GS1-124K5.4 in lung cancer tissues and adjacent tissues of 60 patients with LUSC were de-termined by fluorescence in situ hybridization.The ex-pression level of lncRNA GS1-124K5.4 in human nor-mal lung cells and LUSC cells were determined by qRT-PCR.Two kinds of LUSC cells(NCI-H 1703,SK-MES-1)with highest expression level of lncRNA GS1-124K5.4 were selected for subsequent experi-ments.The distribution of lncRNA GS1-124K5.4 in cells was studied by fluorescence in situ hybridization and prokaryotic separation.The effect of knockdown of lncRNA GS1-124K5.4 on proliferation of NCI-H1703 and SK-MES-1 cells was studied by CCK-8 experiment and cell clone formation experiment;the effect of knockdown of lncRNA GS1-124K5.4 on migration of NCI-H1703 and SK-MES-1 cells was studied by cell scratch experiment and Transwell cell migration experi-ment;and the effect of knockdown of lncRNA GS1-124K5.4 on invasion of NCI-H1703 and SK-MES-1 cells was studied by Transwell invasion experiment.The protein to be bound by lncRNA GS1-124K5.4 was detected by RNA pull-down combined with mass spec-trometry and immune-precipitation.The effect of knockdown of lncRNA GS1-124K5.4 targeting PRDX6 on proliferation,migration and invasion of NCI-H1703 and SK-MES-1 cells was studied.Results(1)The fluorescence intensity of lncRNA GS1-124K5.4 in lung squamous cell carcinoma increased compared with that in adjacent tissues(P<0.05),and the expression of lncRNA GS1-124K5.4 was related with lymph node metastasis and clinical stage(P<0.05).(2)The ex-pression level of lncRNA GS1-124K5.4 in NCI-H1703,NCI-H520 and SK-MES-1 cells significantly increased(P<0.05).(3)The result of fluorescence in situ hybridization experiment and nucleoplasm sepa-ration experiment showed that lncRNA GS1-124K5.4 was mainly distributed in cell nucleus.(4)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of lncRNA GS1-124K5.4 significantly decreased(P<0.05).(5)PRDX6 protein to be bound to LncRNA GS1-124K5.4 was determined by RNA pull-down combined with mass spectrometry and immunoprecipitation.(6)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNA GS1-124K5.4 significantly increased(P<0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of PRDX6 significantly decreased(P<0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNAGS1-124K5.4 and knockdown of PRDX6 showed no signifi-cant change(P>0.05).Conclusions LncRNA GS1-124K5.4 is highly expressed in lung squamous cell carcinoma,and it may promote the proliferation,migration and invasion of lung squamous carcinoma cells by targeting the expression of PRDX6 protein.
9.Quality evaluation of Gegen Formula Granules
Dai-liang ZHANG ; Chun-xia WANG ; Lei SHI ; Yu-kang LIU ; Yong-qiang LIN ; Yu-zhuo WANG ; Jing-hua ZHANG ; Jin-xin LI ; Gui-yun CAO ; Zhao-qing MENG
Chinese Traditional Patent Medicine 2025;47(5):1421-1431
AIM To evaluate the quality of Gegen Formula Granules.METHODS Linear calibration with two reference substances(LCTRS)was adopted in the predicting of retention time with puerarin and daidzein as internal standards.UPLC characteristic chromatograms were established.The contents of 3'-hydroxy puerarin,puerarin(internal standard),3'-methoxy puerarin,puerarin 6"-O-xyloside,puerarin apioside and daidzin were determined by quantitative determination analysis multi-components by a single marker(QAMS),after which their transfer rates were calculated.RESULTS Compared with relative retention time method,LCTRS demonstrated higher positional accuracy for characteristic peaks and wider application range for columns.There were 9 characteristic peaks in the characteristic chromatograms for 14 batches of formula granules and 15 batches of standard decoctions with the similarities of more than 0.95.The contents and transfer rates of various constituents in formula granules and standard decoctions were basically consistent.CONCLUSION The chemical constituents in formula granules and their standard decoctions of Puerariae lobatae Radix display good consistency,reliable preparation process is observable in the former.
10.Evaluation of chemical constituent consistency in formula granules and traditional decoctions of Gouteng Jiangya Formula
Qing-gang ZHANG ; Dai-liang ZHANG ; Hong QI ; Shu-wen DING ; Yu-zhuo WANG ; Yun-lun LI ; Ji-fu HE ; Huan-ying GUO ; Gui-yun CAO ; Zhao-qing MENG
Chinese Traditional Patent Medicine 2025;47(11):3555-3565
AIM To evaluate the chemical constituent consistency in formula granules and traditional decoctions of Gouteng Jiangya Formula.METHODS HPLC characteristic chromatograms were established,the analysis was performed on a 30 ℃ thermostatic YMC-Triart C18 column(4.6 mm× 250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.2%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.Puerarin was used as an internal standard to calculate the relative correction factors of 3'-methoxy puerarin,puerarin apioside,magnolflorine,paeoniflora,daidzin,baicalin,palmatine,berberine,wogonoside and benzoylpaeoniflorin,after which the content detemination was made by quantitative analysis of multi-components by single-marker(QAMS).RESULTS The characteristic chromatograms of 9 batches of formula granules and 15 bacthes of traditional decoctions demonstrated the similarities of more than 0.90 at the detection wavelengths of 192,210,240,260,280,300,320,360 nm,along with similar total peak areas.Eleven constituents showed good linear relationships within their own ranges(r>0.999 0),whose average recoveries were 97.27%-101.64%with the RSDs of 0.36%-1.11%,the result obtained by QAMS and external standard method demonstrated no significant differences(P>0.05).The contents of various constituents in the formula granules approximated those in the traditional decoctions.CONCLUSION The consistent kinds and contents of various constituents are obversable in formula granules and traditional decoctions of Gouteng Jiangya Formula,which can provide a reference for the reasonable clinical application of this formula.

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